Is dyspnea management evidence-based?

PubMed

Aiello-Laws, Lisa B

2013-11-01

Reviewing the articles published in the past 40 years in the Oncology Nursing Forum (ONF) can assist in the identification of trends related to lung cancer treatment and management. Fifty-eight articles or studies published in ONF during that time were specific to lung cancer. The total number of published articles increased with each decade, but no articles were identified in the 1970s. The topics were quite varied, with each of the following represented by three or more articles: symptom clusters, radiation, smoking cessation, dyspnea, nutrition, and quality of life. To better focus this review on a specific aspect of lung cancer management, dyspnea was chosen.

Hemodynamic determinants of dyspnea improvement in acute decompensated heart failure.

PubMed

Solomonica, Amir; Burger, Andrew J; Aronson, Doron

2013-01-01

Dyspnea relief constitutes a major treatment goal and a key measure of treatment efficacy in decompensated heart failure. However, there are no data with regard to the relationship between hemodynamic measurements during treatment and dyspnea improvement. We studied 233 patients assigned to right heart catheterization in the Vasodilation in the Management of Acute Congestive Heart Failure trial. Dyspnea (assessed using a 7-point Likert scale) and hemodynamic parameters were measured simultaneously at 15 and 30 minutes and 1, 2, 3, 6, and 24 hours. Dyspnea relief was defined as moderate or marked improvement. There was a time-dependent association between the reductions in pulmonary capillary wedge pressure (PCWP; 25.4, 24.6, 24.0, 23.5, 23.4, 21.5, and 19.9 mm Hg) and the percentage of patients achieving dyspnea relief (17.7%, 24.6%, 32.2%, 36.2%, 37.8%, 47.4%, and 66.1%, in the respective time points). Multivariable logistic generalized estimating equations modeling demonstrated that reductions of both PCWP and mean pulmonary artery pressure were independently associated with dyspnea relief. Compared with the highest PCWP quartile, the adjusted odds ratios for dyspnea relief were 0.92 (95% confidence interval [CI], 0.67-1.29), 1.07 (95% CI, 0.75-1.55), and 1.80 (95% CI, 1.22-2.65) in the third, second, and first PCWP quartiles, respectively (P(trend)=0.003). Compared with the highest mean pulmonary artery pressure quartile, the adjusted odds ratios for dyspnea relief were 2.0 (95% CI, 1.41-2.82), 2.23 (95% CI, 1.52-3.27), and 2.98 (95% CI, 1.91-4.66) in the third, second, and first mean pulmonary artery pressure quartiles, respectively (P(trend)<0.0001). A clinically significant improvement in dyspnea is associated with a reduction in both PCWP and mean pulmonary artery pressure.

Incidence and causes of new-onset dyspnea in 3,719 patients treated with clopidogrel and aspirin combination after coronary stenting.

PubMed

Serebruany, Victor; Pokov, Ilya; Kuliczkowski, Wiktor; Vahabi, Javad; Atar, Dan

2008-08-01

The experimental oral antiplatelet agent AZD6140 causes dyspnea in randomized trials. Whether clopidogrel may also cause dyspnea remains controversial. We sought to define the incidence and causes of dyspnea in a large post-percutaneous coronary intervention (PCI) cohort based on open-labeled consecutive registry analysis of in-hospital charts and discharge diagnoses. Data were collected at six-month follow-up by means of telephone interviews or returned questionnaires during outpatient visits. Patients undergoing coronary stent implantation were loaded with 600 mg clopidogrel followed by 75 mg/daily in combination with 75-325 mg of aspirin daily for at least six months. Data from 3,719 patients were analyzed. Dyspnea was diagnosed in 157 (4.2%) patients caused by chronic obstructive pulmonary disease (n = 43 or 27% of the dyspnea group), heart failure (n = 30 or 19%), cancer (n = 22 or 14%), pneumonia (n = 17 or 11%); asthma (n = 8 or 5%), pulmonary hypertension (n = 8 or 5%); pericarditis (n = 5 or 3%); cardiac arrhythmias (n = 4 or 2.5%); pleural effusion (n = 1), pulmonary embolism (n = 1), anxiety (n = 1), or unknown (n = 17, or 11%). The incidence of dyspnea at six months in a post-stent cohort treated with aspirin and clopidogrel is low (4.2%). The majority of patients with dyspnea (140/157) exhibit a distinct underlying disease or condition, in contrast to only 17 patients (0.45% of total cohort) in whom the pathogenesis of dyspnea remained unidentified. These data closely match the frequency of dyspnea that was observed in the CAPRIE trial, suggesting that therapy with clopidogrel, and/or aspirin holds very small (if any) risk for dyspnea.

Does nebulized fentanyl relieve dyspnea during exercise in healthy man?

PubMed Central

Kotrach, Houssam G.; Bourbeau, Jean

2015-01-01

Few therapies exist for the relief of dyspnea in restrictive lung disorders. Accumulating evidence suggests that nebulized opioids selective for the mu-receptor subtype may relieve dyspnea by modulating intrapulmonary opioid receptor activity. Our respective primary and secondary objectives were to test the hypothesis that nebulized fentanyl (a mu-opioid receptor agonist) relieves dyspnea during exercise in the presence of abnormal restrictive ventilatory constraints and to identify the physiological mechanisms of this improvement. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of 250 μg nebulized fentanyl, chest wall strapping (CWS), and their interaction on detailed physiological and perceptual responses to constant work rate cycle exercise (85% of maximum incremental work rate) in 14 healthy, fit young men. By design, CWS decreased vital capacity by ∼20% and mimicked the negative consequences of a mild restrictive lung disorder on exercise endurance time and on dyspnea, breathing pattern, dynamic operating lung volumes, and diaphragmatic electromyographic and respiratory muscle function during exercise. Compared with placebo under both unrestricted control and CWS conditions, nebulized fentanyl had no effect on exercise endurance time, integrated physiological response to exercise, sensory intensity, unpleasantness ratings of exertional dyspnea. Our results do not support a role for intrapulmonary opioids in the neuromodulation of exertional dyspnea in health nor do they provide a physiological rationale for the use of nebulized fentanyl in the management of dyspnea due to mild restrictive lung disorders, specifically those arising from abnormalities of the chest wall and not affiliated with airway inflammation. PMID:26031762

Stressors associated with dyspnea in childhood: patients' insights and a case report.

PubMed

Anbar, Ran D

2004-10-01

To highlight the concept that stress can be associated with dyspnea in children. A chart review identified 22 patients (age range, 9-17 years) referred to a pediatric pulmonologist, who were offered instruction in self-hypnosis for treatment of dyspnea that persisted despite medical therapy. Patients were offered the opportunity to use hypnosis to gain insight into the causes of their dyspnea. The dyspnea resolved in 18 of the 22 patients within 1 month of instruction in self-hypnosis for relaxation and symptom reduction. Eight of the 22 patients (age range, 11-16 years) chose to use hypnosis for insight. Using automatic word processing, they explained that their dyspnea was associated with stressful situations, or that it reduced the chances of having to experience an uncomfortable situation. For example, a girl with dyspnea resulting from vocal cord dysfunction realized during hypnosis that she developed her symptom in order to prevent herself from talking about information that might cause discomfort were it disclosed. As soon as the patient decided that she could trust herself to handle the information appropriately, her symptom resolved. Dyspnea may provide patients with a way of expressing their reactions to perceived or anticipated stress. Thus, stress reduction interventions may prove very helpful in resolving this symptom. However, in some cases gaining an insight into the potential cause of the dyspnea may increase the effectiveness of therapy.

The Effect of Using an Electric Fan on Dyspnea in Chinese Patients With Terminal Cancer.

PubMed

Wong, Sio Leng; Leong, Sok Man; Chan, Cheng Man; Kan, Sut Peng; Cheng, Hon Wai Benjamin

2017-02-01

Fan therapy is often suggested for relieving the symptom of dyspnea in patients with advanced cancer, but relevant literature among Asians is limited. Phase 2 clinical trial to assess the clinical feasibility and outcome of using an electric fan to alleviate the symptom of dyspnea in Chinese patients with advanced cancer. Thirty patients with advanced cancer having unresolved breathlessness were recruited from Hospice and Palliative Care Centre of Kiang Wu Hospital in Macau. Participants were randomly and equally allocated to the experimental group and the control group, respectively. Verbal numerical rating scale (NRS) of breathlessness, respiratory rate (RR), and saturation of peripheral oxygen (SpO 2 ) was collected before and after the intervention. T test was used to analyze the data collected. There was a significant difference in the NRS scores of the experimental group ( P < .01), indicating a significant reduction in the patients' sensation of breathlessness after fan therapy, whereas no significant difference was found in the objective statistic results of RR and SpO 2 . No significant difference ( P > .05) was found in the control group for all the 3 variables before and after routine treatment. The results of the study suggested that fan therapy could be effective in alleviating dyspnea in Chinese patients with advanced cancer. It should be considered as one of the nonpharmacological treatment option. Future large-scale phase 3 clinical trials are warranted.

Practical Dyspnea Assessment: Relationship Between the 0–10 Numerical Rating Scale and the Four-Level Categorical Verbal Descriptor Scale of Dyspnea Intensity

PubMed Central

Wysham, Nicholas G.; Miriovsky, Benjamin J.; Currow, David C.; Herndon, James E.; Samsa, Gregory P.; Wilcock, Andrew; Abernethy, Amy P.

2016-01-01

Context Measurement of dyspnea is important for clinical care and research. Objectives To characterize the relationship between the 0–10 Numerical Rating Scale (NRS) and four-level categorical Verbal Descriptor Scale (VDS) for dyspnea assessment. Methods This was a substudy of a double-blind randomized controlled trial comparing palliative oxygen to room air for relief of refractory breathlessness in patients with life-limiting illness. Dyspnea was assessed with both a 0–10 NRS and a four-level categorical VDS over the one-week trial. NRS and VDS responses were analyzed in cross section and longitudinally. Relationships between NRS and VDS responses were portrayed using descriptive statistics and visual representations. Results Two hundred twenty-six participants contributed responses. At baseline, mild and moderate levels of breathlessness were reported by 41.9% and 44.6% of participants, respectively. NRS scores demonstrated increasing mean and median levels for increasing VDS intensity, from a mean (SD) of 0.6 (±1.04) for VDS none category to 8.2 (1.4) for VDS severe category. The Spearman correlation coefficient was strong at 0.78 (P < 0.0001). Based on the distribution of NRS scores within VDS categories, we calculated test characteristics of two different cutpoint models. Both models yielded 75% correct translations from NRS to VDS; however, Model A was more sensitive for moderate or greater dyspnea, with fewer misses downcoded. Conclusion There is strong correlation between VDS and NRS measures for dyspnea. Proposed practical cutpoints for the relationship between the dyspnea VDS and NRS are 0 for none, 1–4 for mild, 5–8 for moderate, and 9–10 for severe. PMID:26004401

Cardiopulmonary laboratory biomarkers in the evaluation of acute dyspnea.

PubMed

Stokes, Natalie R; Dietz, Brett W; Liang, Jackson J

2016-01-01

Dyspnea is a common chief complaint in the emergency department, with over 4 million visits annually in the US. Establishing the correct diagnosis can be challenging, because the subjective sensation of dyspnea can result from a wide array of underlying pathology, including pulmonary, cardiac, neurologic, psychiatric, toxic, and metabolic disorders. Further, the presence of dyspnea is linked with increased mortality in a variety of conditions, and misdiagnosis of the cause of dyspnea leads to poor patient-level outcomes. In combination with the history and physical, efficient, and focused use of laboratory studies, the various cardiopulmonary biomarkers can be useful in establishing the correct diagnosis and guiding treatment decisions in a timely manner. Use and interpretation of such tests must be guided by the clinical context, as well as an understanding of the current evidence supporting their use. This review discusses current standards and research regarding the use of established and emerging cardiopulmonary laboratory markers in the evaluation of acute dyspnea, focusing on recent evidence assessing the diagnostic and prognostic utility of various tests. These markers include brain natriuretic peptide (BNP) and N-terminal prohormone (NT-proBNP), mid-regional peptides proatrial NP and proadrenomedullin, cardiac troponins, D-dimer, soluble ST2, and galectin 3, and included is a discussion on the use of arterial and venous blood gases.

Burden of asthma, dyspnea, and chronic cough in South Asia.

PubMed

Bishwajit, Ghose; Tang, Shangfeng; Yaya, Sanni; Feng, Zhanchun

2017-01-01

Asthma, dyspnea, and chronic cough are well-established risk factors of COPD and often associated with exacerbation of the disease, which is a leading cause of morbidity and mortality in South Asian countries. The aims of this study were to, 1) measure the prevalence of asthma, dyspnea, and chronic cough, and 2) assess the relationship between these respiratory problems and self-reported health status among South Asians. Data for this research came from the World Health Survey (2002-2003) conducted by the World Health Organization. Subjects were 35,929 men and women, aged 18 years and older, selected from Bangladesh, India, Nepal, Pakistan, and Sri Lanka. Crude prevalence rates of asthma, dyspnea, and chronic cough were presented as percentages, and the results of their association with subjective health status were presented as odds ratios and corresponding 95% CIs. Prevalence of daily smoking was highest in Bangladesh (39.9%) and lowest in Sri Lanka (14.1%). Prevalence of asthma was highest in India (6.3%), while Nepal had the highest prevalence of dyspnea (11.3%) and chronic cough (15.3%). Overall prevalence of asthma and dyspnea was higher among women, while that of chronic cough was higher among men. Significant differences were observed in the prevalence rates of all the conditions among regular, occasional, and nonsmokers. A majority of the men and women who had asthma, dyspnea, and chronic cough had higher likelihood of reporting poor health status compared to those who did not have these diseases. Findings suggest that prevalence rates of asthma, dyspnea, and chronic cough were considerably high in all the countries and were significantly associated with poor subjective health. Being a high COPD-prone region, programs targeted to address these diseases could help reduce the burden of COPD and respiratory disease-related mortalities in South Asia.

Relationship between dyspnea, peak expiratory flow rate and wheeze in obstructive lung disease.

PubMed

Srisawai, P

1997-05-01

The relationship between dyspnea and airway obstruction is complex, and it is unclear to what extent measures of each correlate in patients with obstructive lung disease (OLD). Thus, the correlation between subjective assessment of dyspnea (dyspnea score using modified Borg scale) and objective assessment of dyspnea (peak expiratory flow rate using Mini Wright Peak Flow Meter and wheeze score using stethoscope) before and after bronchodilator (1 mg of turbutaline sulphate) were studied in 115 patients (62 males, 53 females) with OLD attending the chest clinic of Royal Irrigation Hospital, Nonthaburi, Thailand. The mean age of these patients was 47.4 +/- 16.4 years. Good correlations were found (r = 0.37 to 0.52; p < 0.001) but dyspnea scores were better correlated with wheeze scores than peak expiratory flow rates. The change in dyspnea scores after bronchodilator also correlated with the change in peak expiratory flow rates and the change in wheeze scores (r = 0.22; p < 0.02 and r = 0.28; p < 0.005 respectively). Analyzing a subgroup of 48 dyspneic patients (prebronchodilator dyspnea score of 2 or more) revealed the following response groups: those with either a bronchodilator or dyspnea response alone, both together, or neither. Twenty-three patients (47.92 per cent) responded both subjectively and objectively. One (2.08 per cent) had a bronchodilator response only. Twenty (41.66 per cent) had a dyspnea response only, while four (8.33 per cent) had neither measurable response. The present study suggests that the assessment of dyspnea by using dyspnea score is vital and may be specially helpful in a situation where the objective assessment cannot be performed. In some individuals the subjective assessment of response to bronchodilator may be at least as valuable as objective data.

Evidence for cognitive-behavioral strategies improving dyspnea and related distress in COPD.

PubMed

Norweg, Anna; Collins, Eileen G

2013-01-01

Dyspnea is a complex, prevalent, and distressing symptom of chronic obstructive pulmonary disease (COPD) associated with decreased quality of life, significant disability, and increased mortality. It is a major reason for referral to pulmonary rehabilitation. We reviewed 23 COPD studies to examine the evidence for the effectiveness of cognitive-behavioral strategies for relieving dyspnea in COPD. Preliminary evidence from randomized controlled trials exists to support cognitive- behavioral strategies, used with or without exercise, for relieving sensory and affective components of dyspnea in COPD. Small to moderate treatment effects for relieving dyspnea were noted for psychotherapy (effect size [ES] = 0.08-0.25 for intensity; 0.26-0.65 for mastery) and distractive auditory stimuli (ES = 0.08-0.33 for intensity; 0.09 to -0.61 for functional burden). Small to large dyspnea improvements resulted from yoga (ES = 0.2-1.21 for intensity; 0.67 for distress; 0.07 for mastery; and -8.37 for functional burden); dyspnea self-management education with exercise (ES = -0.14 to -1.15 for intensity; -0.62 to -0.69 for distress; 1.04 for mastery; 0.14-0.35 for self-efficacy); and slow-breathing exercises (ES = -0.34 to -0.83 for intensity; -0.61 to -0.80 for distress; and 0.62 for self-efficacy). Cognitive-behavioral interventions may relieve dyspnea in COPD by (1) decreasing sympathetic nerve activity, dynamic hyperinflation, and comorbid anxiety, and (2) promoting arterial oxygen saturation, myelinated vagus nerve activity, a greater exercise training effect, and neuroplasticity. While evidence is increasing, additional randomized controlled trials are needed to evaluate the effectiveness of psychosocial and self-management interventions in relieving dyspnea, in order to make them more available to patients and to endorse them in official COPD, dyspnea, and pulmonary rehabilitation practice guidelines. By relieving dyspnea and related anxiety, such interventions may promote

Evidence for cognitive–behavioral strategies improving dyspnea and related distress in COPD

PubMed Central

Norweg, Anna; Collins, Eileen G

2013-01-01

Background Dyspnea is a complex, prevalent, and distressing symptom of chronic obstructive pulmonary disease (COPD) associated with decreased quality of life, significant disability, and increased mortality. It is a major reason for referral to pulmonary rehabilitation. Methods We reviewed 23 COPD studies to examine the evidence for the effectiveness of cognitive–behavioral strategies for relieving dyspnea in COPD. Results Preliminary evidence from randomized controlled trials exists to support cognitive– behavioral strategies, used with or without exercise, for relieving sensory and affective components of dyspnea in COPD. Small to moderate treatment effects for relieving dyspnea were noted for psychotherapy (effect size [ES] = 0.08–0.25 for intensity; 0.26–0.65 for mastery) and distractive auditory stimuli (ES = 0.08–0.33 for intensity; 0.09 to −0.61 for functional burden). Small to large dyspnea improvements resulted from yoga (ES = 0.2–1.21 for intensity; 0.67 for distress; 0.07 for mastery; and −8.37 for functional burden); dyspnea self-management education with exercise (ES = −0.14 to −1.15 for intensity; −0.62 to −0.69 for distress; 1.04 for mastery; 0.14–0.35 for self-efficacy); and slow-breathing exercises (ES = −0.34 to −0.83 for intensity; −0.61 to −0.80 for distress; and 0.62 for self-efficacy). Cognitive–behavioral interventions may relieve dyspnea in COPD by (1) decreasing sympathetic nerve activity, dynamic hyperinflation, and comorbid anxiety, and (2) promoting arterial oxygen saturation, myelinated vagus nerve activity, a greater exercise training effect, and neuroplasticity. Conclusion While evidence is increasing, additional randomized controlled trials are needed to evaluate the effectiveness of psychosocial and self-management interventions in relieving dyspnea, in order to make them more available to patients and to endorse them in official COPD, dyspnea, and pulmonary rehabilitation practice guidelines. By

Dyspnea and Panic Among Patients With Newly Diagnosed Non-Small Cell Lung Cancer

PubMed Central

Shin, Jennifer A.; Kosiba, Jesse D.; Traeger, Lara; Greer, Joseph A.; Temel, Jennifer S.; Pirl, William F.

2014-01-01

Context Among patients with lung cancer, dyspnea is associated with psychological distress, fatigue, and poor coping. Respiratory symptoms are also a common trigger for panic attacks in the general population. Minimal research has addressed the prevalence of panic disorder or the association of dyspnea with risk of panic disorder in lung cancer. Objectives We explored the frequency of panic disorder symptoms and the association of dyspnea with risk of panic disorder symptoms among patients with newly diagnosed non-small cell lung cancer (NSCLC). Methods During 2006–2010, consecutive patients presenting for initial consultation at a thoracic oncology clinic completed a survey of current symptoms, including dyspnea and panic disorder symptoms. We evaluated the frequency of panic disorder symptoms. Logistic regression was used to test the association of dyspnea with risk of panic disorder symptoms, adjusting for age, gender, disease stage, performance status, and major depression symptoms. Results Among 624 patients (M age=63.7 [SD=12.1]; 52.6% female), 48.1% reported that breathing was at least somewhat difficult and 11.2% endorsed panic disorder symptoms. Dyspnea was independently associated with higher risk of panic disorder symptoms (OR=2.19, 95% CI=1.11–4.31, P=0.02). Younger age and major depression symptoms also were associated with higher risk (P’s<0.01). Conclusion Almost half of patients with newly diagnosed NSCLC reported dyspnea, and patients with dyspnea were over twice as likely to endorse panic disorder symptoms relative to patients without dyspnea. Results highlight the need to differentiate panic disorder symptoms among patients who report dyspnea, particularly those who are younger or experiencing major depression symptoms. PMID:24766738

Diagnostic values of NT-proBNP in acute dyspnea among elderly patients

PubMed Central

Su, Qin; Liu, Hongsheng; Zhang, Xian; Dang, Wei; Liu, Runmei; Zhao, Xiaodong; Yuan, Xiaoling; Qin, Yuhong; Zhang, Jianbo; Chen, Chunming; Xia, Yunfeng

2015-01-01

The study aims to evaluate a rapid testing of NT-proBNP in differential diagnosis of cardiac and pulmonary dyspnea among elderly emergency patients. Two hundred sixty-eight dyspnea patients with ages of ≥60 years old participated in the study. Based on their clinical diagnosis, the patients were divided into three groups: group A diagnosed with pulmonary dyspnea (PD), group B diagnosed with congestive heart failure (CHF), and group C diagnosed with combined dyspnea (CHF+PD). NT-proBNP levels among the three groups were compared. NT-proBNP levels in group A were significantly lower than those in groups B and C. No significant difference was observed between groups B and C in terms of NT-proBNP levels (P>0.05). Our data showed that NT-proBNP levels in patients with cardiac dyspnea were significantly higher than those in patients with pulmonary dyspnea. Person linear association analysis revealed that NT-proBNP levels were reversely associated with LVEF (r=-0.675, P<0.01), indicating that higher NT-proBNP levels result in lower LVEF and poorer heart functions. NT-proBNP is a valuable biomarker in differential diagnosis of pulmonary and cardiac dyspnea among elderly patients due to the high sensitivity of the testing method and the strong association with the severity of heart failure. PMID:26722559

An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea

PubMed Central

Parshall, Mark B.; Schwartzstein, Richard M.; Adams, Lewis; Banzett, Robert B.; Manning, Harold L.; Bourbeau, Jean; Calverley, Peter M.; Gift, Audrey G.; Harver, Andrew; Lareau, Suzanne C.; Mahler, Donald A.; Meek, Paula M.; O'Donnell, Denis E.

2012-01-01

Background: Dyspnea is a common, distressing symptom of cardiopulmonary and neuromuscular diseases. Since the ATS published a consensus statement on dyspnea in 1999, there has been enormous growth in knowledge about the neurophysiology of dyspnea and increasing interest in dyspnea as a patient-reported outcome. Purpose: The purpose of this document is to update the 1999 ATS Consensus Statement on dyspnea. Methods: An interdisciplinary committee of experts representing ATS assemblies on Nursing, Clinical Problems, Sleep and Respiratory Neurobiology, Pulmonary Rehabilitation, and Behavioral Science determined the overall scope of this update through group consensus. Focused literature reviews in key topic areas were conducted by committee members with relevant expertise. The final content of this statement was agreed upon by all members. Results: Progress has been made in clarifying mechanisms underlying several qualitatively and mechanistically distinct breathing sensations. Brain imaging studies have consistently shown dyspnea stimuli to be correlated with activation of cortico-limbic areas involved with interoception and nociception. Endogenous and exogenous opioids may modulate perception of dyspnea. Instruments for measuring dyspnea are often poorly characterized; a framework is proposed for more consistent identification of measurement domains. Conclusions: Progress in treatment of dyspnea has not matched progress in elucidating underlying mechanisms. There is a critical need for interdisciplinary translational research to connect dyspnea mechanisms with clinical treatment and to validate dyspnea measures as patient-reported outcomes for clinical trials. PMID:22336677

Dyspnea in Chronic Fatigue Syndrome (CFS): Comparison of Two Prospective Cross-Sectional Studies

PubMed Central

Ravindran, Murugan K.; Adewuyi, Oluwatoyin; Zheng, Yin; Rayhan, Rakib U.; Le, Uyenphuong; Timbol, Christian R.; Merck, Samantha; Esteitie, Rania; Cooney, Michelle; Read, Charles; Baraniuk, James N.

2013-01-01

Chronic Fatigue Syndrome (CFS) subjects have many systemic complaints including shortness of breath. Dyspnea was compared in two CFS and control cohorts to characterize pathophysiology. Cohort 1 of 257 CFS and 456 control subjects were compared using the Medical Research Council chronic Dyspnea Scale (MRC Score; range 0-5). Cohort 2 of 106 CFS and 90 controls answered a Dyspnea Severity Score (range 0-20) adapted from the MRC Score. Subsets of both cohorts completed CFS Severity Scores, fatigue, and other questionnaires. A subset had pulmonary function and total lung capacity measurements. Results show MRC Scores were equivalent between sexes in Cohort 1 CFS (1.92 [1.72-2.16]; mean [95% C.I.]) and controls (0.31 [0.23-0.39]; p<0.0001). Receiver-operator curves identified 2 as the threshold for positive MRC Scores in Cohort 1. This indicated 54% of CFS, but only 3% of controls, had significant dyspnea. In Cohort 2, Dyspnea Score threshold of 4 indicated shortness of breath in 67% of CFS and 23% of controls. Cohort 2 Dyspnea Scores were higher for CFS (7.80 [6.60-9.00]) than controls (2.40 [1.60-3.20]; p<0.0001). CFS had significantly worse fatigue and other complaints compared to controls. Pulmonary function was normal in CFS, but Borg scores and sensations of chest pain and dizziness were significantly greater during testing than controls. General linear model of Cohort 2 CFS responses linked Dyspnea with rapid heart rate, chest pain and dizziness. In conclusion, sensory hypersensitivity without airflow limitation contributed to dyspnea in CFS. Correlates of dyspnea in controls were distinct from CFS suggesting different mechanisms. PMID:23445698

Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies.

PubMed

Ravindran, Murugan; Adewuyi, Oluwatoyin; Zheng, Yin; Rayhan, Rakib U; Le, Uyenphuong; Timbol, Christian; Merck, Samantha; Esteitie, Rania; Read, Charles; Cooney, Michelle; Baraniuk, James

2012-12-12

Chronic Fatigue Syndrome (CFS) subjects have many systemic complaints including shortness of breath. Dyspnea was compared in two CFS and control cohorts to characterize pathophysiology. Cohort 1 of 257 CFS and 456 control subjects were compared using the Medical Research Council chronic Dyspnea Scale (MRC Score; range 0-5). Cohort 2 of 106 CFS and 90 controls answered a Dyspnea Severity Score (range 0-20) adapted from the MRC Score. Subsets of both cohorts completed CFS Severity Scores, fatigue, and other questionnaires. A subset had pulmonary function and total lung capacity measurements. Results show MRC Scores were equivalent between sexes in Cohort 1 CFS (1.92 [1.72-2.16]; mean [95% C.I.]) and controls (0.31 [0.23-0.39]; p<0.0001). Receiver-operator curves identified 2 as the threshold for positive MRC Scores in Cohort 1. This indicated 54% of CFS, but only 3% of controls, had significant dyspnea. In Cohort 2, Dyspnea Score threshold of 4 indicated shortness of breath in 67% of CFS and 23% of controls. Cohort 2 Dyspnea Scores were higher for CFS (7.80 [6.60-9.00]) than controls (2.40 [1.60-3.20]; p<0.0001). CFS had significantly worse fatigue and other complaints compared to controls. Pulmonary function was normal in CFS, but Borg scores and sensations of chest pain and dizziness were significantly greater during testing than controls. General linear model of Cohort 2 CFS responses linked Dyspnea with rapid heart rate, chest pain and dizziness. In conclusion, sensory hypersensitivity without airflow limitation contributed to dyspnea in CFS. Correlates of dyspnea in controls were distinct from CFS suggesting different mechanisms.

Validation of the dyspnea index in adolescents with exercise-induced paradoxical vocal fold motion.

PubMed

De Guzman, Vanessa; Ballif, Catherine L; Maurer, Rie; Hartnick, Christopher J; Raol, Nikhila

2014-09-01

Paradoxical vocal fold motion (PVFM) affects almost 1 million adolescents in the United States. However, to date, no disease-specific objective measure exists to assess symptom severity and response to treatment in adolescents with exercise-induced PVFM. To validate the Dyspnea Index (DI) quality-of-life instrument (previously validated for adults with breathing disorders) in children aged 12 to 18 years with exercise-induced PVFM and to determine the minimum significant DI change corresponding to patient-reported or caregiver-reported improvement or worsening of symptoms. A longitudinal study of 56 patients (age range, 12-18 years) diagnosed as having exercise-induced PVFM and their caregivers from February 1, 2013, to September 30, 2013, in an outpatient pediatric otolaryngology office practice. The DI was administered to patients and caregivers, with items modified to reflect the perspective of caregivers. Appropriate DI change was measured to reflect improvement or worsening of symptoms. Test-retest reliability was accomplished by having a subset of patients and caregivers complete the instrument twice within 2 weeks before therapy. Internal consistency was assessed by calculation of Cronbach α. Discriminant validity and convergent validity were determined by comparing DIs with assessment of global change in symptoms. The patient and caregiver mean (SD) DI changes were -12.9 (9.6) and -14.7 (9.3), respectively (P < .001 for both). Reliability was established by test-retest analysis with an intraclass correlation coefficient of 0.8 and by calculation of Cronbach α = 0.80, demonstrating internal consistency. Discriminant validity was determined by assessing for a significant DI change when patients globally perceived that a change existed after treatment (P < .001). A DI change of 8 or higher (P < .001) correlated with patient-reported significant change. Convergent validity was demonstrated by evaluating for significant DI change when no change was reported

[Effects of an inpatient pulmonary rehabilitation program on dyspnea, exercise capacity, and health related quality of life for patients with chronic lung disease].

PubMed

Lee, Chang Kwan

2007-04-01

The purpose of this study was to examine the effects of an inpatient pulmonary rehabilitation program on dyspnea, exercise capacity, and health related quality of life in inpatients with chronic lung disease. This quasi experimental study was designed with a nonequivalent control group pre-post test time series. Twenty three patients were assigned to the experimental group and nineteen to the control group. The inpatient pulmonary rehabilitation program was composed of upper and lower extremity exercise, breathing retraining, inspiratory muscle training, education, relaxation and telephone contacts. This program consisted of 4 sessions with inpatients and 4 weeks at home after discharge. The control group was given a home based pulmonary rehabilitation program at the time of discharge. The outcomes were measured by the Borg score, 6MWD and the Chronic Respiratory Disease Questionnaire(CRQ). There was a statistically significant difference in dyspnea between the experimental group and control group, but not among time sequence, or interaction between groups and time sequence. Also significant improvements in exercise capacity and health related quality of life were found only in the experimental group. An Inpatient pulmonary rehabilitation program may be a useful intervention to reduce dyspnea, and increase exercise capacity and health related quality of life for chronic lung disease patients.

Relationship between Dyspnea Descriptors and Underlying Causes of the Symptom; a Cross-sectional Study.

PubMed

Sajadi, Seyyed Mohammad Ali; Majidi, Alireza; Abdollahimajd, Fahimeh; Jalali, Fatemeh

2017-01-01

History taking and physical examination help clinicians identify the patient's problem and effectively treat it. This study aimed to evaluate the descriptors of dyspnea in patients presenting to emergency department (ED) with asthma, congestive heart failure (CHF), and chronic obstructive pulmonary disease (COPD). This cross-sectional study was conducted on all patients presenting to ED with chief complaint of dyspnea, during 2 years. The patients were asked to describe their dyspnea by choosing three items from the valid and reliable questionnaire or articulating their sensation. The relationship between dyspnea descriptors and underlying cause of symptom was evaluated using SPSS version 16. 312 patients with the mean age of 60.96±17.01 years were evaluated (53.2% male). Most of the patients were > 65 years old (48.7%) and had basic level of education (76.9%). "My breath doesn't go out all the way" with 83.1%, "My chest feels tight " with 45.8%, and "I feel that my airway is obstructed" with 40.7%, were the most frequent dyspnea descriptors in asthma patients. "My breathing requires work" with 46.3%, "I feel that I am suffocating" with 31.5%, and "My breath doesn't go out all the way" with 29.6%, were the most frequent dyspnea descriptors in COPD patients. "My breathing is heavy" with 74.4%, "A hunger for more air" with 24.4%, and "I cannot get enough air" with 23.2%, were the most frequent dyspnea descriptors in CHF patients. Except for "My breath does not go in all the way", there was significant correlation between studied dyspnea descriptors and underlying disease (p = 0.001 for all analyses). It seems that dyspnea descriptors along with other findings from history and physical examination could be helpful in differentiating the causes of the symptom in patients presenting to ED suffering from dyspnea.

An official American Thoracic Society workshop report: assessment and palliative management of dyspnea crisis.

PubMed

Mularski, Richard A; Reinke, Lynn F; Carrieri-Kohlman, Virginia; Fischer, Mark D; Campbell, Margaret L; Rocker, Graeme; Schneidman, Ann; Jacobs, Susan S; Arnold, Robert; Benditt, Joshua O; Booth, Sara; Byock, Ira; Chan, Garrett K; Curtis, J Randall; Donesky, Doranne; Hansen-Flaschen, John; Heffner, John; Klein, Russell; Limberg, Trina M; Manning, Harold L; Morrison, R Sean; Ries, Andrew L; Schmidt, Gregory A; Selecky, Paul A; Truog, Robert D; Wang, Angela C C; White, Douglas B

2013-10-01

In 2009, the American Thoracic Society (ATS) funded an assembly project, Palliative Management of Dyspnea Crisis, to focus on identification, management, and optimal resource utilization for effective palliation of acute episodes of dyspnea. We conducted a comprehensive search of the medical literature and evaluated available evidence from systematic evidence-based reviews (SEBRs) using a modified AMSTAR approach and then summarized the palliative management knowledge base for participants to use in discourse at a 2009 ATS workshop. We used an informal consensus process to develop a working definition of this novel entity and established an Ad Hoc Committee on Palliative Management of Dyspnea Crisis to further develop an official ATS document on the topic. The Ad Hoc Committee members defined dyspnea crisis as "sustained and severe resting breathing discomfort that occurs in patients with advanced, often life-limiting illness and overwhelms the patient and caregivers' ability to achieve symptom relief." Dyspnea crisis can occur suddenly and is characteristically without a reversible etiology. The workshop participants focused on dyspnea crisis management for patients in whom the goals of care are focused on palliation and for whom endotracheal intubation and mechanical ventilation are not consistent with articulated preferences. However, approaches to dyspnea crisis may also be appropriate for patients electing life-sustaining treatment. The Ad Hoc Committee developed a Workshop Report concerning assessment of dyspnea crisis; ethical and professional considerations; efficient utilization, communication, and care coordination; clinical management of dyspnea crisis; development of patient education and provider aid products; and enhancing implementation with audit and quality improvement.

Dalhousie dyspnea scales: construct and content validity of pictorial scales for measuring dyspnea.

PubMed

McGrath, Patrick J; Pianosi, Paul T; Unruh, Anita M; Buckley, Chloe P

2005-08-30

Because there are no child-friendly, validated, self-report measures of dyspnea or breathlessness, we developed, and provided initial validation, of three, 7-item, pictorial scales depicting three sub-constructs of dyspnea: throat closing, chest tightness, and effort. We developed the three scales (Throat closing, Chest tightness, and Effort) using focus groups with 25 children. Subsequently, seventy-nine children (29 children with asthma, 30 children with cystic fibrosis. and 20 children who were healthy) aged 6 to 18 years rated each picture in each series, using a 0-10 scale. In addition, each child placed each picture in each series on a 100-cm long Visual Analogue Scale, with the anchors "not at all" and "a lot". Children aged eight years or older rated the scales in the correct order 75% to 98% correctly, but children less than 8 years of age performed unreliably. The mean distance between each consecutive item in each pictorial scale was equal. Preliminary results revealed that children aged 8 to 18 years understood and used these three scales measuring throat closing, chest tightness, and effort appropriately. The scales appear to accurately measure the construct of breathlessness, at least at an interval level. Additional research applying these scales to clinical situations is warranted.

Evidence-based recommendations for cancer fatigue, anorexia, depression, and dyspnea.

PubMed

Dy, Sydney M; Lorenz, Karl A; Naeim, Arash; Sanati, Homayoon; Walling, Anne; Asch, Steven M

2008-08-10

PURPOSE The experience of patients with cancer often involves symptoms of fatigue, anorexia, depression, and dyspnea. METHODS We developed a set of standards through an iterative process of structured literature review and development and refinement of topic areas and standards and subjected recommendations to rating by a multidisciplinary expert panel. Results For fatigue, providers should screen patients at the initial visit, for newly identified advanced cancer, and at chemotherapy visits; assess for depression and insomnia in newly identified fatigue; and follow up after treatment for fatigue or a secondary cause. For anorexia, providers should screen at the initial visit for cancer affecting the oropharynx or gastrointestinal tract or advanced cancer, evaluate for associated symptoms, treat underlying causes, provide nutritional counseling for patients undergoing treatment that may affect nutritional intake, and follow up patients given appetite stimulants. For depression, providers should screen newly diagnosed patients, those started on chemotherapy or radiotherapy, those with newly identified advanced disease, and those expressing a desire for hastened death; document a treatment plan in diagnosed patients; and follow up response after treatment. For general dyspnea, providers should evaluate for causes of new or worsening dyspnea, treat or symptomatically manage underlying causes, follow up to evaluate treatment effectiveness, and offer opioids in advanced cancer when other treatments are unsuccessful. For dyspnea and malignant pleural effusions, providers should offer thoracentesis, follow up after thoracentesis, and offer pleurodesis or a drainage procedure for patients with reaccumulation and dyspnea. CONCLUSION These standards provide a framework for evidence-based screening, assessment, treatment, and follow-up for cancer-associated symptoms.

Temporal stability and coherence of anxiety, dyspnea, and physiological variables in panic disorder

PubMed Central

Burkhardt, Susan C. A.; Wilhelm, Frank H.; Meuret, Alicia E.; Blechert, Jens; Roth, Walton T.

2010-01-01

Twenty-five panic disorder (PD) patients, 19 social phobics (SP), and 20 healthy controls (HC) sat quietly for 15 minutes, rating their anxiety and dyspnea every 30 seconds while respiratory, cardiovascular, and electrodermal responses were recorded. No panic attacks were reported. For self-reported anxiety and dyspnea, within-subject variability over time was higher in PD than in SP or HC. In PD within-subject correlations across 30-second epochs were significant for (a) self-reported anxiety versus dyspnea, end-tidal pCO2, minute volume, duty cycle, skin conductance level, and interbeat interval, and for (b) dyspnea versus end-tidal pCO2, minute volume, tidal volume, and inspiratory flow rate. Several positive or negative correlations were greater in PD than in other groups. Thus in PD, experienced anxiety and dyspnea are temporally unstable but are correlated with each other and with fluctuations in respiratory and autonomic variables, even in the absence of panic attacks. PMID:20637257

Relationship between Dyspnea Descriptors and Underlying Causes of the Symptom; a Cross-sectional Study

PubMed Central

Sajadi, Seyyed Mohammad Ali; Majidi, Alireza; Abdollahimajd, Fahimeh; jalali, Fatemeh

2017-01-01

Introduction: History taking and physical examination help clinicians identify the patient’s problem and effectively treat it. This study aimed to evaluate the descriptors of dyspnea in patients presenting to emergency department (ED) with asthma, congestive heart failure (CHF), and chronic obstructive pulmonary disease (COPD). Method: This cross-sectional study was conducted on all patients presenting to ED with chief complaint of dyspnea, during 2 years. The patients were asked to describe their dyspnea by choosing three items from the valid and reliable questionnaire or articulating their sensation. The relationship between dyspnea descriptors and underlying cause of symptom was evaluated using SPSS version 16. Results: 312 patients with the mean age of 60.96±17.01 years were evaluated (53.2% male). Most of the patients were > 65 years old (48.7%) and had basic level of education (76.9%). "My breath doesn’t go out all the way" with 83.1%, “My chest feels tight " with 45.8%, and "I feel that my airway is obstructed" with 40.7%, were the most frequent dyspnea descriptors in asthma patients. "My breathing requires work" with 46.3%, "I feel that I am suffocating" with 31.5%, and "My breath doesn’t go out all the way" with 29.6%, were the most frequent dyspnea descriptors in COPD patients. "My breathing is heavy" with 74.4%, "A hunger for more air” with 24.4%, and "I cannot get enough air" with 23.2%, were the most frequent dyspnea descriptors in CHF patients. Except for “My breath does not go in all the way”, there was significant correlation between studied dyspnea descriptors and underlying disease (p = 0.001 for all analyses). Conclusion: It seems that dyspnea descriptors along with other findings from history and physical examination could be helpful in differentiating the causes of the symptom in patients presenting to ED suffering from dyspnea. PMID:28894777

Observational study to analyze patterns of treatment of breakthrough dyspnea in cancer patients in clinical practice.

PubMed

Cabezón-Gutiérrez, Luis; Delgado-Mingorance, Ignacio; Nabal-Vicuña, María; Jiménez-López, Antonio Javier; Cabezón-Álvarez, Ana; Soler-López, Begoña

2018-06-12

Although breakthrough dyspnea is very frequent in cancer patients, there are no precise recommendations for treating it. The main objective of this study was to analyze what treatments are used in clinical practice for the management of breakthrough dyspnea in cancer patients in Spain and the secondary objectives were to describe the characteristics of cancer patients with breakthrough dyspnea and the attributes of the disorder. Cancer patients over 18 years of age, with breakthrough dyspnea and a Karnofsky performance score of ≥30, who were treated at departments of oncology in institutes across Spain were included in this cross-sectional observational study. The characteristics of breakthrough dyspnea, history of treatment, anthropometric variables, Mahler dyspnea index, Borg scale, Edmonton Symptoms Assessment Scale, and patient satisfaction with current breakthrough dyspnea treatment were assessed. The mean age of the 149 included patients was 66 years (95% confidence interval: 64.3 to 67.9), and 53 were females (35.6%). The mean breakthrough dyspnea intensity was 5.85 (95% confidence interval 5.48 to 6.22, Borg scale). A total of 55.1% of the first-choice treatments consisted of opioids, followed by oxygen (17.3%). A total of 119 patients (79.9%) received monotherapy for breakthrough dyspnea. Patients presenting with basal dyspnea received oxygen in a greater proportion of cases (21.1% vs 7.4%; p = 0.07). Patients with predictable dyspnea received a greater proportion of opioids (70.9% vs 44.4%; p = 0.01). Opioids constitute first-line therapy for breakthrough dyspnea in routine clinical practice, though the scientific evidence supporting their use is scarce. Further information derived from controlled clinical trials is needed regarding the comparative efficacy of the different treatments in order to justify their use.

Palliative management of refractory dyspnea in COPD

PubMed Central

Uronis, Hope E; Currow, David C; Abernethy, Amy P

2006-01-01

COPD is a progressive illness with worldwide impact. Patients invariably reach a point at which they require palliative interventions. Dyspnea is the most distressing symptom experienced by these patients; when not relieved by traditional COPD management strategies it is termed “refractory dyspnea” and palliative approaches are required. The focus of care shifts from prolonging survival to reducing symptoms, increasing function, and improving quality of life. Numerous pharmacological and non-pharmacological interventions can achieve these goals, though evidence supporting their use is variable. This review provides a summary of the options for the management of refractory dyspnea in COPD, outlining currently available evidence and highlighting areas for further investigation. Topics include oxygen, opioids, psychotropic drugs, inhaled furosemide, Heliox, rehabilitation, nutrition, psychosocial support, breathing techniques, and breathlessness clinics. PMID:18046866

Measurement of Dyspnea in Ambulatory African Americans With Heart Failure and a Preserved or Reduced Ejection Fraction.

PubMed

Vuckovic, Karen M; DeVon, Holli A; Piano, Mariann R

2016-01-01

Dyspnea is a burdensome and disabling heart failure (HF) symptom. Few studies examining dyspnea in HF have included African Americans (AAs), despite their developing HF at a younger age and having the highest mortality rates. The purpose of this cross-sectional study was to examine dyspnea in AA patients with HF and a preserved ejection fraction (HFpEF) compared with those with a reduced ejection fraction (HFrEF), before and after the 6-minute walk test (6MWT). A convenience sample of ambulatory AA patients (HFrEF, n = 26; HFpEF, n = 19) 50 years or older was recruited from an urban HF clinic. The Borg Scale and a visual analog scale (VAS) were used to measure dyspnea intensity before and after the 6MWT. Activity limitations related to dyspnea were described using the modified Medical Research Council Dyspnea Scale. Group comparisons were analyzed using repeated-measures analysis of variance and χ 2tests. Convergent validity was determined between the Borg and VAS using Bland-Altman plots. No significant differences were found in age, gender, and comorbidities between HF groups. Most HFpEF patients reported dyspnea at baseline (Borg, 63%; VAS, 73%) and after the 6MWT (Borg, 78%; VAS, 79%). In the HFrEF group, the prevalence of baseline dyspnea was greater when measured with the VAS (Borg, 34%; VAS, 80%) but was similar between instruments after the 6MWT (Borg, 64%; VAS, 77%). Both groups reported a similar change in dyspnea intensity during and after the 6MWT. The Bland-Altman plots indicated moderate agreement at each time point. Most patients described walking hurriedly or uphill as dyspnea-provoking on the Modified Respiratory Council Dyspnea Scale. The prevalence of dyspnea at baseline and after the 6MWT was high for both groups, but intensity varied with the dyspnea instrument used.

Patient-Reported Dyspnea Correlates Poorly with Aerobic Exercise Capacity Measured During Cardiopulmonary Exercise Testing.

PubMed

Gaspard, Dany; Kass, Jonathan; Akers, Stephen; Hunter, Krystal; Pratter, Melvin

2017-10-01

Patient-reported dyspnea plays a central role in assessing cardiopulmonary disease. There is little evidence, however, that dyspnea correlates with objective exercise capacity measurements. If the correlation is poor, dyspnea as a proxy for objective assessment may be misleading. To compare patient's perception of dyspnea with maximum oxygen uptake (MaxVO2) during cardiopulmonary exercise testing (CPET). Fifty patients undergoing CPET for dyspnea evaluation were studied prospectively. Dyspnea assessment was measured by a metabolic equivalent of task (METs) table, Mahler Dyspnea Index, Borg Index, number of blocks walked, and flights of stairs climbed before stopping due to dyspnea. These descriptors were compared to MaxVO2. MaxVO2 showed low correlation with METs table (r = 0.388, p = 0.005) and no correlation with Mahler Index (r = 0.24, p = 0.093), Borg Index (r = -0.017, p = 0.905), number of blocks walked (r = 0.266, p = 0.077) or flights of stairs climbed (r = 0.188, p = 0.217). When adjusted for weight (maxVO2/kg), there was significant correlation between MaxVO2 and METs table (r = 0.711, p < 0.001), moderate correlation with blocks walked (r = 0.614, p < 0.001), and low correlation with Mahler Index (r = 0.488 p = 0.001), Borg Index (r = -0.333 p = 0.036), and flights of stairs (r = 0.457 p = 0.004). Subgroup analysis showed worse correlation when patients with normal CPET were excluded (12/50 excluded). Patients with BMI < 30 had no correlation between Max VO2 and the assessment methods, while patients with BMI > 30 had moderate correlation between MaxVO2 and METs table (r = 0.568, p = 0.002). Patient-reported dyspnea correlates poorly with MaxVO2 and fails to predict exercise capacity. Reliance on reported dyspnea may result in suboptimal categorization of cardiopulmonary disease severity.

Speaking-Related Dyspnea in Healthy Adults

ERIC Educational Resources Information Center

Hoit, Jeannette D.; Lansing, Robert W.; Perona, Kristen E.

2007-01-01

Purpose: To reveal the qualities and intensity of speaking-related dyspnea in healthy adults under conditions of high ventilatory drive, in which the behavioral and metabolic control of breathing must compete. Method: Eleven adults read aloud while breathing different levels of inspired carbon dioxide (CO[subscript 2]). After the highest level,…

Using opioids to treat dyspnea in advanced COPD

PubMed Central

Young, Joanne; Donahue, Margaret; Farquhar, Morag; Simpson, Cathy; Rocker, Graeme

2012-01-01

Abstract Objective To explore the experiences of family physicians and respiratory therapists in treating advanced chronic obstructive pulmonary disease (COPD) and their attitudes to the use of opioids for dyspnea in this context. Design Qualitative methodology using one-on-one semistructured interviews. Setting Southern New Brunswick (St Stephen to Sussex). Participants Ten family physicians and 8 respiratory therapists who worked in primary care settings. Methods Participant interviews were audiorecorded, transcribed verbatim, coded conceptually, and thematically analyzed using interpretive description. Main findings Participants reported that patients with advanced COPD often suffered from inadequate control of their dyspnea in advanced stages and that they saw the potential value of opioids in this context; however, family physicians described discomfort prescribing opioids. Barriers included insufficient knowledge, lack of education and guidelines, and fear of censure. Those with palliative care experience tended to be more comfortable with opioid prescribing. Conclusion Findings suggest an important need to address barriers related to more effective treatment of refractory dyspnea in advanced COPD. Further, findings indicate these efforts should focus on effective palliation and innovative educational initiatives, as well as the development, promotion, and uptake of evidence-based practice guidelines related to prescribing opioids for these patients. PMID:22798476

Clinical Model of Exercise-Related Dyspnea in Adult Patients With Cystic Fibrosis.

PubMed

Stevens, Daniel; Neyedli, Heather F

2018-05-01

Dyspnea is a highly distressing symptom of pulmonary disease that can make performing physical activities challenging. However, little is known regarding the strongest predictors of exercise-related dyspnea in adult cystic fibrosis (CF). Therefore, the purpose of the present study was to determine the best clinical model of exercise-related dyspnea in this patient group. A retrospective analysis of pulmonary function and cardiopulmonary exercise testing data from patients with CF being followed up at the Adult CF Program at St Michael's Hospital, Toronto, Canada, from 2002 to 2008 were used for the analysis. Patients (n = 88) were male 66%; aged 30.4 ± 9.4 years; body mass index (BMI) 23.1 ± 3.3 kg/m; forced expiratory volume in 1 second (FEV1) 70% ± 19% predicted; and peak oxygen uptake 74% ± 20% predicted. A multivariate linear regression model assessing the effects of age, sex, BMI, airway obstruction (FEV1), perceived muscular leg fatigue, and dynamic hyperinflation explained 54% of the variance in dyspnea severity at peak exercise (P < .01). Relative importance analysis showed that the presence of dynamic hyperinflation and perceived muscular leg fatigue were the largest contributors. Pulmonary rehabilitation programs may consider strategies to reduce dynamic hyperinflation and promote muscular function to best improve exercise-related dyspnea in this patient group.

Imaging-based assessment of dyspnea in cigarette smokers

NASA Astrophysics Data System (ADS)

Galvin, Jeffrey R.; Chang, Paul J.; Schwartz, David A.; Hunninghake, Gary W.; Helmers, Richard; Mori, Masaki

1994-05-01

Patients with pulmonary fibrosis frequently smoke cigarettes. The cause of dyspnea in these patients is often complex because of the coexistence of multiple disease processes. We investigated 10 cigarette smokers with pulmonary fibrosis who were referred for evaluation of new onset or worsening dyspnea. Chest radiographs and pulmonary function tests were obtained in addition to high-resolution computed tomography (HRCT). In those patients with HRCT evidence of both diseases, spirometry and lung volumes were most often normal. Although plain films provided a reasonable assessment of fibrosis, they underestimated the severity of emphysema. Quantitation of both emphysema and fibrosis by HRCT was reproducible and correlated with key pulmonary function tests. Our findings indicate that the HRCT scan is a useful diagnostic test in patients with pulmonary fibrosis who are also cigarette smokers.

Unexplained dyspnea in a patient of chronic arsenicosis: A diagnostic challenge and learning curve for physicians

PubMed Central

Sengupta, Amitabha; Maji, Arnab; Jash, Debraj; Maikap, Malay

2015-01-01

Chronic arsenic exposure causes cutaneous effects like hyperkeratosis, peripheral vascular disease, hypertension, ischemic heart disease, non-cirrhotic portal hypertension, hepatomegaly, peripheral neuropathy, respiratory involvement, bad obstetrical outcome, hematological disturbances, and diabetes mellitus. Here we present a case of a 24-year-old lady, with chronic exposure to arsenic, presenting to us with progressive dyspnea. We found pulmonary arterial hypertension (PAH) as a cause of her dyspnea. PAH can occur in arsenicosis, secondary to arsenic-induced chronic obstructive pulmonary disease (COPD), lung fibrosis, and portal hypertension, which we excluded by appropriate investigations in our case. We also excluded a familial or heritable form of PAH. Thus, with the exclusion of all these secondary causes of PAH, as well as a hereditary cause, we came to a conclusion that this PAH might be due to chronic arsenic exposure. To the best of our knowledge, no case of PAH in chronic arsenicosis has been reported to date. PMID:25814805

Physical inactivity in COPD and increased patient perception of dyspnea.

PubMed

Katajisto, Milla; Kupiainen, Henna; Rantanen, Piritta; Lindqvist, Ari; Kilpeläinen, Maritta; Tikkanen, Heikki; Laitinen, Tarja

2012-01-01

To study patients' levels of exercise activity and the clinical characteristics that relate to physical activity and inactivity among patients with chronic obstructive pulmonary disease (COPD). A postal questionnaire was administered to 719 patients with COPD in 2010; patients were recruited from the Helsinki and Turku University Central Hospitals in Finland and have been followed since 2005. The questionnaire asked participants about their exercise routines and other daily activities, potential restrictions to exercise, health-related quality of life, and subjective sensations of dyspnea upon exertion. A total of 50% of the participants reported exercising>2 times a week throughout the year. The proportion of the exercise inactive patients increased in parallel with disease progression, but the participants exhibited great variation in the degree of activity as well as in sport choices. Year-round activity was better maintained among patients who exercised both indoors and outdoors. Training activity was significantly correlated with patients' reported subjective dyspnea (r=0.32, P<0.001), health-related quality of life (r=0.25, P<0.001), mobility score (r=0.37, P<0.001), and bronchial obstruction (r=0.18, P<0.001). Active patients did not differ from inactive patients in terms of sex, age, smoking status, somatic comorbidities, or body mass index. Irrespective of the level of severity of patients' COPD, the most significant barrier to exercising was the subjective sensation of dyspnea. When a patient with COPD suffers from dyspnea and does not have regular exercise routines, the patient will most likely benefit from an exercise program tailored to his or her physical capabilities.

Effects of inspiratory muscle training on respiratory muscle electromyography and dyspnea during exercise in healthy men.

PubMed

Ramsook, Andrew H; Molgat-Seon, Yannick; Schaeffer, Michele R; Wilkie, Sabrina S; Camp, Pat G; Reid, W Darlene; Romer, Lee M; Guenette, Jordan A

2017-05-01

Inspiratory muscle training (IMT) has consistently been shown to reduce exertional dyspnea in health and disease; however, the physiological mechanisms remain poorly understood. A growing body of literature suggests that dyspnea intensity can be explained largely by an awareness of increased neural respiratory drive, as measured indirectly using diaphragmatic electromyography (EMGdi). Accordingly, we sought to determine whether improvements in dyspnea following IMT can be explained by decreases in inspiratory muscle electromyography (EMG) activity. Twenty-five young, healthy, recreationally active men completed a detailed familiarization visit followed by two maximal incremental cycle exercise tests separated by 5 wk of randomly assigned pressure threshold IMT or sham control (SC) training. The IMT group ( n = 12) performed 30 inspiratory efforts twice daily against a 30-repetition maximum intensity. The SC group ( n = 13) performed a daily bout of 60 inspiratory efforts against 10% maximal inspiratory pressure (MIP), with no weekly adjustments. Dyspnea intensity was measured throughout exercise using the modified 0-10 Borg scale. Sternocleidomastoid and scalene EMG was measured using surface electrodes, whereas EMGdi was measured using a multipair esophageal electrode catheter. IMT significantly improved MIP (pre: -138 ± 45 vs. post: -160 ± 43 cmH 2 O, P < 0.01), whereas the SC intervention did not. Dyspnea was significantly reduced at the highest equivalent work rate (pre: 7.6 ± 2.5 vs. post: 6.8 ± 2.9 Borg units, P < 0.05), but not in the SC group, with no between-group interaction effects. There were no significant differences in respiratory muscle EMG during exercise in either group. Improvements in dyspnea intensity ratings following IMT in healthy humans cannot be explained by changes in the electrical activity of the inspiratory muscles. NEW & NOTEWORTHY Exertional dyspnea intensity is thought to reflect an increased awareness of neural respiratory

Effects of inspiratory muscle training on respiratory muscle electromyography and dyspnea during exercise in healthy men

PubMed Central

Molgat-Seon, Yannick; Schaeffer, Michele R.; Wilkie, Sabrina S.; Camp, Pat G.; Reid, W. Darlene; Romer, Lee M.

2017-01-01

Inspiratory muscle training (IMT) has consistently been shown to reduce exertional dyspnea in health and disease; however, the physiological mechanisms remain poorly understood. A growing body of literature suggests that dyspnea intensity can be explained largely by an awareness of increased neural respiratory drive, as measured indirectly using diaphragmatic electromyography (EMGdi). Accordingly, we sought to determine whether improvements in dyspnea following IMT can be explained by decreases in inspiratory muscle electromyography (EMG) activity. Twenty-five young, healthy, recreationally active men completed a detailed familiarization visit followed by two maximal incremental cycle exercise tests separated by 5 wk of randomly assigned pressure threshold IMT or sham control (SC) training. The IMT group (n = 12) performed 30 inspiratory efforts twice daily against a 30-repetition maximum intensity. The SC group (n = 13) performed a daily bout of 60 inspiratory efforts against 10% maximal inspiratory pressure (MIP), with no weekly adjustments. Dyspnea intensity was measured throughout exercise using the modified 0–10 Borg scale. Sternocleidomastoid and scalene EMG was measured using surface electrodes, whereas EMGdi was measured using a multipair esophageal electrode catheter. IMT significantly improved MIP (pre: −138 ± 45 vs. post: −160 ± 43 cmH2O, P < 0.01), whereas the SC intervention did not. Dyspnea was significantly reduced at the highest equivalent work rate (pre: 7.6 ± 2.5 vs. post: 6.8 ± 2.9 Borg units, P < 0.05), but not in the SC group, with no between-group interaction effects. There were no significant differences in respiratory muscle EMG during exercise in either group. Improvements in dyspnea intensity ratings following IMT in healthy humans cannot be explained by changes in the electrical activity of the inspiratory muscles. NEW & NOTEWORTHY Exertional dyspnea intensity is thought to reflect an increased awareness of neural respiratory

Continuous subcutaneous infusion of compound oxycodone for the relief of dyspnea in patients with terminally ill cancer: a retrospective study.

PubMed

Kawabata, Masahiro; Kaneishi, Keisuke

2013-05-01

Pain and dyspnea are the most prevalent and distressing symptoms in patients with terminally ill cancer. Evidences have accumulated for the effects of morphine on dyspnea, whereas little is known about the effects of oxycodone on dyspnea. We investigated the effectiveness of oxycodone for dyspnea in patients with terminally ill cancer. The injectable form of compound oxycodone (iOC) containing hydrocotarnine was administered continuously via subcutaneous route. We administered iOC to 136 patients. The effect on dyspnea was less conspicuous than pain, yet iOC was effective for dyspnea with varying degrees. None of the adverse effects observed were serious. These results suggest that continuous subcutaneous administration of oxycodone could be one of the reasonable alternatives in the management of dyspnea in patients with terminally ill cancer.

Point-of-Care Ultrasonography for Evaluation of Acute Dyspnea in the ED.

PubMed

Zanobetti, Maurizio; Scorpiniti, Margherita; Gigli, Chiara; Nazerian, Peiman; Vanni, Simone; Innocenti, Francesca; Stefanone, Valerio T; Savinelli, Caterina; Coppa, Alessandro; Bigiarini, Sofia; Caldi, Francesca; Tassinari, Irene; Conti, Alberto; Grifoni, Stefano; Pini, Riccardo

2017-06-01

Acute dyspnea is a common symptom in the ED. The standard approach to dyspnea often relies on radiologic and laboratory results, causing excessive delay before adequate therapy is started. Use of an integrated point-of-care ultrasonography (PoCUS) approach can shorten the time needed to formulate a diagnosis, while maintaining an acceptable safety profile. Consecutive adult patients presenting with dyspnea and admitted after ED evaluation were prospectively enrolled. The gold standard was the final diagnosis assessed by two expert reviewers. Two physicians independently evaluated the patient; a sonographer performed an ultrasound evaluation of the lung, heart, and inferior vena cava, while the treating physician requested traditional tests as needed. Time needed to formulate the ultrasound and the ED diagnoses was recorded and compared. Accuracy and concordance of the ultrasound and the ED diagnoses were calculated. A total of 2,683 patients were enrolled. The average time needed to formulate the ultrasound diagnosis was significantly lower than that required for ED diagnosis (24 ± 10 min vs 186 ± 72 min; P = .025). The ultrasound and the ED diagnoses showed good overall concordance (κ = 0.71). There were no statistically significant differences in the accuracy of PoCUS and the standard ED evaluation for the diagnosis of acute coronary syndrome, pneumonia, pleural effusion, pericardial effusion, pneumothorax, and dyspnea from other causes. PoCUS was significantly more sensitive for the diagnosis of heart failure, whereas a standard ED evaluation performed better in the diagnosis of COPD/asthma and pulmonary embolism. PoCUS represents a feasible and reliable diagnostic approach to the patient with dyspnea, allowing a reduction in time to diagnosis. This protocol could help to stratify patients who should undergo a more detailed evaluation. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Dyspnea on exertion in obese women: association with an increased oxygen cost of breathing.

PubMed

Babb, Tony G; Ranasinghe, Kamalini G; Comeau, Laurie A; Semon, Trisha L; Schwartz, Belinda

2008-07-15

Although exertional dyspnea in obesity is an important and prolific clinical concern, the underlying mechanism remains unclear. To investigate whether dyspnea on exertion in otherwise healthy obese women was associated with an increase in the oxygen cost of breathing or cardiovascular deconditioning. Obese women with and without dyspnea on exertion participated in two independent experiments (n = 16 and n = 14). All participants underwent pulmonary function testing, hydrostatic weighing, ratings of perceived breathlessness during cycling at 60 W, and determination of the oxygen cost of breathing during eucapnic voluntary hyperpnea at 40 and 60 L/min. Cardiovascular exercise capacity, fat distribution, and respiratory mechanics were determined in 14 women in experiment 2. Data were analyzed between groups by independent t test, and the relationship between the variables was determined by regression analysis. In both experiments, breathlessness during 60 W cycling was markedly increased in over 37% of the obese women (P < 0.01). Age, height, weight, lung function, and %body fat were not different between the groups in either experiment. In contrast, the oxygen cost of breathing was significantly (P < 0.01) and markedly (38-70%) greater in the obese women with dyspnea on exertion. The oxygen cost of breathing was significantly (P < 0.001) correlated with the rating of perceived breathlessness obtained during the 60 W exercise in experiment 1 (r(2) = 0.57) and experiment 2 (r(2) = 0.72). Peak cardiovascular exercise capacity, fat distribution, and respiratory mechanics were not different between groups in experiment 2. Dyspnea on exertion is prevalent in otherwise healthy obese women, which seems to be strongly associated with an increased oxygen cost of breathing. Exercise capacity is not reduced in obese women with dyspnea on exertion.

Emergency endotracheal intubation under fluoroscopy guidance for patients with acute dyspnea or asphyxia.

PubMed

Jiao, Dechao; Xie, Na; Han, Xinwei; Wu, Gang

2016-11-01

To evaluate the feasibility and effectiveness of emergency endotracheal intubation (EEI) under fluoroscopy guidance for patients with acute dyspnea or asphyxia. From October 2011 to October 2014, of 1521 patients with acute dyspnea or asphyxia who required EEI in 6 departments, 43 patients who experienced intubation difficulty or failure were entered into this study. Data on technical success, procedure time, complications, and clinical outcome were collected. The pulse oxygen saturation and Hugh-Jones classification changes were analyzed. Fluoroscopy-guided EEI was technically successful in all patients. Acute dyspnea had resolved in all patients with clinical success rate 100% after the procedure. There were no serious complications during or after the procedure. The pulse oxygen saturation and Hugh-Jones classification showed significant increase after EEI (P < .05). Further treatments, including tracheal stents (n = 21), surgical resection (n = 16), palliative tracheotomy (n = 4), and bronchoscopic treatment (n = 2), were performed 1 to 72 hours after EEI. During a mean follow-up period of 13.2 months, 13 patients had died and 30 patients remained alive without dyspnea. Fluoroscopy-guided EEI is a safe and feasible procedure, and may serve as an alternative treatment option for patients when traditional EEI is unsuccessful. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of N-terminal prohormone brain natriuretic peptide assay for etiologic diagnosis of acute dyspnea in elderly patients.

PubMed

Berdagué, Philippe; Caffin, Pierre-Yves; Barazer, Isabelle; Vergnes, Christine; Sedighian, Shahin; Letrillard, Sébastien; Pilossof, Romain; Goutorbe, Frédéric; Piot, Christophe; Reny, Jean-Luc

2006-03-01

B-type peptide assay (brain natriuretic peptide [BNP] and N-terminal prohormone brain natriuretic peptide [NT-proBNP]) is useful for the diagnosis of heart failure (HF), but few data are available on the use of these markers in elderly subjects. The aim of this study was to evaluate NT-proBNP assay for the diagnosis of acute left HF in patients older than 70 years hospitalized for acute dyspnea. We prospectively enrolled 256 elderly patients with acute dyspnea. They were categorized by 2 cardiologists unaware of NT-proBNP values into a cardiac dyspnea subgroup (left HF) and a noncardiac dyspnea subgroup (all other causes). Mean age was 81 +/- 7 years, and 52% of the patients were women. The diagnoses made in the emergency setting were incorrect or uncertain in 45% of cases. The median NT-proBNP value was higher (P < .0001) in patients with cardiac dyspnea (n = 142; 7906 pg/mL) than in patients with noncardiac dyspnea (n = 112; 1066 pg/mL). The area under the receiver operating characteristic curve was 0.86 (95% CI 0.81-0.91). At a cutoff of 2000 pg/mL, NT-proBNP had a sensitivity of 86%, a specificity of 71%, and an overall accuracy of 80% for cardiac dyspnea. The use of 2 cutoffs (< 1200 and > 4500 pg/mL) resulted in an 8% error rate and a gray area englobing 32% of values. NT-proBNP appears to be a sensitive and specific means of distinguishing pulmonary from cardiac causes of dyspnea in elderly patients. An optimal diagnostic strategy requires the use of 2 cutoffs and further investigations of patients with values in the gray area.

Greater dyspnea is associated with lower health-related quality of life among European patients with COPD

PubMed Central

Gruenberger, Jean-Bernard; Vietri, Jeffrey; Keininger, Dorothy L; Mahler, Donald A

2017-01-01

Objective Dyspnea is a defining symptom in the classification and treatment of chronic obstructive pulmonary disease (COPD). However, the degree of variation in burden among symptomatic COPD patients and the possible correlates of burden remain unclear. This study was conducted to characterize patients in Europe currently being treated for COPD according to the level of dyspnea in terms of sociodemographics, health-related quality of life, work productivity impairment, and health care resource use assessed by patient reports. Methods Data were derived from the 5-EU 2013 National Health and Wellness Survey (N=62,000). Respondents aged ≥40 years who reported currently using a prescription for COPD were grouped according to their level of dyspnea as per the Global Initiative for Chronic Obstructive Lung Disease guidelines and compared on health status (revised Short Form 36 [SF-36]v2), work impairment (Work Productivity and Activity Impairment questionnaire), and number of health care visits in the past 6 months using generalized linear models with appropriate distributions and link functions. Results Of the 768 respondents who met the inclusion criteria, 245 (32%) were considered to have higher dyspnea (equivalent to modified Medical Research Council score ≥2). Higher dyspnea was associated with decrements ranging from 3.9 to 8.2 points in all eight domains of the SF-36 health profile after adjustment for sociodemographics, general health characteristics, and length of COPD diagnosis; mental component summary scores and Short Form-6D health utility scores were lower by 3.5 and 0.06 points, respectively. Adjusted mean activity impairment (55% vs 37%, P<0.001) and number of emergency room visits (0.61 vs 0.40, P=0.030) were higher in patients with greater dyspnea. Conclusion Many European patients with COPD continue to experience dyspnea despite treatment and at levels associated with notable impairments in the patients’ ability to function across a multitude of

Greater dyspnea is associated with lower health-related quality of life among European patients with COPD.

PubMed

Gruenberger, Jean-Bernard; Vietri, Jeffrey; Keininger, Dorothy L; Mahler, Donald A

2017-01-01

Dyspnea is a defining symptom in the classification and treatment of chronic obstructive pulmonary disease (COPD). However, the degree of variation in burden among symptomatic COPD patients and the possible correlates of burden remain unclear. This study was conducted to characterize patients in Europe currently being treated for COPD according to the level of dyspnea in terms of sociodemographics, health-related quality of life, work productivity impairment, and health care resource use assessed by patient reports. Data were derived from the 5-EU 2013 National Health and Wellness Survey (N=62,000). Respondents aged ≥40 years who reported currently using a prescription for COPD were grouped according to their level of dyspnea as per the Global Initiative for Chronic Obstructive Lung Disease guidelines and compared on health status (revised Short Form 36 [SF-36]v2), work impairment (Work Productivity and Activity Impairment questionnaire), and number of health care visits in the past 6 months using generalized linear models with appropriate distributions and link functions. Of the 768 respondents who met the inclusion criteria, 245 (32%) were considered to have higher dyspnea (equivalent to modified Medical Research Council score ≥2). Higher dyspnea was associated with decrements ranging from 3.9 to 8.2 points in all eight domains of the SF-36 health profile after adjustment for sociodemographics, general health characteristics, and length of COPD diagnosis; mental component summary scores and Short Form-6D health utility scores were lower by 3.5 and 0.06 points, respectively. Adjusted mean activity impairment (55% vs 37%, P <0.001) and number of emergency room visits (0.61 vs 0.40, P =0.030) were higher in patients with greater dyspnea. Many European patients with COPD continue to experience dyspnea despite treatment and at levels associated with notable impairments in the patients' ability to function across a multitude of domains. These patients may benefit

[Dyspnea in the terminal stage].

PubMed

Binsack, T

2001-10-01

From all symptoms in palliative medicine those concerning respiration are most excruciating and most difficult to treat. No other symptom is more dependent on psychosocial circumstances and on the atmosphere around the patient. Therefore the relief of respiratory problems is as important as the therapy of pain. A consequent therapy comprises besides drug therapy (adrenocortical steroids, brochodilators, opioids, sedatives and sometimes antibiotics) also physiotherapy and in special cases oncological treatment and radiotherapy. A team present twenty-four hours a day, the training of relatives and friends, the frank dealing with the patient's anxiety of suffocation are the basis of all therapeutic measures. Dyspnea often is the reason for a longer stay in a palliative care unit.

Relation of dyspnea in patients unable to perform exercise stress testing to outcome and myocardial ischemia.

PubMed

Bernheim, Alain M; Kittipovanonth, Maytinee; Scott, Christopher G; McCully, Robert B; Tsang, Teresa S; Pellikka, Patricia A

2009-07-15

Limited information exists regarding the significance of dyspnea in patients who are unable to exercise and the contribution of myocardial ischemia to this symptom. To assess this, we evaluated results of dobutamine stress echocardiography (DSE) and long-term outcome of patients with dyspnea referred for DSE. We studied 6,376 consecutive patients who were unable to perform an exercise test and were referred for DSE. Patients were classified according to presenting symptoms and followed for 5.5 +/- 2.8 years. End points were cardiac ischemic events (myocardial infarction or revascularization), hospitalization for heart failure (HF), and death. Dobutamine stress echocardiogram was positive for ischemia in 19% of patients with dyspnea versus 24% (p = 0.002) of those with typical angina and 17% (p = 0.2) of asymptomatic patients. In multivariate analysis, risk of death was increased in dyspneic patients versus asymptomatic patients (hazard ratio [HR] 1.14, p = 0.02) and patients with chest pain (HR 1.20, p <0.001). Hospitalization for HF occurred more often in patients with dyspnea (HR 1.26, p = 0.05 vs asymptomatic; HR 1.24, p = 0.06 vs chest pain), especially in the subset without previous HF (HR 1.45, p = 0.006 vs chest pain). Risk of cardiac ischemic events in patients with dyspnea was similar versus asymptomatic patients (HR 0.92, p = 0.39) and decreased versus patients with chest pain (HR 0.70, p <0.001). In conclusion, in patients referred for DSE, dyspnea was associated with a poor outcome. This increased hazard seems not to be linked to myocardial ischemia, but instead to HF and death.

Patients who are near death are frequently unable to self-report dyspnea.

PubMed

Campbell, Margaret L; Templin, Thomas; Walch, Julia

2009-10-01

Standard measures of dyspnea rely on the patient's self-report. Declining consciousness and/or cognitive function and nearness to death may interfere with dyspnea reporting making the patient vulnerable to undertreatment or overtreatment. An observational design was used with 89 consecutive patients referred for inpatient palliative care consultation. Patients were included if they were at risk for dyspnea because of one or more of the following: lung cancer, chronic obstructive pulmonary disease (COPD), heart failure, or pneumonia. Patients were asked "Are you short of breath?" and asked to quantify any distress by pointing to a visual analogue scale (VAS). Other measures included: consciousness, cognitive state, terminal illness severity, and patient demographics. More than half of the patients (54%) were unable to provide a yes or no response. Only 20 of 41 (49%) able to respond with yes or no were able to quantify any distress with the VAS. Ability to self-report was positively associated with consciousness (p < 0.01), cognitive state (p < 0.01), and terminal illness severity (p < 0.01). A significant inverse relationship was found between consciousness and terminal illness severity (p < 0.01). Declines in consciousness and cognitive state were strongly correlated with nearness to death (p < 0.01). Declining consciousness and/or cognitive state are expected when patients are near death. The ability to give even the simplest self-report (yes or no) about dyspnea is lost in the near-death phase of terminal illness, yet the ability to experience distress may persist and may be overlooked and undertreated or overtreated. Other methods for symptom assessment are needed in this context.

Managing dyspnea in patients with advanced chronic obstructive pulmonary disease: A Canadian Thoracic Society clinical practice guideline

PubMed Central

Marciniuk, Darcy D; Goodridge, Donna; Hernandez, Paul; Rocker, Graeme; Balter, Meyer; Bailey, Pat; Ford, Gordon; Bourbeau, Jean; O’Donnell, Denis E; Maltais, Francois; Mularski, Richard A; Cave, Andrew J; Mayers, Irvin; Kennedy, Vicki; Oliver, Thomas K; Brown, Candice

2011-01-01

Dyspnea is a cardinal symptom of chronic obstructive pulmonary disease (COPD), and its severity and magnitude increases as the disease progresses, leading to significant disability and a negative effect on quality of life. Refractory dyspnea is a common and difficult symptom to treat in patients with advanced COPD. There are many questions concerning optimal management and, specifically, whether various therapies are effective in this setting. The present document was compiled to address these important clinical issues using an evidence-based systematic review process led by a representative interprofessional panel of experts. The evidence supports the benefits of oral opioids, neuromuscular electrical stimulation, chest wall vibration, walking aids and pursed-lip breathing in the management of dyspnea in the individual patient with advanced COPD. Oxygen is recommended for COPD patients with resting hypoxemia, but its use for the targeted management of dyspnea in this setting should be reserved for patients who receive symptomatic benefit. There is insufficient evidence to support the routine use of anxiolytic medications, nebulized opioids, acupuncture, acupressure, distractive auditory stimuli (music), relaxation, hand-held fans, counselling programs or psychotherapy. There is also no evidence to support the use of supplemental oxygen to reduce dyspnea in nonhypoxemic patients with advanced COPD. Recognizing the current unfamiliarity with prescribing and dosing of opioid therapy in this setting, a potential approach for their use is illustrated. The role of opioid and other effective therapies in the comprehensive management of refractory dyspnea in patients with advanced COPD is discussed. PMID:21499589

Aerobic exercise: effects on parameters related to fatigue, dyspnea, weight and body composition in HIV-infected adults.

PubMed

Smith, B A; Neidig, J L; Nickel, J T; Mitchell, G L; Para, M F; Fass, R J

2001-04-13

The purpose of the study was to examine the effects of aerobic exercise on physiological fatigue (time on treadmill), dyspnea [rate of perceived exertion (RPE) and forced expiratory volume at 1 s (FEV1)], weight, and body composition in HIV-1-infected adults (200-499 x 106 CD4+ cells/l). The study was a randomized, wait-listed, controlled clinical trial of aerobic exercise in HIV-1-infected adults on signs and symptoms associated with HIV-1 infection or its treatment. Sixty subjects were recruited and randomized to two groups. Experimental subjects completed a 12-week supervised exercise program. Control subjects continued usual activity from baseline to week 12 and were then were enrolled in the exercise program. At baseline, the groups were similar in age, weight, body mass index [mean body mass index (BMI) > 27], time since diagnosis, number of symptoms, CD4+ cell count, and number on protease inhibitor therapy (n = 7). Despite disproportionate attrition from the exercise group (38%), exercise subjects were able to remain on the treadmill longer, lost weight, decreased BMI, subcutaneous fat, and abdominal girth when compared to controls. The improvement in weight and body composition occurred without a decrease in kilocalories consumed. Exercise did not seem to have an effect on RPE, a surrogate for dyspnea, and FEV1. There was no significant difference in either the change in CD4+ cell count, percentage or copies of plasma HIV-1 RNA between groups. We conclude that supervised aerobic exercise training safely decreases fatigue, weight, BMI, subcutaneous fat and abdominal girth (central fat) in HIV-1-infected individuals. It did not appear to have an effect on dyspnea.

World Trade Center dyspnea: bronchiolitis obliterans with functional improvement: a case report.

PubMed

Mann, Jack M; Sha, Kenneth K; Kline, Gary; Breuer, Frank-Uwe; Miller, Albert

2005-09-01

Bronchiolitis obliterans is a severe, often progressive, lung disease characterized by cough, exertional dyspnea, and airflow obstruction. It has been ascribed to specific causes such as lung or bone marrow transplant, medications for rheumatoid disease, and most recently in association with exposure to environmental agents. A 42-year-old, previously healthy New York City Highway Patrol officer who arrived at the World Trade Center (WTC), "ground zero," early on September 11, 2001 was evaluated. He has been followed for over 2 years with serial chest radiographs, CT scans, and pulmonary function studies. He eventually underwent an open lung biopsy. His dyspnea started on September 12, 2001 and progressed despite aggressive therapy with inhaled bronchodilator as well as oral and inhaled corticosteroids. At no time did he have any radiographic evidence of pulmonary disease. His forced vital capacity (FVC) decreased from 5.32 L in October 2001 to 2.86 L in January 2003. He underwent an open lung biopsy because of the persistent exertional dyspnea coupled with the loss of over 2 L of lung volume. The pathological findings were chronic bronchiolitis with focal obliterative bronchiolitis and rare non-necrotizing granuloma. Symptoms and pulmonary function improved after therapy with Azithromycin was added to his treatment. This process is believed to be secondary to his massive exposure to the cloud of dust that followed the collapse of the WTC. It is our conviction that many of those present at the WTC on September 11 who have persistent dyspnea and deterioration of pulmonary function may have a similar pathologic process despite absence of abnormalities on CT of the chest. In view of the many signs and symptoms seen in first responders we feel that these findings provide important information about the pathophysiology and treatment of progressive disease resulting from this exposure.

'Flooding' of the lungs and severe dyspnea in a patient with bronchoalveolar carcinoma.

PubMed

Keizer, Ron J; Beijnen, Jos H; Baas, Paul

2011-09-01

In this case report, we describe a patient with bronchoalveolar carcinoma that experienced severe bronchorrhea and dyspnea after inhalation of N-acetylcysteine. The adverse reactions occurred both after oral and nebulized administration of N-acetylcysteine, resulting in severe dyspnea and the feeling of 'drowning'. Bronchorrhea has previously been reported as an uncommon but serious complication of bronchoalveolar carcinoma. We strongly suspect the administration of N-acetylcysteine to be implicated, as the complications occurred immediately after administration of this drug. As the patient suffered from hyperhomocysteinemia, we speculate that an additive or synergistic interaction with homocysteine may have been involved as well.

Dyspnea descriptors developed in Brazil: application in obese patients and in patients with cardiorespiratory diseases.

PubMed

Teixeira, Christiane Aires; Rodrigues Júnior, Antonio Luiz; Straccia, Luciana Cristina; Vianna, Elcio Dos Santos Oliveira; Silva, Geruza Alves da; Martinez, José Antônio Baddini

2011-01-01

To develop a set of descriptive terms applied to the sensation of dyspnea (dyspnea descriptors) for use in Brazil and to investigate the usefulness of these descriptors in four distinct clinical conditions that can be accompanied by dyspnea. We collected 111 dyspnea descriptors from 67 patients and 10 health professionals. These descriptors were analyzed and reduced to 15 based on their frequency of use, similarity of meaning, and potential pathophysiological value. Those 15 descriptors were applied in 50 asthma patients, 50 COPD patients, 30 patients with heart failure, and 50 patients with class II or III obesity. The three best descriptors, as selected by the patients, were studied by cluster analysis. Potential associations between the identified clusters and the four clinical conditions were also investigated. The use of this set of descriptors led to a solution with seven clusters, designated sufoco (suffocating), aperto (tight), rápido (rapid), fadiga (fatigue), abafado (stuffy), trabalho/inspiração (work/inhalation), and falta de ar (shortness of breath). Overlapping of descriptors was quite common among the patients, regardless of their clinical condition. Asthma was significantly associated with the sufoco and trabalho/inspiração clusters, whereas COPD and heart failure were associated with the sufoco, trabalho/inspiração, and falta de ar clusters. Obesity was associated only with the falta de ar cluster. In Brazil, patients who are accustomed to perceiving dyspnea employ various descriptors in order to describe the symptom, and these descriptors can be grouped into similar clusters. In our study sample, such clusters showed no usefulness in differentiating among the four clinical conditions evaluated.

Physiological mechanisms of dyspnea during exercise with external thoracic restriction: Role of increased neural respiratory drive

PubMed Central

Mendonca, Cassandra T.; Schaeffer, Michele R.; Riley, Patrick

2013-01-01

We tested the hypothesis that neuromechanical uncoupling of the respiratory system forms the mechanistic basis of dyspnea during exercise in the setting of “abnormal” restrictive constraints on ventilation (VE). To this end, we examined the effect of chest wall strapping (CWS) sufficient to mimic a “mild” restrictive lung deficit on the interrelationships between VE, breathing pattern, dynamic operating lung volumes, esophageal electrode-balloon catheter-derived measures of the diaphragm electromyogram (EMGdi) and the transdiaphragmatic pressure time product (PTPdi), and sensory intensity and unpleasantness ratings of dyspnea during exercise. Twenty healthy men aged 25.7 ± 1.1 years (means ± SE) completed symptom-limited incremental cycle exercise tests under two randomized conditions: unrestricted control and CWS to reduce vital capacity (VC) by 21.6 ± 0.5%. Compared with control, exercise with CWS was associated with 1) an exaggerated EMGdi and PTPdi response; 2) no change in the relationship between EMGdi and each of tidal volume (expressed as a percentage of VC), inspiratory reserve volume, and PTPdi, thus indicating relative preservation of neuromechanical coupling; 3) increased sensory intensity and unpleasantness ratings of dyspnea; and 4) no change in the relationship between increasing EMGdi and each of the intensity and unpleasantness of dyspnea. In conclusion, the increased intensity and unpleasantness of dyspnea during exercise with CWS could not be readily explained by increased neuromechanical uncoupling but likely reflected the awareness of increased neural respiratory drive (EMGdi) needed to achieve any given VE during exercise in the setting of “abnormal” restrictive constraints on tidal volume expansion. PMID:24356524

Exertional dyspnea associated with chest wall strapping is reduced when external dead space substitutes for part of the exercise stimulus to ventilation.

PubMed

Garske, Luke A; Lal, Ravin; Stewart, Ian B; Morris, Norman R; Cross, Troy J; Adams, Lewis

2017-05-01

Chest wall strapping has been used to assess mechanisms of dyspnea with restrictive lung disease. This study examined the hypothesis that dyspnea with restriction depends principally on the degree of reflex ventilatory stimulation. We compared dyspnea at the same (iso)ventilation when added dead space provided a component of the ventilatory stimulus during exercise. Eleven healthy men undertook a randomized controlled crossover trial that compared four constant work exercise conditions: 1 ) control (CTRL): unrestricted breathing at 90% gas exchange threshold (GET); 2 ) CTRL+dead space (DS): unrestricted breathing with 0.6-l dead space, at isoventilation to CTRL due to reduced exercise intensity; 3 ) CWS: chest wall strapping at 90% GET; and 4 ) CWS+DS: chest strapping with 0.6-l dead space, at isoventilation to CWS with reduced exercise intensity. Chest strapping reduced forced vital capacity by 30.4 ± 2.2% (mean ± SE). Dyspnea at isoventilation was unchanged with CTRL+DS compared with CTRL (1.93 ± 0.49 and 2.17 ± 0.43, 0-10 numeric rating scale, respectively; P = 0.244). Dyspnea was lower with CWS+DS compared with CWS (3.40 ± 0.52 and 4.51 ± 0.53, respectively; P = 0.003). Perceived leg fatigue was reduced with CTRL+DS compared with CTRL (2.36 ± 0.48 and 2.86 ± 0.59, respectively; P = 0.049) and lower with CWS+DS compared with CWS (1.86 ± 0.30 and 4.00 ± 0.79, respectively; P = 0.006). With unrestricted breathing, dead space did not change dyspnea at isoventilation, suggesting that dyspnea does not depend on the mode of reflex ventilatory stimulation in healthy individuals. With chest strapping, dead space presented a less potent stimulus to dyspnea, raising the possibility that leg muscle work contributes to dyspnea perception independent of the ventilatory stimulus. NEW & NOTEWORTHY Chest wall strapping was applied to healthy humans to simulate restrictive lung disease. With chest wall strapping, dyspnea was

Effect of palliative oxygen versus medical (room) air in relieving breathlessness in patients with refractory dyspnea: a double-blind randomized controlled trial

PubMed Central

Abernethy, Amy P.; McDonald, Christine F.; Frith, Peter A.; Clark, Katherine; Herndon, James E.; Marcello, Jennifer; Young, Iven H.; Bull, Janet; Wilcock, Andrew; Booth, Sara; Wheeler, Jane L.; Tulsky, James A.; Crockett, Alan J.; Currow, David C.

2010-01-01

Background Palliative oxygen therapy is widely used for dyspnea in individuals with life-limiting illness ineligible for long-term oxygen therapy. Methods This international double-blind randomized controlled trial evaluatedeffectiveness of oxygen vs. medical (room) air for relieving breathlessness in patients with life-limiting illness, refractory dyspnea, and PaO2>55 mm Hg. Participants were recruited from outpatient clinics at 9 sites (Australia, United States, England). Participants received oxygen or medical air via concentrator through nasal cannulae at 2 liters/minute for 7 days. The primary outcome measure was breathlessness (0-10 numerical rating scale [NRS]), measured twice daily. Findings Participants (N=239) were: mean age, 73 (standard deviation [SD] 10); 62% male; mean PaO2, 77 mm Hg (SD 12); mean morning dyspnea, 4.5 on NRS (SD 2.2); chronic obstructive pulmonary disease, 64%; cancer, 16%. Oxygen was not significantly superior to medical air for relief of breathlessness. Over the 7-day period, after provision of medical gas, mean morning and evening dyspnea decreased by -0.8 (95% confidence interval [CI]: -1.1, -0.5) and -0.4 (CI: -0.7, 0.1), respectively (p<0.001), regardless of intervention. Baseline dyspnea predicted improvement with medical gas; participants with moderate (4-6 NRS) and severe (7-10 NRS) baseline dyspnea had average decreases in morning dyspnea of -0.7 (CI: -1.1, -0.4) and -2.4 (CI: -3.0, -1.8), respectively. Interpretation There is no additional symptomatic benefit of oxygen over room air delivered by nasal cannulae for relieving refractory dyspnea related to life-limiting illness in patients with PaO2>55 mm Hg. Dyspnea intensity decreased in both study arms, temporally related to provision of medical gas. PMID:20816546

Type A Behavior Pattern, Impulsiveness, Risk Propensity, and Empathy as Predictors of Dyspnea and Number of Infections in Men with Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.

PubMed

Witusik, Andrzej; Mokros, Łukasz; Kuna, Piotr; Nowakowska-Domagała, Katarzyna; Antczak, Adam; Pietras, Tadeusz

2018-06-06

BACKGROUND Stress and psychological factors can induce dyspnea in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to assess selected elements of the clinical presentation of COPD in the context of the severity of type A pattern of behavior, impulsiveness, and tendency for empathy. MATERIAL AND METHODS This was a cross-sectional study. The study group consisted of 179 men with COPD and the control group consisted of 31 healthy male smokers. In all patients, the number of infectious exacerbations over the past year, the result on the dyspnea scale (MRC), and the FEV1-to- predicted FEV1 ratio was assessed. The A pattern of behavior was measured using the Type A scale. To measure impulsivity, risk propensity, and empathy, the IVE impulsivity questionnaire was used. RESULTS An increase in the number of infectious exacerbations was associated with an increased score on the Type A scale, an increase in risk propensity, and a decrease in impulsivity score. Increased severity of dyspnea was associated with an increase in Type A behavior pattern score and an increase in the risk propensity score. CONCLUSIONS Type A behavior pattern and risk propensity are independent predictors of the number of infections in the last year and of the subjective severity of dyspnea among men with COPD and healthy male smokers.

Relationship Among Pulmonary Hypertension, Autoimmunity, Thyroid Hormones and Dyspnea in Patients With Hyperthyroidism.

PubMed

Zuhur, Sayid Shafi; Baykiz, Derya; Kara, Sonat Pinar; Sahin, Ertan; Kuzu, Idris; Elbuken, Gulsah

2017-04-01

Previous studies have reported conflicting results regarding the mechanisms underlying the pathophysiology of pulmonary hypertension (PHT) in patients with hyperthyroidism. Therefore, in this study, we investigated the association between PHT and thyroid-stimulating hormone (TSH) receptor antibody, thyroid peroxidase antibody, thyroglobulin antibody, TSH, fT3, fT4 and dyspnea during daily activities in a large population of patients with hyperthyroidism. A total of 129 consecutive patients with hyperthyroidism, 37 with hypothyroidism and 38 euthyroid controls were enrolled in this study. The modified medical research council scale was used for the assessment of dyspnea in daily activities. All the patients and euthyroid controls underwent transthoracic echocardiography for the assessment of PHT. Mild PHT was present in 35%, 36%, 13.5% and 5% of the patients with Graves׳ disease, toxic multinodular goiter, hypothyroidism and euthyroid controls, respectively. Pulmonary vascular resistance (PVR) was higher in hyperthyroid patients with PHT than in those without PHT. Moreover, a significant positive correlation was found between modified medical research council scale and pulmonary artery systolic pressure as well as PVR in patients with hyperthyroidism. No association was found between PHT and serum TSH receptor antibody, thyroid peroxidase antibody, thyroglobulin antibody, TSH, fT3 and fT4 levels. Mild PHT is present in a significant proportion of patients with hyperthyroidism, regardless of etiology. PVR appears to be the main cause of PHT in patients with hyperthyroidism, and neither autoimmunity nor thyroid hormones are associated with PHT in these patients. Mild dyspnea during daily activities in patients with hyperthyroidism may be related to PHT; however, severe dyspnea requires further evaluation. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Evaluation of the Appropriate Washout Period Following Fan Therapy for Dyspnea in Patients With Advanced Cancer: A Pilot Study.

PubMed

Kako, Jun; Morita, Tatsuya; Yamaguchi, Takuhiro; Sekimoto, Asuko; Kobayashi, Masamitsu; Kinoshita, Hiroya; Ogawa, Asao; Zenda, Sadamoto; Uchitomi, Yosuke; Inoguchi, Hironobu; Matsushima, Eisuke

2018-02-01

To clarify the duration required for dyspnea to return to baseline severity after fan therapy, to evaluate whether fan-to-legs therapy or no fan therapy would be a suitable control therapy, and to investigate changes in patients' face surface temperature after fan therapy. In this pilot study, all participants received 3 interventions in the following order: no fan, fan to legs, and fan to face. Participants used a fan for 5 minutes, and they scored their dyspnea at 10-minute intervals for 60 minutes or until the score had returned to its baseline value, whichever occurred first. Nine patients with advanced cancer admitted to a palliative care unit were included; they had dyspnea at rest and rated its severity as at least 3 points on a 0- to 10-point numerical rating scale. Descriptive statistics and the Wilcoxon signed rank test were used to analyze the data. All patients completed the study. Of the 9 participants, 6 experienced a clinical benefit from using a fan to their faces. Of these patients, only 2 participants' (2 of 6) dyspnea scores returned to baseline by the end of the 60-minute assessment period after exposure to fan-to-face therapy. In fan-to-legs and no fan settings, there was no change in the dyspnea scores. There were significant differences between the baseline face surface temperature and that after fan-to-face and fan-to-legs settings. When using a crossover design to investigate the effect of fan therapy on dyspnea, 1 hour is an insufficient washout period.

Dyspnea, chest wall hyperinflation, and rib cage distortion in exercising patients with chronic obstructive pulmonary disease.

PubMed

Bruni, Giulia Innocenti; Gigliotti, Francesco; Binazzi, Barbara; Romagnoli, Isabella; Duranti, Roberto; Scano, Giorgio

2012-06-01

Whether dyspnea, chest wall dynamic hyperinflation, and abnormalities of rib cage motion are interrelated phenomena has not been systematically evaluated in patients with chronic obstructive pulmonary disease (COPD). Our hypothesis that they are not interrelated was based on the following observations: (i) externally imposed expiratory flow limitation is associated with no rib cage distortion during strenuous incremental exercise, with indexes of hyperinflation not being correlated with dyspnea, and (ii) end-expiratory chest wall volume may either increase or decrease during exercise in patients with COPD, with those who hyperinflate being as breathless as those who do not. Sixteen patients breathed either room air or 50% supplemental O2 at 75% of peak exercise in randomized order. We evaluated the volume of chest wall (V(cw)) and its compartments: the upper rib cage (V(rcp)), lower rib cage (V(rca)), and abdomen (V(ab)) using optoelectronic plethysmography; rib cage distortion was assessed by measuring the phase angle shift between V(rcp) and V(rca). Ten patients increased end-expiratory V(cw) (V(cw,ee)) on air. In seven hyperinflators and three non-hyperinflators, the lower rib cage paradoxed inward during inspiration with a phase angle of 63.4° ± 30.7° compared with a normal phase angle of 16.1° ± 2.3° recorded in patients without rib cage distortion. Dyspnea (by Borg scale) averaged 8.2 and 9 at the end of exercise on air in patients with and without rib cage distortion, respectively. At iso-time during exercise with oxygen, decreased dyspnea was associated with a decrease in ventilation regardless of whether patients distorted the rib cage, dynamically hyperinflated, or deflated the chest wall. Dyspnea, chest wall dynamic hyperinflation, and rib cage distortion are not interrelated phenomena.

Diagnostic accuracy and reproducibility of pleural and lung ultrasound in discriminating cardiogenic causes of acute dyspnea in the emergency department.

PubMed

Cibinel, Gian Alfonso; Casoli, Giovanna; Elia, Fabrizio; Padoan, Monica; Pivetta, Emanuele; Lupia, Enrico; Goffi, Alberto

2012-02-01

Dyspnea is a common symptom in patients admitted to the Emergency Department (ED), and discriminating between cardiogenic and non-cardiogenic dyspnea is often a clinical dilemma. The initial diagnostic work-up may be inaccurate in defining the etiology and the underlying pathophysiology. The aim of this study was to evaluate the diagnostic accuracy and reproducibility of pleural and lung ultrasound (PLUS), performed by emergency physicians at the time of a patient's initial evaluation in the ED, in identifying cardiac causes of acute dyspnea. Between February and July 2007, 56 patients presenting to the ED with acute dyspnea were prospectively enrolled in this study. In all patients, PLUS was performed by emergency physicians with the purpose of identifying the presence of diffuse alveolar-interstitial syndrome (AIS) or pleural effusion. All scans were later reviewed by two other emergency physicians, expert in PLUS and blinded to clinical parameters, who were the ultimate judges of positivity for diffuse AIS and pleural effusion. A random set of 80 recorded scannings were also reviewed by two inexperienced observers to assess inter-observer variability. The entire medical record was independently reviewed by two expert physicians (an emergency medicine physician and a cardiologist) blinded to the ultrasound (US) results, in order to determine whether, for each patient, dyspnea was due to heart failure, or not. Sensitivity, specificity, and positive/negative predictive values were obtained; likelihood ratio (LR) test was used. Cohen's kappa was used to assess inter-observer agreement. The presence of diffuse AIS was highly predictive for cardiogenic dyspnea (sensitivity 93.6%, specificity 84%, positive predictive value 87.9%, negative predictive value 91.3%). On the contrary, US detection of pleural effusion was not helpful in the differential diagnosis (sensitivity 83.9%, specificity 52%, positive predictive value 68.4%, negative predictive value 72.2%). Finally

Dyspnea descriptors translated from English to Portuguese: application in obese patients and in patients with cardiorespiratory diseases.

PubMed

Teixeira, Christiane Aires; Rodrigues Júnior, Antonio Luiz; Straccia, Luciana Cristina; Vianna, Elcio Dos Santos Oliveira; Silva, Geruza Alves da; Martinez, José Antônio Baddini

2011-01-01

To investigate the usefulness of descriptive terms applied to the sensation of dyspnea (dyspnea descriptors) that were developed in English and translated to Brazilian Portuguese in patients with four distinct clinical conditions that can be accompanied by dyspnea. We translated, from English to Brazilian Portuguese, a list of 15 dyspnea descriptors reported in a study conducted in the USA. Those 15 descriptors were applied in 50 asthma patients, 50 COPD patients, 30 patients with heart failure, and 50 patients with class II or III obesity. The three best descriptors, as selected by the patients, were studied by cluster analysis. Potential associations between the identified clusters and the four clinical conditions were also investigated. The use of this set of descriptors led to a solution with nine clusters, designated expiração (exhalation), fome de ar (air hunger), sufoco (suffocating), superficial (shallow), rápido (rapid), aperto (tight), falta de ar (shortness of breath), trabalho (work), and inspiração (inhalation). Overlapping of the descriptors was quite common among the patients, regardless of their clinical condition. Asthma, COPD, and heart failure were significantly associated with the inspiração cluster. Heart failure was also associated with the trabalho cluster, whereas obesity was not associated with any of the clusters. In our study sample, the application of dyspnea descriptors translated from English to Portuguese led to the identification of distinct clusters, some of which were similar to those identified in a study conducted in the USA. The translated descriptors were less useful than were those developed in Brazil regarding their ability to generate significant associations among the clinical conditions investigated here.

[Development of an activity of daily living scale for patients with COPD: the Activity of Daily Living Dyspnea scale].

PubMed

Yoza, Yoshiyasu; Ariyoshi, Koya; Honda, Sumihisa; Taniguchi, Hiroyuki; Senjyu, Hideaki

2009-10-01

Patients with COPD often experience restriction in their activities of daily living (ADL) due to dyspnea. This type of restriction is unique to patients with COPD and cannot be adequately evaluated by the generic ADL scales. This study developed an ADL scale (the Activity of Daily Living Dyspnea scale [ADL-D scale]) for patients with COPD and investigated its validity and internal consistency. Patients with stable COPD were recruited and completed a pilot 26-item questionnaire. Patients also performed the Incremental Shuttle Walk Test (ISWT), and completed the St George's Respiratory Questionnaire (SGRQ), and Medical Research Council (MRC) dyspnea grade. There were 83 male participants who completed the pilot questionnaire. Following the pilot, 8 items that were not undertaken by the majority of subjects, and 3 items judged to be of low clinical importance by physical therapists were removed from the pilot questionnaire. The final ADL-D scale contained 15 items. Scores obtained with the ADL-D scale were significantly correlated with the MRC dyspnea grades, distance walked on the ISWT and SGRQ scores. The ADL-D scores were significantly different across the five grades of the MRC dyspnea grade. The ADL-D scale showed high consistency (Chronbach's alpha coefficient of 0.96). The ADL-D scale is a useful scale for assessing impairments in ADL in Japanese male patients with COPD.

Assessing validity by comparing transition and static measures of dyspnea in patients with acute decompensated heart failure.

PubMed

Smithline, Howard A; Caglar, Selin; Blank, Fidela S J

2010-01-01

This study assessed the convergent validity of 2 dyspnea measures, the transition measure and the change measure, by comparing them with each other in patients admitted to the hospital with acute decompensated heart failure. Static measures of dyspnea were obtained at baseline (pre-static measure) and at time 1 hour and 4 hour (post-static measures). The change measure was calculated as the difference between the pre-static and post-static measures. Transition measures were obtained at time 1 hour and 4 hour. Visual analog scales and Likert scales were used. Both physicians and patients measured the dyspnea independently. A total of 112 patients had complete data sets at time 0 and 1 hour and 86 patients had complete data sets at all 3 time points. Correlations were calculated between the transition measures and static measures (pre-static, post-static, and change measure). Bland-Altman plots were generated and the mean difference and limits of agreement between the transition measures and the change measures were calculated. In general, short-term dyspnea assessment using transition measures and serial static measures can not be used to validate each other in this population of patients being admitted with acute decompensated heart failure. © 2010 Wiley Periodicals, Inc.

Geographic Health's Way to Prevention of Diseases: A Case Study on Arsenic Spatial Dispersion and Dyspnea in Isfahan Province

PubMed Central

Rashidi, Maasoume; Poursafa, Parinaz

2014-01-01

Background: As geographic science discusses the analysis of environment, human beings and their mutual relations, thus the field of medical geography consists of being inspired from the relations between these two factors, analyzing environmental factors, their identification them and the state of their effects on human health, as well as determining the location of these factors. Some hazards that threat human health are the results of environmental factors and the relevant pollutions. Some important categories of diseases including (Shortness of Breath or, Dyspnea) have considerable differences in various places, as observed in their spatial prevalence and distribution maps. Methods: The record of patients with Dyspnea diseases were prepared for this descriptive research, for the period of 2009-2011, from the provincial health center, with the questionnaires were excluded patients with a family history of disease and the spatial diagram for disease prevalence was drawn according to the prepared data. The arsenic geographical distribution diagram in Isfahan province was also prepared and then the relation between an element of Arsenic in the province and the Dyspnea diseases were analyzed. Results: The analyses showed that the highest rate of Arsenic is entered the soil via fertilizers to come eventually into the food cycle of humans. By analyzing the amount of used fertilizers in Isfahan province and the dispersion diagram of Arsenic in Isfahan province, it was found that the highest frequency of Arsenic is in places having agricultural base. The spatial dispersion of Dyspnea diseases also showed that the spreading of Dyspnea diseases is greater in places with higher scale of Arsenic. Conclusions: This study is a logical justification between the two diagrams to confirm the hypothesis regarding the effect of arsenic on Dyspnea. PMID:25538832

[NT-proBNP as a diagnostic marker in dogs with dyspnea and in asymptomatic dogs with heart murmur].

PubMed

Haßdenteufel, E; Kresken, J-G; Henrich, E; Hildebrandt, N; Schneider, C; Stosic, A; Schneider, M

2012-01-01

The cardiac biomarker NT-proBNP indicates cardiac load in terms of myocardial wall stress. The objective of the study was to compare the results of NT-proBNP measurements in healthy dogs and dogs with dyspnea as well as asymptomatic dogs with heart murmur with the literature. Between April 2007 and December 2007 dogs with dyspnea of non-cardiac origin (n=11), dogs with dyspnea of cardiac origin (n=18) and asymptomatic dogs with heart murmur (n=22) were included. Twelve clinically healthy dogs served as a control group. All animals underwent cardiologic examination including echocardiography and measurement of serum NT-proBNP concentration. Serum was centrifuged and frozen within 30 minutes and was stored frozen until analysis was performed. Median NT-proBNP concentration in healthy dogs was 240 pmol/l (range 131-546 pmol/l). Dogs with dyspnea and primary respiratory disease displayed a median NT-proBNP concentration of 876 pmol/l (range 97-2614 pmol/l). In patients with dyspnea of non-cardiac origin, there was a difference in the values of NT-proBNP of dogs with and without pulmonary hypertension diagnosed by echocardiography. Dogs with dyspnea of cardiac origin displayed a median NT-proBNP concentration of 2000 pmol/l (range 137-2614 pmol/l). Low normal NT-proBNP values were only found in patients with pericardial effusion. Median NT-proBNP concentration in asymptomatic dogs with heart murmur was 698.5 pmol/l (range 121-2614 pmol/l). Considerably increased values were particularly measured in asymptomatic patients with severe congenital heart disease. NT-proBNP represents a useful additional diagnostic parameter in veterinary clinical cardiology to assess the severity of cardiac disease. Interpretation must take into consideration the clinical picture of the patient, as dogs with severe arrhythmias, sepsis and pulmonary thromboembolism may display high NT-proBNP levels without congestive heart failure. Our results indicate the following cut-off values: <500 pmol

Perspectives of patients, family caregivers and physicians about the use of opioids for refractory dyspnea in advanced chronic obstructive pulmonary disease

PubMed Central

Rocker, Graeme; Young, Joanne; Donahue, Margaret; Farquhar, Morag; Simpson, Catherine

2012-01-01

Background: A recent national practice guideline recommends the use of opioids for the treatment of refractory dyspnea in patients with advanced chronic obstructive pulmonary disease (COPD). We conducted two qualitative studies to explore the experiences of patients and family caregivers with opioids for refractory COPD-related dyspnea and the perspectives and attitudes of physicians toward opioids in this context. Methods: Patients (n = 8; 5 men, 3 women), their caregivers (n = 12; 5 men, 7 women) and physicians (n = 28, 17 men, 11 women) in Nova Scotia participated in the studies. Semistructured interviews were recorded, transcribed verbatim, coded conceptually and analyzed for emergent themes using interpretive description methodology. Results: Patients reported that opioids provided a sense of calm and relief from severe dyspnea. Family caregivers felt that opioids helped patients to breathe more “normally,” observed improvements in patients’ symptoms of anxiety and depression, and experienced reductions in their own stress. Patients reported substantial improvements in their quality of life. All patients and family caregivers wanted opioid therapy to continue. Most physicians were reluctant to prescribe opioids for refractory dyspnea, describing a lack of related knowledge and experience, and fears related to the potential adverse effects and legal censure. Interpretation: Discrepancies between the positive experiences of patients and family caregivers with opioids and the reluctance of physicians to prescribe opioids for refractory dyspnea constitute an important gap in care. Bridging this gap will require initiatives to improve the uptake of practice guidelines and to increase confidence in prescribing opioids for dyspnea refractory to conventional treatment. PMID:22529167

Perspectives of patients, family caregivers and physicians about the use of opioids for refractory dyspnea in advanced chronic obstructive pulmonary disease.

PubMed

Rocker, Graeme; Young, Joanne; Donahue, Margaret; Farquhar, Morag; Simpson, Catherine

2012-06-12

A recent national practice guideline recommends the use of opioids for the treatment of refractory dyspnea in patients with advanced chronic obstructive pulmonary disease (COPD). We conducted two qualitative studies to explore the experiences of patients and family caregivers with opioids for refractory COPD-related dyspnea and the perspectives and attitudes of physicians toward opioids in this context. Patients (n = 8; 5 men, 3 women), their caregivers (n = 12; 5 men, 7 women) and physicians (n = 28, 17 men, 11 women) in Nova Scotia participated in the studies. Semistructured interviews were recorded, transcribed verbatim, coded conceptually and analyzed for emergent themes using interpretive description methodology. Patients reported that opioids provided a sense of calm and relief from severe dyspnea. Family caregivers felt that opioids helped patients to breathe more "normally," observed improvements in patients' symptoms of anxiety and depression, and experienced reductions in their own stress. Patients reported substantial improvements in their quality of life. All patients and family caregivers wanted opioid therapy to continue. Most physicians were reluctant to prescribe opioids for refractory dyspnea, describing a lack of related knowledge and experience, and fears related to the potential adverse effects and legal censure. Discrepancies between the positive experiences of patients and family caregivers with opioids and the reluctance of physicians to prescribe opioids for refractory dyspnea constitute an important gap in care. Bridging this gap will require initiatives to improve the uptake of practice guidelines and to increase confidence in prescribing opioids for dyspnea refractory to conventional treatment.

[Unexpected treatable dyspnea caused by intratracheal granuloma in an amyotrophic lateral sclerosis patient with mechanical ventilation].

PubMed

Ishida, Shimon; Kimura, Fumiharu; Hosokawa, Takafumi; Satoh, Toshihiko; Furutama, Daisuke; Sugino, Masakazu

2007-09-01

Respiratory insufficiency is a problem that develops in nearly all people diagnosed with amyotrophic lateral sclerosis (ALS). A 46-year-old man with ALS, who had been in a bedridden state with tracheal ventilation support, complained of faintness and dyspnea. The airway pressure of the ventilator had increased, and bleeding from the trachea had occurred several times. A fiberoptic bronchoscopy showed granulation located on the anterior wall of the trachea and severe airway obstruction of the tracheostomy tube. Although a long tracheostomy tube had been intubated for the initial management of the tracheal granulation, a tumor on the posterior tracheal wall had relapsed and occluded the tracheal lumen. A self-expandable metallic airway stent was placed into the tracheal stenosis. After stenting, his symptoms of dyspnea and syncope imploved, and the increased airway pressure of the ventilator was normalized. We speculated that the tracheal granuloma had occurred due to a tracheal mucosal injury related to endotracheal suctioning. We should pay attention to complaints of dyspnea in ALS patients with tracheostomy and make a careful consideration to airway care including suction management.

[Nasal flaring as a predictor of mortality in patients with severe dyspnea].

PubMed

Zorrilla Riveiro, José Gregorio; Arnau Bartés, Anna; García Pérez, Dolors; Rafat Sellarés, Ramón; Mas Serra, Arantxa; Fernández Fernández, Rafael

2015-02-01

To determine whether the presence of nasal flaring is a clinical sign of severity and a predictor of hospital mortality in emergency patients with dyspnea. Prospective, observational, single-center study. We enrolled patients older than 15 years of age who required attention for dyspnea categorized as level II or III emergencies according to the Andorran Medical Triage system. Two observers evaluated the presence of nasal flaring. We recorded demographic and clinical variables, including respiratory effort, vital signs, arterial blood gases, and clinical course (hospital admission and mortality). Bivariable analysis was performed and multivariable logistic regression models were constructed. We enrolled 246 patients with a mean (SD) age of 77 (13) years; 52% were female. Nasal flaring was present in 19.5%. Patients with nasal flaring had triage levels indicating greater severity and they had more severe tachypnea, worse oxygenation, and greater acidosis and hypercapnia. Bivariable analysis detected that the following variables were associated with mortality: age (odds ratio [OR], 1.05; 95% CI, 1.01-1.10), prehospital care from the emergency medical service (OR, 3.97; 95% CI, 1.39-11.39), triage level II (OR, 4.19; 95% CI, 1.63-10.78), signs of respiratory effort such as nasal flaring (OR, 3.79; 95% CI, 1.65-8.69), presence of acidosis (OR, 7.09; 95% CI, 2.97-16.94), and hypercapnia (OR, 2.67; 95% CI, 1,11-6,45). The factors that remained independent predictors of mortality in the multivariable analysis were age, severity (triage level), and nasal flaring. In patients requiring emergency care for dyspnea, nasal flaring is a clinical sign of severity and a predictor of mortality.

Psychogenic dyspnea and therapeutic chest radiograph.

PubMed

Kaufman, Kenneth R; Endres, Jennifer K; Kaufman, Nathaniel D

2007-04-01

Conversion disorders, the physical expression of unresolved psychological pain, can be associated with mourning. This case report is third in a series of articles by the authors on childhood mourning reflecting the effects of multiple losses (K. R. Kaufman & N. D. Kaufman, 2005; K. R. Kaufman & N. D. Kaufman, 2006). In this case report, perception of potential death (self or parent) after a motor vehicle accident precipitated psychogenic dyspnea. A "therapeutic" chest radiograph was an effective initial treatment. Rapid intervention with explanation of the functional nature of the conversion symptom, why this symptom developed, and how to address the underlying stresses in the future led to an excellent outcome. Psychosocial intervention should be included in the multidisciplinary approach toward the child with conversion disorder, be it in an ambulatory, ER, or inpatient setting. The clinician must remember that medically unexplained symptoms in childhood may represent a child's expression of mourning.

Pulmonary rehabilitation improves exercise capacity and dyspnea in air pollution-related respiratory disease.

PubMed

Miyamoto, Naomi; Senjyu, Hideaki; Tanaka, Takako; Asai, Masaharu; Yanagita, Yorihide; Yano, Yudai; Nishinakagawa, Tsuyoshi; Kotaki, Kenji; Kitagawa, Chika; Rikitomi, Naoto; Kozu, Ryo; Honda, Sumihisa

2014-01-01

Air pollution in Japan caused respiratory disease, such as chronic bronchitis and asthma, in many individuals in the 1960s. Although air pollution has decreased, many victims of air pollution-related respiratory disease are limited in their activities of daily living because of respiratory symptoms. The purpose of this study was to evaluate the efficacy of pulmonary rehabilitation in victims of air pollution-related chronic bronchitis or asthma. Subjects were enrolled in a 12-week (2-week inpatient followed by 10-week outpatient) pulmonary rehabilitation program. The program comprised conditioning, strength training, endurance training, and patient education. We assessed the Modified Medical Research Council (MMRC) dyspnea grade, pulmonary function, peripheral muscle force, incremental shuttle walk distance (ISWD), and physical activity at baseline and immediately after the program. Twenty-nine subjects (mean age 74.2 ± 10.1 years, 11 males) completed the program, including 11 subjects with COPD and 18 subjects with asthma. Following rehabilitation, the participants (n = 29) showed significant improvements in MMRC dyspnea grade, vital capacity % predicted, quadriceps force and ISWD (all P < 0.05). Sub-group analyses revealed that all these variables were significantly improved in subjects with asthma. In contrast, subjects with COPD showed significant improvements only in quadriceps force and ISWD (both P < 0.05). Thus, pulmonary rehabilitation is an effective method of improving exercise capacity and dyspnea in officially acknowledged victims of air pollution-related asthma. In conclusion, we recommend that patients with chronic bronchitis or asthma, resulting from exposure to air pollution, are referred for pulmonary rehabilitation.

Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

PubMed Central

2014-01-01

Background We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbon monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions Candidate proteins and mi

Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea.

PubMed

Brown, Joseph N; Brewer, Heather M; Nicora, Carrie D; Weitz, Karl K; Morris, Michael J; Skabelund, Andrew J; Adkins, Joshua N; Smith, Richard D; Cho, Ji-Hoon; Gelinas, Richard

2014-10-05

We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbon monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Candidate proteins and miRNAs associated with the general diagnosis of

Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Joseph N.; Brewer, Heather M.; Nicora, Carrie D.

Background: We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods: Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbonmore » monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results: Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions: Candidate proteins

Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

DOE PAGES

Brown, Joseph N.; Brewer, Heather M.; Nicora, Carrie D.; ...

2014-10-05

Background: We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods: Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbonmore » monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results: Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions: Candidate proteins

Verbal numerical scales are as reliable and sensitive as visual analog scales for rating dyspnea in young and older subjects.

PubMed

Morris, N R; Sabapathy, S; Adams, L; Kingsley, R A; Schneider, D A; Stulbarg, M S

2007-08-01

This study compared the use of a simple verbal 0-10 numerical rating scale (verbal NRS) and a visual analog scale (VAS) for the rating of dyspnea during exercise in a group of young and older subjects. Twelve younger (32+/-9 yr) and 12 older (71+/-7 yr) subjects used either the verbal NRS or the VAS in a randomised fashion to rate dyspnea during 60 s of uphill treadmill walking (range 5.6-8.8 km h(-1)) performed at either a low (17% grade) or high workload (26% grade) and then during recovery. Rating scales were evaluated twice on separate days (day 1 and day 2) at each workload. While the verbal NRS scores proved to be reliable throughout exercise and recovery, VAS scores were significantly (p<0.05) lower on day 2 during the low workload test (younger group) and the high workload test (older group). Verbal NRS ratings were consistently greater than VAS ratings at both workloads (p<0.001) for both young and older groups. The intra-class correlation coefficients for rating peak dyspnea using either the VAS or verbal NRS were consistently lower for the older subjects (range: r=0.54-0.67) than the younger subjects (range: r=0.70-0.86). Overall, subjects preferred the verbal NRS to the VAS. These results suggest that the verbal NRS compares favourably with the VAS for rating dyspnea during exercise without mask or mouthpiece. However, when rating peak dyspnea both scales appear less reliable when used by the older compared to young subjects.

A 26-year-old man with dyspnea and chest pain.

PubMed

Mittal, Saurabh; Jain, Akanksha; Arava, Sudheer; Hadda, Vijay; Mohan, Anant; Guleria, Randeep; Madan, Karan

2017-01-01

A 26-year-old smoker male presented with a history of sudden onset dyspnea and right-sided chest pain. Chest radiograph revealed large right-sided pneumothorax which was managed with tube thoracostomy. High-resolution computed tomography thorax revealed multiple lung cysts, and for a definite diagnosis, a video-assisted thoracoscopic surgery-guided lung biopsy was performed followed by pleurodesis. This clinicopathologic conference discusses the clinical and radiological differential diagnoses, utility of lung biopsy, and management options for patients with such a clinical presentation.

Nasal flaring as a clinical sign of respiratory acidosis in patients with dyspnea.

PubMed

Zorrilla-Riveiro, José Gregorio; Arnau-Bartés, Anna; Rafat-Sellarés, Ramón; García-Pérez, Dolors; Mas-Serra, Arantxa; Fernández-Fernández, Rafael

2017-04-01

To determine whether the presence of nasal flaring is a clinical sign of respiratory acidosis in patients attending emergency departments for acute dyspnea. Single-center, prospective, observational study of patients aged over 15 requiring urgent attention for dyspnea, classified as level II or III according to the Andorran Triage Program and who underwent arterial blood gas test on arrival at the emergency department. The presence of nasal flaring was evaluated by two observers. Demographic and clinical variables, signs of respiratory difficulty, vital signs, arterial blood gases and clinical outcome (hospitalization and mortality) were recorded. Bivariate and multivariate analyses were performed using logistic regression models. The sample comprised 212 patients, mean age 78years (SD=12.8), of whom 49.5% were women. Acidosis was recorded in 21.2%. Factors significantly associated with the presence of acidosis in the bivariate analysis were the need for pre-hospital medical care, triage level II, signs of respiratory distress, presence of nasal flaring, poor oxygenation, hypercapnia, low bicarbonates and greater need for noninvasive ventilation. Nasal flaring had a positive likelihood ratio for acidosis of 4.6 (95% CI 2.9-7.4). In the multivariate analysis, triage level II (aOR 5.16; 95% CI: 1.91 to 13.98), the need for oxygen therapy (aOR 2.60; 95% CI: 1.13-5.96) and presence of nasal flaring (aOR 6.32; 95% CI: 2.78-14.41) were maintained as factors independently associated with acidosis. Nasal flaring is a clinical sign of severity in patients requiring urgent care for acute dyspnea, which has a strong association with acidosis and hypercapnia. Copyright © 2016 Elsevier Inc. All rights reserved.

Sinus venosus atrial septal defect as a cause of palpitations and dyspnea in an adult: a diagnostic imaging challenge.

PubMed

Donovan, Michael S; Kassop, David; Liotta, Robert A; Hulten, Edward A

2015-01-01

Sinus venosus atrial septal defects (SV-ASD) have nonspecific clinical presentations and represent a diagnostic imaging challenge. Transthoracic echocardiography (TTE) remains the initial diagnostic imaging modality. However, detection rates have been as low as 12%. Transesophageal echocardiography (TEE) improves diagnostic accuracy though it may not detect commonly associated partial anomalous pulmonary venous return (PAPVR). Cardiac magnetic resonance (CMR) imaging provides a noninvasive, highly sensitive and specific imaging modality of SV-ASD. We describe a case of an adult male with exercise-induced, paroxysmal supraventricular tachycardia who presented with palpitations and dyspnea. Despite nondiagnostic imaging results on TTE, CMR proved to be instrumental in visualizing a hemodynamically significant SV-ASD with PAPVR that ultimately led to surgical correction.

Sinus Venosus Atrial Septal Defect as a Cause of Palpitations and Dyspnea in an Adult: A Diagnostic Imaging Challenge

PubMed Central

Donovan, Michael S.; Kassop, David; Liotta, Robert A.; Hulten, Edward A.

2015-01-01

Sinus venosus atrial septal defects (SV-ASD) have nonspecific clinical presentations and represent a diagnostic imaging challenge. Transthoracic echocardiography (TTE) remains the initial diagnostic imaging modality. However, detection rates have been as low as 12%. Transesophageal echocardiography (TEE) improves diagnostic accuracy though it may not detect commonly associated partial anomalous pulmonary venous return (PAPVR). Cardiac magnetic resonance (CMR) imaging provides a noninvasive, highly sensitive and specific imaging modality of SV-ASD. We describe a case of an adult male with exercise-induced, paroxysmal supraventricular tachycardia who presented with palpitations and dyspnea. Despite nondiagnostic imaging results on TTE, CMR proved to be instrumental in visualizing a hemodynamically significant SV-ASD with PAPVR that ultimately led to surgical correction. PMID:25705227

A 26-year-old man with dyspnea and chest pain

PubMed Central

Mittal, Saurabh; Jain, Akanksha; Arava, Sudheer; Hadda, Vijay; Mohan, Anant; Guleria, Randeep; Madan, Karan

2017-01-01

A 26-year-old smoker male presented with a history of sudden onset dyspnea and right-sided chest pain. Chest radiograph revealed large right-sided pneumothorax which was managed with tube thoracostomy. High-resolution computed tomography thorax revealed multiple lung cysts, and for a definite diagnosis, a video-assisted thoracoscopic surgery-guided lung biopsy was performed followed by pleurodesis. This clinicopathologic conference discusses the clinical and radiological differential diagnoses, utility of lung biopsy, and management options for patients with such a clinical presentation. PMID:29099006

A 68-Year-Old Man With Dyspnea on Exertion and Cough.

PubMed

Agrawal, Abhinav; Sikachi, Rutuja R; Koenig, Seth; Khanijo, Sameer

2018-06-01

A 68-year-old man with a history of chronic lymphocytic leukemia well controlled on ibrutinib, hypertension, obesity, and a remote history of smoking (10 pack-years) presented with increasing dyspnea on exertion and cough. He had previously finished two courses of oral antibiotics for his symptoms without significant improvement. On presentation, he had no fevers or sputum production. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Why Is Your Patient Still Short of Breath? Understanding the Complex Pathophysiology of Dyspnea in Chronic Kidney Disease.

PubMed

Salerno, Fabio Rosario; Parraga, Grace; McIntyre, Christopher William

2017-01-01

Dyspnea is one of the most common symptoms associated with CKD. It has a profound influence on the quality of life of CKD patients, and its underlying causes are often associated with a negative prognosis. However, its pathophysiology is poorly understood. While hemodialysis may address fluid overload, it often does not significantly improve breathlessness, suggesting multiple and co-existing alternative issues exist. The aim of this article is to discuss the main pathophysiologic mechanisms and the most important putative etiologies underlying dyspnea in CKD patients. Congestive heart failure, unrecognized chronic lung disease, pulmonary hypertension, lung fibrosis, air microembolism, dialyzer bio-incompatibility, anemia, sodium, and fluid overload are potential frequent causes of breathing disorders in this population. However, the relative contributions in any one given patient are poorly understood. Systemic inflammation is a common theme and contributes to the development of endothelial dysfunction, lung fibrosis, anemia, malnutrition, and muscle wasting. The introduction of novel multimodal imaging techniques, including pulmonary functional magnetic resonance imaging with inhaled contrast agents, could provide new insights into the pathophysiology of dyspnea in CKD patients and ultimately contribute to improving our clinical management of this symptom. © 2016 Wiley Periodicals, Inc.

Rapid evaluation by lung-cardiac-inferior vena cava (LCI) integrated ultrasound for differentiating heart failure from pulmonary disease as the cause of acute dyspnea in the emergency setting

PubMed Central

2012-01-01

Background Rapid and accurate diagnosis and management can be lifesaving for patients with acute dyspnea. However, making a differential diagnosis and selecting early treatment for patients with acute dyspnea in the emergency setting is a clinical challenge that requires complex decision-making in order to achieve hemodynamic balance, improve functional capacity, and decrease mortality. In the present study, we examined the screening potential of rapid evaluation by lung-cardiac-inferior vena cava (LCI) integrated ultrasound for differentiating acute heart failure syndromes (AHFS) from primary pulmonary disease in patients with acute dyspnea in the emergency setting. Methods Between March 2011 and March 2012, 90 consecutive patients (45 women, 78.1 ± 9.9 years) admitted to the emergency room of our hospital for acute dyspnea were enrolled. Within 30 minutes of admission, all patients underwent conventional physical examination, rapid ultrasound (lung-cardiac-inferior vena cava [LCI] integrated ultrasound) examination with a hand-held device, routine laboratory tests, measurement of brain natriuretic peptide, and chest X-ray in the emergency room. Results The final diagnosis was acute dyspnea due to AHFS in 53 patients, acute dyspnea due to pulmonary disease despite a history of heart failure in 18 patients, and acute dyspnea due to pulmonary disease in 19 patients. Lung ultrasound alone showed a sensitivity, specificity, negative predictive value, and positive predictive value of 96.2, 54.0, 90.9, and 75.0%, respectively, for differentiating AHFS from pulmonary disease. On the other hand, LCI integrated ultrasound had a sensitivity, specificity, negative predictive value, and positive predictive value of 94.3, 91.9, 91.9, and 94.3%, respectively. Conclusions Our study demonstrated that rapid evaluation by LCI integrated ultrasound is extremely accurate for differentiating acute dyspnea due to AHFS from that caused by primary pulmonary disease in the

Diagnostic performance of multi-organ ultrasound with pocket-sized device in the management of acute dyspnea.

PubMed

Sforza, Alfonso; Mancusi, Costantino; Carlino, Maria Viviana; Buonauro, Agostino; Barozzi, Marco; Romano, Giuseppe; Serra, Sossio; de Simone, Giovanni

2017-06-19

The availability of ultra-miniaturized pocket ultrasound devices (PUD) adds diagnostic power to the clinical examination. Information on accuracy of ultrasound with handheld units in immediate differential diagnosis in emergency department (ED) is poor. The aim of this study is to test the usefulness and accuracy of lung ultrasound (LUS) alone or combined with ultrasound of the heart and inferior vena cava (IVC) using a PUD for the differential diagnosis of acute dyspnea (AD). We included 68 patients presenting to the ED of "Maurizio Bufalini" Hospital in Cesena (Italy) for AD. All patients underwent integrated ultrasound examination (IUE) of lung-heart-IVC, using PUD. The series was divided into patients with dyspnea of cardiac or non-cardiac origin. We used 2 × 2 contingency tables to analyze sensitivity, specificity, positive predictive value and negative predictive value of the three ultrasonic methods and their various combinations for the diagnosis of cardiogenic dyspnea (CD), comparing with the final diagnosis made by an independent emergency physician. LUS alone exhibited a good sensitivity (92.6%) and specificity (80.5%). The highest accuracy (90%) for the diagnosis of CD was obtained with the combination of LUS and one of the other two methods (heart or IVC). The IUE with PUD is a useful extension of the clinical examination, can be readily available at the bedside or in ambulance, requires few minutes and has a reliable diagnostic discriminant ability in the setting of AD.

Loxoprofen-induced interstitial pneumonia: a case report.

PubMed

Kato, Motoyasu; Sasaki, Shinichi; Sekimoto, Yasuhito; Arano, Naoko; Jo, Hitomi; Suina, Kentaro; Kuriyama, Sachiko; Muraki, Keiko; Nagashima, Osamu; Yoshioka, Yasuko; Tominaga, Shigeru; Takahashi, Kazuhisa

2016-05-25

Loxoprofen is a nonsteroidal anti-inflammatory drug used in the treatment of many diseases. However, there are no case reports about loxoprofen-induced pneumonia. We have encountered a rare case of loxoprofen-induced pneumonia. We report the case of a 71-year-old Japanese woman who was initially treated with loxoprofen for fever. She was admitted to our hospital because of worsening of her symptoms, including fever and dyspnea. Her symptoms improved after treatment with ceftriaxone. Seven days after admission, she again developed high fever. She was again treated with loxoprofen and levofloxacin. However, acute respiratory failure developed after initiation of loxoprofen treatment. Chest computed tomography showed peribronchovascular consolidation. She was diagnosed with loxoprofen-induced pneumonia for which she was administered steroids. After treatment, her dyspnea and radiological findings improved. The findings in this case report reveal an association between treatment with a nonsteroidal anti-inflammatory drug and pneumonia. This rare case was diagnosed after accidental retreatment with loxoprofen. This is the first report of loxoprofen-induced pneumonia.

Inhibition of poly(ADP-ribose) polymerase prevents allergen-induced asthma-like reaction in sensitized Guinea pigs.

PubMed

Suzuki, Ylenia; Masini, Emanuela; Mazzocca, Cosimo; Cuzzocrea, Salvatore; Ciampa, Anna; Suzuki, Hisanori; Bani, Daniele

2004-12-01

Poly(ADP-ribose) polymerase (PARP) plays an important role in tissue injury in conditions associated with oxidative stress and inflammation. Because asthma is a chronic inflammatory disorder of the airways, we designed the present experimental study to evaluate the effects of PARP inhibition on allergen-induced asthma-like reaction in ovalbumin-sensitized guinea pigs. Cough and dyspnea in response to ovalbumin aerosol were absent in naive guinea pigs, whereas they became severe in the sensitized animals. In the latter ones, ovalbumin aerosol also induced a rapid increase in PARP activity, bronchiolar constriction, pulmonary air space inflation, mast cell degranulation, poly(ADP-ribose) and nitrotyrosine immunostaining, myeloperoxidase activity, and malondialdehyde in lung tissue, as well as a rise in the amounts of nitrites and tumor necrosis factor-alpha in bronchoalveolar lavage fluid. Pretreatment with the PARP inhibitors 3-aminobenzamide (10 mg/kg b.wt.) or 5-aminoisoquinolinone (0.5 mg/kg b.wt.) given i.p. 3 h before ovalbumin challenge significantly reduced the severity of cough and the occurrence of dyspnea and delayed the onset of respiratory abnormalities. Both PARP inhibitors were also able to prevent the above morphological and biochemical changes of lung tissue or bronchoalveolar lavage fluid induced by ovalbumin challenge. Conversely, p-aminobenzoic acid, the inactive analog of 3-aminobenzamide, had no effects.

Experimentally-induced dissociation impairs visual memory.

PubMed

Brewin, Chris R; Mersaditabari, Niloufar

2013-12-01

Dissociation is a phenomenon common in a number of psychological disorders and has been frequently suggested to impair memory for traumatic events. In this study we explored the effects of dissociation on visual memory. A dissociative state was induced experimentally using a mirror-gazing task and its short-term effects on memory performance were investigated. Sixty healthy individuals took part in the experiment. Induced dissociation impaired visual memory performance relative to a control condition; however, the degree of dissociation was not associated with lower memory scores in the experimental group. The results have theoretical and practical implications for individuals who experience frequent dissociative states such as patients with posttraumatic stress disorder (PTSD). Copyright © 2013 Elsevier Inc. All rights reserved.

The O-C2 angle established at occipito-cervical fusion dictates the patient's destiny in terms of postoperative dyspnea and/or dysphagia.

PubMed

Izeki, Masanori; Neo, Masashi; Takemoto, Mitsuru; Fujibayashi, Shunsuke; Ito, Hiromu; Nagai, Koutatsu; Matsuda, Shuichi

2014-02-01

We have revealed that the cause of postoperative dyspnea and/or dysphagia after occipito-cervical (O-C) fusion is mechanical stenosis of the oropharyngeal space and the O-C2 alignment, rather than total or subaxial alignment, is the key to the development of dyspnea and/or dysphagia. The purpose of this study was to confirm the impact of occipito-C2 angle (O-C2A) on the oropharyngeal space and to investigate the chronological impact of a fixed O-C2A on the oropharyngeal space and dyspnea and/or dysphagia after O-C fusion. We reviewed 13 patients who had undergone O-C2 fusion, while retaining subaxial segmental motion (OC2 group) and 20 who had subaxial fusion without O-C2 fusion (SA group). The O-C2A, C2-C6 angle and the narrowest oropharyngeal airway space were measured on lateral dynamic X-rays preoperatively, when dynamic X-rays were taken for the first time postoperatively, and at the final follow-up. We also recorded the current dyspnea and/or dysphagia status at the final follow-up of patients who presented with it immediately after the O-C2 fusion. There was no significant difference in the mean preoperative values of the O-C2A (13.0 ± 7.5 in group OC2 and 20.1 ± 10.5 in group SA, Unpaired t test, P = 0.051) and the narrowest oropharyngeal airway space (17.8 ± 6.0 in group OC2 and 14.9 ± 3.9 in group SA, Unpaired t test, P = 0.105). In the OC2 group, the narrowest oropharyngeal airway space changed according to the cervical position preoperatively, but became constant postoperatively. In contrast, in the SA group, the narrowest oropharyngeal airway space changed according to the cervical position at any time point. Three patients who presented with dyspnea and/or dysphagia immediately after O-C2 fusion had not resolved completely at the final follow-up. The narrowest oropharyngeal airway space and postoperative dyspnea and/or dysphagia did not change with time once the O-C2A had been established at O-C fusion. The O-C2A established at O

Differential Effect of Modified Medical Research Council Dyspnea, COPD Assessment Test, and Clinical COPD Questionnaire for Symptoms Evaluation Within the New GOLD Staging and Mortality in COPD.

PubMed

Casanova, Ciro; Marin, Jose M; Martinez-Gonzalez, Cristina; de Lucas-Ramos, Pilar; Mir-Viladrich, Isabel; Cosio, Borja; Peces-Barba, German; Solanes-García, Ingrid; Agüero, Ramón; Feu-Collado, Nuria; Calle-Rubio, Miryam; Alfageme, Inmaculada; de Diego-Damia, Alfredo; Irigaray, Rosa; Marín, Margarita; Balcells, Eva; Llunell, Antonia; Galdiz, Juan Bautista; Golpe, Rafael; Lacarcel, Celia; Cabrera, Carlos; Marin, Alicia; Soriano, Joan B; Lopez-Campos, Jose Luis; Soler-Cataluña, Juan José; de-Torres, Juan P

2015-07-01

The modified Medical Research Council (mMRC) dyspnea, the COPD Assessment Test (CAT), and the Clinical COPD Questionnaire (CCQ) have been interchangeably proposed by GOLD (Global Initiative for Chronic Obstructive Lung Disease) for assessing symptoms in patients with COPD. However, there are no data on the prognostic value of these tools in terms of mortality. We endeavored to evaluate the prognostic value of the CAT and CCQ scores and compare them with mMRC dyspnea. We analyzed the ability of these tests to predict mortality in an observational cohort of 768 patients with COPD (82% men; FEV1, 60%) from the COPD History Assessment in Spain (CHAIN) study, a multicenter observational Spanish cohort, who were monitored annually for a mean follow-up time of 38 months. Subjects who died (n = 73; 9.5%) had higher CAT (14 vs 11, P = .022), CCQ (1.6 vs 1.3, P = .033), and mMRC dyspnea scores (2 vs 1, P < .001) than survivors. Receiver operating characteristic analysis showed that higher CAT, CCQ, and mMRC dyspnea scores were associated with higher mortality (area under the curve: 0.589, 0.588, and 0.649, respectively). CAT scores ≥ 17 and CCQ scores > 2.5 provided a similar sensitivity than mMRC dyspnea scores ≥ 2 to predict all-cause mortality. The CAT and the CCQ have similar ability for predicting all-cause mortality in patients with COPD, but were inferior to mMRC dyspnea scores. We suggest new thresholds for CAT and CCQ scores based on mortality risk that could be useful for the new GOLD grading classification. ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.

Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial.

PubMed

Davies, Helen E; Mishra, Eleanor K; Kahan, Brennan C; Wrightson, John M; Stanton, Andrew E; Guhan, Anur; Davies, Christopher W H; Grayez, Jamal; Harrison, Richard; Prasad, Anjani; Crosthwaite, Nicola; Lee, Y C Gary; Davies, Robert J O; Miller, Robert F; Rahman, Najib M

2012-06-13

Malignant pleural effusion causes disabling dyspnea in patients with a short life expectancy. Palliation is achieved by fluid drainage, but the most effective first-line method has not been determined. To determine whether indwelling pleural catheters (IPCs) are more effective than chest tube and talc slurry pleurodesis (talc) at relieving dyspnea. Unblinded randomized controlled trial (Second Therapeutic Intervention in Malignant Effusion Trial [TIME2]) comparing IPC and talc (1:1) for which 106 patients with malignant pleural effusion who had not previously undergone pleurodesis were recruited from 143 patients who were treated at 7 UK hospitals. Patients were screened from April 2007-February 2011 and were followed up for a year. Indwelling pleural catheters were inserted on an outpatient basis, followed by initial large volume drainage, education, and subsequent home drainage. The talc group were admitted for chest tube insertion and talc for slurry pleurodesis. Patients completed daily 100-mm line visual analog scale (VAS) of dyspnea over 42 days after undergoing the intervention (0 mm represents no dyspnea and 100 mm represents maximum dyspnea; 10 mm represents minimum clinically significant difference). Mean difference was analyzed using a mixed-effects linear regression model adjusted for minimization variables. Dyspnea improved in both groups, with no significant difference in the first 42 days with a mean VAS dyspnea score of 24.7 in the IPC group (95% CI, 19.3-30.1 mm) and 24.4 mm (95% CI, 19.4-29.4 mm) in the talc group, with a difference of 0.16 mm (95% CI, −6.82 to 7.15; P = .96). There was a statistically significant improvement in dyspnea in the IPC group at 6 months, with a mean difference in VAS score between the IPC group and the talc group of −14.0 mm (95% CI, −25.2 to −2.8 mm; P = .01). Length of initial hospitalization was significantly shorter in the IPC group with a median of 0 days (interquartile range [IQR], 0-1 day) and 4 days

Effects of nutraceutical diet integration, with coenzyme Q10 (Q-Ter multicomposite) and creatine, on dyspnea, exercise tolerance, and quality of life in COPD patients with chronic respiratory failure

PubMed Central

2013-01-01

A patients also showed significant: 1) improvement in the degree of dyspnea (VAS: p < 0.05; Borg: p < 0.05; MRC: p < 0.001; BDI1: p < 0.05; BDI3: p < 0.03), and independence level in activities of daily living (p < 0.03); 2) improvement in quality of life in activity section (- 6.63 pt) and in total score (- 5.43 pt); 3) exacerbation number decrease (p < 0.02). No significant differences were found (end of study vs baseline) in group B. Conclusions The nutraceutical diet integration with Q-Ter and creatine, in COPD patients with CRF in O2TLT induced an increasing lean body mass and exercise tolerance, reducing dyspnea, quality of life and exacerbations. These results provide a first demonstration that acting on protein synthesis and muscular efficiency can significantly modify the systemic consequences of the disease. PMID:23800154

Excess Ventilation in Chronic Obstructive Pulmonary Disease-Heart Failure Overlap. Implications for Dyspnea and Exercise Intolerance.

PubMed

Rocha, Alcides; Arbex, Flavio F; Sperandio, Priscilla A; Souza, Aline; Biazzim, Ligia; Mancuso, Frederico; Berton, Danilo C; Hochhegger, Bruno; Alencar, Maria Clara N; Nery, Luiz E; O'Donnell, Denis E; Neder, J Alberto

2017-11-15

An increased ventilatory response to exertional metabolic demand (high [Formula: see text]e/[Formula: see text]co 2 relationship) is a common finding in patients with coexistent chronic obstructive pulmonary disease and heart failure. We aimed to determine the mechanisms underlying high [Formula: see text]e/[Formula: see text]co 2 and its impact on operating lung volumes, dyspnea, and exercise tolerance in these patients. Twenty-two ex-smokers with combined chronic obstructive pulmonary disease and heart failure with reduced left ventricular ejection fraction undertook, after careful treatment optimization, a progressive cycle exercise test with capillary (c) blood gas collection. Regardless of the chosen metric (increased [Formula: see text]e-[Formula: see text]co 2 slope, [Formula: see text]e/[Formula: see text]co 2 nadir, or end-exercise [Formula: see text]e/[Formula: see text]co 2 ), ventilatory inefficiency was closely related to Pc CO 2 (r values from -0.80 to -0.84; P < 0.001) but not dead space/tidal volume ratio. Ten patients consistently maintained exercise Pc CO 2 less than or equal to 35 mm Hg (hypocapnia). These patients had particularly poor ventilatory efficiency compared with patients without hypocapnia (P < 0.05). Despite the lack of between-group differences in spirometry, lung volumes, and left ventricular ejection fraction, patients with hypocapnia had lower resting Pa CO 2 and lung diffusing capacity (P < 0.01). Excessive ventilatory response in this group was associated with higher exertional Pc O 2 . The group with hypocapnia, however, had worse mechanical inspiratory constraints and higher dyspnea scores for a given work rate leading to poorer exercise tolerance compared with their counterparts (P < 0.05). Heightened neural drive promoting a ventilatory response beyond that required to overcome an increased "wasted" ventilation led to hypocapnia and poor exercise ventilatory efficiency in chronic obstructive pulmonary disease

Bevacizumab-induced chronic interstitial pneumonia during maintenance therapy in non-small cell lung cancer.

PubMed

Sekimoto, Yasuhito; Kato, Motoyasu; Shukuya, Takehiko; Koyama, Ryo; Nagaoka, Tetsutaro; Takahashi, Kazuhisa

2016-04-01

Bevacizumab is a monoclonal antibody targeting the vascular endothelial growth factor receptor and a key drug for advanced non-small cell lung cancer. There are few reports describing bevacizumab-induced chronic interstitial pneumonia. A 62-year-old man with advanced non-small cell lung cancer was admitted to our hospital with dyspnea. He previously received four courses of carboplatin plus paclitaxel with bevacizumab combination therapy and thereafter received four courses of maintenance bevacizumab monotherapy. A chest-computed tomography scan on admission revealed diffuse ground glass opacity. He had not received any other drugs and did not have pneumonia. Thus, he was diagnosed with bevacizumab-induced chronic interstitial pneumonia and was treated with a high dose of corticosteroids. After steroid treatment, his dyspnea and radiological findings improved. This case report is the first description of bevacizumab-induced chronic interstitial pneumonia during maintenance therapy in a patient with non-small cell lung cancer.

In vivo Expression of Inducible Nitric Oxide Synthase in Experimentally Induced Neurologic Diseases

NASA Astrophysics Data System (ADS)

Koprowski, Hilary; Zheng, Yong Mu; Heber-Katz, Ellen; Fraser, Nigel; Rorke, Lucy; Fu, Zhen Fang; Hanlon, Cathleen; Dietzschold, Bernhard

1993-04-01

The purpose of this study was to investigate the induction of inducible nitric oxide synthase (iNOS) mRNA in the brain tissue of rats and mice under the following experimental conditions: in rats infected with borna disease virus and rabies virus, in mice infected with herpes simplex virus, and in rats after the induction of experimental allergic encephalitis. The results showed that iNOS mRNA, normally nondetectable in the brain, was present in animals after viral infection or after induction of experimental allergic encephalitis. The induction of iNOS mRNA coincided with the severity of clinical signs and in some cases with the presence of inflammatory cells in the brain. The results indicate that nitric oxide produced by cells induced by iNOS may be the toxic factor accounting for cell damage and this may open the door to approaches to the study of the pathogenesis of neurological diseases.

Diaphragmatic mobility: relationship with lung function, respiratory muscle strength, dyspnea, and physical activity in daily life in patients with COPD.

PubMed

Rocha, Flávia Roberta; Brüggemann, Ana Karla Vieira; Francisco, Davi de Souza; Medeiros, Caroline Semprebom de; Rosal, Danielle; Paulin, Elaine

2017-01-01

To evaluate diaphragmatic mobility in relation to lung function, respiratory muscle strength, dyspnea, and physical activity in daily life (PADL) in patients with COPD. We included 25 patients with COPD, classified according to the Global Initiative for Chronic Obstructive Lung Disease criteria, and 25 healthy individuals. For all of the participants, the following were evaluated: anthropometric variables, spirometric parameters, respiratory muscle strength, diaphragmatic mobility (by X-ray), PADL, and the perception of dyspnea. In the COPD group, diaphragmatic mobility was found to correlate with lung function variables, inspiratory muscle strength, and the perception of dyspnea, whereas it did not correlate with expiratory muscle strength or PADL. In patients with COPD, diaphragmatic mobility seems to be associated with airway obstruction and lung hyperinflation, as well as with ventilatory capacity and the perception of dyspnea, although not with PADL. Avaliar a relação da mobilidade diafragmática com a função pulmonar, força muscular respiratória, dispneia e atividade física de vida diária (AFVD) em pacientes com DPOC. Foram avaliados 25 pacientes com diagnóstico de DPOC, classificados de acordo com critérios da Global Initiative for Chronic Obstructive Lung Disease, e 25 indivíduos saudáveis. Todos foram submetidos às seguintes avaliações: mensuração antropométrica, espirometria, força muscular respiratória, mobilidade diafragmática (por radiografia), AFVD e percepção de dispneia. No grupo DPOC, houve correlações da mobilidade diafragmática com variáveis de função pulmonar, força muscular inspiratória e percepção de dispneia. Não houve correlações da mobilidade diafragmática com força muscular expiratória e AFVD. A mobilidade diafragmática parece estar associada tanto com a obstrução das vias aéreas quanto com a hiperinsuflação pulmonar em pacientes com DPOC, assim como com a capacidade ventilatória e percep

The impact of carrying supplemental oxygen on exercise capacity and dyspnea in patients with interstitial lung disease.

PubMed

Ramadurai, Deepa; Riordan, Maeveen; Graney, Bridget; Churney, Tara; Olson, Amy L; Swigris, Jeffrey J

2018-05-01

May patients with interstitial lung disease (ILD) require supplementary oxygen (O 2 ) therapy to maintain normoxia. However, ambulatory O 2 delivery devices are constraining and cumbersome. The physiologic and symptomatic impact of these devices on ILD patients is unknown. We conducted a prospective study of 30 clinically stable ILD patients (with varying disease severity), half of whom used O 2 at baseline. Each subject completed two six-minute walk tests (6MWTs); for O 2 users, one walk was completed while wearing a backpack (weight 7.2 pounds) containing a tank with compressed O 2 , and for non-users, one walk was completed with a similarly-weighted backpack. For each subject, during the second walk, no backpack was worn; for the second walk, O 2 users received oxygen via a stationary delivery system. For both walks, O 2 non-users wore a portable metabolic system, which measured variables related to respiratory physiology and gas exchange. Borg dyspnea and exertion ratings were recorded after each walk. Wearing the O 2 -containing backpack resulted in decreased distance covered during the 6MWT, and increased dyspnea and perceived exertion among O 2 users. While wearing the weighted backpack, O 2 non-users had a significantly lower peripheral O 2 saturation and distance-saturation product. Compared with carrying O 2 in the backpack, receiving O 2 via the stationary concentrator resulted in the largest improvement in walk distance for the three subjects with greatest impairment at baseline (6MWT ≤ 300 m). Among ILD patients, carrying portable O 2 versus receiving O 2 via a stationary concentrator results in significantly greater dyspnea and shorter distances covered in timed testing. Patients with the greatest impairment may be affected most. When prescribing O 2 , practitioners should alert patients to this effect and help patients decide on the best O 2 delivery mode to meet their needs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pulmonary Gas Exchange Abnormalities in Mild Chronic Obstructive Pulmonary Disease. Implications for Dyspnea and Exercise Intolerance.

PubMed

Elbehairy, Amany F; Ciavaglia, Casey E; Webb, Katherine A; Guenette, Jordan A; Jensen, Dennis; Mourad, Sahar M; Neder, J Alberto; O'Donnell, Denis E

2015-06-15

Several studies in mild chronic obstructive pulmonary disease (COPD) have shown a higher than normal ventilatory equivalent for carbon dioxide ([Formula: see text]e/[Formula: see text]co2) during exercise. Our objective was to examine pulmonary gas exchange abnormalities and the mechanisms of high [Formula: see text]e/[Formula: see text]co2 in mild COPD and its impact on dyspnea and exercise intolerance. Twenty-two subjects (11 patients with GOLD [Global Initiative for Chronic Obstructive Lung Disease] grade 1B COPD, 11 age-matched healthy control subjects) undertook physiological testing and a symptom-limited incremental cycle exercise test with arterial blood gas collection. Patients (post-bronchodilator FEV1: 94 ± 10% predicted; mean ± SD) had evidence of peripheral airway dysfunction and reduced peak oxygen uptake compared with control subjects (80 ± 18 vs. 113 ± 24% predicted; P<0.05). Arterial blood gases were within the normal range and effective alveolar ventilation was not significantly different from control subjects throughout exercise. The alveolar-arterial O2 tension gradient was elevated at rest and throughout exercise in COPD (P<0.05). [Formula: see text]e/[Formula: see text]co2, dead space to tidal volume ratio (Vd/Vt), and arterial to end-tidal CO2 difference were all higher (P<0.05) in patients with COPD than in control subjects during exercise. In patients with COPD versus control subjects, there was significant dynamic hyperinflation and greater tidal volume constraints (P<0.05). Standardized dyspnea intensity ratings were also higher (P<0.05) in patients with COPD versus control subjects in association with higher ventilatory requirements. Within all subjects, Vd/Vt correlated with the [Formula: see text]e/[Formula: see text]co2 ratio during submaximal exercise (r=0.780, P<0.001). High Vd/Vt was the most consistent gas exchange abnormality in smokers with only mild spirometric abnormalities. Compensatory increases in minute

A randomized controlled trial on the benefits and respiratory adverse effects of morphine for refractory dyspnea in patients with COPD: Protocol of the MORDYC study.

PubMed

Verberkt, C A; van den Beuken-van Everdingen, M H J; Franssen, F M E; Dirksen, C D; Schols, J M G A; Wouters, E F M; Janssen, D J A

2016-03-01

Dyspnea is one of the most reported symptoms of patients with advanced Chronic Obstructive Pulmonary Disease (COPD) and is often undertreated. Morphine has proven to be an effective treatment for dyspnea and is recommended in clinical practice guidelines, but questions concerning benefits and respiratory adverse effects remain. This study primarily evaluates the impact of oral sustained release morphine (morphine SR) on health-related quality of life and respiratory adverse effects in patients with COPD. Secondary objectives include the impact on exercise capacity, the relationship between description and severity of dyspnea and the presence of a clinically relevant response to morphine, and cost-effectiveness. A single-center, randomized, double blind, placebo controlled intervention study will be performed in 124 patients with COPD who recently completed a comprehensive pulmonary rehabilitation program. Participants will receive 20-30 mg/24h morphine SR or placebo for four weeks. After the intervention, participants will be followed for twelve weeks. Outcomes include: the COPD Assessment Test, six minute walking test, Multidimensional Dyspnea Scale and a cost diary. Furthermore, lung function and arterial blood gasses will be measured. These measures will be assessed during a baseline and outcome assessment, two home visits, two phone calls, and three follow-up assessments. The intervention and control group will be compared using uni- and multivariate regression analysis and logistic regression analysis. Finally, an economic evaluation will be performed from a societal and healthcare perspective. The current manuscript describes the rationale and methods of this study and provides an outline of the possible strengths, weaknesses and clinical consequences. Copyright © 2016 Elsevier Inc. All rights reserved.

Intensive symptom control of opioid-refractory dyspnea in congestive heart failure: Role of milrinone in the palliative care unit.

PubMed

Silvestre, Julio; Montoya, Maria; Bruera, Eduardo; Elsayem, Ahmed

2015-12-01

We describe an exemplary case of congestive heart failure (CHF) symptoms controlled with milrinone. We also analyze the benefits and risks of milrinone administration in an unmonitored setting. We describe the case of a patient with refractory leukemia and end-stage CHF who developed severe dyspnea after discontinuation of milrinone. At that point, despite starting opioids, she had been severely dyspneic and anxious, requiring admission to the palliative care unit (PCU) for symptom control. After negotiation with hospital administrators, milrinone was administered in an unmonitored setting such as the PCU. A multidisciplinary team approach was also provided. Milrinone produced a dramatic improvement in the patient's symptom scores and performance status. The patient was eventually discharged to home hospice on a milrinone infusion with excellent symptom control. This case suggests that milrinone may be of benefit for short-term inpatient administration for dyspnea management, even in unmonitored settings and consequently during hospice in do-not-resuscitate (DNR) patients. This strategy may reduce costs and readmissions to the hospital related to end-stage CHF.

Reliability and validity of an arabic version of the dyspnea-12 questionnaire for Saudi nationals with chronic obstructive pulmonary disease.

PubMed

Alyami, Mohammed M; Jenkins, Sue C; Lababidi, Hani; Hill, Kylie

2015-01-01

Dyspnea is a distressing symptom experienced by people with chronic obstructive pulmonary disease (COPD). The dyspnea-12 (D-12) questionnaire comprises of 12 items and assesses the quality of this symptom, its severity and the emotional response. The original (English) version of the D-12 is reliable and valid for the measurement of dyspnea in pulmonary diseases. To translate the D-12 into Arabic and determine whether this version is reliable and valid in Saudi nationals with COPD. The D-12 was translated into Arabic version and reviewed by an expert panel before being back-translated into English. The Arabic version was administered to five patients with COPD to test whether it was easily understood after which a final Arabic version was produced. Thereafter, 40 patients with COPD (aged 63 ΁ 9 years; 33 [82.5%] males; forced expiratory volume in one second (FEV 1) 47 ΁ 16% predicted) completed the D-12, the COPD Assessment Test (CAT) and the Chronic Respiratory Disease Questionnaire (CRDQ). Lung function and 6-minute walk distance were also measured. The D-12 was re-administered two weeks later. The Arabic version of the D-12 demonstrated good reliability over the two administration (intraclass correlation coefficient = 0.94, P = 0.01). Strong associations were demonstrated between the (1) total score for the D-12 and the CAT, (2) quality sub-score of the D-12 and the CAT and (3) emotional response sub-score of the D-12 and emotional function domain of the CRDQ (r ≥ 0.6, all P < 0.01). The Arabic version of the D-12 is a reliable and valid instrument in Saudi nationals with COPD.

Experimentally induced otitis and audiogenic seizure in the mouse.

PubMed

Niaussat, M M

1977-04-15

Audiogenic seizures can be induced in genetically non-susceptible 17-day-old mice (Rb/3 strain) with various results. Priming only induces 9% of seizures, auditory insulation 3,8%, while experimental otitis leads to 79%. The hypothesis concerning disuse supersensitivity subsequent to acoustic deprivation was not confirmed by the experiment. However, modification of acoustic transmission at middle ear level induced by otitis or ear physical damage during the maturation period, exposes the upper nervous centers to intense stimulation to which the reaction is a recruiting response.

A 29-Year-Old Man With Nonproductive Cough, Exertional Dyspnea, and Chest Discomfort.

PubMed

Halpenny, Darragh; Suh, James; Garofano, Suzette; Alpert, Jeffrey

2015-09-01

A 29-year-old man presented with a 5-month history of worsening dry cough, exertional dyspnea, chest tightness, and palpitations. He had been treated by his primary care physician with trials of guaifenesin/codeine, azithromycin, albuterol, and omeprazole without improvement. He denied wheezing, fever, sweats, anorexia, joint pain, swelling, or rash. He had no past medical history. He denied a history of tobacco smoking or IV drug use. He kept no pets, worked as a manager in an office environment, and had no history of occupational inhalational exposure. He reported using aerosolized insect spray to eradicate bed bugs in his house shortly before the cough began but did not report any acute symptoms when using the spray.

Experimental realization of noise-induced adiabaticity in nuclear magnetic resonance

NASA Astrophysics Data System (ADS)

Wang, Bi-Xue; Xin, Tao; Kong, Xiang-Yu; Wei, Shi-Jie; Ruan, Dong; Long, Gui-Lu

2018-04-01

The adiabatic evolution is the dynamics of an instantaneous eigenstate of a slowly varing Hamiltonian. Recently, an interesting phenomenon shows up that white noises can enhance and even induce adiabaticity, which is in contrast to previous perception that environmental noises always modify and even ruin a designed adiabatic passage. We experimentally realized a noise-induced adiabaticity in a nuclear magnetic resonance system. Adiabatic Hadamard gate and entangled state are demonstrated. The effect of noise on adiabaticity is experimentally exhibited and compared with the noise-free process. We utilized a noise-injected method, which can be applied to other quantum systems.

Dyspnea in a nonagenarian: The usual suspects, an unexpected culprit.

PubMed

Madeira, Sérgio; Raposo, Luís; David, Raquel; Marques, Alexandre; Andrade Gomes, José; Cardim, Nuno; Anjos, Rui

2015-09-01

Platypnea-orthodeoxia syndrome (POS) is an uncommon syndrome characterized by dyspnea and hypoxemia triggered by orthostatism and relieved by recumbency. It is often associated with an interatrial shunt through a patent foramen ovale (PFO). We report the case of a 92-year-old woman initially admitted in the setting of a traumatic femoral neck fracture (successfully treated with hip replacement surgery) in whom a reversible decline in transcutaneous oxygen saturation from 98% (in the supine position) to 84% (in the upright position) was noted early post-operatively. Thoracic multislice computed tomography excluded pulmonary embolism and severe parenchymal lung disease. The diagnosis of POS was confirmed by tilt-table contrast transesophageal echocardiography, which demonstrated a dynamic and position-dependent right-to-left shunt (torrential when semi-upright and minimal in the supine position) through a PFO. The patient underwent percutaneous closure of the PFO with an Amplatzer device, which led to prompt symptom relief and full functional recovery. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Experimental Investigation of the Induced Airflow of Corona Discharge

NASA Astrophysics Data System (ADS)

Huang, Yong; Zhang, Xin; Wang, Xun-Nian; Wang, Wan-Bo; Huang, Zong-Bo; Li, Hua-Xing

2013-09-01

In order to improve the acceleration effect of corona discharge acting on air, we present an experimental study on the induced airflow produced by corona discharge between two parallel electrodes. The parameters investigated are the type of electrodes, actuation voltage and the distance in the absence of free airflow. The induced flow velocity is measured directly in the accelerated region using the particle image velocimetry technology. The results show that if corona discharge is not developed into arc discharge, the induced airflow velocity increases nearly linearly with the applied voltage and the maximum induced airflow velocity near the needle electrode reaches 36 m/s. It is expected that in the future, the result can be referred to in the research about effect of active flow control to reach much higher induced airflow speed.

Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction.

PubMed

Walsted, Emil S; Faisal, Azmy; Jolley, Caroline J; Swanton, Laura L; Pavitt, Matthew J; Luo, Yuan-Ming; Backer, Vibeke; Polkey, Michael I; Hull, James H

2018-02-01

Exercise-induced laryngeal obstruction (EILO), a phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnea in young individuals. The physiological ventilatory impact of EILO and its relationship to dyspnea are poorly understood. The objective of this study was to evaluate exercise-related changes in laryngeal aperture on ventilation, pulmonary mechanics, and respiratory neural drive. We prospectively evaluated 12 subjects (6 with EILO and 6 healthy age- and gender-matched controls). Subjects underwent baseline spirometry and a symptom-limited incremental exercise test with simultaneous and synchronized recording of endoscopic video and gastric, esophageal, and transdiaphragmatic pressures, diaphragm electromyography, and respiratory airflow. The EILO and control groups had similar peak work rates and minute ventilation (V̇e) (work rate: 227 ± 35 vs. 237 ± 35 W; V̇e: 103 ± 20 vs. 98 ± 23 l/min; P > 0.05). At submaximal work rates (140-240 W), subjects with EILO demonstrated increased work of breathing ( P < 0.05) and respiratory neural drive ( P < 0.05), developing in close temporal association with onset of endoscopic evidence of laryngeal closure ( P < 0.05). Unexpectedly, a ventilatory increase ( P < 0.05), driven by augmented tidal volume ( P < 0.05), was seen in subjects with EILO before the onset of laryngeal closure; there were however no differences in dyspnea intensity between groups. Using simultaneous measurements of respiratory mechanics and diaphragm electromyography with endoscopic video, we demonstrate, for the first time, increased work of breathing and respiratory neural drive in association with the development of EILO. Future detailed investigations are now needed to understand the role of upper airway closure in causing exertional dyspnea and exercise limitation. NEW & NOTEWORTHY Exercise-induced laryngeal obstruction is a prevalent cause of exertional dyspnea in young

PHARMACOLOGIC TREATMENT OF HYPERALGESIA EXPERIMENTALLY INDUCED BY NUCLEUS PULPOSUS

PubMed Central

de Souza Grava, André Luiz; Ferrari, Luiz Fernando; Parada, Carlos Amílcar; Defino, Helton Luiz Aparecido

2015-01-01

Objective: To evaluate the effect of anti-inflammatory drugs (dexamethasone, indomethacin, atenolol and indomethacin plus atenolol) and analgesic drugs (morphine) on hyperalgesia experimentally induced by the nucleus pulposus (NP) in contact with the L5 dorsal root ganglion (DRG). Methods: Thirty male Wistar rats of weights ranging from 220 to 250 g were used in the study. Hyperalgesia was induced by means of a fragment of NP removed from the sacrococcygeal region that was placed in contact with the L5 dorsal root ganglion. The 30 animals were divided into experimental groups according to the drug used. The drugs were administered for two weeks after the surgical procedure to induce hyperalgesia. Mechanical and thermal hyperalgesia was evaluated using the paw pressure test, von Frey electronic test and Hargreaves test, over a seven-week period. Results: The greatest reduction of hyperalgesia was observed in the group of animals treated with morphine, followed by dexamethasone, indomethacin and atenolol. Reductions in hyperalgesia were observed after drug administration ceased, except for the group of animals treated with morphine, in which there was an increase in hyperalgesia after discontinuation of the treatment. Conclusion: Hyperalgesia induced by NP contact with the DRG can be reduced through administration of anti-inflammatory and analgesic drugs, but a greater reduction was observed with the administration of dexamethasone. PMID:27026966

Experimentally Induced Learned Helplessness: How Far Does it Generalize?

ERIC Educational Resources Information Center

Tuffin, Keith; And Others

1985-01-01

Assessed whether experimentally induced learned helplessness on a cognitive training task generalized to a situationally dissimilar social interaction test task. No significant differences were observed between groups on the subsequent test task, showing that helplessness failed to generalize. (Author/ABB)

[Is BNP assay useful for the diagnosis of acute dyspnea in emergencies departments?].

PubMed

Lakhdhar, Rim; Hamouda, Chokri; Ben Ammar, Lotfi; Majed, Kamel; Moncef, Fekih; Kaabachi, Naziha; Drissa, Habiba; Borsali Falfoul, Nebiha

2013-01-01

It would be interesting to the emergency doctor to have at his disposal a helpful diagnostic tool like brain natriuretic peptide (BNP). Such assay is simple, available and reliable. To report our experience on the role of BNP in the etiological diagnosis of acute dyspnea (AD) in emergency room (ER) and to assess the cost-effectiveness ratio of such diagnosis strategy. A prospective study conducted in the ER of Rabta university teaching hospital of Tunis, from March 1st to June 20th 2010, involving 30 consecutive patients presenting to the emergency for AD. All patients underwent echocardiography in their acute phase and benefited from the dosage of BNP during the first 4 hours. The echocardiography parameters were collected by a single operator who was unaware of the results of the BNP dosage. The mean age of patients was 72.8years with a sex ratio of 1.5. AD was of orthopnea type in 9 cases and stage III NYHA dyspnea in the other patients. Clinical and radiological signs of left heart failure were noted in 30% of cases. Ultrasound data have objectified systolic dysfunction in 4 cases, diastolic in 3 cases and systolic plus diastolic in 10 cases. The BNP levels were below 100 pg/ml in 10 cases with pulmonary origin of the AD. A BNP level between 100 and 400 pg/ml was noted in 3 cases. In our study, the clinical probability of AHF prior to performing the test was estimated at 53% and estimated at 100% after the BNP assay. The BNP assay has reduced the length of stay in the emergency department 4 to 5 days and saved nearly 50% of the cost of care per patient. The BNP assay, has allowed us to confirm the AHF all cases. Given the prognostic value and economic benefit of this test we recommend its use in ER of our country.

Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

DTIC Science & Technology

2011-10-01

patients with mild asthma, allergic rhinitis and upper respiratory infection, which makes these patients more susceptible to the bronchoconstriction...and other respiratory dysfunctions induced by thermal stress. There are two specific aims for the first year of this translational project: 1) To...dyspnea, airway constriction, cough, etc) in healthy volunteers, and in patients with mild asthma, allergic rhinitis and post upper respiratory

Resveratrol regulates hyperglycemia-induced modulations in experimental diabetic animal model.

PubMed

Rehman, Kanwal; Saeed, Kiran; Munawar, Syeda Mehak; Akash, Muhammad Sajid Hamid

2018-06-01

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is associated with variable degrees of glucose intolerance, impaired insulin secretion, insulin resistance and increased hepatic glucose production. The aim of present study was to investigate the therapeutic potentials of resveratrol (RSV) alone and/or in combination with vitamin-E (Vit-E) against hyperglycemia-induced modulations using experimentally alloxan-induced diabetic animal model. Alloxan was used to induce diabetes mellitus in white albino rats and metformin (MF) was used as standard anti-diabetic drug to compare the therapeutic potentials of RSV (alone and/or with Vit-E) by estimating the effect of treatment on glycemia, insulin resistance, liver and kidney function biomarkers, anti-oxidant status, and serum levels of calcium and magnesium. The results of present study indicate the RSV (P < 0.001) alone and/or in combination with Vit-E (P < 0.001) exhibited a highly significant therapeutic potentials by ameliorating the glycemia-induced modulations. Moreover, we also found that RSV in combination with Vit-E also exhibited a better therapeutic effects when compared with that of MF (P < 0.001) and Vit-E (P < 0.05), respectively. Hence, we conclude that RSV alone and/or in combination with Vit-E exhibit its significant therapeutic potentials against hyperglycemia-induced modulations in experimental diabetic animal model and may be one of the most exciting prospect for future treatment of T2DM. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A Systematic Review and Narrative Synthesis to Explore the Effectiveness of Exercise-Based Interventions in Improving Fatigue, Dyspnea, and Depression in Lung Cancer Survivors.

PubMed

Henshall, Catherine L; Allin, Lizzie; Aveyard, Helen

2018-05-21

Lung cancer survival rates are increasing; however, lung cancer survivors' mental and physical well-being can suffer from experiencing symptoms of fatigue, dyspnea, and depression. Exercise can improve these symptoms. However, no studies have examined the effects of different exercise interventions on these symptoms. This review aims to examine the evidence on the effects of exercise interventions on fatigue, dyspnea, and depression in lung cancer survivors. PRISMA guidelines were followed. CINAHL, MEDLINE, EMBASE, and Cochrane databases were searched between 2000 and May 2017. Gray literature was searched. All identified studies were screened for inclusion. Quantitative data were narratively synthesized. From 852 records retrieved and screened, 10 full-text articles were included. Seven studies had a high risk of bias, 2 had an unclear risk, and 1 study had a low risk, limiting the robustness of findings. Exercise interventions included pulmonary rehabilitation, aerobic exercise, resistance training, exercise and balance programs, and medical qigong. Six studies reported statistically significant reductions in fatigue; 2 reported significant improvements in dyspnea, and one a significant reduction in depression postintervention. Exercise interventions may be effective and are unlikely to cause harm for lung cancer survivors. However, evidence quality is limited. More rigorous study designs are required to provide guidance about which interventions may help lung cancer survivors self-manage these symptoms. Health professionals should provide comprehensive, customized exercise screening and treatment plans to lung cancer survivors to complement their lifestyle needs and ensure appropriate recommendations aimed at improving symptom control are communicated to them.

Severe non-anion gap metabolic acidosis induced by topiramate: a case report.

PubMed

Shiber, Joseph R

2010-05-01

A non-anion gap acidosis can be induced by topiramate, causing symptomatic dyspnea and confusion. Discuss the pathophysiology of the hyperchloremic metabolic acidosis caused by topiramate, the typical clinical presentation, and the recommended treatment. This case presents a young woman with a clinically significant non-anion gap metabolic acidosis believed to be caused by topiramate. She had been taking the medication for several months without prior adverse effects. Once she began having dyspnea as a respiratory response to the renal tubule acidosis, she had decreased oral intake of food and fluids, which induced a pre-renal acute renal failure that worsened her acidemia. In the Emergency Department, she received intravenous fluids and sodium bicarbonate, and later was intubated for mechanical ventilation due to respiratory fatigue. With the topiramate withdrawn, the patient had a full recovery of her renal function and metabolic acid-base status over the next 72 h. This case serves to increase awareness of this possible adverse effect and the recommended treatment as topiramate becomes more widely used. Topiramate can induce a renal tubule acidosis resulting in a hyperchloremic metabolic acidosis. Recognition of the underlying cause is crucial so that the drug can be withdrawn while supportive care is provided. Copyright (c) 2010 Elsevier Inc. All rights reserved.

[A case of flomoxef-induced pneumonitis].

PubMed

Wako, Y; Hamauzu, T; Tamura, M; Yokote, M; Yokote, M; Shoji, S; Takikawa, H; Miyake, K; Yamanaka, M; Goto, H

1992-04-01

We report a case of flomoxef-induced pneumonitis. A 22-year-old man was treated with flomoxef following liver biopsy. A few days later he developed a high fever and severe dyspnea, and his chest X-ray film revealed diffuse reticulo-nodular shadows in both lung fields. We suspected interstitial pneumonitis due to flomoxef, and pulse therapy with methylprednisolone was started. He showed rapid recovery of symptoms and marked regression of pulmonary infiltration in his chest X-ray. Lymphocyte stimulation test was positive to flomoxef, which was compatible with the diagnosis of drug-induced pneumonitis. To our knowledge, there has been no previous case of pulmonary hypersensitivity to flomoxef reported in Japan.

Protective effects of ebselen on sodium-selenite-induced experimental cataract in rats.

PubMed

Aydemir, Orhan; Güler, Mete; Kaya, Mehmet Kaan; Deniz, Nurettin; Üstündağ, Bilal

2012-12-01

To determine whether ebselen has a protective effect or antioxidative potential in a sodium-selenite-induced experimental cataract model. Fırat University, Elazığ, Turkey. Experimental study. Twenty-one Sprague-Dawley rat pups were randomly divided into a control group, a sodium-selenite-induced-cataract group, and an ebselen-treated group; each group contained 7 rat pups. Rats in the control group received dimethyl sulfoxide (DMSO) intraperitoneally only and rats in the sodium-selenite-induced-cataract group received 30 nmol/g body weight sodium selenite subcutaneously and DMSO intraperitoneally 10 days postpartum. Rats in the ebselen group received 30 nmol/g body weight sodium selenite subcutaneously 10 days postpartum and were treated with 5 mg/kg body weight ebselen once a day for 4 consecutive days. Cataract development was assessed weekly for 3 weeks by slitlamp examination and graded using a scale. Reduced glutathione (GSH), total nitrite, and malondialdehyde (MDA) levels in lens supernatants were measured at the end of 3 weeks. In the control group, all lenses were clear. In the ebselen-treated group, the mean cataract stage was significantly lower than in the sodium-selenite-induced-cataract group (P = .022). The GSH levels were significantly lower in the sodium-selenite-induced-cataract group than in the control and ebselen groups (P < .001). The MDA levels were lower in the ebselen group than in the sodium-selenite-induced-cataract group (P < .001). The mean total nitrite level was significantly lower in the sodium-selenite-induced-cataract group than in the ebselen group (P = .001). Ebselen had a protective effect on cataract development in a sodium-selenite-induced experimental model. The protective effect of ebselen appears to be due to inhibition of oxidative stress. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Experimental Sleep Restriction Facilitates Pain and Electrically Induced Cortical Responses

PubMed Central

Matre, Dagfinn; Hu, Li; Viken, Leif A.; Hjelle, Ingri B.; Wigemyr, Monica; Knardahl, Stein; Sand, Trond; Nilsen, Kristian Bernhard

2015-01-01

Study Objectives: Sleep restriction (SR) has been hypothesized to sensitize the pain system. The current study determined whether experimental sleep restriction had an effect on experimentally induced pain and pain-elicited electroencephalographic (EEG) responses. Design: A paired crossover study. Intervention: Pain testing was performed after 2 nights of 50% SR and after 2 nights with habitual sleep (HS). Setting: Laboratory experiment at research center. Participants: Self-reported healthy volunteers (n = 21, age range: 18–31 y). Measurements and Results: Brief high-density electrical stimuli to the forearm skin produced pinprick-like pain. Subjective pain ratings increased after SR, but only in response to the highest stimulus intensity (P = 0.018). SR increased the magnitude of the pain-elicited EEG response analyzed in the time-frequency domain (P = 0.021). Habituation across blocks did not differ between HS and SR. Event-related desynchronization (ERD) was reduced after SR (P = 0.039). Pressure pain threshold of the trapezius muscle region also decreased after SR (P = 0.017). Conclusion: Sleep restriction (SR) increased the sensitivity to pressure pain and to electrically induced pain of moderate, but not low, intensity. The increased electrical pain could not be explained by a difference in habituation. Increased response magnitude is possibly related to reduced processing within the somatosensory cortex after partial SR. Citation: Matre D, Hu L, Viken LA, Hjelle IB, Wigemyr M, Knardahl S, Sand T, Nilsen KB. Experimental sleep restriction facilitates pain and electrically induced cortical responses. SLEEP 2015;38(10):1607–1617. PMID:26194577

Mechanisms of methylmercury-induced neurotoxicity: evidence from experimental studies

PubMed Central

Farina, Marcelo; Rocha, João B. T.; Aschner, Michael

2011-01-01

Neurological disorders are common, costly, and can cause enduring disability. Although mostly unknown, a few environmental toxicants are recognized causes of neurological disorders and subclinical brain dysfunction. One of the best known neurotoxins is methylmercury (MeHg), a ubiquitous environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. In the aquatic environment, MeHg is accumulated in fish, which represent a major source of human exposure. Although several episodes of MeHg poisoning have contributed to the understanding of the clinical symptoms and histological changes elicited by this neurotoxicant in humans, experimental studies have been pivotal in elucidating the molecular mechanisms that mediate MeHg-induced neurotoxicity. The objective of this mini-review is to summarize data from experimental studies on molecular mechanisms of MeHg-induced neurotoxicity. While the full picture has yet to be unmasked, in vitro approaches based on cultured cells, isolated mitochondria and tissue slices, as well as in vivo studies based mainly on the use of rodents, point to impairment in intracellular calcium homeostasis, alteration of glutamate homeostasis and oxidative stress as important events in MeHg-induced neurotoxicity. The potential relationship among these events is discussed, with particular emphasis on the neurotoxic cycle triggered by MeHg-induced excitotoxicity and oxidative stress. The particular sensitivity of the developing brain to MeHg toxicity, the critical role of selenoproteins and the potential protective role of selenocompounds are also discussed. These concepts provide the biochemical bases to the understanding of MeHg neurotoxicity, contributing to the discovery of endogenous and exogenous molecules that counteract such toxicity and provide efficacious means for ablating this vicious cycle. PMID:21683713

Neuroendocrine mechanisms of development of experimental hyperandrogen-induced anovulation.

PubMed

Reznikov, A G; Sinitsyn, P V; Tarasenko, L V; Polyakova, L I

2003-10-01

An experimental model of hyperandrogen-induced anovulatory infertility (s.c. implantation of Silastic capsules containing testosterone into adult female rats) was used to study morphological, hormonal, and biochemical measures characterizing the state of the hypothalamo-hypophyseal-ovarian system. Impairments in functional androgen metabolism in the hypothalamus were seen, with decreases in the Luliberin sensitivity of the hypophysis, changes in the structure of estral cycles, and morphological changes in the ovaries; these findings are evidence for neuroendocrine disturbances in the control of ovulation. Flutamide, an experimental antiandrogen, led to partial normalization of the hormonal, biochemical, and morphological characteristics, as well as to recovery of fertility in females with anovulatory infertility.

Experimental evidence on microwave induced electron losses from ECRIS plasma

NASA Astrophysics Data System (ADS)

Sakildien, M.; Tarvainen, O.; Kronholm, R.; Izotov, I.; Skalyga, V.; Kalvas, T.; Jones, P.; Koivisto, H.

2018-06-01

The balance between warm and hot (>1 keV) electron density and their losses from the magnetic confinement system of an Electron Cyclotron Resonance Ion Source (ECRIS) plasma is considered to be one of the main factors determining the rate of the high charge state ion production. One of the key loss channels for heated electrons is thought to be induced by the injected microwaves. While this loss mechanism, referred to as rf-induced pitch angle scattering, has been studied theoretically and with computational tools, direct experimental evidence of its significance in minimum-B ECRIS plasmas remains limited. In this work, experimental evidence of microwave induced electron losses in the axial direction is presented in both continuous wave (CW) and pulsed operation of a 14 GHz ECRIS. In the CW mode, the experiment was carried out by comparing the characteristic X-ray emission from the plasma volume and from the surface of the biased disc located in the flux of the escaping electron at the axial magnetic mirror. Parametric sweeps of magnetic field, neutral gas pressure, and microwave power were conducted to determine their effect on electron losses. In the pulsed mode, the experiment was conducted by measuring the flux of escaping electrons through aluminum foils of different thicknesses providing some energy resolution. Both diagnostics support the view that rf-induced losses account for up to 70% of total hot electron losses and their importance depends on the source parameters, especially power and neutral gas pressure.

Dyspnea during Advanced Cancer

MedlinePlus

... to Cancer Off-Label Drug Use Access to Experimental Drugs Complementary & Alternative Medicine (CAM) CAM for Patients ... pressure on the heart. Treatment may be to control the symptoms of ... vena cava syndrome (SVCS) is a group of signs and symptoms that occur when the ...

Hypolipidemic effect of arborium plus in experimentally induced hypercholestermic rabbits.

PubMed

Murty, Devarakonda; Rajesh, Enjamoori; Raghava, Doonaboina; Raghavan, Tangaraj Vijaya; Surulivel, Mukanthan Karupiah Munirajan

2010-06-01

Hypercholesteremia is one of the risk factors for coronary artery disease. The present study highlights the efficacy of the ayurvedic herbal formulation Arborium Plus [Hyppophae ramnoides L. fruit juice (S) and Rhododendron arboreum Sm. Linn flower juice (R) in a 1:4 ratio] on triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), atherogenic index (AI), high-density lipoprotein (HDL), and high-sensitivity c-reactive protein (hs CRP) in experimentally induced hypercholesterolemic rabbits. Four groups of rabbits were subjected to different treatments for 8 weeks: control group, CHOL group (1% w/w cholesterol for 8 weeks), S+R group (1% w/w cholesterol and Arborium Plus for 8 weeks), and A group (1% w/w cholesterol and atorvastatin for 8 weeks). The results showed significant increases in TG, TC, LDL, AI, and hs CRP in hypercholesterolemic rabbits which was significantly reduced in Arborium Plus-treated hypercholesterolemic rabbits. The data demonstrated that the Arborium Plus formulation was associated with hypolipidemic effects in experimentally induced hypercholesterolemic rabbits.

The iothalamate clearance in cats with experimentally induced renal failure.

PubMed

Ohashi, F; Kuroda, K; Shimada, T; Shimada, Y; Ota, M

1996-08-01

Plasma iothalamate (IOT) disappearance rates were measured after a single-injection of IOT (113.8 mg/kg, IV) in cats with experimentally induced renal failure. The disappearance rates especially fitted into the one compartment model. The mean value of plasma disappearance rates of IOT in these cats with induced renal failure (2.16 +/- 0.240 x 10(-3) micrograms/ml/min) was markedly lower than that of clinically healthy cats (4.10 +/- 1.00 x 10(-3) micrograms/ml/min). These results demonstrate that IOT clearance is available for evaluation of renal function in cats.

Analysis of antigen-induced changes in pulmonary mechanics in sensitized inbred rats.

PubMed

Holroyde, M C; Smith, S Y; Holme, G

1982-05-01

An inbred line of rats was derived which develop marked and consistent dyspnea following sensitization and then exposure to aerosolized antigen. This pulmonary response was investigated in detail by determining forced pulmonary mechanics to derive respiratory rate, peak expiratory flow rate (PEFR), forced vital capacity (FVC), forced expiratory volume in 0.1 s (FEV0.1), and maximal midexpiratory flow rate (MMFR). Challenging anesthetized rats for 5 min with an aerosol of 3% egg albumin produced minimal change in respiratory rate, a 20% fall in PEFR, a 50% fall in FVC, and a 30% decrease in FEV0.1 and MMFR. The response could be inhibited or reversed by salbutamol (0.5 mg/kg, i.v.) and aminophylline (25 mg/kg, i.v.) administered either before or after challenge. The pulmonary changes are consistent with antigen-induced asthma in the rats. The response shows similarities to human asthma and may provide a relevant experimental model.

The effects of short-term and long-term pulmonary rehabilitation on functional capacity, perceived dyspnea, and quality of life.

PubMed

Verrill, David; Barton, Cole; Beasley, Will; Lippard, W Michael

2005-08-01

The purposes of this study were as follows: (1) to determine whether physical performance, quality of life, and dyspnea with activities of daily living improved following both short-term and long-term pulmonary rehabilitation (PR) across multiple hospital outpatient programs; (2) to examine the differences in these parameters between men and women; and (3) to determine what relationships existed between the psychosocial parameters and the results of the 6-min walk (6MW) test performance across programs. Non-experimental, prospective, and comparative. Seven outpatient hospital PR programs from urban and rural settings across North Carolina. Three hundred nine women and 281 men who were 20 to 93 years of age (mean [+/- SD] age, 66.7 +/- 11.1 years) with chronic lung disease. All 6MW tests and health surveys were administered prior to and immediately following 12 and 24 weeks of supervised PR participation. Scores from the 6MW tests, the Ferrans and Powers quality of life index-pulmonary version III (QLI), the Medical Outcomes Study 36-item short form (SF-36), and the University of California at San Diego shortness of breath questionnaire (SOBQ) were compared at PR entry, at 12 weeks, and at 24 weeks for differences by gender with repeated-measures analysis of variance. The study entry and follow-up SF-36 physical and mental component summary scores, the QLI health/function and overall scores, and the SOBQ scores were also compared to the 6MW test scores with Pearson correlation coefficient analysis. The mean summary scores on the SF-36 and the QLI increased after 12 weeks of PR (p < 0.05), and improvements were maintained by 24 weeks of PR participation (p < 0.05). Scores on the SOBQ improved after 12 weeks (p < 0.001) among the short-term participants, but not until after 24 weeks among the long-term participants (p = 0.009). The 6MW test performance improved after 12 weeks (p < 0.001) and again from 12 to 24 weeks (p = 0.002) in the long-term participants. No

Ichnocarpus frutescens Ameliorates Experimentally Induced Convulsion in Rats

PubMed Central

Singh, Narendra Kumar; Laloo, Damiki; Garabadu, Debapriya; Singh, Tryambak Deo; Singh, Virendra Pratap

2014-01-01

The present study was carried out to evaluate the anticonvulsant activity and probable mechanism of action of the methanol root extract from I. frutescens (MEIF) using different experimental animal models. Anticonvulsant activity of the single dose of MEIF (100, 200, and 400 mg/kg, p.o.) was evaluated in maximal electroshock- (MES-), pentylenetetrazole- (PTZ-), and isoniazid- (INH-) induced convulsions models in rats. The levels of γ-amino butyric acid (GABA), glutamate, GABA-transaminase (GABA-T) activity and oxidative stress markers were measured in pretreated rat's brain homogenate to corroborate the mechanism of observed anticonvulsant activity. MEIF (200–400 mg/kg, p.o.) protected the animals in all the behavioral models used. Pretreatment of MEIF (200–400 mg/kg, p.o.) and diazepam (1.0 mg/kg, i.p.) to the animals in INH-induced convulsion model showed 100% and 80% protection, respectively, as well as significant restoration of GABA and glutamate level in the rat's brain. MEIF and vigabatrin (50 mg/kg, i.p.) reduced the PTZ-induced increase in the activity of GABA-T (46%) in the brain. Further, MEIF reversed the PTZ-induced increase in lipid peroxidase (LPO) and decrease in reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. The findings of this study validate the anticonvulsant activity of I. frutescens. PMID:27379268

Spontaneous progression of experimentally induced periimplantitis.

PubMed

Zitzmann, N U; Berglundh, T; Ericsson, I; Lindhe, J

2004-10-01

Periimplantitis represents an inflammatory condition that is associated with the presence of a submarginal biofilm and with advanced breakdown of soft and mineralized tissues surrounding endosseous implants. Animal models have been used to describe mechanisms involved in the pathogenesis and treatment of the soft and hard tissue lesions of periimplantitis. The aim of the present experiment was to study the presence and progression of inflammatory lesions in tissues surrounding implants exposed to "experimental periimplantitis". Five Labrador dogs were used. In each dog, 2 or 3 implants were placed in both the left and right edentulous premolar regions of the mandible. Abutment connection was performed 4 months later and a plaque control regimen was initiated and maintained for 5 months. "Experimental periimplantitis" was subsequently induced by ligature placement and plaque accumulation was allowed to progress until about 40% of the height of the supporting bone had been lost. The ligatures were removed, but plaque formation was allowed to continue for an additional 12 months. Radiographs of all implant sites were obtained before and after active "experimental periimplantitis" as well as at the end of the experiment. Biopsies were harvested from the implant sites in 3 of the dogs. The tissue samples were prepared for light microscopy and the sections were used for histometric and morphometric examinations. One implant was lost during the first 2 months of "experimental periimplantitis" and two implants were lost during the 12 months that followed ligature removal. The radiographic examination indicated that varying amounts of additional bone loss occurred in the majority of the implant sites also following ligature removal. The mucosa of all implant sites harbored inflammatory lesions that extended apically of the pocket epithelium. The lesions were separated from the marginal bone by a zone of apparently normal connective tissue. A remission of the destructive

Enhancement of carbachol-induced amylase secretion in parotid glands from rats with experimental periodontitis.

PubMed

Miozza, Valeria; Sánchez, Gabriel; Sterin-Borda, Leonor; Busch, Lucila

2011-12-01

In a previous study we observed that parotid glands from rats with experimental periodontitis showed an increase in basal amylase release as a result of an increase in cAMP accumulation induced by PGE(2) production. The aim of this work was to study whether this change in amylase release influences the secretory effect of carbachol. Experimental periodontitis was induced through placing a black thread around the cervix of the two lower first molars. Experiments were done 22 days after ligature induced periodontitis. Amylase release was evaluated in vitro and determined using a colorimetric method which uses starch as substrate. The effect of carbachol was increased in parotid glands from periodontitis rats. The effect of 10(-6)M carbachol was inhibited by 4-DAMP (10(-6)M), U-73122 (5 × 10(-6)M) and trifluoperazine (5 × 10(-6)M) in both groups. No changes were observed in the binding sites and affinity in parotid membranes from rats with experimental periodontitis. The inhibition of the adenylyl cyclase and the cyclooxygenase induced a right shift of the carbachol concentration-response curve in periodontitis group whilst the opposite effect was observed in control group in the presence of db-cAMP and PGE(2). Parotid glands from rats with experimental periodontitis release more amylase in response to carbachol suggesting an interaction between Ca(2+) and cAMP in the fusion/exocytosis step of secretory vesicles. Copyright © 2011 Elsevier Ltd. All rights reserved.

Abnormal experimentally- and behaviorally-induced LTP-like plasticity in focal hand dystonia.

PubMed

Belvisi, Daniele; Suppa, Antonio; Marsili, Luca; Di Stasio, Flavio; Parvez, Ahmad Khandker; Agostino, Rocco; Fabbrini, Giovanni; Berardelli, Alfredo

2013-02-01

Idiopathic focal hand dystonia (FHD) arises from abnormal plasticity in the primary motor cortex (M1) possibly reflecting abnormal sensori-motor integration processes. In this transcranial magnetic stimulation (TMS) study in FHD, we evaluated changes in motor evoked potentials (MEPs) after intermittent theta burst stimulation (iTBS) and paired associative stimulation (PAS), techniques that elicit different forms of experimentally-induced long-term potentiation (LTP)-like plasticity in M1. We also examined behaviorally-induced LTP-like plasticity as reflected by early motor learning of a simple motor task. We studied 14 patients with FHD and 14 healthy subjects. MEPs were recorded before and after iTBS and PAS at the 25 ms interstimulus interval (PAS(25)) in separate sessions. Subjects did a simple motor task entailing repetitive index finger abductions. To measure early motor learning we tested practice-related improvement in peak velocity and peak acceleration. In FHD patients iTBS failed to elicit the expected MEP changes and PAS(25) induced abnormally increased MEPs in target and non-target muscles. In the experiment testing early motor learning, patients lacked the expected practice-related changes in kinematic variables. In FHD, the degree of early motor learning correlated with patients' clinical features. We conclude that experimentally-induced (iTBS and PAS) and behaviorally-induced LTP-like plasticity are both altered in FHD. Copyright © 2012 Elsevier Inc. All rights reserved.

Experimental gastric ulcers induced by immobilization and electric shock of rats and their pharmacotherapy

NASA Technical Reports Server (NTRS)

Zabrodin, O. N.

1980-01-01

The mechanism of development of experimental gastric ulcers, induced in rats by combined immobilization and electric shock, was analyzed pharmacologically with peripheral neurotropic agents. It is concluded that: (1) The most marked preventive effect in the development of the experimentally induced gastric ulcers was displayed by agents capable of blocking the ascending activation system of the reticular formation. (2) Sympathetic fibers, which disrupt the trophism of the gastric wall, form the efferent portion of the reflex arc. (3) Gastric secretion does not appear to be the primary cause of ulceration.

Experimentally induced cam impingement in the sheep hip.

PubMed

Siebenrock, Klaus A; Fiechter, Ruth; Tannast, Moritz; Mamisch, Tallal C; von Rechenberg, Brigitte

2013-04-01

Sheep hips have a natural non-spherical femoral head similar to a cam-type deformity in human beings. By performing an intertrochanteric varus osteotomy, cam-type femoro-acetabular impingement (FAI) during flexion can be created. We tested the hypotheses that macroscopic lesions of the articular cartilage and an increased Mankin score (MS) can be reproduced by an experimentally induced cam-type FAI in this ovine in vivo model. Furthermore, we hypothesized that the MS increases with longer ambulatory periods. Sixteen sheep underwent unilateral intertrochanteric varus osteotomy of the hip with the non-operated hip as a control. Four sheep were sacrificed after 14, 22, 30, and 38-weeks postoperatively. We evaluated macroscopic chondrolabral alterations, and recorded the MS, based on histochemical staining, for each ambulatory period. A significantly higher prevalence of macroscopic chondrolabral lesions was found in the impingement zone of the operated hips. The MS was significantly higher in the acetabular/femoral cartilage of the operated hips. Furthermore, these scores increased as the length of the ambulatory period increased. Cam-type FAI can be induced in an ovine in vivo model. Localized chondrolabral degeneration of the hip, similar to that seen in humans (Tannast et al., Clin Orthop Relat Res 2008; 466: 273-280; Beck et al., J Bone Joint Surg Br 2005; 87: 1012-1018), can be reproduced. This experimental sheep model can be used to study cam-type FAI. Copyright © 2012 Orthopaedic Research Society.

Activity and milk compositional changes following experimentally induced Streptococcus uberis bovine mastitis.

PubMed

Kester, H J; Sorter, D E; Hogan, J S

2015-02-01

Milk constituents and physical activity of cows experimentally infected with Streptococcus uberis mastitis were compared with those of uninfected cows. Twelve late-lactation Holsteins cows were paired based on milk production and parity. One cow in each pair was experimentally infected in the right front mammary gland with Strep. uberis. The remaining cow in each pair served as an uninfected control. Real-time analyses of milk constituents provided fat, protein, and lactose percentages at each milking. Pedometers were placed on the left front leg of all cows and activity was measured. Intramammary infections with Strep. uberis reduced milk yield in experimental cows by approximately 1.6kg/d in the first week after challenge compared with control cows. Lactose percentage in milk was reduced on d 3, 4, 5, and 6 after challenge in treatment cows compared with controls. Percentages of fat and protein in milk did not differ between infected and uninfected cows the week after infections were induced. Total steps per day were reduced and minutes resting per day were increased the week after experimental challenge in infected cows compared with control cows. The number of resting bouts did not differ between infected and uninfected cows. Changes in percentage of lactose in milk and animal activity caused by experimentally induced Strep. uberis mastitis were detected by the automated milk analyzer and pedometer systems. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Computational Modeling and Experimental Validation of Shock Induced Damage in Woven E-Glass/Vinylester Laminates

NASA Astrophysics Data System (ADS)

Hufner, D. R.; Augustine, M. R.

2018-05-01

A novel experimental method was developed to simulate underwater explosion pressure pulses within a laboratory environment. An impact-based experimental apparatus was constructed; capable of generating pressure pulses with basic character similar to underwater explosions, while also allowing the pulse to be tuned to different intensities. Having the capability to vary the shock impulse was considered essential to producing various levels of shock-induced damage without the need to modify the fixture. The experimental apparatus and test method are considered ideal for investigating the shock response of composite material systems and/or experimental validation of new material models. One such test program is presented herein, in which a series of E-glass/Vinylester laminates were subjected to a range of shock pulses that induced varying degrees of damage. Analysis-test correlations were performed using a rate-dependent constitutive model capable of representing anisotropic damage and ultimate yarn failure. Agreement between analytical predictions and experimental results was considered acceptable.

Laser-induced fluorescence detection of lead atoms in a laser-induced plasma: An experimental analytical optimization study

NASA Astrophysics Data System (ADS)

Laville, Stéphane; Goueguel, Christian; Loudyi, Hakim; Vidal, François; Chaker, Mohamed; Sabsabi, Mohamad

2009-04-01

The combination of the laser-induced breakdown spectroscopy (LIBS) and laser-induced fluorescence (LIF) techniques was investigated to improve the limit of detection (LoD) of trace elements in solid matrices. The influence of the main experimental parameters on the LIF signal, namely the ablation fluence, the excitation energy, and the inter-pulse delay, was studied experimentally and a discussion of the results was presented. For illustrative purpose we considered detection of lead in brass samples. The plasma was produced by a Q-switched Nd:YAG laser and then re-excited by a nanosecond Optical Parametric Oscillator (OPO) laser. The experiments were performed in air at atmospheric pressure. We found out that the optimal conditions were obtained for our experimental set-up using relatively weak ablation fluence of 2-3 J/cm 2 and an inter-pulse delay of about 5-10 μs. Also, a few tens of microjoules was typically required to maximize the LIF signal. Using the LIBS-LIFS technique, a single-shot LoD for lead of about 1.5 part per million (ppm) was obtained while a value of 0.2 ppm was obtained after accumulating over 100 shots. These values represent an improvement of about two orders of magnitude with respect to LIBS.

Immediate effects of chocolate on experimentally induced mood states.

PubMed

Macht, Michael; Mueller, Jochen

2007-11-01

In this work two hypotheses were tested: (1) that eating a piece of chocolate immediately affects negative, but not positive or neutral mood, and (2) that this effect is due to palatability. Experiment 1 (48 normal-weight and healthy women and men) examined the effects of eating a piece of chocolate and drinking water on negative, positive and neutral mood states induced by film clips. Eating chocolate reduced negative mood compared to drinking water, whereas no or only marginal effects were found on neutral and positive moods. Experiment 2 (113 normal-weight and healthy women and men) compared effects of eating palatable and unpalatable chocolate on negative mood, and examined the duration of chocolate-induced mood change. Negative mood was improved after eating palatable chocolate as compared to unpalatable chocolate or nothing. This effect was short lived, i.e., it disappeared after 3 min. In both experiments, chocolate-induced mood improvement was associated with emotional eating. The present studies demonstrate that eating a small amount of sweet food improves an experimentally induced negative mood state immediately and selectively and that this effect of chocolate is due to palatability. It is hypothesized that immediate mood effects of palatable food contribute to the habit of eating to cope with stress.

Local and Systemic Inflammatory Responses to Experimentally Induced Gingivitis

PubMed Central

Leishman, Shaneen J.; Seymour, Gregory J.; Ford, Pauline J.

2013-01-01

This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P < 0.001). These results support the concept that gingivitis adds to the systemic inflammatory burden of an individual. PMID:24227893

Local and systemic inflammatory responses to experimentally induced gingivitis.

PubMed

Leishman, Shaneen J; Seymour, Gregory J; Ford, Pauline J

2013-01-01

This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P < 0.001). These results support the concept that gingivitis adds to the systemic inflammatory burden of an individual.

Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum

PubMed Central

Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R.; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

2015-01-01

Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain. PMID:25871402

Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum.

PubMed

Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

2015-05-10

Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain.

Protective effect of Clerodendron glandulosum extract against experimentally induced metabolic syndrome in rats.

PubMed

Jadeja, Ravirajsinh N; Thounaojam, Menaka C; Ansarullah; Patel, Vaibhav B; Devkar, Ranjitsinh V; Ramachandran, A V

2010-12-01

Metabolic syndrome (MetS) has become one of the major health burdens worldwide. To date, no single pharmacological agent has been developed to correct metabolic abnormalities associated with MetS. Use of indigenous medicinal plants as alternative medicines against MetS could be beneficial due to multiple therapeutic usage, easy availability, and relatively few side effects. To investigate the protective effect of Clerodendron glandulosum Coleb. (Verbenaceae) aqueous leaf extract (CgE) against experimentally induced MetS in rats. Changes in body weight, food and fluid intake, plasma glucose, insulin, fasting insulin resistance index (FIRI), plasma total lipid profile, free fatty acids (FFA), oral glucose tolerance test (OGTT), blood pressure and vascular reactivity have been investigated in various experimental groups. Fructose+CgE groups recorded significant decrement (P <0.05) in plasma glucose, insulin, FIRI, total cholesterol, triglycerides, LDL, VLDL and FFA, whereas plasma HDL level was significantly increased (P <0.05) along with an efficient clearance of glucose during OGTT and lowered area under curve values. FRU+CgE groups also showed significantly decreased (P <0.05) mean arterial blood pressure along with decreased vasoconstriction and increased vasorelaxation in response to administration of various pharmacological agents. These results were comparable with metformin treated rats. C. glandulosum leaf extract ameliorates experimentally induced MetS by improving dyslipidemia and insulin resistance. This study provides the first pharmacological evidence for the protective role of C. glandulosum leaves against experimentally induced MetS. Thus, therapeutic use of C. glandulosum in controlling MetS is indicated.

Duration of Analgesia Induced by Acupuncture-Like TENS on Experimental Heat Pain.

PubMed

Tousignant-Laflamme, Yannick; Brochu, Marilyne; Dupuis-Michaud, Cynthia; Pagé, Catherine; Popovic, Draga; Simard, Marie-Eve

2013-01-01

Background. Acupuncture-like TENS (AL-TENS) is a treatment modality that can be used to temporarily reduce pain. However, there is no clear data in the literature regarding the specific duration of analgesia induced by AL-TENS. Objectives. To describe and quantify the duration and magnitude of AL-TENS analgesia on experimental heat pain in healthy subjects and verify if the duration or magnitude of analgesia induced by the AL-TENS was influenced by the duration of the application of the AL-TENS (15 versus 30 minutes). Methods. A repeated-measures, intrasubject randomized experimental design was used, where each participant was his/her own control. 22 healthy volunteers underwent heat pain stimulations with a contact thermode before (pretest) and after (posttest) AL-TENS application (15 and 30 minutes). Outcome measures included subjective pain during AL-TENS, duration, and magnitude of AL-TENS-induced analgesia. Results. Survival analysis showed that the median duration of AL-TENS analgesia was 10 minutes following the application of either 15 or 30 minutes of AL-TENS. The magnitude of analgesia following either application was comparable at all points in time (P values > 0.05) and ranged between -20% and -36% pain reduction. Conclusion. Only half of the participants still had heat-pain analgesia induced by the AL-TENS at 15 minutes postapplication.

Experimental Investigations in Nonlinear Viscous Behavior of Subgrade Soils Under Traffic-Induced Loading

DOT National Transportation Integrated Search

1999-08-01

This paper concerns experimental investigations of nonlinear viscosity of : subgrade soils under vehicle-induced loading. Subgrade soil samples--collected : from the Soil/Aggregate Laboratory at the Geotechnical Exploration Division at : the Maryland...

Experimental pleurodesis induced by antibiotics (macrolides or quinolones).

PubMed

Teixeira, Lisete R; Vargas, Francisco S; Acencio, Milena M P; Bumlai, Renan U M; Antonangelo, Leila; Marchi, Evaldo

2006-12-01

Chemical pleurodesis is a therapeutic tool for the treatment of recurrent pleural effusions, mainly those of neoplastic etiology. In the past, tetracycline was the sclerosant agent of choice in clinical practice, but presently, there is no consensus about an ideal agent. The aim of this study was to evaluate the effectiveness of macrolides (azithromycin and clarithromycin) or quinolones (levofloxacin and gatifloxacin) in inducing experimental pleurodesis in rabbits. Forty New Zealand rabbits randomized into groups of 10 received (at a total volume of 2 mL for each animal) 1 of the 4 drugs by intrapleural injection. After 28 days, the animals were euthanized and the pleural cavity was evaluated macroscopically and microscopically. The intensity of the macroscopic adhesions was mild in all groups. On microscopic analysis, minimal pleural fibrosis and inflammation were observed in all animals. The macrolides (azithromycin or clarithromycin) and the quinolones (levofloxacin or gatifloxacin) when injected into the normal pleural space of rabbits are not effective in promoting pleurodesis. Additional research is required to identify sclerosing agents capable of inducing pleurodesis.

Comparison of the alkalizing effects of bicarbonate precursors in calves with experimentally induced metabolic acidosis.

PubMed

Nakagawa, Mitsuhide; Suzuki, Kazuyuki; Takahashi, Fumito; Kamikatano, Kazuhiro; Koiwa, Masateru; Taguchi, Kiyoshi

2009-06-01

The aims of this study were to confirm whether commercial acetated Ringer's solution, which contains 28 mM of sodium acetate, is superior to commercial lactated Ringer's solution in alkalizing effects in calves with experimentally induced metabolic acidosis. Twenty calves with experimentally induced mild acidosis were intravenously administered isotonic saline, DL-lactated, L-lactated or acetated Ringer's solution at a dose of 80 ml/kg body weight (BW). The acetated Ringer's solution induced a significantly greater increase in venous HCO(3)(-) and base excess concentrations than the other fluids during the early phases of extracellular fluid replacement in mild metabolic acidosis. Therefore, the alkalizing effect of commercial acetated Ringer's solution is superior to commercial DL- and L-lactated Ringer's solution in treatment of mild metabolic acidosis in calves.

Stethoscope versus point-of-care ultrasound in the differential diagnosis of dyspnea: a randomized trial.

PubMed

Özkan, Behzat; Ünlüer, Erden E; Akyol, Pinar Y; Karagöz, Arif; Bayata, Mehmet S; Akoğlu, Haldun; Oyar, Orhan; Dalli, Ayşe; Topal, Fatih E

2015-12-01

We aimed to determine the accuracies of point-of-care ultrasound (PoCUS) and stethoscopes as part of the physical examinations of patients with dyspnea. Three emergency medicine specialists in each of two groups of ultrasound and stethoscope performers underwent didactic and hands-on training on PoCUS and stethoscope usage. All the patients enrolled were randomized to one of two predetermined PoCUS or stethoscope groups. The diagnostic performance of ultrasonography was higher than that of the stethoscope in the diagnoses of heart failure (90 vs. 86%, 1.00 vs. 0.89, and 5.00 vs. 4.92, respectively) and pneumonia (90 vs. 86.7%, 0.75 vs. 0.73, and 16.50 vs. 13.82, respectively). No significant differences were observed in the utility parameters of these modalities in these diagnoses. Although some authors argue that it is time to abandon the 'archaic tools' of past centuries, we believe that it is too early to discontinue the use of the stethoscope.

Nontraumatic head and neck emergencies: a clinical approach. Part 1: cervicofacial swelling, dysphagia, and dyspnea.

PubMed

Brea Álvarez, B; Tuñón Gómez, M; Esteban García, L; García Hidalgo, C Y; Ruiz Peralbo, R M

2016-01-01

Nontraumatic emergencies of the head and neck represent a challenge in the field of neuroradiology for two reasons: first, they affect an area where the thorax joins the cranial cavity and can thus compromise both structures; second, they are uncommon, so they are not well known. Various publications focus on nontraumatic emergencies of the head and neck from the viewpoints of anatomic location or of particular diseases. However, these are not the most helpful viewpoints for dealing with patients in the emergency department, who present with particular signs and symptoms. We propose an analysis starting from the four most common clinical presentations of patients who come to the emergency department for nontraumatic head and neck emergencies: cervical swelling, dysphagia, dyspnea, and loss of vision. Starting from these entities, we develop an approach to the radiologic management and diagnosis of these patients. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Experimental Sleep Restriction Facilitates Pain and Electrically Induced Cortical Responses.

PubMed

Matre, Dagfinn; Hu, Li; Viken, Leif A; Hjelle, Ingri B; Wigemyr, Monica; Knardahl, Stein; Sand, Trond; Nilsen, Kristian Bernhard

2015-10-01

Sleep restriction (SR) has been hypothesized to sensitize the pain system. The current study determined whether experimental sleep restriction had an effect on experimentally induced pain and pain-elicited electroencephalographic (EEG) responses. A paired crossover study. Pain testing was performed after 2 nights of 50% SR and after 2 nights with habitual sleep (HS). Laboratory experiment at research center. Self-reported healthy volunteers (n = 21, age range: 18-31 y). Brief high-density electrical stimuli to the forearm skin produced pinprick-like pain. Subjective pain ratings increased after SR, but only in response to the highest stimulus intensity (P = 0.018). SR increased the magnitude of the pain-elicited EEG response analyzed in the time-frequency domain (P = 0.021). Habituation across blocks did not differ between HS and SR. Event-related desynchronization (ERD) was reduced after SR (P = 0.039). Pressure pain threshold of the trapezius muscle region also decreased after SR (P = 0.017). Sleep restriction (SR) increased the sensitivity to pressure pain and to electrically induced pain of moderate, but not low, intensity. The increased electrical pain could not be explained by a difference in habituation. Increased response magnitude is possibly related to reduced processing within the somatosensory cortex after partial SR. © 2015 Associated Professional Sleep Societies, LLC.

Infectious bovine rhinotracheitis: study on the experimentally induced disease and its prevention using an inactivated, adjuvanted vaccine.

PubMed

Soulebot, J P; Guillemin, F; Brun, A; Dubourget, P; Espinasse, J; Terre, J

1982-01-01

Experimentally induced IBR was studied in calves. Intranasal challenge enabled reproducible results to be obtained, both from qualitative (clinical aspect) and quantitative points of view (virus excretion, temperature); local and general immunity were also evaluated. This challenge method is useful when studying IBR vaccines. The disease was also experimentally induced by putting healthy animals into contact with diffusor calves. A single injection of inactivated vaccine in oily adjuvant already conferred good protection; it was 100% successful against the experimentally induced disease when administered two times at a 7 or 14 day interval. Immunity obtained was long-lasting and even persisted up to one year. Therefore, this vaccine is advised for vaccination in both contaminated and high risk areas. Results obtained for both safety and potency suggest that this killed vaccine should be used rather than live vaccines.

Experimental and predicted cavitation performance of an 80.6 deg helical inducer in high temperature water

NASA Technical Reports Server (NTRS)

Kovich, G.

1972-01-01

The cavitating performance of a stainless steel 80.6 degree flat-plate helical inducer was investigated in water over a range of liquid temperatures and flow coefficients. A semi-empirical prediction method was used to compare predicted values of required net positive suction head in water with experimental values obtained in water. Good agreement was obtained between predicted and experimental data in water. The required net positive suction head in water decreased with increasing temperature and increased with flow coefficient, similar to that observed for a like inducer in liquid hydrogen.

Belching, regurgitation, chest tightness and dyspnea: not gastroesophageal reflux disease but asthma.

PubMed

Zhang, Jing-Xi; Zhan, Xian-Bao; Bai, Chong; Li, Qiang

2015-02-07

Belching is a common symptom of gastroesophageal reflux disease. If the symptoms are not relieved after anti-reflux treatment, another etiology should be considered. Here, we report a case of a 43-year-old man who presented with belching, regurgitation, chest tightness and dyspnea for 18 mo, which became gradually more severe. Gastroscopic examination suggested superficial gastritis. Twenty-four-hour esophageal pH monitoring showed that the Demeester score was 11.4, in the normal range. High-resolution manometry showed that integrated relaxation pressure and intrabolus pressure were higher than normal (20 mmHg and 22.4 mmHg, respectively), indicating gastroesophageal junction outflow tract obstruction. Pulmonary function test showed severe obstructive ventilation dysfunction [forced expiratory volume in 1 second (FEV1)/forced vital capacity 32%, FEV1 was 1.21 L, occupying 35% predicted value after salbuterol inhalation], and positive bronchial dilation test (∆FEV1 260 mL, ∆FEV1% 27%). Skin prick test showed Dermatophagoides farinae (++), house dust mite (++++), and shrimp protein (++). Fractional exhaled nitric oxide measurement was 76 ppb. All the symptoms were alleviated completely and pulmonary function increased after combination therapy with corticosteroids and long-acting β2-agonist. Bronchial asthma was eventually diagnosed by laboratory tests and the effect of anti-asthmatic treatment, therefore, physicians, especially the Gastrointestinal physicians, should pay attention to the belching symptoms of asthma.

Effects of a simple prototype respiratory muscle trainer on respiratory muscle strength, quality of life and dyspnea, and oxidative stress in COPD patients: a preliminary study.

PubMed

Leelarungrayub, Jirakrit; Pinkaew, Decha; Puntumetakul, Rungthip; Klaphajone, Jakkrit

2017-01-01

The aim of this study was to evaluate the efficiency of a simple prototype device for training respiratory muscles in lung function, respiratory muscle strength, walking capacity, quality of life (QOL), dyspnea, and oxidative stress in patients with COPD. Thirty COPD patients with moderate severity of the disease were randomized into three groups: control (n=10, 6 males and 4 females), standard training (n=10, 4 males and 6 females), and prototype device (n=10, 5 males and 5 females). Respiratory muscle strength (maximal inspiratory pressure [PImax] and maximal expiratory pressure [PEmax]), lung function (forced vital capacity [FVC], percentage of FVC, forced expiratory volume in 1 second [FEV 1 ], percentage of FEV 1 [FEV 1 %], and FEV 1 /FVC), 6-minute walking distance (6MWD), QOL, and oxidative stress markers (total antioxidant capacity [TAC]), glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) were evaluated before and after 6 weeks of training. Moreover, dyspnea scores were assessed before; during week 2, 4, and 6 of training; and at rest after training. All parameters between the groups had no statistical difference before training, and no statistical change in the control group after week 6. FVC, FEV 1 /FVC, PImax, PEmax, QOL, MDA, and NO showed significant changes after 6 weeks of training with either the standard or prototype device, compared to pre-training. FEV 1 , FEV 1 %, 6MWD, TAC, and GSH data did not change statistically. Furthermore, the results of significant changes in all parameters were not statistically different between training groups using the standard and prototype device. The peak dyspnea scores increased significantly in week 4 and 6 when applying the standard or prototype device, and then lowered significantly at rest after 6 weeks of training, compared to pre-training. This study proposes that a simple prototype device can be used clinically in COPD patients as a standard device to train respiratory muscles, improving lung

T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis

PubMed Central

de Oliveira, Leandro Licursi; Coltri, Kely Cristine; Cardoso, Cristina Ribeiro Barros; Roque-Barreira, Maria-Cristina; Panunto-Castelo, Ademilson

2008-01-01

Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1–stimulating adjuvant in P. brasiliensis–infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans. PMID:18335066

Analytical and experimental studies of flow-induced vibration of SSME components

NASA Technical Reports Server (NTRS)

Chen, S. S.; Jendrzejczyk, J. A.; Wambsganss, M. W.

1987-01-01

Components of the Space Shuttle Main Engines (SSMEs) are subjected to a severe environment that includes high-temperature, high-velocity flows. Such flows represent a source of energy that can induce and sustain large-amplitude vibratory stresses and/or result in fluidelastic instabilities. Three components are already known to have experienced failures in evaluation tests as a result of flow-induced structural motion. These components include the liquid-oxygen (LOX) posts, the fuel turbine bellows shield, and the internal inlet tee splitter vane. Researchers considered the dynamic behavior of each of these components with varying degrees of effort: (1) a theoretical and experimental study of LOX post vibration excited by a fluid flow; (2) an assessment of the internal inlet tee splitter vane vibration (referred to as the 4000-Hz vibration problem); and (3) a preliminary consideration of the bellows shield problem. Efforts to resolve flow-induced vibration problems associated with the SSMEs are summarized.

Radiological and histopathological evaluation of experimentally-induced periapical lesion in rats

PubMed Central

TEIXEIRA, Renata Cordeiro; RUBIRA, Cassia Maria Fischer; ASSIS, Gerson Francisco; LAURIS, José Roberto Pereira; CESTARI, Tania Mary; RUBIRA-BULLEN, Izabel Regina Fischer

2011-01-01

Objective This study evaluated experimentally-induced periapical bone loss sites using digital radiographic and histopathologic parameters. Material and Methods Twenty-seven Wistar rats were submitted to coronal opening of their mandibular right first molars. They were radiographed at 2, 15 and 30 days after the operative procedure by two digital radiographic storage phosphor plates (Digora®). The images were analyzed by creating a region of interest at the periapical region of each tooth (ImageJ) and registering the corresponding pixel values. After the sacrifice, the specimens were submitted to microscopic analysis in order to confirm the pulpal and periapical status of the tooth. Results There was significant statistically difference between the control and test sides in all the experimental periods regarding the pixel values (two-way ANOVA; p<0.05). Conclusions The microscopic analysis proved that a periapical disease development occurred during the experimental periods with an evolution from pulpal necrosis to periapical bone resorption. PMID:21922123

The effect of experimentally induced hypothyroidism on the isoflurane minimum alveolar concentration in dogs.

PubMed

Berry, Stephanie H; Panciera, David L

2015-01-01

To determine the effect of experimentally induced hypothyroidism on isoflurane (ISO) minimum alveolar concentration (MAC) in dogs. Prospective experimental study. Eighteen adult female mongrel dogs, age 2-4 years and weighing 8.2-13.1 kg. Hypothyroidism was induced in nine dogs by the intravenous administration of 1 mCi kg(-1) of (131) Iodine. The remaining nine dogs served as controls. Dogs were studied 9-12 months after the induction of hypothyroidism. Anesthesia was induced with ISO in oxygen via a mask. The trachea was intubated, and anesthesia was maintained using ISO in oxygen using a semi-closed rebreathing circle system. The dogs were mechanically ventilated to maintain an end-tidal carbon dioxide concentration between 35 and 45 mmHg. End-tidal ISO concentrations were measured with an infrared gas analyzer. The MAC was determined in duplicate using a tail clamp technique. The mean values for the groups were compared using a two sample t-test. The mean ± SD MAC of isoflurane in the hypothyroid and euthyroid dogs was 0.98 ± 0.31% and 1.11 ± 0.26%, respectively. The mean MAC of isoflurane in hypothyroid dogs was not significantly different from the mean MAC of isoflurane in the control dogs (p = 0.3553). The MAC of ISO in dogs was not significantly affected by experimentally induced hypothyroidism. The dose of ISO in dogs with hypothyroidism does not need to be altered. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Experimental invalidation of phase-transition-induced elastic softening in CrN

NASA Astrophysics Data System (ADS)

Wang, Shanmin; Yu, Xiaohui; Zhang, Jianzhong; Chen, Miao; Zhu, Jinlong; Wang, Liping; He, Duanwei; Lin, Zhijun; Zhang, Ruifeng; Leinenweber, Kurt; Zhao, Yusheng

2012-08-01

We report experimental results of phase stability and incompressibility of CrN. The obtained bulk moduli for cubic and orthorhombic CrN are 257 and 262 GPa, respectively. These results invalidate the conclusion of phase-transition-induced elastic softening recently reported based on nonmagnetic simulations for cubic CrN [Nature Mater.NMAACR1476-112210.1038/nmat2549 8, 947 (2009)]. On the other hand, they provide the only experimental evidence to support the computational models involving the local magnetic moment of Cr atoms [Nature Mater.NMAACR1476-112210.1038/nmat2722 9, 283 (2010)], indicating that atomic spin has a profound influence on the material's elastic properties. We also demonstrate that nonstoichiometry in CrNx has strong effects on its structural stability.

Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities.

PubMed

Koromilas, Christos; Liapi, Charis; Zarros, Apostolos; Stolakis, Vasileios; Tsagianni, Anastasia; Skandali, Nikolina; Al-Humadi, Hussam; Tsakiris, Stylianos

2014-06-01

Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological problems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na(+),K(+)-ATPase and Mg(2+)-ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation. As our findings regarding the pattern of effects that maternal hypothyroidism has on the above-mentioned crucial offspring brain enzyme activities are compared to those reported in the literature, several differences are revealed that could be attributed to both the mode of the experimental simulation approach followed as well as to the time-frames examined. These findings could provide the basis for a debate on the need of a more consistent experimental approach to hypothyroidism during neurodevelopment as well as for a further evaluation of the herein presented and discussed neurochemical (and, ultimately, neurodevelopmental) effects of experimentally-induced maternal hypothyroidism, in a brain region-specific manner. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

Inflammation-induced preterm lung maturation: lessons from animal experimentation.

PubMed

Moss, Timothy J M; Westover, Alana J

2017-06-01

Intrauterine inflammation, or chorioamnionitis, is a major contributor to preterm birth. Prematurity per se is associated with considerable morbidity and mortality resulting from lung immaturity but exposure to chorioamnionitis reduces the risk of neonatal respiratory distress syndrome (RDS) in preterm infants. Animal experiments have identified that an increase in pulmonary surfactant production by the preterm lungs likely underlies this decreased risk of RDS in infants exposed to chorioamnionitis. Further animal experimentation has shown that infectious or inflammatory agents in amniotic fluid exert their effects on lung development by direct effects within the developing respiratory tract, and probably not by systemic pathways. Differences in the effects of intrauterine inflammation and glucocorticoids demonstrate that canonical glucocorticoid-mediated lung maturation is not responsible for inflammation-induced changes in lung development. Animal experimentation is identifying alternative lung maturational pathways, and transgenic animals and cell culture techniques will allow identification of novel mechanisms of lung maturation that may lead to new treatments for the prevention of RDS. Copyright © 2016. Published by Elsevier Ltd.

Expectation-induced placebo responses fail to accelerate wound healing in healthy volunteers: results from a prospective controlled experimental trial.

PubMed

Vits, Sabine; Dissemond, Joachim; Schadendorf, Dirk; Kriegler, Lisa; Körber, Andreas; Schedlowski, Manfred; Cesko, Elvir

2015-12-01

Placebo responses have been shown to affect the symptomatology of skin diseases. However, expectation-induced placebo effects on wound healing processes have not been investigated yet. We analysed whether subjects' expectation of receiving an active drug accelerates the healing process of experimentally induced wounds. In 22 healthy men (experimental group, n = 11; control group, n = 11) wounds were induced by ablative laser on both thighs. Using a deceptive paradigm, participants in the experimental group were informed that an innovative 'wound gel' was applied on one of the two wounds, whereas a 'non-active gel' was applied on the wound of the other thigh. In fact, both gels were identical hydrogels without any active components. A control group was informed to receive a non-active gel on both wounds. Progress in wound healing was documented via planimetry on days 1, 4 and 7 after wound induction. From day 9 onwards wound inspections were performed daily accompanied by a change of the dressing and a new application of the gel. No significant differences could be observed with regard to duration or process of wound healing, either by intraindividual or by interindividual comparisons. These data document no expectation-induced placebo effect on the healing process of experimentally induced wounds in healthy volunteers. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Aerophagia induced by the nasal obstruction on experimental animals.

PubMed

Nakajima, K; Ohi, G

1977-04-01

The excessive accumulation of gas in the gastrointestinal tracts was invariably induced on experimental animals (mice, rats, guinea pigs, hamsters and rabbits) by simply obstructing nasal passages. The analysis of the gas showed the almost identical composition to the ambient air or flutus which was largely due to swallowed air. Also the numerous small foams were found on and underneath the epithelial lining of small intestine. The pathological evaluation was done both macroscopically and microscopically. Dying animals after nasal obstruction showed hemorrhagic and necrotic changes in the jejunum and ileum. This observation may cast some light to the pathogenesis of necrotizing enterocolitis in human neonatal.

Inflammation-induced pain sensitization in men and women: does sex matter in experimental endotoxemia?

PubMed Central

Wegner, Alexander; Elsenbruch, Sigrid; Rebernik, Laura; Roderigo, Till; Engelbrecht, Elisa; Jäger, Marcus; Engler, Harald; Schedlowski, Manfred; Benson, Sven

2015-01-01

Abstract A role of the innate immune system is increasingly recognized as a mechanism contributing to pain sensitization. Experimental administration of the bacterial endotoxin lipopolysaccharide (LPS) constitutes a model to study inflammation-induced pain sensitization, but all existing human evidence comes from male participants. We assessed visceral and musculoskeletal pain sensitivity after low-dose LPS administration in healthy men and women to test the hypothesis that women show greater LPS-induced hyperalgesia compared with men. In this randomized, double-blind, placebo-controlled crossover study, healthy men (n = 20) and healthy women using oral contraceptives (n = 20) received an intravenous injection of 0.4 ng/kg body weight LPS or placebo. Pain sensitivity was assessed with established visceral and musculoskeletal pain models (ie, rectal pain thresholds; pressure pain thresholds for different muscle groups), together with a heartbeat perception (interoceptive accuracy) task. Plasma cytokines (tumor necrosis factor-α and interleukin-6) were measured along with state anxiety at baseline and up to 6-hour postinjection. Lipopolysaccharide application led to significant increases in plasma cytokines and state anxiety and decreased interoceptive awareness in men and women (P < 0.001, condition effects), with more pronounced LPS-induced cytokine increases in women (P < 0.05, interaction effects). Although both rectal and pressure pain thresholds were significantly decreased in the LPS condition (all P < 0.05, condition effect), no sex differences in endotoxin-induced sensitization were observed. In summary, LPS-induced systemic immune activation leads to visceral and musculoskeletal hyperalgesia, irrespective of biological sex. These findings support the broad applicability of experimental endotoxin administration as a translational preclinical model of inflammation-induced pain sensitization in both sexes. PMID:26058036

Ethylenediaminetetraacetic acid induces antioxidant and anti-inflammatory activities in experimental liver fibrosis.

PubMed

González-Cuevas, J; Navarro-Partida, J; Marquez-Aguirre, A L; Bueno-Topete, M R; Beas-Zarate, C; Armendáriz-Borunda, J

2011-01-01

Experimental liver fibrosis induced by carbon tetrachloride (CCl(4)) is associated with oxidative stress, lipid peroxidation, and inflammation. This work was focused on elucidating the anti-inflammatory and antioxidant effects of ethylenediaminetetraacetic acid (EDTA) in this model of hepatotoxicity. Wistar male rats were treated with CCl(4) and EDTA (60, 120, or 240 mg/kg). Morphometric analyses were carried out in Masson's stained liver sections to determine fibrosis index. Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) were also determined. Gene expression for transforming growth factor beta (TGF-beta1), alpha1(I) procollagen gene (alpha1 Col I), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and superoxide dismutase (SOD) was monitored by real-time PCR. Antioxidant effect of EDTA was measured by its effects on lipid peroxidation; biological activity of ceruloplasmin (Cp), SOD, and catalase (Cat) were analyzed by zymography assays. Animals with CCl(4)-hepatic injury that received EDTA showed a decrement in fibrosis (20%) and lipid peroxidation (22%). The mRNA expression for TNF-alpha (55%), TGF-beta1 (50%), IL-6 (52%), and alpha1 Col I (60%) was also decreased. This group of animals showed increased Cp (62%) and SOD (25%) biological activities. Coagulation blood tests, Cat activity, and gene expression for SOD were not modified by EDTA treatment. This study demonstrates that EDTA treatment induces the activity of antioxidant enzymes, decreases lipid peroxidation, hepatic inflammation, and fibrosis in experimental liver fibrosis induced by CCl(4).

Role of Nigella sativa and Its Constituent Thymoquinone on Chemotherapy-Induced Nephrotoxicity: Evidences from Experimental Animal Studies

PubMed Central

Cascella, Marco; Palma, Giuseppe; Barbieri, Antonio; Bimonte, Sabrina; Amruthraj, Nagoth Joseph; Muzio, Maria Rosaria; del Vecchio, Vitale; Rea, Domenica; Falco, Michela; Luciano, Antonio; Arra, Claudio; Cuomo, Arturo

2017-01-01

Background: Most chemotherapeutic drugs are known to cause nephrotoxicity. Therefore, new strategies have been considered to prevent chemotherapy-induced nephrotoxicity. It is of note that Nigella sativa (NS), or its isolated compound Thymoquinone (TQ), has a potential role in combating chemotherapy-induced nephrotoxicity. AIM: To analyze and report the outcome of experimental animal studies on the protective effects of NS/TQ on chemotherapy-associated kidney complications. Design: Standard systematic review and narrative synthesis. Data Sources: MEDLINE, EMBASE databases were searched for relevant articles published up to March 2017. Additionally, a manual search was performed. Criteria for a study’s inclusion were: conducted in animals, systematic reviews and meta-analysis, containing data on nephroprotective effects of NS/TQ compared to a placebo or other substance. All strains and genders were included. Results: The database search yielded 71 studies, of which 12 (cisplatin-induced nephrotoxicity 8; methotrexate-induced nephrotoxicity 1; doxorubicin-induced nephrotoxicity 2; ifosfamide-induced nephrotoxicity 1) were included in this review. Conclusions: Experimental animal studies showed the protective effect of NS, or TQ, on chemotherapy-induced nephrotoxicity. These effects are caused by decreasing lipid peroxidation and increasing activity of antioxidant enzymes in renal tissue of chemotherapy-treated animals. PMID:28629150

A proposal for the experimental detection of CSL induced random walk

PubMed Central

Bera, Sayantani; Motwani, Bhawna; Singh, Tejinder P.; Ulbricht, Hendrik

2015-01-01

Continuous Spontaneous Localization (CSL) is one possible explanation for dynamically induced collapse of the wave-function during a quantum measurement. The collapse is mediated by a stochastic non-linear modification of the Schrödinger equation. A consequence of the CSL mechanism is an extremely tiny violation of energy-momentum conservation, which can, in principle, be detected in the laboratory via the random diffusion of a particle induced by the stochastic collapse mechanism. In a paper in 2003, Collett and Pearle investigated the translational CSL diffusion of a sphere, and the rotational CSL diffusion of a disc, and showed that this effect dominates over the ambient environmental noise at low temperatures and extremely low pressures (about ten-thousandth of a pico-Torr). In the present paper, we revisit their analysis and argue that this stringent condition on pressure can be relaxed, and that the CSL effect can be seen at the pressure of about a pico-Torr. A similar analysis is provided for diffusion produced by gravity-induced decoherence, where the effect is typically much weaker than CSL. We also discuss the CSL induced random displacement of a quantum oscillator. Lastly, we propose possible experimental set-ups justifying that CSL diffusion is indeed measurable with the current technology. PMID:25563619

[Mechanisms of opioid-induced overdose: experimental approach to clinical concerns].

PubMed

Baud, F-J

2009-09-01

The widely used term "overdose" denotes a toxic effect: opioid-induced intoxication and a mechanism: the poisoning results only from an overdose. Surprisingly, our understanding of the pathophysiology of this deadly complication is limited. In drug users, we attempted to: (1) improve knowledge of drug-induced respiratory effects; (2) clarify the mechanisms of drug interactions; (3) identify factors of variability and vulnerability. A prospective study of opioid overdoses confirmed that poisonings involving buprenorphine do exist. However, the mechanisms of buprenorphine poisoning are more complex than only an overdose, particularly the severity is less than that induced by heroin. In contrast, methadone overdose is life-threatening. Experimental studies addressed several clinical questions and also showed limited discrepancies. At pharmacological doses, opioids decrease the ventilatory response to CO(2). However, this effect does not account for the morbimortality of opioid poisonings. The mechanisms of opioid-induced morbimortality are different. Buprenorphine at doses near its median lethal dose did not induce acute respiratory failure as defined by a decrease in the partial pressure of oxygen in arterial blood (PaO(2)). In contrast, the combination of buprenorphine with flunitrazepam results in a decrease in PaO(2). This harmful interaction does not exist with other benzodiazepines in the rat, except for very high doses of nordazepam. The interaction results from a pharmacokinetic process. In contrast, methadone causes a dose-dependent decrease in PaO(2,) even significant before hypercapnia. We are assessing the relationships between on one hand alterations of ventilatory pattern and of arterial blood gas and on the other hand the different types of opiate receptors in the rats.

Aerobic exercise training without weight loss reduces dyspnea on exertion in obese women

PubMed Central

Bernhardt, Vipa; Stickford, Jonathon L.; Bhammar, Dharini M.; Babb, Tony G.

2015-01-01

Dyspnea on exertion (DOE) is a common symptom in obesity. We investigated whether aerobic exercise training without weight loss could reduce DOE. Twenty-two otherwise healthy obese women participated in a 12-week supervised aerobic exercise training program, exercising 30 min/day at 70–80% heart rate reserve, 4 days/week. Subjects were grouped based on their Ratings of Perceived Breathlessness (RPB) during constant load 60W cycling: +DOE (n = 12, RPB ≥ 4, 37 ± 7 years, 34 ± 4kg/m2) and −DOE (n = 10, RPB ≤ 2, 32 ± 6 years, 33 ± 3kg/m2). No significant differences between the groups in body composition, pulmonary function, or cardiorespiratory fitness were observed pre-training. Post-training, peak was improved significantly in both groups (+DOE: 12 ± 7, −DOE: 14 ± 8%). RPB was significantly decreased in the + DOE (4.7 ± 1.0–2.5 ± 1.0) and remained low in the −DOE group (1.2 ± 0.6–1.3 ± 1.0) (interaction p < 0.001). The reduction in RPB was not significantly correlated with the improvement in cardiorespiratory fitness. Aerobic exercise training improved cardiorespiratory fitness and DOE and thus appears to be an effective treatment for DOE in obese women. PMID:26593640

Global proteome profiling of dental cementum under experimentally-induced apposition.

PubMed

Salmon, Cristiane R; Giorgetti, Ana Paula O; Paes Leme, Adriana Franco; Domingues, Romênia R; Sallum, Enilson Antonio; Alves, Marcelo C; Kolli, Tamara N; Foster, Brian L; Nociti, Francisco H

2016-06-01

Dental cementum (DC) covers the tooth root and has important functions in tooth attachment and position. DC can be lost to disease, and regeneration is currently unpredictable due to limited understanding of DC formation. This study used a model of experimentally-induced apposition (EIA) in mice to identify proteins associated with new DC formation. Mandibular first molars were induced to super-erupt for 6 and 21days after extracting opposing maxillary molars. Decalcified and formalin-fixed paraffin-embedded mandible sections were prepared for laser capture microdissection. Microdissected protein extracts were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), and the data submitted to repeated measure ANOVA test (RM-ANOVA, alpha=5%). A total of 519 proteins were identified, with 97 (18.6%) proteins found exclusively in EIA sites and 50 (9.6%) proteins exclusively expressed in control sites. Fifty six (10.7%) proteins were differentially regulated by RM-ANOVA (p<0.05), with 24 regulated by the exclusive effect of EIA (12 proteins) or the interaction between EIA and time (12 proteins), including serpin 1a, procollagen C-endopeptidase enhancer, tenascin X (TNX), and asporin (ASPN). In conclusion, proteomic analysis demonstrated significantly altered protein profile in DC under EIA, providing new insights on DC biology and potential candidates for tissue engineering applications. Dental cementum (DC) is a mineralized tissue that covers the tooth root surface and has important functions in tooth attachment and position. DC and other periodontal tissues can be lost to disease, and regeneration is currently unpredictable due to lack of understanding of DC formation. This study used a model of experimentally-induced apposition (EIA) in mice to promote new cementum formation, followed by laser capture microdissection (LCM) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) proteomic analysis. This approach identified

Analytical and experimental study of flow phenomena in noncavitating rocket pump inducers

NASA Technical Reports Server (NTRS)

Lakshminarayana, B.

1981-01-01

The flow processes in rocket pump inducers are summarized. The experimental investigations were carried out with air as the test medium. The major characteristics features of the rocket pump inducers are low flow coefficient (0.05 to 0.2) large stagger angle (70 deg to 85 deg) and high solidity blades of little or no camber. The investigations are concerned with the effect of viscosity not the effects of cavitation. Flow visualization, conventional and hot wire probe measurement inside and at the exit of the blade passage, were the analytical methods used. The experiment was carried out using four three and two bladed inducers with cambered blades. Both the passage and the exit flow were measured. The basic research and boundary layer investigation was carried out using a helical flat plate (of some dimensions as the inducer blades tested), and flat plate helical inducer (four bladed). Detailed mean and turbulence flow field inside the passage as well as the exit of the rotor were derived from these measurement. The boundary layer, endwall, and other passage data reveal extremely complex nature of the flow, with major effects of viscosity present across the entire passage. Several analyses were carried out to predict the flow field in inducers. These included an approximate analysis, the shear pumping analysis, and a numerical solution of exact viscous equations with approximate modeling for the viscous terms.

An experimental setup to characterize MR switched gradient-induced potentials.

PubMed

Fokapu, Odette; El-Tatar, Aziz

2013-06-01

We have developed an experimental setup as an in vitro research tool for studying the contamination of electrophysiological signals (EPS) by MRI environment; particularly, when due to the switched gradient-induced potentials. The system is composed of: 1) a MRI compatible module for the transmission of the EPS into the MRI tunnel, 2) a gelatin-based tissue-mimicking phantom, placed inside the tunnel, in which EPS is injected, 3) a detection module composed of a five input channel MRI compatible transmitter placed inside the tunnel, allowing an on-site pre-amplification of the bio-potentials and their transmission, via an optical fiber cable, to a four filtered output per channel receiver (350 Hz, 160 Hz, 80 Hz, and 40 Hz, for a total of 20 channels) placed in the control room, and 4) a signal processing algorithm used to analyze the generated induced potentials. A set of tests were performed to validate the electronic performances of the setup. We also present in this work an interesting application of the setup, i.e., the acquisition and analysis of the induced potentials with respect of the slice orientation for a given MRI sequence. Significant modifications of the time and frequency characteristics were observed with respect to axial, coronal or sagittal orientations.

Regression of experimentally induced endometriosis with a new selective cyclooxygenase-2 enzyme inhibitor.

PubMed

Kilico, Ismail; Kokcu, Arif; Kefeli, Mehmet; Kandemir, Bedri

2014-01-01

Cyclooxygenase-2 (COX-2) levels increase in women with endometriosis. COX-2, via increasing prostaglandin E2, contributes to an increase in vascular endothelial growth factor. In this way, COX-2 may contribute to the progression and continuity of endometriosis. We investigated the effect of dexketoprofen trometamol, a new selective COX-2 enzyme inhibitor, on experimentally induced endometriotic cysts. Experimental endometriotic cysts were created in 60 adult female Wistar albino rats. The rats were randomized to 2 equal groups, a control (group Con) and a dexketoprofen (group Dex) group. Six weeks later, cyst volumes were measured as in vivo (volume 1). Following volume 1 measurement, for 4 weeks group Con received 0.1 ml distilled water; group Dex received 0.375 mg dexketoprofen trometamol/0.1 ml distilled water, intramuscularly, twice a day. At the end of administration, the cyst volumes were remeasured (volume 2), and the cysts totally excised and weighed. Glandular (GT) and stromal tissues (ST) and natural killer (NK) cell contents in the cyst wall were scored. NK cell content and volume 1 were not different between the 2 groups. Volume 2, cyst weight, and GT and ST contents in group Dex were significantly lower than those in group Con. Dexketoprofen trometamol significantly reduced the development of experimentally induced endometriotic cysts both macroscopically and microscopically.

Recombinant human acetylcholine receptor alpha-subunit induces chronic experimental autoimmune myasthenia gravis.

PubMed

Lennon, V A; Lambert, E H; Leiby, K R; Okarma, T B; Talib, S

1991-04-01

A synthetic gene encoding the 210 N-terminal residues of the alpha-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human alpha 1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 micrograms. With 6.6 to 22 micrograms, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 micrograms or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the alpha 1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.

Experimental investigation of flow induced dust acoustic shock waves in a complex plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jaiswal, S., E-mail: surabhijaiswal73@gmail.com; Bandyopadhyay, P.; Sen, A.

2016-08-15

We report on experimental observations of flow induced large amplitude dust-acoustic shock waves in a complex plasma. The experiments have been carried out in a Π shaped direct current glow discharge experimental device using kaolin particles as the dust component in a background of Argon plasma. A strong supersonic flow of the dust fluid is induced by adjusting the pumping speed and neutral gas flow into the device. An isolated copper wire mounted on the cathode acts as a potential barrier to the flow of dust particles. A sudden change in the gas flow rate is used to trigger themore » onset of high velocity dust acoustic shocks whose dynamics are captured by fast video pictures of the evolving structures. The physical characteristics of these shocks are delineated through a parametric scan of their dynamical properties over a range of flow speeds and potential hill heights. The observed evolution of the shock waves and their propagation characteristics are found to compare well with model numerical results based on a modified Korteweg-de-Vries-Burgers type equation.« less

Prognostic validation of the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index in inoperable non-small-cell lung cancer.

PubMed

Denehy, Linda; Hornsby, Whitney E; Herndon, James E; Thomas, Samantha; Ready, Neal E; Granger, Catherine L; Valera, Lauren; Kenjale, Aarti A; Eves, Neil D; Jones, Lee W

2013-12-01

To investigate the prognostic utility of the body mass index, severity of airflow obstruction, measures of exertional dyspnea, and exercise capacity (BODE) index in patients with inoperable non-small-cell lung cancer (NSCLC). One hundred consecutive patients with inoperable NSCLC and performance status 0 to 3 completed pulmonary function testing, the modified Medical Research Council dyspnea scale, a 6-minute walk test, and body mass index-the multidimensional 10-point BODE index. Cox proportional models were used to estimate the risk of all-cause mortality according to the BODE index with or without adjustment for traditional prognostic factors. Median follow-up was 31.5 months; 61 deaths (61%) were reported during this period. There was a significant univariate association between the BODE index score and mortality (adjusted p(trend) = 0.027). Compared with patients with a BODE index of 0, the adjusted hazard ratio for risk of death was 1.37 (95% confidence interval [CI], 0.74-2.55) for a BODE index of 1, 1.22 (95% CI, 0.45-3.25) for a BODE index of 2, and 2.44 (95% CI, 1.19-4.99) for a BODE index more than 2. The BODE index provided incremental prognostic information beyond that provided traditional markers of prognosis (adjusted p(trend) = 0.051). Every one-point increase in the BODE index, the risk of death increased by 25% (hazard ratio = 1.25; 95% CI, 1.27-4.64). The BODE index is a strong independent predictor of survival in inoperable NSCLC beyond traditional risk factors. Use of this multidimensional tool may improve risk stratification and prognostication in NSCLC.

Swimming-induced pulmonary oedema an uncommon condition diagnosed with POCUS ultrasound.

PubMed

Alonso, Joaquín Valle; Chowdhury, Motiur; Borakati, Raju; Gankande, Upali

2017-12-01

Swimming Induced Pulmonary Edema, or SIPE, is an emerging condition occurring in otherwise healthy individuals during surface swimming or diving that is characterized by cough, dyspnea, hemoptysis, and hypoxemia. It is typically found in those who spend time in cold water exercise with heavy swimming and surface swimming, such as civilian training for iron Man, triathalon, and military training. We report the case of a highly trained young female swimmer in excellent cardiopulmonary health, who developed acute alveolar pulmonary oedema in an open water swimming training diagnosed in the emergency department using POCUS ultrasound. Copyright © 2017 Elsevier Inc. All rights reserved.

Exercise during cardiac catheterization distinguishes between pulmonary and left ventricular causes of dyspnea in systemic sclerosis patients.

PubMed

Hager, W David; Collins, Irina; Tate, Janet P; Azrin, Michael; Foley, Raymond; Lakshminarayanan, Santha; Rothfield, Naomi F

2013-07-01

The cause for shortness of breath among systemic sclerosis (SSc) patients is often lacking. We sought to characterize the hemodynamics of these patients by using simple isotonic arm exercise during cardiac catheterization. Catheterization was performed in 173 SSc patients when resting echocardiographic pulmonary systolic pressures were <40 but >40 mmHg post stress. Patients with resting mean pulmonary arterial pressures (mPAP) ≤ 25 and pulmonary arterial wedge pressures (PAWP) ≤ 15 mmHg exercised with 1-pound hand weights. Normal exercise was defined as a change in mPAP divided by the change in cardiac output (CO) (ΔmPAP/ΔCO) ratio ≤ 2 for patients <50 years (≤3 for >50). An abnormal ΔmPAP/ΔCO ratio, an exercise transpulmonary gradient (TPG) ≥ 15, a PAWP < 20, a ΔTPG > ΔPAWP and a pulmonary vascular resistance (PVR) which increased defined exercise-induced pulmonary arterial hypertension (EIPAH). An abnormal ΔmPAP/ΔCO ratio, an exercise TPG < 15, a PAWP ≥ 20, a ΔTPG < ΔPAWP and a drop in PVR defined left ventricular diastolic dysfunction (DD). Twelve patients without SSc served as controls. Pulmonary pressures increased with exercise in 53 patients. Six had EIPAH and 47 had DD. With exercise, mPAP and PAWP were 20 ± 4 and 13 ± 2 in controls, 36 ± 3 and 12 ± 4 in EIPAH and 34 ± 6 and 26 ± 4 in DD. Control ΔmPAP/ΔCO was 0.8 ± 0.7, 7.5 ± 3.9 in EIPAH and 9.1 ± 7.2 in DD. Rest and exercise TPG was normal for control and DD patients but increased (12 ± 4 to 23 ± 4) in EIPAH (P < 0.0001). PVR decreased in DD but increased in EIPAH with exercise. Exercise during catheterization elucidates the pathophysiology of dyspnea and distinguishes EIPAH from the more common DD in SSc patients. © 2012 John Wiley & Sons Ltd.

The effect of various drugs on experimentally induced ulcers in immobilized rats

NASA Technical Reports Server (NTRS)

Schramm, H.

1978-01-01

Experiments related to the importance of functional disorders in the central nervous system in connection with stomach diseases were performed on Wistar rats. Assuming that severe mental strains may be triggering factors for such disorders, testing of the effects of different drugs on experimentally induced ulcers in these rats was done. The immobilization method described by Bonfils was used. Particular importance was placed on the sex related difference which appeared.

An experimental/computational study of sharp fin induced shock wave/turbulent boundary layer interactions at Mach 5 - Experimental results

NASA Technical Reports Server (NTRS)

Rodi, Patrick E.; Dolling, David S.

1992-01-01

A combined experimental/computational study has been performed of sharp fin induced shock wave/turbulent boundary layer interactions at Mach 5. The current paper focuses on the experiments and analysis of the results. The experimental data include mean surface heat transfer, mean surface pressure distributions and surface flow visualization for fin angles of attack of 6, 8, 10, 12, 14 and 16-degrees at Mach 5 under a moderately cooled wall condition. Comparisons between the results and correlations developed earlier show that Scuderi's correlation for the upstream influence angle (recast in a conical form) is superior to other such correlations in predicting the current results, that normal Mach number based correlations for peak pressure heat transfer are adequate and that the initial heat transfer peak can be predicted using pressure-interaction theory.

Polymethoxy flavonoids, nobiletin and tangeretin, prevent lipopolysaccharide-induced inflammatory bone loss in an experimental model for periodontitis.

PubMed

Tominari, Tsukasa; Hirata, Michiko; Matsumoto, Chiho; Inada, Masaki; Miyaura, Chisato

2012-01-01

Nobiletin, a polymethoxy flavonoid (PMF), inhibits systemic bone resorption and maintains bone mass in estrogen-deficient ovariectomized mice. This study examined the anti-inflammatory effects of PMFs, nobiletin, and tangeretin on lipopolysaccharide (LPS)-induced bone resorption. Nobiletin and tangeretin suppressed LPS-induced osteoclast formation and bone resorption and suppressed the receptor activator of NFκB ligand-induced osteoclastogenesis in RAW264.7 macrophages. Nobiletin clearly restored the alveolar bone mass in a mouse experimental model for periodontitis by inhibiting LPS-induced bone resorption. PMFs may therefore provide a new therapeutic approach for periodontal bone loss.

Experimental Gingivitis Induces Systemic Inflammatory Markers in Young Healthy Individuals: A Single-Subject Interventional Study

PubMed Central

Luchtefeld, Maren; Heuer, Wieland; Schuett, Harald; Divchev, Dimitar; Scherer, Ralph; Schmitz-Streit, Ruth; Langfeldt, Daniela; Stumpp, Nico; Staufenbiel, Ingmar

2013-01-01

Objectives We here investigated whether experimental gingivitis enhances systemic markers of inflammation which are also known as surrogate markers of atherosclerotic plaque development. Background Gingivitis is a low-level oral infection induced by bacterial deposits with a high prevalence within Western populations. A potential link between the more severe oral disease periodontitis and cardiovascular disease has already been shown. Methods 37 non-smoking young volunteers with no inflammatory disease or any cardiovascular risk factors participated in this single-subject interventional study with an intra-individual control. Intentionally experimental oral inflammation was induced by the interruption of oral hygiene for 21 days, followed by a 21-days resolving phase after reinitiation of oral hygiene. Primary outcome measures at baseline, day 21 and 42 were concentrations of hsCRP, IL-6, and MCP-1, as well as adhesion capacity and oxLDL uptake of isolated blood monocytes. Results The partial cessation of oral hygiene procedures was followed by the significant increase of gingival bleeding (34.0%, P<0.0001). This local inflammation was associated with a systemic increase in hsCRP (0.24 mg/L, P = 0.038), IL-6 (12.52 ng/L, P = 0.0002) and MCP-1 (9.10 ng/l, P = 0.124) in peripheral blood samples between baseline and day 21, which decreased at day 42. Monocytes showed an enhanced adherence to endothelial cells and increased foam cell formation after oxLDL uptake (P<0.050) at day 21 of gingivitis. Conclusions Bacterial-induced gingival low-level inflammation induced a systemic increase in inflammatory markers. Dental hygiene almost completely reversed this experimental inflammatory process, suggesting that appropriate dental prophylaxis may also limit systemic markers of inflammation in subjects with natural gingivitis. International Clinical Trials Register Platform of the World Health Organization, registry number: DRKS00003366, URL: http

Experimental realization of an on-chip all-optical analogue to electromagnetically induced transparency.

PubMed

Xu, Qianfan; Sandhu, Sunil; Povinelli, Michelle L; Shakya, Jagat; Fan, Shanhui; Lipson, Michal

2006-03-31

We provide the first experimental observation of structure tuning of the electromagnetically induced transparency-like spectrum in integrated on-chip optical resonator systems. The system consists of coupled silicon ring resonators with 10 microm diameter on silicon, where the coherent interference between the two coupled resonators is tuned. We measured a transparency-resonance mode with a quality factor of 11,800.

Experimental coronary sclerosis induced by immobilization of rabbits: A new model of arteriosclerosis

NASA Technical Reports Server (NTRS)

Tyavokin, V. V.; Tjawokin, W. W.

1980-01-01

A new method for producing arteriosclerosis with coronary insufficiency in rabbits by means of immobilization is described and discussed. The experimentally induced atherosclerosis develops due to hypodynamics imposed by the reduced muscular activity without overloading with exogenous cholesterol. The atherosclerosis and coronary insufficiency are associated. With variations in the duration and extent of immobilization, coronary insufficiency alone or with atherosclerosis can be produced.

Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia.

PubMed

Hemanth Kumar, Boyina; Arun Reddy, Ravula; Mahesh Kumar, Jerald; Dinesh Kumar, B; Diwan, Prakash V

2017-01-01

This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.

Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins.

PubMed

Morimoto, A; Nakamori, T; Watanabe, T; Ono, T; Murakami, N

1988-04-01

To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1 alpha (IL-1), and prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2 alpha had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2 alpha and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.

DETECTORS AND EXPERIMENTAL METHODS: Equivalent properties of single event burnout induced by different sources

NASA Astrophysics Data System (ADS)

Yang, Shi-Yu; Cao, Zhou; Da, Dao-An; Xue, Yu-Xiong

2009-05-01

The experimental results of single event burnout induced by heavy ions and 252Cf fission fragments in power MOSFET devices have been investigated. It is concluded that the characteristics of single event burnout induced by 252Cf fission fragments is consistent to that in heavy ions. The power MOSFET in the “turn-off" state is more susceptible to single event burnout than it is in the “turn-on" state. The thresholds of the drain-source voltage for single event burnout induced by 173 MeV bromine ions and 252Cf fission fragments are close to each other, and the burnout cross section is sensitive to variation of the drain-source voltage above the threshold of single event burnout. In addition, the current waveforms of single event burnouts induced by different sources are similar. Different power MOSFET devices may have different probabilities for the occurrence of single event burnout.

Aromatase inhibitors decrease radiation-induced lung fibrosis: Results of an experimental study.

PubMed

Altinok, A Y; Yildirim, S; Altug, T; Sut, N; Ober, A; Ozsahin, E M; Azria, D; Bese, N S

2016-08-01

In experimental and clinical trials, tamoxifen (TAM) has been shown to increase radiation-induced lung fibrosis (RILF). Furthermore, aromatase inhibitors (AI) have been shown to be superior to TAM in the adjuvant setting and preclinical data suggest that letrozole (LET) sensitizes breast cancer cells to ionizing radiation in other studies. In this experimental study, we evaluated whether AI have any impact on the development of RILF in rats. 60 female wistar- albino rats were divided into 6 groups: Control (group A), RT alone (group B), RT + TAM (group C), RT + anastrozole (ANA group D), RT + LET (group E), and RT + exemestane (EXE, group F). RT consisted of 30 Gy in 10 fractions to both lungs with an anterior field at 2 cm depth. Equivalent doses for 60 kg adult dose per day of TAM, ANA, LET, and EXE were calculated according to the mean weight of rats and orally administrated with a feeding tube. Percentage of lung with fibrosis was quantified with image analysis of histological sections of the lung. The mean score values were calculated for each group. the significance of the differences among groups were calculated using one way ANOVA test and Tukey HSD post-hoc test. Mean values of fibrosis were 1.7, 5.9, 6.7, 2.5, 2 and 2.2 for groups A, B, C, D, E, and F, respectively (p = 0.000). TAM increased RT-induced lung fibrosis but without statistical significance. Groups treated with RT + AI showed significantly less lung fibrosis than groups treated with RT alone or RT + TAM (p = 0.000). RT + AI groups showed nearly similar RT-induced lung fibrosis than control group. In this study, we found that AI decreased RT-induced lung fibrosis to the control group level suggesting protective effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Effect of Capsicum annum L (pucunucho, ají mono) in gastric ulcer experimentally induced in rats].

PubMed

Delgado Montero, Rocío; Flores Cortez, Daisy; Villalobos Pacheco, Eduardo

2015-01-01

To examine the effects of the Capsicum annum L lyophilized fruit extract in experimentally-induced gastric ulcer in rats. We used the model of indomethacin gastric ulcer-induced and the gastric ulcer model induced by pylorus ligation in rats. The rats were divided in five treatment groups as follow: G1: Distilled water 1 ml/Kg; G2: Ranitidine 50 mg/kg, G3: Capsicum 10mg/kg, G4: Capsicum 100 mg/kg, G5: Capsicum 1000 mg/kg. The results of the first model showed an ulcer inhibition of 60,4% and 66,7% using the doses of Capsicum at 10 mg/kg and 100 mg/kg, respectively. The results of the second model showed that neither the pH nor the volume of the gastric content were modified by the administered extract (p >0.05); however, by using the doses of Capsicum at 100 mg/kg and 1000 mg/kg, there was clearly an ulcer inhibition of 75.59% and 81.63% respectively, which were even greater than the inhibition obtained by ranitidine (75.51%). Therefore, in this experiment we demonstrated that the Capsicum annum L lyophilized fruit extract has a gastroprotective effect in experimentally-induced gastric ulcer in rats.

Clinical and Experimental Evidences of Hydrogen Sulfide Involvement in Lead-Induced Hypertension

PubMed Central

Possomato-Vieira, José Sérgio; do Nascimento, Regina Aparecida; Wandekin, Rodrigo Roldão; Caldeira-Dias, Mayara; Chimini, Jessica Sabbatine; da Silva, Maria Luiza Santos

2018-01-01

Lead- (Pb-) induced hypertension has been shown in humans and experimental animals and cardiovascular effects of hydrogen sulfide (H2S) have been reported previously. However, no studies examined involvement of H2S in Pb-induced hypertension. We found increases in diastolic blood pressure and mean blood pressure in Pb-intoxicated humans followed by diminished H2S plasmatic levels. In order to expand our findings, male Wistar rats were divided into four groups: Saline, Pb, NaHS, and Pb + NaHS. Pb-intoxicated animals received intraperitoneally (i.p.) 1st dose of 8 μg/100 g of Pb acetate and subsequent doses of 0.1 μg/100 g for seven days and sodium hydrosulfide- (NaHS-) treated animals received i.p. NaHS injections (50 μmol/kg/twice daily) for seven days. NaHS treatment blunted increases in systolic blood pressure, increased H2S plasmatic levels, and diminished whole-blood lead levels. Treatment with NaHS in Pb-induced hypertension seems to induce a protective role in rat aorta which is dependent on endothelium and seems to promote non-NO-mediated relaxation. Pb-intoxication increased oxidative stress in rats, while treatment with NaHS blunted increases in plasmatic MDA levels and increased antioxidant status of plasma. Therefore, H2S pathway may be involved in Pb-induced hypertension and treatment with NaHS exerts antihypertensive effect, promotes non-NO-mediated relaxation, and decreases oxidative stress in rats with Pb-induced hypertension. PMID:29789795

An experimental infection model to induce digital dermatitis infection in cattle.

PubMed

Gomez, A; Cook, N B; Bernardoni, N D; Rieman, J; Dusick, A F; Hartshorn, R; Socha, M T; Read, D H; Döpfer, D

2012-04-01

Bovine digital dermatitis (DD), also known as papillomatous digital dermatitis (foot warts), has been recognized as a major cause of lameness in cattle, with important economic and welfare consequences. The evaluation of therapeutic and preventive interventions aiming to control DD infections in dairy cattle is often challenged by the complex multifactorial etiology of the disease. An experimental infection model to induce acute DD lesions in a controlled environment is proposed. The goal was to provide a standard way of reproducing DD infections independent of external factors that could confound the natural course of the disease, such as management practices or infection pressure, resulting in transmission of DD between animals. A group of 4 yearling Holstein heifers free of any clinical evidence of hoof disease was recruited from a commercial dairy farm and housed in an experimental facility in 1 pen with slatted flooring. The hind feet were wrapped to mimic conditions of prolonged moisture (maceration) and reduced access to air (closure) and inoculated at the heel and dewclaw areas with a homogenate of a naturally occurring DD lesion skin biopsy or a culture broth of Treponema spp. After a period of 12 to 25 d, 4 of 6 and 1 of 4 dewclaw areas inoculated with biopsied DD lesion or a Treponema spp. culture, respectively, had gross lesions compatible with DD. Histopathology confirmed the gross diagnosis in the sites inoculated with tissue homogenate. In the site inoculated with Treponema spp. culture broth, histopathology revealed an incipient DD lesion. Treponema spp. were detected by PCR in both naturally occurring DD homogenate and Treponema spp. culture broth inoculation sites. An experimental infection model to induce acute DD in cattle was developed, which may be used to evaluate interventions to control DD and study the pathogenesis of this infectious hoof disease in a controlled manner. Copyright © 2012 American Dairy Science Association. Published by

A Computational and Experimental Study of Nonlinear Aspects of Induced Drag

NASA Technical Reports Server (NTRS)

Smith, Stephen C.

1996-01-01

performance of the split-tip wing was also investigated by wing tunnel experiments. Induced drag was determined from force measurements by subtracting the estimated viscous drag, and from an analytical drag-decomposition method using a wake survey. The experimental results confirm the computational prediction.

Marginal biotin deficiency can be induced experimentally in humans using a cost-effective outpatient design.

PubMed

Stratton, Shawna L; Henrich, Cindy L; Matthews, Nell I; Bogusiewicz, Anna; Dawson, Amanda M; Horvath, Thomas D; Owen, Suzanne N; Boysen, Gunnar; Moran, Jeffery H; Mock, Donald M

2012-01-01

To date, marginal, asymptomatic biotin deficiency has been successfully induced experimentally by the use of labor-intensive inpatient designs requiring rigorous dietary control. We sought to determine if marginal biotin deficiency could be induced in humans in a less expensive outpatient design incorporating a self-selected, mixed general diet. We sought to examine the efficacy of three outpatient study designs: two based on oral avidin dosing and one based on a diet high in undenatured egg white for a period of 28 d. In study design 1, participants (n = 4; 3 women) received avidin in capsules with a biotin binding capacity of 7 times the estimated dietary biotin intake of a typical self-selected diet. In study design 2, participants (n = 2; 2 women) received double the amount of avidin capsules (14 times the estimated dietary biotin intake). In study design 3, participants (n = 5; 3 women) consumed egg-white beverages containing avidin with a biotin binding capacity of 7 times the estimated dietary biotin intake. Established indices of biotin status [lymphocyte propionyl-CoA carboxylase activity; urinary excretion of 3-hydroxyisovaleric acid, 3-hydroxyisovaleryl carnitine (3HIA-carnitine), and biotin; and plasma concentration of 3HIA-carnitine] indicated that study designs 1 and 2 were not effective in inducing marginal biotin deficiency, but study design 3 was as effective as previous inpatient study designs that induced deficiency by egg-white beverage. Marginal biotin deficiency can be induced experimentally by using a cost-effective outpatient design by avidin delivery in egg-white beverages. This design should be useful to the broader nutritional research community.

Influence of intramuscular granisetron on experimentally induced muscle pain by acidic saline.

PubMed

Louca, S; Ernberg, M; Christidis, N

2013-06-01

The aim of this study was to investigate whether intramuscular administration of the 5-HT(3) receptor antagonist granisetron reduces experimental muscle pain induced by repeated intramuscular injections of acidic saline into the masseter muscles. Twenty-eight healthy and pain-free volunteers, fourteen women and fourteen men participated in this randomized, double-blind and placebo-controlled study. After a screening examination and registration of the baseline pressure-pain threshold (PPT), the first simultaneous bilateral injections of 0·5 mL acidic saline (9 mg mL(-1) , pH 3·3) into the masseter muscles were performed. Two days later, PPT and pain (VAS) were re-assessed. The masseter muscle was then pre-treated with 0·5 mL granisetron (Kytril(®) 1 mg mL(-1) pH 5·3) on one side and control substance (isotonic saline, 9 mg mL(-1) pH 6) on the contralateral side. Two minutes thereafter a bilateral simultaneous injection of 0·5 mL acidic saline followed. The evoked pain intensity, pain duration, pain area and PPT were assessed. The volunteers returned 1 week later to re-assess VAS and PPT. On the side pre-treated with granisetron, the induced pain had significantly lower intensity and shorter duration (P < 0·05) compared with the side pre-treated with control. A subgroup analysis showed that the effect of granisetron on pain duration was significant only in women (P < 0·001), while the effect on peak pain and pain area were significant in both sexes. The results showed no significant change in PPT. In conclusion, these results indicate that granisetron has a pain-reducing effect on experimentally induced muscle pain by repeated acidic saline injection. © 2013 John Wiley & Sons Ltd.

Effects of Experimental Sarcocystis neurona-Induced Infection on Immunity in an Equine Model

PubMed Central

Lewis, S. Rochelle; Ellison, Siobhan P.; Dascanio, John J.; Lindsay, David S.; Gogal, Robert M.; Werre, Stephen R.; Surendran, Naveen; Breen, Meghan E.; Heid, Bettina M.; Andrews, Frank M.; Buechner-Maxwell, Virginia A.; Witonsky, Sharon G.

2014-01-01

Sarcocystis neurona is the most common cause of Equine Protozoal Myeloencephalitis (EPM), affecting 0.5–1% horses in the United States during their lifetimes. The objective of this study was to evaluate the equine immune responses in an experimentally induced Sarcocystis neurona infection model. Neurologic parameters were recorded prior to and throughout the 70-day study by blinded investigators. Recombinant SnSAG1 ELISA for serum and CSF were used to confirm and track disease progression. All experimentally infected horses displayed neurologic signs after infection. Neutrophils, monocytes, and lymphocytes from infected horses displayed significantly delayed apoptosis at some time points. Cell proliferation was significantly increased in S. neurona-infected horses when stimulated nonspecifically with PMA/I but significantly decreased when stimulated with S. neurona compared to controls. Collectively, our results suggest that horses experimentally infected with S. neurona manifest impaired antigen specific response to S. neurona, which could be a function of altered antigen presentation, lack of antigen recognition, or both. PMID:26464923

Effects of Experimental Sarcocystis neurona-Induced Infection on Immunity in an Equine Model.

PubMed

Lewis, S Rochelle; Ellison, Siobhan P; Dascanio, John J; Lindsay, David S; Gogal, Robert M; Werre, Stephen R; Surendran, Naveen; Breen, Meghan E; Heid, Bettina M; Andrews, Frank M; Buechner-Maxwell, Virginia A; Witonsky, Sharon G

2014-01-01

Sarcocystis neurona is the most common cause of Equine Protozoal Myeloencephalitis (EPM), affecting 0.5-1% horses in the United States during their lifetimes. The objective of this study was to evaluate the equine immune responses in an experimentally induced Sarcocystis neurona infection model. Neurologic parameters were recorded prior to and throughout the 70-day study by blinded investigators. Recombinant SnSAG1 ELISA for serum and CSF were used to confirm and track disease progression. All experimentally infected horses displayed neurologic signs after infection. Neutrophils, monocytes, and lymphocytes from infected horses displayed significantly delayed apoptosis at some time points. Cell proliferation was significantly increased in S. neurona-infected horses when stimulated nonspecifically with PMA/I but significantly decreased when stimulated with S. neurona compared to controls. Collectively, our results suggest that horses experimentally infected with S. neurona manifest impaired antigen specific response to S. neurona, which could be a function of altered antigen presentation, lack of antigen recognition, or both.

Experimental investigation on the characteristics of supersonic fuel spray and configurations of induced shock waves.

PubMed

Wang, Yong; Yu, Yu-Song; Li, Guo-Xiu; Jia, Tao-Ming

2017-01-05

The macro characteristics and configurations of induced shock waves of the supersonic sprays are investigated by experimental methods. Visualization study of spray shape is carried out with the high-speed camera. The macro characteristics including spray tip penetration, velocity of spray tip and spray angle are analyzed. The configurations of shock waves are investigated by Schlieren technique. For supersonic sprays, the concept of spray front angle is presented. Effects of Mach number of spray on the spray front angle are investigated. The results show that the shape of spray tip is similar to blunt body when fuel spray is at transonic region. If spray entered the supersonic region, the oblique shock waves are induced instead of normal shock wave. With the velocity of spray increasing, the spray front angle and shock wave angle are increased. The tip region of the supersonic fuel spray is commonly formed a cone. Mean droplet diameter of fuel spray is measured using Malvern's Spraytec. Then the mean droplet diameter results are compared with three popular empirical models (Hiroyasu's, Varde's and Merrigton's model). It is found that the Merrigton's model shows a relative good correlation between models and experimental results. Finally, exponent of injection velocity in the Merrigton's model is fitted with experimental results.

Experimental febrile seizures induce age-dependent structural plasticity and improve memory in mice.

PubMed

Tao, K; Ichikawa, J; Matsuki, N; Ikegaya, Y; Koyama, R

2016-03-24

Population-based studies have demonstrated that children with a history of febrile seizure (FS) perform better than age-matched controls at hippocampus-dependent memory tasks. Here, we report that FSs induce two distinct structural reorganizations in the hippocampus and bidirectionally modify future learning abilities in an age-dependent manner. Compared with age-matched controls, adult mice that had experienced experimental FSs induced by hyperthermia (HT) on postnatal day 14 (P14-HT) performed better in a cognitive task that requires dentate granule cells (DGCs). The enhanced memory performance correlated with an FS-induced persistent increase in the density of large mossy fiber terminals (LMTs) of the DGCs. The memory enhancement was not observed in mice that had experienced HT-induced seizures at P11 which exhibited abnormally located DGCs in addition to the increased LMT density. The ectopic DGCs of the P11-HT mice were abolished by the diuretic bumetanide, and this pharmacological treatment unveiled the masked memory enhancement. Thus, this work provides a novel basis for age-dependent structural plasticity in which FSs influence future brain function. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Experimentally induced chocolate craving leads to an attentional bias in increased distraction but not in speeded detection.

PubMed

Smeets, Elke; Roefs, Anne; Jansen, Anita

2009-12-01

In the present study, the causal influence of chocolate craving on attentional bias for chocolate-related information was examined by experimentally inducing chocolate craving in a sample of high trait chocolate cravers vs. low trait chocolate cravers. A sample of 35 high trait chocoholics and 33 low trait chocolate cravers were randomly assigned to either the exposure condition in which craving was manipulated or the non-exposure condition. To measure attentional bias, a pictorial version of the visual search paradigm [Smeets, E., Roefs, A., van Furth, E., & Jansen, A. (2008). Attentional bias for body and food in eating disorders: increased distraction, speeded detection, or both? Behaviour Research and Therapy, 46, 229-238] was used, assessing two components: distraction and detection. It was found that experimentally induced chocolate craving led to increased distraction by chocolate pictures in the high trait chocolate cravers, in comparison to the low trait chocolate cravers. Moreover, this measure of distraction correlated strongly with self-reported craving, but only in the chocoholics and in the exposure condition. In the non-exposure condition, high trait chocolate cravers showed speeded detection of chocolate pictures relative to non-chocoholics, but this component did not correlate with self-reported craving. It is concluded that experimentally induced craving for chocolate causes a bias in, specifically the increased distraction component of attention in high trait chocolate cravers.

Exercise-associated Excessive Dynamic Airway Collapse in Military Personnel.

PubMed

Weinstein, Daniel J; Hull, James E; Ritchie, Brittany L; Hayes, Jackie A; Morris, Michael J

2016-09-01

Evaluation of military personnel for exertional dyspnea can present a diagnostic challenge, given multiple unique factors that include wide variation in military deployment. Initial consideration is given to common disorders such as asthma, exercise-induced bronchospasm, and inducible laryngeal obstruction. Excessive dynamic airway collapse has not been reported previously as a cause of dyspnea in these individuals. To describe the clinical and imaging characteristics of military personnel with exertional dyspnea who were found to have excessive dynamic collapse of large airways during exercise. After deployment to Afghanistan or Iraq, 240 active U.S. military personnel underwent a standardized evaluation to determine the etiology of persistent dyspnea on exertion. Study procedures included full pulmonary function testing, impulse oscillometry, exhaled nitric oxide measurement, methacholine challenge testing, exercise laryngoscopy, cardiopulmonary exercise testing, and fiberoptic bronchoscopy. Imaging included high-resolution computed tomography with inspiratory and expiratory views. Selected individuals underwent further imaging with dynamic computed tomography. A total of five men and one woman were identified as having exercise-associated excessive dynamic airway collapse on the basis of the following criteria: (1) exertional dyspnea without resting symptoms, (2) focal expiratory wheezing during exercise, (3) functional collapse of the large airways during bronchoscopy, (4) expiratory computed tomographic imaging showing narrowing of a large airway, and (5) absence of underlying apparent pathology in small airways or pulmonary parenchyma. Identification of focal expiratory wheezing correlated with bronchoscopic and imaging findings. Among 240 military personnel evaluated after presenting with postdeployment exertional dyspnea, a combination of symptoms, auscultatory findings, imaging, and visualization of the airways by bronchoscopy identified six individuals

Protective effect of proanthocyanidins on endotoxin induced experimental periodontitis in rats.

PubMed

Govindaraj, Jayamathi; Emmadi, Pamela; Deepalakshmi; Rajaram, Vijayalakshmi; Prakash, Geetha; Puvanakrishnan, Rengarajulu

2010-02-01

The pathogenesis of periodontitis involves anaerobic oral bacteria as well as the host response to infection and several drugs have been developed which can curtail these deleterious effects. Proanthocyanidin, a novel flavanoid extracted from grape seeds, has been shown to provide a significant therapeutic effect on endotoxin (Escherichia coli) induced experimental periodontitis in rats. In this study, protective action of different doses of proanthocyanidins was investigated in blood by assaying the reactive oxygen species such as hydrogen peroxide, superoxide anion, myeloperoxidase and lipid peroxides, lysosomal enzyme activities such as cathepsin B, cathepsin D, beta-glucuronidase and acid phosphatase, nonenzymatic antioxidants such as ascorbic acid, alpha-tocopherol, ceruloplasmin, reduced glutathione and antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione-s-transferase. Experimental periodontitis rats showed a reduction in body weight and body weight gain could be noticed when they were administered proanthocyanidins. The levels of reactive oxygen species and lysosomal enzymes were found to increase whereas antioxidant levels were decreased significantly in experimental periodontitis. Proanthocyanidins at an effective dose of 30 mg/kg body weight, sc, for 30 days effected a decrease in serum reactive oxygen species, lipid peroxides, lysosomal enzymes, acute phase proteins and an increase in antioxidant levels. Histopathological evidence of experimental periodontitis showed cellular infiltration of inflammatory cells while proanthocyanidin treated groups demonstrated only scattered inflammatory cells and blood vessels. Thus, the results showed that dietary supplementation of proanthocyanidin enhanced the host resistance as well as the inhibition of the biological and mechanical irritants involved in the onset of gingivitis and the progression of periodontal disease.

Experimental investigation of effective parameters on signal enhancement in spark assisted laser induced breakdown spectroscopy

NASA Astrophysics Data System (ADS)

Hassanimatin, M. M.; Tavassoli, S. H.

2018-05-01

A combination of electrical spark and laser induced breakdown spectroscopy (LIBS), which is called spark assisted LIBS (SA-LIBS), has shown its capability in plasma spectral emission enhancement. The aim of this paper is a detailed study of plasma emission to determine the effect of plasma and experimental parameters on increasing the spectral signal. An enhancement ratio of SA-LIBS spectral lines compared with LIBS is theoretically introduced. The parameters affecting the spectral enhancement ratio including ablated mass, plasma temperature, the lifetime of neutral and ionic spectral lines, plasma volume, and electron density are experimentally investigated and discussed. By substitution of the effective parameters, the theoretical spectral enhancement ratio is calculated and compared with the experimental one. Two samples of granite as a dielectric and aluminum as a metal at different laser pulse energies are studied. There is a good agreement between the calculated and the experimental enhancement ratio.

Analytical and experimental study of mean flow and turbulence characteristics inside the passages of an axial flow inducer

NASA Technical Reports Server (NTRS)

Gorton, C. A.; Lakshminarayana, B.

1974-01-01

The effort conducted to gather additional understanding of the complex inviscid and viscid effects existing within the passages of a three-bladed axial flow inducer operating at a flow coefficient of 0.065 is summarized. The experimental investigations included determination of the blade static pressure and blade limiting streamline angle distributions, and measurement of the three components of mean velocity, turbulence intensities and turbulence stresses at locations inside the inducer blade passage utilizing a rotating three-sensor hotwire probe. Applicable equations were derived for the hotwire data reduction analysis and solved numerically to obtain the appropriate flow parameters. Analytical investigations were conducted to predict the three-dimensional inviscid flow in the inducer by numerically solving the exact equations of motion, and to approximately predict the three-dimensional viscid flow by incorporating the dominant viscous terms into the exact equations. The analytical results are compared with the experimental measurements and design values where appropriate.

Chocolate eating in healthy men during experimentally induced sadness and joy.

PubMed

Macht, M; Roth, S; Ellgring, H

2002-10-01

The study compared influences of qualitatively different emotions on eating. Motivation to eat, affective responses to chocolate and chewing of chocolate were investigated in healthy normal weight males during experimentally induced emotions. Subjects abstained from eating 2 h (n = 24) or 8 h (n = 24) before testing. They received pieces of chocolate after viewing film clips presented to induce anger, fear, sadness and joy. Motivation to eat and most affective responses to eating chocolate were higher after 8 h than after 2 h of deprivation. Sadness and joy affected motivation to eat in opposite directions: joy increased and sadness decreased appetite (p < 0.001). In joy, a higher tendency to eat more chocolate was reported (p < 0.001), and chocolate tasted more pleasant (p < 0.001) and was experienced as more "stimulating" than in sadness (p < 0.01). No effects of deprivation could be found for chewing time and number of chews. Results indicate that the quality of emotions can affect motivation to eat and affective responses to eating chocolate. Our findings on decreased eating responses to sadness in healthy males and the contradictory increased eating responses to sadness reported by others supports two types of emotion-induced changes of eating: emotion-congruent modulation of eating and eating to regulate emotions. Copyright 2002 Elsevier Science Ltd.

Morphological and functional determinants of fluoxetine (Prozac)-induced pulmonary disease in an experimental model.

PubMed

Capelozzi, Marco A; Leick-Maldonado, Edna A; Parra, Edwin R; Martins, Mílton A; Tibério, Iolanda F L C; Capelozzi, Vera L

2007-05-14

Fluoxetine treatment effects were determined by evaluating respiratory mechanics (elastance/resistance) and exhaled nitric oxide, as well as mononuclear and polymorphonuclear cell recruitment into the lungs, in an experimental guinea pig model. Guinea pigs were divided into four groups: Fl (fluoxetine only, n=7); Fl+Sw (fluoxetine and forced swimming, n=7); Ns+Sw (normal saline and forced swimming, n=8); and Ns (normal saline only, n=8). Treated animals received oral fluoxetine (10 mg/(kg day)) for 30 consecutive days. On day 31, all animals were anesthetized and mechanically ventilated so that respiratory system elastance and resistance, as well exhaled nitric oxide, could be determined. The lungs were then excised en bloc for histological and immunohistochemical evaluation. Forced swimming induced bronchodilation in untreated animals and bronchoconstriction in fluoxetine-treated animals. Fluoxetine treatment was also associated with mononuclear infiltration (predominantly into alveolar walls) and neutrophil recruitment. In addition, levels of exhaled nitric oxide, an inflammatory marker, were higher in fluoxetine-treated animals. Swimming-induced stress also amplified mononuclear cell recruitment to the lungs. These results show that, in this experimental model, fluoxetine treatment reproduces the pathology of chronic interstitial pneumonia in humans.

Experimental observation and determination of the laser-induced frequency shift of hyperfine levels of ultracold polar molecules

NASA Astrophysics Data System (ADS)

Liu, Wenliang; Wang, Xiaofeng; Wu, Jizhou; Su, Xingliang; Wang, Shen; Sovkov, Vladimir B.; Ma, Jie; Xiao, Liantuan; Jia, Suotang

2017-08-01

We report on the experimental observation and quantitative determination of the laser-induced frequency shift (LIFS) of the ultracold polar molecules formed by photoassociation (PA). The experiments are performed by detecting a series of double PA spectra with a molecular hyperfine structure, which are induced by two PA lasers with a precise and adjustable frequency reference. We find that the LIFS of the molecular hyperfine levels shows a linear dependence on PA laser intensity.

Experimental chaotic quantification in bistable vortex induced vibration systems

NASA Astrophysics Data System (ADS)

Huynh, B. H.; Tjahjowidodo, T.

2017-02-01

The study of energy harvesting by means of vortex induced vibration systems has been initiated a few years ago and it is considered to be potential as a low water current energy source. The energy harvester is realized by exposing an elastically supported blunt structure under water flow. However, it is realized that the system will only perform at a limited operating range (water flow) that is attributed to the resonance phenomenon that occurs only at a frequency that corresponds to the fluid flow. An introduction of nonlinear elements seems to be a prominent solution to overcome the problem. Among many nonlinear elements, a bistable spring is known to be able to improve the harvested power by a vortex induced vibrations (VIV) based energy converter at the low velocity water flows. However, it is also observed that chaotic vibrations will occur at different operating ranges that will erratically diminish the harvested power and cause a difficulty in controlling the system that is due to the unpredictability in motions of the VIV structure. In order to design a bistable VIV energy converter with improved harvested power and minimum negative effect of chaotic vibrations, the bifurcation map of the system for varying governing parameters is highly on demand. In this study, chaotic vibrations of a VIV energy converter enhanced by a bistable stiffness element are quantified in a wide range of the governing parameters, i.e. damping and bistable gap. Chaotic vibrations of the bistable VIV energy converter are simulated by utilization of a wake oscillator model and quantified based on the calculation of the Lyapunov exponent. Ultimately, a series of experiments of the system in a water tunnel, facilitated by a computer-based force-feedback testing platform, is carried out to validate the existence of chaotic responses. The main challenge in dealing with experimental data is in distinguishing chaotic response from noise-contaminated periodic responses as noise will smear

Experimental investigation of cavitation induced air release

NASA Astrophysics Data System (ADS)

Kowalski, Karoline; Pollak, Stefan; Hussong, Jeanette

Variations in cross-sectional areas may lead to pressure drops below a critical value, such that cavitation and air release are provoked in hydraulic systems. Due to a relatively slow dissolution of gas bubbles, the performance of hydraulic systems will be affected on long time scales by the gas phase. Therefore predictions of air production rates are desirable to describe the system characteristics. Existing investigations on generic geometries such as micro-orifice flows show an outgassing process due to hydrodynamic cavitation which takes place on time scales far shorter than diffusion processes. The aim of the present investigation is to find a correlation between global, hydrodynamic flow characteristics and cavitation induced undissolved gas fractions generated behind generic flow constrictions such as an orifice or venturi tube. Experimental investigations are realised in a cavitation channel that enables an independent adjustment of the pressure level upstream and downstream of the orifice. Released air fractions are determined by means of shadowgraphy imaging. First results indicate that an increased cavitation activity leads to a rapid increase in undissolved gas volume only in the choking regime. The frequency distribution of generated gas bubble size seems to depend only indirectly on the cavitation intensity driven by an increase of downstream coalescence events due to a more densely populated bubbly flow.

Experimental investigation on the characteristics of supersonic fuel spray and configurations of induced shock waves

PubMed Central

Wang, Yong; Yu, Yu-song; Li, Guo-xiu; Jia, Tao-ming

2017-01-01

The macro characteristics and configurations of induced shock waves of the supersonic sprays are investigated by experimental methods. Visualization study of spray shape is carried out with the high-speed camera. The macro characteristics including spray tip penetration, velocity of spray tip and spray angle are analyzed. The configurations of shock waves are investigated by Schlieren technique. For supersonic sprays, the concept of spray front angle is presented. Effects of Mach number of spray on the spray front angle are investigated. The results show that the shape of spray tip is similar to blunt body when fuel spray is at transonic region. If spray entered the supersonic region, the oblique shock waves are induced instead of normal shock wave. With the velocity of spray increasing, the spray front angle and shock wave angle are increased. The tip region of the supersonic fuel spray is commonly formed a cone. Mean droplet diameter of fuel spray is measured using Malvern’s Spraytec. Then the mean droplet diameter results are compared with three popular empirical models (Hiroyasu’s, Varde’s and Merrigton’s model). It is found that the Merrigton’s model shows a relative good correlation between models and experimental results. Finally, exponent of injection velocity in the Merrigton’s model is fitted with experimental results. PMID:28054555

True Triaxial Experimental Study of Rockbursts Induced By Ramp and Cyclic Dynamic Disturbances

NASA Astrophysics Data System (ADS)

Su, Guoshao; Hu, Lihua; Feng, Xiating; Yan, Liubin; Zhang, Gangliang; Yan, Sizhou; Zhao, Bin; Yan, Zhaofu

2018-04-01

A modified rockburst testing system was utilized to reproduce rockbursts induced by ramp and cyclic dynamic disturbances with a low-intermediate strain rate of 2 × 10-3-5 × 10-3 s-1 in the laboratory. The experimental results show that both the ramp and cyclic dynamic disturbances play a significant role in inducing rockbursts. In the tests of rockbursts induced by a ramp dynamic disturbance, as the static stress before the dynamic disturbance increases, both the strength of specimens and the kinetic energy of the ejected fragments first increase and then decrease. In the tests of rockbursts induced by a cyclic dynamic disturbance, there exists a rockburst threshold of the static stress and the dynamic disturbance amplitude, and the kinetic energy of the ejected fragments first increases and then decreases as the cyclic dynamic disturbance frequency increases. The main differences between rockbursts induced by ramp dynamic disturbances and those induced by cyclic dynamic disturbances are as follows: the rockburst development process of the former is characterized by an impact failure feature, while that of the latter is characterized by a fatigue failure feature; the damage evolution curve of the specimen of the former has a leap-developing form with a significant catastrophic feature, while that of the latter has an inverted S-shape with a remarkable fatigue damage characteristic; the energy mechanism of the former involves the ramp dynamic disturbance giving extra elastic strain energy to rocks, while that of the latter involves the cyclic dynamic disturbance decreasing the ultimate energy storage capacity of rocks.

Combined experimental and numerical investigation of energy harness utilizing vortex induced vibration over half cylinder using piezoelectric beams

NASA Astrophysics Data System (ADS)

Ahmed, Md. Tusher; Hossain, Md. Tanver; Rahman, Md. Ashiqur

2017-06-01

Energy harvesting technology has the ability to create self-powered electronic systems that do not rely on battery power for their operation. Wind energy can be converted into electricity via a piezoelectric transducer during the air flow over a cylinder. The vortex-induced vibration over the cylinder causes the piezoelectric beam to vibrate. Thus useful electric energy at the range 0.2-0.3V is found which can be useful for self-powering small electronic devices. In the present study, prototypes of micro-energy harvester with a shape of 65 mm × 37 mm × 0.4 mm are developed and tested for airflow over D-shaped bluff body for diameters of 15, 20 and 28mm in an experimental setup consisting of a long wind tunnel of 57cm × 57cm with variable speeds of the motor for different flow velocities and the experimental setup is connected at the downstream where flow velocity is the maximum. Experimental results show that the velocity and induced voltage follows a regular linear pattern. A maximum electrical potential of 140 mV for velocity of 1.1 ms-1 at a bluff body diameter of 15 mm is observed in the energy harvester that can be applied in many practical cases for self-powering electronic devices. The simulation of this energy harvesting phenomena is then simulated using COMSOLE multi-physics. Diameter of the bluff bodies as well as flow velocity and size of cantilever beam are varied and the experimental findings are found to be in good agreement with the simulated ones. The simulations along with the experimental data show the possibility of generating electricity from vortex induced vibration and can be applied in many practical cases for self-powering electronic devices.

Marginal Biotin Deficiency Can Be Induced Experimentally in Humans Using a Cost-Effective Outpatient Design123

PubMed Central

Stratton, Shawna L.; Henrich, Cindy L.; Matthews, Nell I.; Bogusiewicz, Anna; Dawson, Amanda M.; Horvath, Thomas D.; Owen, Suzanne N.; Boysen, Gunnar; Moran, Jeffery H.; Mock, Donald M.

2012-01-01

To date, marginal, asymptomatic biotin deficiency has been successfully induced experimentally by the use of labor-intensive inpatient designs requiring rigorous dietary control. We sought to determine if marginal biotin deficiency could be induced in humans in a less expensive outpatient design incorporating a self-selected, mixed general diet. We sought to examine the efficacy of three outpatient study designs: two based on oral avidin dosing and one based on a diet high in undenatured egg white for a period of 28 d. In study design 1, participants (n = 4; 3 women) received avidin in capsules with a biotin binding capacity of 7 times the estimated dietary biotin intake of a typical self-selected diet. In study design 2, participants (n = 2; 2 women) received double the amount of avidin capsules (14 times the estimated dietary biotin intake). In study design 3, participants (n = 5; 3 women) consumed egg-white beverages containing avidin with a biotin binding capacity of 7 times the estimated dietary biotin intake. Established indices of biotin status [lymphocyte propionyl-CoA carboxylase activity; urinary excretion of 3-hydroxyisovaleric acid, 3-hydroxyisovaleryl carnitine (3HIA-carnitine), and biotin; and plasma concentration of 3HIA-carnitine] indicated that study designs 1 and 2 were not effective in inducing marginal biotin deficiency, but study design 3 was as effective as previous inpatient study designs that induced deficiency by egg-white beverage. Marginal biotin deficiency can be induced experimentally by using a cost-effective outpatient design by avidin delivery in egg-white beverages. This design should be useful to the broader nutritional research community. PMID:22157538

Protective effect of asiatic acid in an experimental cerulein-induced model of acute pancreatitis in mice

PubMed Central

Xiao, Wenqin; Jiang, Weiliang; Li, Kai; Hu, Yangyang; Li, Sisi; Zhou, Li; Wan, Rong

2017-01-01

Asiatic acid (AA), a triterpenoid derived from the medicinal plant Centella asiatica, is considered to have anti-inflammatory, anti-fibrotic and anti-tumor effects, but its effects in acute pancreatitis (AP) are unknown. Our purpose of this study was to investigate the effects of AA in a mouse model of cerulein-induced pancreatitis. We evaluated AA in an experimental model of AP induced in mice by six hourly intraperitoneal injections of cerulein 50 µg/kg. Mice were pretreated with vehicle or AA 50 mg/kg 2 h before the first cerulein injection. The severity of AP was evaluated histologically and by biochemistry, myeloperoxidase activity, proinflammatory cytokine production, and nuclear factor (NF)-κB activity. Administration of AA significantly reduced the severity of AP, and was associated with reduction of serum amylase and lipase levels, decreased pancreatic histological damage, and decreased myeloperoxidase activity. The serum levels and mRNA expression of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and NF-κB activity were reduced. AA also significantly improved the in vitro viability of pancreatic acinar cells induced by cholecystokinin (CCK) and suppressed NF-κB activity. AA protected against experimental AP, possibly by reducing production of proinflammatory cytokines via suppression NF-κB activation. PMID:28861174

The effects of experimental pain and induced optimism on working memory task performance.

PubMed

Boselie, Jantine J L M; Vancleef, Linda M G; Peters, Madelon L

2016-07-01

Pain can interrupt and deteriorate executive task performance. We have previously shown that experimentally induced optimism can diminish the deteriorating effect of cold pressor pain on a subsequent working memory task (i.e., operation span task). In two successive experiments we sought further evidence for the protective role of optimism on pain-induced working memory impairments. We used another working memory task (i.e., 2-back task) that was performed either after or during pain induction. Study 1 employed a 2 (optimism vs. no-optimism)×2 (pain vs. no-pain)×2 (pre-score vs. post-score) mixed factorial design. In half of the participants optimism was induced by the Best Possible Self (BPS) manipulation, which required them to write and visualize about a life in the future where everything turned out for the best. In the control condition, participants wrote and visualized a typical day in their life (TD). Next, participants completed either the cold pressor task (CPT) or a warm water control task (WWCT). Before (baseline) and after the CPT or WWCT participants working memory performance was measured with the 2-back task. The 2-back task measures the ability to monitor and update working memory representation by asking participants to indicate whether the current stimulus corresponds to the stimulus that was presented 2 stimuli ago. Study 2 had a 2 (optimism vs. no-optimism)×2 (pain vs. no-pain) mixed factorial design. After receiving the BPS or control manipulation, participants completed the 2-back task twice: once with painful heat stimulation, and once without any stimulation (counter-balanced order). Continuous heat stimulation was used with temperatures oscillating around 1°C above and 1°C below the individual pain threshold. In study 1, the results did not show an effect of cold pressor pain on subsequent 2-back task performance. Results of study 2 indicated that heat pain impaired concurrent 2-back task performance. However, no evidence was found

Experimental system for the control of surgically induced infections

NASA Technical Reports Server (NTRS)

1971-01-01

The results are presented of the development tests performed on the experimental system for the control of surgically induced infections. Tests were performed on the portable clean room to demonstrate assembly, collapsability, portability and storage. Collapsing, relocating and storing within the surgery room can be accomplished in 12 minutes. The storage envelope dimensions are 1.64 m x 4.24 m x 2.62 m high. The disassembly transfer to another room, and reassembly were demonstrated. The laminar air flow velocity profile within the enclosure was measured. In the undisturbed area of the enclosure the air flow met the Federal Standard 209a requirements of 27.45 meters per minute + or - 6.10 meters per minute. Smoke tests with simulated surgery equipment and personnel in the enclosure did not indicate any detrimental air flow patterns. It is concluded that the system as designed will perform the functions required for its intended use.

Experimentally induced mastitis and metritis modulate soy bean derived isoflavone biotransformation in diary cows.

PubMed

Kowalczyk-Zieba, I; Woclawek-Potocka, I; Piskula, M K; Piotrowska-Tomala, K K; Boruszewska, D; Bah, M M; Siemieniuch, M J; Skarzynski, D J

2011-12-01

The present study compared the changes in isoflavone (daidzein and genistein) and their metabolite (equol and para-ethyl-phenol) concentrations in the blood plasma of cows with induced mastitis and metritis after feeding with soy bean. Sixteen cows were divided into four groups: control for mastitis group, cows with induced mastitis group, control for metritis group, and cows with induced metritis group. All cows were fed a single dose of 2.5 kg of soy bean and then blood samples were taken from the jugular vein for 8 h at predetermined intervals. The concentrations of soy bean-derived isoflavones and their active metabolites were measured in the blood plasma on HPLC system. β-Glucuronidase activity in the blood plasma of cows was measured by fluorometric method. In the blood plasma of cows with induced mastitis and metritis, we found considerably higher concentrations and time-dependent increase in isoflavone metabolites (equol and para-ethyl-phenol) with reference to cyclic cows (P < 0.05). Moreover, we noticed significant decrease of genistein in the blood plasma of the cows with induced metritis compared with control cows (P < 0.05). In addition, in the blood plasma of the cows with induced metritis, we found an increase in β-glucuronidase activity compared with control cows (P < 0.05). In conclusion, health status of the females influenced the concentrations of isoflavone metabolites in the blood plasma of the cows. Experimentally induced mastitis and metritis increased isoflavone absorption, biotransformation and metabolism. Therefore, we suggest that cows with induced mastitis and metritis are more exposed to active isoflavone metabolite actions than healthy cows. Copyright © 2011. Published by Elsevier Inc.

The effect of preferred music genre selection versus preferred song selection on experimentally induced anxiety levels.

PubMed

Walworth, Darcy DeLoach

2003-01-01

The purpose of this study was to investigate the differences of experimentally induced anxiety levels reached by subjects listening to no music (n = 30), subjects listening to music selected by the experimenter from the subject's preferred genre or artist listed as relaxing (n = 30), and subjects listening to a specific song they listed as relaxing (n = 30). Subjects consisted of 90 individuals, male and female, randomly assigned to one of the three groups mentioned above. Subjects in either music group filled out a questionnaire prior to participating in the study indicating their preference of music used for relaxation purposes. Subjects in Experimental Group 1 marked their preferred genres and/or artists, and Experimental Group 2 marked specific songs used for relaxation purposes. While the experimenter hypothesized subjects in Experimental Group 2 would show less anxiety than both the control group and Experimental Group 1, there were no significant differences found between the 2 music groups in anxiety levels reached. However, there was a statistically significant difference between the no music control group and both music groups in the anxiety level reached by subjects. Subjects listening to music, both songs chosen by the experimenter and subject selected songs, showed significantly less anxiety than subjects not listening to music.

Theoretical and experimental evaluation of effective stress-induced sorption capacity change and its influence on coal permeability

NASA Astrophysics Data System (ADS)

Li, Chengwu; Dong, Lihui; Xu, Xiaomeng; Hu, Po; Tian, Jianwei; Zhang, Yihuai; Yang, Leilei

2017-06-01

The gas sorption effect is an important factor affecting the gas permeability of a coal seam, which has been proved in many previous experimental measurements and analytical permeability studies. However, the sorption capacity of coal is usually not static due to the complexity of external stress variation and internal gas media features. The stress-induced sorption capacity variation and its effect on the coal permeability change have not been fully identified yet. Thus, in this paper we present a preliminary evaluation of the stress-induced sorption capacity change by introducing the adsorption capacity modified term, and an experiment is carried out to verify the influence of the altered effective stress on coal permeability. Langmuir-like adsorption deformation constant parameters were combined into the modified coal permeability model and were given values to fully estimate the influence on permeability caused by the modification term. We found that different change modes of effective stress would yield different change effects on the permeability, that is, with the same effective stress change amount, the altered external stress-induced change had less influence than the altered-pore pressure-induced change; however, both modes demonstrated that the model taking sorption capacity change into consideration is more consistent with the experimental data. The effect of sorption capacity change on coal permeability variation was also found to be tightly connected with the physical and mechanical properties of the coal itself. It is proved that considering stress-induced sorption ability change has a critical role in characterizing the permeability variation of coal.

Beneficial influence of ellagic acid on biochemical indexes associated with experimentally induced colon carcinogenesis.

PubMed

Syed, Umesalma; Ganapasam, Sudhandiran

2017-01-01

To elucidate the key biochemical indexes associated with 1, 2-dimethylhydrazine (DMH)-induced colon carcinogenesis and the modulatory efficacy of a dietary polyphenol, ellagic acid (EA). Wistar rats were chosen to study objective, and were divided into 4 groups; Group 1-control rats; Group 2-rats received EA (60 mg/kg body weight/day, orally); rats in Group 3-induced with DMH (20 mg/kg body weight) subcutaneously for 15 weeks; DMH-induced Group 4 rats were initiated with EA treatment. We examined key citric acid cycle enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and the activities of respiratory chain enzymes NADH dehydrogenase and Cytochrome-C-oxidase and membrane-bound enzyme profiles (Na +/K + ATPase, Ca 2+ ATPase and Mg 2+ ATPase), activities of lysosomal proteases such as β-D-glucuronidase, β-galactosidase and N-acety-β-D-glucosaminidase and cellular thiols (oxidized glutathione, protein thiols, and total thiols). It was found that administration of DMH to rats decreased both mitochondrial and membrane-bound enzymes activities, increased activities of lysosomal enzymes and further modulates cellular thiols levels. Treatment with EA significantly restored the mitochondrial and ATPases levels and further reduced lysosomal enzymes to near normalcy thereby restoring harmful effects induced by DMH. EA treatment was able to effectively restore the detrimental effects induced by DMH, which proves the chemoprotective function of EA against DMH-induced experimental colon carcinogenesis.

Functional outcomes of endoscopic arytenoid abduction lateropexy for unilateral vocal cord paralysis with dyspnea.

PubMed

Matievics, Vera; Bach, Adam; Sztano, Balazs; Bere, Zsofia; Tobias, Zoltan; Castellanos, Paul F; Mueller, Andreas H; Rovo, Laszló

2017-10-01

In unilateral vocal cord paralysis (UVCP), hoarseness is usually the leading symptom; however, the diminished airway might lead to breathing problems as well, especially with exertion. The application of the classic resection glottis enlarging or medialization procedures might shift the breathing and/or the voice to a worse condition. The non-destructive endoscopic arytenoid abduction lateropexy (EAAL) might be a solution for this problem. The aim of our study was to analyze the phonatory and respiratory outcomes of this treatment concept. The first year phoniatric [Jitter, Shimmer, harmonics-to-noise ratio (HNR), maximum phonation time (MPT), fundamental frequency (F 0 ), Voice Handicap Index (VHI), Dysphonia Severity Index (DSI), Global-Roughness-Breathiness scale (GRB)], peak inspiratory flow (PIF), and quality of life (QoL) were evaluated in ten UVCP patients treated by EAAL for dyspnea generally presented on exertion. PIF, Jitter, QoL, GRB, and VHI significantly improved. DSI, HNR, and MPT got non-significantly better. F 0 slightly increased in all patients, a mild deterioration of shimmer was observed. These results prove that improving respiratory function is not necessarily associated with a deterioration in voice quality. The EAAL provides a significant improvement in breathing and the vibratory parameters of the postoperative, more tensed and straightened vocal cords proved to be more advantageous than the original (para) median 'loose' position. The over-adduction of the contralateral side more or less compensates for the disadvantageous, more lateral position of the operated side. EAAL might be an alternative treatment for unilateral vocal cord paralysis associated with breathing problems.

Ameliorative effects of Panax quinquefolium on experimentally induced reflux oesophagitis in rats

PubMed Central

Singh, Pratibha; Singh, Neetu; Sengupta, Shibani; Palit, Gautam

2012-01-01

Background & objectives: Reflux oesophagitis (RE), is one of the most prevalent chronic gastrointestinal disorders commonly referred to as gastroesophageal reflux disease (GERD) and requires long term therapy. The present study was designed to investigate the protective effects of Panax quinquefolium (PQ), administered with variable doses, on experimentally induced reflux oesophagitis (RE) in rats. Methods: Forty two female Sprague-Dawley (180-220 g) rats were randomly divided to receive standardized root powder of PQ (50-200mg/kg, po), standard anti-reflux (omeprazole, 5 mg/kg, ip) and anti-oxidant (α-tocopherol, 16 mg/kg, po). After 45 min drug pretreatment, RE was produced in rats by simultaneous ligation of the pyloric end and forestomach. Several parameters, including macroscopic lesion index, glutathione system, lipid peroxidation (LPO) and tissue myeloperoxidase (MPO) activity were measured. Alterations in ICAM-1, CINC-2 and MCP-1 gene expression were examined through reverse transcriptase polymerase chain reaction (RT-PCR). Results: PQ significantly attenuated the severity of the macroscopic signs of RE-induced tissue damage, replenished the depleted GSH level and reduced the RE-associated LPO levels dose dependently. In contrast, omeprazole though effectively improved the mucosal damage, it failed to bring significant attenuation of RE-associated changes in LPO, GSH level and MPO activity. α-Tocopherol significantly ameliorated RE-induced tissue injury and improved LPO level and GSH/GSSG ratio but failed to counteract RE-induced MPO activity. PQ at dose of 100 mg/kg significantly downregulated ICAM-1 and CINC-2 expression whereas it showed no effect over MCP-1 expression. Interpretation & conclusions: The present data indicate that PQ protects against RE-induced oesophageal damage via a mechanism that inhibits the influx of inflammatory cell to oesophagus and a consequence excessive oxidative load, opening the avenue to its promising protective role in

Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage

PubMed Central

2012-01-01

Background Subarachnoid hemorrhage (SAH) frequently results in several complications, including cerebral vasospasm, associated with high mortality. Although cerebral vasospasm is a major cause of brain damages after SAH, other factors such as inflammatory responses and oxidative stress also contribute to high mortality after SAH. Trehalose is a non-reducing disaccharide in which two glucose units are linked by α,α-1,1-glycosidic bond, and has been shown to induce tolerance to a variety of stressors in numerous organisms. In the present study, we investigated the effect of trehalose on cerebral vasospasm, inflammatory responses, and oxidative stress induced by blood in vitro and in vivo. Methods Enzyme immunoassay for eicosanoids, pro-inflammatory cytokines, and endothelin-1, and western blotting analysis for cyclooxygenase-2, inducible nitric oxide synthase, and inhibitor of NF-κB were examined in macrophage-like cells treated with hemolysate. After treatment with hemolysate and hydrogen peroxide, the levels of lipid peroxide and amounts of arachidonic acid release were also analyzed. Three hours after the onset of experimental SAH, 18 Japanese White rabbits received an injection of saline, trehalose, or maltose into the cisterna magna. Angiographic and histological analyses of the basilar arteries were performed. In a separate study, the femoral arteries from 60 rats were exposed to fresh autologous blood. At 1, 3, 5, 7, 10, and 20 days after treatment, cryosections prepared from the femoral arteries were histologically analyzed. Results When cells were treated with hemolysate, trehalose inhibited the production of several inflammatory mediators and degradation of the inhibitor of NF-κB and also suppressed the lipid peroxidation, the reactive oxygen species-induced arachidonic acid release in vitro. In the rabbit model, trehalose produced an inhibitory effect on vasospasm after the onset of experimental SAH, while maltose had only a moderate effect. When the

Saturation of the laser-induced narrowband coherent synchrotron radiation process: Experimental observation at a storage ring

NASA Astrophysics Data System (ADS)

Hosaka, M.; Yamamoto, N.; Takashima, Y.; Szwaj, C.; Le Parquier, M.; Evain, C.; Bielawski, S.; Adachi, M.; Zen, H.; Tanikawa, T.; Kimura, S.; Katoh, M.; Shimada, M.; Takahashi, T.

2013-02-01

We study the efficiency limitation affecting laser-induced coherent synchrotron radiation (CSR) at high laser power. Experiments are made on the UVSOR-II storage ring in conditions of narrowband terahertz CSR emission. While, at moderate power, CSR power increases quadratically with laser power, a noticeable decrease in efficiency and eventually a decrease in CSR power is observed experimentally at high power. Details of the underlying process are analyzed numerically. As the saturation effect depends almost instantaneously on the laser intensity, the saturation occurs locally in longitudinal space. This has important consequences on the modulation pattern induced on the electron bunch.

Human experimental anxiety: actual public speaking induces more intense physiological responses than simulated public speaking.

PubMed

Zuardi, Antonio Waldo; Crippa, José Alexandre de Souza; Hallak, Jaime Eduardo Cecílio; Gorayeb, Ricardo

2013-01-01

a) To perform a systematic and meta-analytic review to verify whether the Simulated Public Speaking Task (SPST) leads to a greater increase in self-rated anxiety than in physiological correlates of anxiety; and b) to compare the results obtained with the SPST with an actual public speaking task involving healthy volunteers. a) The PubMed and ISI Web of Knowledge databases were searched for studies involving the SPST prior to 2012. Eleven publications were eligible and provided data from 143 healthy volunteers for meta-analysis; b) 48 university students without somatic or psychiatric disorders were divided into three experimental groups of 16 subjects to undergo one of the following: SPST, real-world public speaking task (real-world), and control situation (control). The meta-analysis showed that the SPST induced a significant increase in the Visual Analogue Mood Scale (VAMS) anxiety factor, but no significant increases in systolic blood pressure or heart rate. The empirical study showed that the real-world public speaking task increased heart rate, systolic blood pressure and diastolic blood pressure significantly more than the control and SPST conditions. These results suggest that real public speaking might be better than SPST in inducing experimental anxiety.

Experimental and theoretical characterization of deep penetration welding threshold induced by 1-μm laser

NASA Astrophysics Data System (ADS)

Zou, J. L.; He, Y.; Wu, S. K.; Huang, T.; Xiao, R. S.

2015-12-01

The deep penetration-welding threshold (DPWT) is the critical value that describes the welding mode transition from the thermal conduction to the deep penetration. The objective of this research is to clarify the DPWT induced by the lasers with wavelength of 1 μm (1-μm laser), based on experimental observation and theoretical analysis. The experimental results indicated that the DPWT was the ratio between laser power and laser spot diameter (P/d) rather than laser power density (P/S). The evaporation threshold was smaller than the DPWT, while the jump threshold of the evaporated mass flux in the molten pool surface was consistent with the DPWT. Based on the force balance between the evaporation recoil pressure and the surface tension pressure at the gas-liquid interface of the molten pool as well as the temperature field, we developed a self-focusing model, which further confirmed the experimental results.

Chemopreventive effect of Cynodon dactylon (L.) Pers. extract against DMH-induced colon carcinogenesis in experimental animals.

PubMed

Albert-Baskar, Arul; Ignacimuthu, Savarimuthu

2010-07-01

The present study was aimed at evaluating the chemopreventive property of Cynodon dactylon. The antioxidant, antiproliferative and apoptotic potentials of the plant were investigated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, nitric oxide radical scavenging activity (NO(-)) and MTT assay on four cancer cell lines (COLO 320 DM, MCH-7, AGS, A549) and a normal cell line (VERO). In vivo chemopreventive property of the plant extract was studied in DMH-induced colon carcinogenesis. The methanolic extract of C. dactylon was found to be antiproliferative and antioxidative at lower concentrations and induced apoptotic cell death in COLO 320 DM cells. Treatment with methanolic extract of C. dactylon increased the levels of antioxidant enzymes and reduced the number of dysplastic crypts in DMH-induced colon of albino rats. The present investigation revealed the anticancer potential of methanolic extract of C. dactylon in COLO 320 DM cells and experimentally induced colon carcinogenesis in rats.

Effects of normal saline and selenium-enriched hot spring water on experimentally induced rhinosinusitis in rats.

PubMed

Kim, Dong-Hyun; Yeo, Sang Won

2013-01-01

This prospective, randomized, and controlled study examined the effects of normal saline and selenium-enriched hot spring water on experimentally induced rhinosinusitis in rats. The study comprised two control groups (untreated and saline-treated) and three experimental groups of Sprague Dawley rats. The experimental groups received an instillation of lipopolysaccharide (LPS) only, LPS+normal saline (LPS/saline), or LPS+selenium-enriched hot spring water (LPS/selenium). Histopathological changes were identified using hematoxylin-eosin staining. Leakage of exudate was identified using fluorescence microscopy. Microvascular permeability was measured using the Evans blue dye technique. Expression of the Muc5ac gene was measured using reverse transcription-polymerase chain reaction. Mucosal edema and expression of the Muc5ac gene were significantly lower in the LPS/saline group than in the LPS group. Microvascular permeability, mucosal edema, and expression of the Muc5ac gene were significantly lower in the LPS/selenium group than in the LPS group. Mucosal edema was similar in the LPS/selenium group and LPS/saline group, but capillary permeability and Muc5ac expression were lower in the LPS/selenium group. This study shows that normal saline and selenium-enriched hot spring water reduce inflammatory activity and mucus hypersecretion in LPS-induced rhinosinusitis in rats. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Analytical and Experimental Characterization of Gravity Induced Deformations In Subscale Gossamer Structures

NASA Technical Reports Server (NTRS)

Johnston, John D.; Blandino, Joseph R.; McEvoy, Kiley C.

2004-01-01

The development of gossamer space structures such as solar sails and sunshields presents many challenges due to their large size and extreme flexibility. The post-deployment structural geometry exhibited during ground testing may significantly depart from the in-space configuration due to the presence of gravity-induced deformations (gravity sag) of lightly preloaded membranes. This paper describes a study carried out to characterize gravity sag in two subscale gossamer structures: a single quadrant from a 2 m, 4 quadrant square solar sail and a 1.7 m membrane layer from a multi-layer sunshield The behavior of the test articles was studied over a range of preloads and in several orientations with respect to gravity. An experimental study was carried out to measure the global surface profiles using photogrammetry, and nonlinear finite element analysis was used to predict the behavior of the test articles. Comparison of measured and predicted surface profiles shows that the finite dement analysis qualitatively predicts deformed shapes comparable to those observed in the laboratory. Quantitatively, finite element analysis predictions for peak gravity-induced deformations in both test articles were within 10% of measured values. Results from this study provide increased insight into gravity sag behavior in gossamer structures, and demonstrates the potential to analytically predict gravity-induced deformations to within reasonable accuracy.

Theoretical and Experimental Investigation of the Translational Diffusion of Proteins in the Vicinity of Temperature-Induced Unfolding Transition.

PubMed

Molchanov, Stanislav; Faizullin, Dzhigangir A; Nesmelova, Irina V

2016-10-06

Translational diffusion is the most fundamental form of transport in chemical and biological systems. The diffusion coefficient is highly sensitive to changes in the size of the diffusing species; hence, it provides important information on the variety of macromolecular processes, such as self-assembly or folding-unfolding. Here, we investigate the behavior of the diffusion coefficient of a macromolecule in the vicinity of heat-induced transition from folded to unfolded state. We derive the equation that describes the diffusion coefficient of the macromolecule in the vicinity of the transition and use it to fit the experimental data from pulsed-field-gradient nuclear magnetic resonance (PFG NMR) experiments acquired for two globular proteins, lysozyme and RNase A, undergoing temperature-induced unfolding. A very good qualitative agreement between the theoretically derived diffusion coefficient and experimental data is observed.

Anti-glaucoma potential of Heliotropium indicum Linn in experimentally-induced glaucoma.

PubMed

Kyei, Samuel; Koffuor, George Asumeng; Ramkissoon, Paul; Owusu-Afriyie, Osei

2015-01-01

Heliotropium indicum is used as a traditional remedy for hypertension in Ghana. The aim of the study was to evaluate the anti-glaucoma potential of an aqueous whole plant extract of H. indicum to manage experimentally-induced glaucoma. The percentage change in intraocular pressure (IOP), after inducing acute glaucoma (15 mLkg(-1) of 5 % dextrose, i.v.), in New Zealand White rabbits pretreated with Heliotropium indicum aqueous extract (HIE) (30-300 mgkg(-1)), acetazolamide (5 mgkg(-1)), and normal saline (10 mLkg(-1)) per os were measured. IOPs were also monitored in chronic glaucoma in rabbits (induced by 1 % prednisolone acetate drops, 12 hourly for 21 days) after treatments with the same doses of HIE, acetazolamide, and normal saline for 2 weeks. The anti-oxidant property of the extract was assessed by assaying for glutathione levels in the aqueous humour. Glutamate concentration in the vitreous humour was also determined using ELISA technique. Histopathological assessment of the ciliary bodies was made. The extract significantly reduced intraocular pressure (p ≤ 0.05-0.001) in acute and chronic glaucoma, preserved glutathione levels and glutamate concentration (p ≤ 0.01-0.001). Histological assessment of the ciliary body showed a decrease in inflammatory infiltration in the extract and acetazolamide-treated group compared with the normal saline-treated group. The aqueous whole plant extract of Heliotropium indicum has ocular hypotensive, anti-oxidant and possible neuro-protective effects, which therefore underscore its plausible utility as an anti-glaucoma drug with further investigation.

Experimentally-induced Increases in Early Gesture Lead to Increases in Spoken Vocabulary

PubMed Central

LeBarton, Eve Sauer; Goldin-Meadow, Susan; Raudenbush, Stephen

2014-01-01

Differences in vocabulary that children bring with them to school can be traced back to the gestures they produce at 1;2, which, in turn, can be traced back to the gestures their parents produce at the same age (Rowe & Goldin-Meadow, 2009b). We ask here whether child gesture can be experimentally increased and, if so, whether the increases lead to increases in spoken vocabulary. Fifteen children aged 1;5 participated in an 8-week at-home intervention study (6 weekly training sessions plus follow-up 2 weeks later) in which all were exposed to object words, but only some were told to point at the named objects. Before each training session and at follow-up, children interacted naturally with caregivers to establish a baseline against which changes in communication were measured. Children who were told to gesture increased the number of gesture meanings they conveyed, not only during training but also during interactions with caregivers. These experimentally-induced increases in gesture led to larger spoken repertoires at follow-up. PMID:26120283

Naturally occurring and experimentally induced castor bean (Ricinus communis) poisoning in ducks

USGS Publications Warehouse

Jensen, Wayne I.; Allen, J.P.

1981-01-01

Castor bean (Ricinus communis) poisoning accounted for the death of several thousand ducks in the Texas panhandle in the fall and winter months of 1969-1971.Signs of intoxication resembled those of botulism, except for mucoid, blood-tinged excreta. The most common lesions were severe fatty change in the liver, widely distributed internal petechial hemorrhages or ecchymoses, and catarrhal enteritis.Nearly intact castor beans were found in the stomach of one duck during field necropsy. Fragments of seed coat resembling castor bean were found in the stomachs of 10 of 14 ducks examined in the laboratory.Clinical signs and postmortem lesions observed in wild ducks were induced experimentally in mallards (Anas platyrhynchos) by force-feeding intact castor beans. Toxicity titrations were erratic, but the LD50 appeared to be between three and four seeds.The mouse toxicity test, used to detect Clostridium botulinum toxin in the blood serum of intoxicated ducks, was negative in every case. Hemagglutination and precipitin tests generally failed to detect castor bean in extracts of excreta or intestinal contents of experimentally intoxicated ducks.

Gender differences in loss of psychological resources following experimentally-induced vicarious stress.

PubMed

Ben-Zur, Hasida; Zeidner, Moshe

2012-07-01

The present research focuses on gender differences in resource loss, perceived threat, and negative affective reactions induced by experimental manipulation of vicarious stress. Israeli students (54.7% women) were randomly allocated to one of two conditions: (1) Threat Condition (n=98), in which participants were exposed to a video film depicting terror attacks and (2) Control Condition (n=30), in which participants viewed a video film depicting a series of non-emotive news broadcasts. Participants also completed measures of mastery, optimism, and self-esteem. The data indicated that whereas under the Threat Condition women scored lower on psychological resources and higher on perceived threat than men, no significant gender differences were observed under the Control Condition. A path analysis revealed that gender was directly related to perceived threat and resource loss, which, in turn, were related to negative affect. In addition, a greater sense of mastery was related to lower resource loss. Overall, these experimental findings suggest that gender and mastery bear prominent effects on cognitive and emotional reactions to vicarious life threat.

Nigella sativa amliorates inflammation and demyelination in the experimental autoimmune encephalomyelitis-induced Wistar rats

PubMed Central

Noor, Neveen A; Fahmy, Heba M; Mohammed, Faten F; Elsayed, Anwar A; Radwan, Nasr M

2015-01-01

Multiple sclerosis (MS) is the major, immune-mediated, demyelinating neurodegenerative disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of MS. The aim of the present study was to investigate the protective and ameliorative effects of N. sativa seeds (2.8 g/kg body weight) in EAE-induced Wistar rats. EAE-induced rats were divided into: 1- EAE-induced rats (“EAE” group). 2- “N. sativa + EAE” group received daily oral administration of N. sativa 2 weeks prior EAE induction until the end of the experiment. 3- “EAE + N. sativa” group received daily oral administration of N. sativa after the appearance of first clinical signs until the end of the experiment. All animals were decapitated at the 28th day post EAE-induction. EAE was investigated using histopathological, immunohistochemical and ultrastructural examinations in addition to determination of some oxidative stress parameters in the cerebellum and medulla. N. sativa suppressed inflammation observed in EAE-induced rats. In addition, N. sativa enhanced remyelination in the cerebellum. Moreover, N. sativa reduced the expression of transforming growth factor beta 1 (TGF β1). N. sativa seeds could provide a promising agent effective in both the protection and treatment of EAE. PMID:26261504

Visualization of Oxidative Stress Induced by Experimental Periodontitis in Keap1-Dependent Oxidative Stress Detector-Luciferase Mice.

PubMed

Kataoka, Kota; Ekuni, Daisuke; Tomofuji, Takaaki; Irie, Koichiro; Kunitomo, Muneyoshi; Uchida, Yoko; Fukuhara, Daiki; Morita, Manabu

2016-11-16

The aim of this study was to investigate whether a Keap1-dependent oxidative stress detector-luciferase (OKD-LUC) mouse model would be useful for the visualization of oxidative stress induced by experimental periodontitis. A ligature was placed around the mandibular first molars for seven days to induce periodontitis. Luciferase activity was measured with an intraperitoneal injection of d-luciferin on days 0, 1, and 7. The luciferase activity in the periodontitis group was significantly greater than that in the control group at seven days. The expressions of heme oxygenase-1 (HO-1) and malondialdehyde in periodontal tissue were significantly higher in the periodontitis group than in the control group. Immunofluorescent analysis confirmed that the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) occurred more frequently in the periodontitis group than in the control group. This study found that under oxidative stress induced by experimental periodontitis, the Nrf2/antioxidant defense pathway was activated and could be visualized from the luciferase activity in the OKD-LUC model. Thus, the OKD-LUC mouse model may be useful for exploring the mechanism underlying the relationship between the Nrf2/antioxidant defense pathway and periodontitis by enabling the visualization of oxidative stress over time.

Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway.

PubMed

Yue, Rongzheng; Zuo, Chuan; Zeng, Jing; Su, Baihai; Tao, Ye; Huang, Songmin; Zeng, Rui

2017-11-01

To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism. Healthy male Sprague-Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors. After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p < .05) and ameliorated the contrast-induced acute kidney injury (p < .05) and significantly reduced Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (Myd88), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein expression and relative mRNA expression levels (p < .05) and significantly decreased expression levels of downstream inflammatory factors (p < .05). Different atorvastatin doses have protective effects on contrast-induced acute renal tubular injury in rats, possibly by targeting TLR4, suppressing TLR4 expression, regulating the TLR4/Myd88 signaling pathway, and inhibiting the expression of downstream inflammatory factors.

Spatial structure of plasma density perturbations, induced in the ionosphere modified by powerful HF radio waves: Review of experimental results

NASA Astrophysics Data System (ADS)

Frolov, Vladimir

2015-06-01

In the review, the results of experimental studies of spatial structure of small-, middle-, and large scale plasma density perturbations induced in the ionosphere by its pumping by powerful HF O-mode (ordinary) radio waves, are analyzed. It is shown that the region with induced plasma density perturbations occupied all ionosphere body from its E-region up to the topside ionosphere in the height and it has the horizontal length of about of 300-500 km. Peculiarities of generation of artificial ionosphere irregularities of different scale-lengths in the magnetic zenith region are stated. Experimental results obtained under conditions of ionosphere periodical pumping when the generation of travel ionosphere disturbances is revealed are also discussed.

Tachykinin-mediated respiratory effects in conscious guinea pigs: modulation by NK1 and NK2 receptor antagonists.

PubMed

Kudlacz, E M; Logan, D E; Shatzer, S A; Farrell, A M; Baugh, L E

1993-09-07

Tachykinins, in particular neurokinin A and substance P, produce a number of airway effects which may contribute to respiratory diseases such as asthma. We examined the ability of aerosolized substance P, neurokinin A or capsaicin to produce respiratory alterations in conscious guinea pigs using modified whole body plethysmography. Substance P-mediated dyspnea and significant respiratory events were inhibited by the NK1 receptor antagonist, CP-96,345. Neurokinin A-mediated respiratory effects were ablated by the NK2 receptor antagonists: MEN 10207, MDL 29,913 and SR 48,968, the latter being the most potent. The peptide-based antagonist, MEN 10207, produced respiratory effects itself suggesting partial agonist activity. The cyclic hexapeptide, MDL 29,913, relaxed airway smooth muscle via mechanisms other than tachykinin antagonism. NK2 but not NK1 receptor antagonists were able to delay the onset of capsaicin-induced dyspnea, although alone they did not usually (in approximately 10% of the animals) eliminate the response. However, when NK2 receptor antagonists were combined with CP-96,345, the incidence of dyspnea induced by capsaicin decreased significantly (40%) suggesting that both tachykinins contribute to dyspnea in this system.

Confabulation versus experimentally induced false memories in Korsakoff patients.

PubMed

Van Damme, Ilse; d'Ydewalle, Géry

2010-09-01

The present study focuses on both the clinical symptom of confabulation and experimentally induced false memories in patients suffering from Korsakoff's syndrome. Despite the vast amount of case studies of confabulating patients and studies investigating false memories in the Deese-Roediger-McDermott (DRM) paradigm, the nature of Korsakoff patients' confabulatory behaviour and its association with DRM false memories have been rarely examined. Hence, the first aim of the present study was to evaluate confabulatory responses in a large sample of chronic Korsakoff patients and matched controls by means of the Dalla Barba Confabulation Battery. Second, the association between (provoked) confabulation and the patients' DRM false recognition performance was investigated. Korsakoff patients mainly confabulated in response to questions about episodic memory and questions to which the answer was unknown. A positive association was obtained between confabulation and the tendency to accept unstudied distractor words as being old in the DRM paradigm. On the other hand, there was a negative association between confabulation and false recognition of critical lures. The latter could be attributed to the importance of strategic retrieval at delayed memory testing.

[Experimental mitral regurgitation in ischemia-induced papillary muscle dysfunction].

PubMed

Matsuzaki, M; Yonezawa, F; Toma, Y; Miura, T; Katayama, K; Fujii, T; Kohtoku, N; Otani, N; Ono, S; Tateno, S

1988-01-01

Mitral regurgitation (MR) reportedly develops by ischemia of the papillary muscles, which is called papillary muscle dysfunction. This report deals with the roles of papillary muscles and left ventricular walls on the pathogenesis of MR using graded injuries of these structures in 23 dogs. Implanted ultrasonic microcrystal and occluder with an electromagnetic flowmetry for the left circumflex coronary artery were the main experimental setting. Graded occlusion of the artery was done by the six-step approach regarding coronary blood flow (CBF) reduction (C1-C6). Left ventricular (LV) pressure, systolic thickening (%W: sonomicrometry) of the LV anterior (AW) and posterior walls (PW), and systolic longitudinal shortening (%S: sonomicrometry) of both the anterior and posterior papillary muscles (PPM) were measured. MR was assessed by left ventricular contrast two-dimensional echocardiography. In eight dogs, all the data were adequate for analysis. In category 3 (C3: 55-70% CBF of control), %S in PPM decreased, but %W did not change significantly, and only mild MR developed in three of the eight dogs. MR clearly developed in category 4 (C4: 40-54% CBF as compared with the control stage), where %S was replaced by holosystolic lengthening and %W reduced to 50% of the control state, and total occlusion (C6) accompanied by significant thinning of both the PW and AW. Thus, the asynergy of the LVPW was needed to induce the MR in seven of the eight dogs. It was concluded that the injury of the PPM alone is not sufficient to cause MR, and the associated ischemic changes of the LV free wall as well as LV dilatation are necessary to induce severe MR.

Nifedipine-induced gingival overgrowth in rats: brief review and experimental study.

PubMed

Fu, E; Nieh, S; Hsiao, C T; Hsieh, Y D; Wikesjö, U M; Shen, E C

1998-07-01

The first case report of gingival overgrowth induced by nifedipine (NIF), a calcium-beta blocker, was in 1984. However, the association between gingival alterations and the drug therapy of sodium diphenyl hydantoinate was initially described in 1939. The purpose of the experimental study was to examine the effect of NIF on gingival morphology in an animal model. Forty-five male Sprague-Dawley rats were randomly divided into 3 groups. Animals in each group daily received NIF in dimethyl sulfoxide by gastric feeding at a dosage of 0 (control), 30, or 50 mg/kg body weight for 9 weeks. Gingival gross morphology was assessed tri-weekly from stone models obtained from the mandibular incisal region. Animals were sacrificed at the end of study and tissue blocks were processed for histopathologic and histometric evaluation. Histometric analysis was performed at 5 selected tissue levels. Macro- and microscopic significantly increased gingival dimensions were demonstrated in NIF-treated animals compared to control. Although a fibrovascular tissue was observed in the tooth-gingiva interface for both NIF-treated and control animals, it was thicker and appeared earlier in NIF-treated animals. The results of the present study suggest that gingival overgrowth can be induced by NIF in rats and that the gingival overgrowth appears dose dependent.

The Cell Nucleus in Physiological and Experimentally Induced Hypometabolism

NASA Astrophysics Data System (ADS)

Malatesta, M.

The main problem for manned space mission is, at present, represented by the mass penalty associated to the human presence. An efficient approach could be the induction of a hypometabolic stasis in the astronauts, thus drastically reducing the physical and psychological requirements of the crew. On the other hand, in the wild, a reduction in resource consumptions physiologi- cally occurs in certain animals which periodically enter hibernation, a hypometabolic state in which both the energy need and energy offer are kept at a minimum. During the last twelve years, we have been studying different tissues of hibernating dormice, with the aim of analyzing their features during the euthermia -hibernation-arousal cycle as well as getting insight into the mechanisms allowing adaptation to hypometabolism. We paid particular attention to the cell nucleus, as it is the site of chief metabolic functions, such as DNA replication and RNA transcription. Our observations revealed no significant modification in the basic features of cell nuclei during hibernation; however, the cell nuclei of hibernating dormice showed unusual nuclear bodies containing molecules involved in RNA pathways. Therefore, we supposed that they could represent storage/assembly sites of several factors for processing some RNA which could be slowly synthesised during hibernation and rapidly and abundantly released in early arousal in order to meet the increased metabolic needs of the cell. The nucleolus also underwent structural and molecular modifications during hibernation, maybe to continue important nucleolar functions, or, alternatively, permit a most efficient reactivation upon arousal. On the basis of the observations made in vivo , we recently tried to experimentally induce a reversible hypometabolic state in in vitro models, using cell lines derived from hibernating and non-hibernating species. By administering the synthetic opioid DADLE, we could significantly reduce both RNA transcrip- tion and

Observational Study on Safety of Prehospital BLS CPAP in Dyspnea.

PubMed

Sahu, Novneet; Matthews, Patrick; Groner, Kathryn; Papas, Mia A; Megargel, Ross

2017-12-01

appropriately monitor the status of these patients. The majority of patients who received CPAP by BLS providers had improvement in their clinical status and vital signs. The findings suggest that CPAP can be safely used by BLS providers with appropriate training. Sahu N , Matthews P , Groner K , Papas MA , Megargel R . Observational study on safety of prehospital BLS CPAP in dyspnea. Prehosp Disaster Med. 2017;32(6):610-614.

Immunologic responses in corn snakes (Pantherophis guttatus) after experimentally induced infection with ferlaviruses.

PubMed

Neul, Annkatrin; Schrödl, Wieland; Marschang, Rachel E; Bjick, Tina; Truyen, Uwe; von Buttlar, Heiner; Pees, Michael

2017-04-01

OBJECTIVE To measure immunologic responses of snakes after experimentally induced infection with ferlaviruses. ANIMALS 42 adult corn snakes (Pantherophis guttatus) of both sexes. PROCEDURES Snakes were inoculated intratracheally with genogroup A (n = 12), B (12), or C (12) ferlavirus (infected groups) or cell-culture supernatant (6; control group) on day 0. Three snakes from each infected group were euthanized on days 4, 16, 28, and 49, and 3 snakes from the control group were euthanized on day 49. Blood samples were collected from live snakes on days -6 (baseline), 4, 16, 28, and 49. Hematologic tests were performed and humoral responses assessed via hemagglutination-inhibition assays and ELISAs. Following euthanasia, gross pathological and histologic evaluations and virus detection were performed. RESULTS Severity of clinical signs of and immunologic responses to ferlavirus infection differed among snake groups. Hematologic values, particularly WBC and monocyte counts, increased between days 4 and 16 after infection. A humoral response was identified between days 16 and 28. Serum IgM concentrations increased from baseline earlier than IgY concentrations, but the IgY relative increase was higher at the end of the study. The hemagglutination-inhibition assay revealed that the strongest reactions in all infected groups were against the strain with which they had been infected. Snakes infected with genogroup A ferlavirus had the strongest immune response, whereas those infected with genogroup B had the weakest responses. CONCLUSIONS AND CLINICAL RELEVANCE Results of this experimental study suggested that the ferlavirus strain with the highest virulence induced the weakest immune response in snakes.

Epigallocatechin gallate attenuates experimental non-alcoholic steatohepatitis induced by high fat diet.

PubMed

Kuzu, Nalan; Bahcecioglu, Ibrahim Halil; Dagli, Adile Ferda; Ozercan, Ibrahim Hanifi; Ustündag, Bilal; Sahin, Kazim

2008-08-01

In the present study, we examined the preventive role of epigallocatechin gallate (EGCG) in an experimental non-alcoholic steatohepatitis model induced by a high fat diet. The study included 21 male Sprague-Dawley rats, which were equally divided into three groups. The first group was fed on a standard rat diet, the second group on a high fat diet (HFD), and the third group on a HFD + EGCG. The study concluded after 6 weeks. Histopathological examination was performed. Plasma and tissue MDA levels, glucose, insulin, alanine aminotransferase (ALT), aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, triglyceride, and cholesterol levels were studied. Insulin resistance was calculated by the homeostasis model of insulin resistance method. Steatosis, inflammation, ballooning degeneration, and necrosis increased significantly in the HFD group, compared to the control group (P < 0.01). Steatosis and inflammation decreased in the HFD + EGCG group, in comparison to the HFD group (P < 0.05, for each). There was a significant decline in ALT (P < 0.01), triglyceride (P < 0.01), insulin (P < 0.05), and glucose (P < 0.05) levels in the HFD + EGCG group, when compared to the HFD group. Plasma and liver MDA levels in the HFD + EGCG group were lower than those of the HFD group; the difference was significant (P < 0.01 for each). Glutathione levels in the HFD + EGCG group was significantly higher those in the HFD group. CYP 2E1 and alpha-smooth muscle actin expression decreased in the HFD + EGCG group, in comparison to the HFD group (P < 0.01, P < 0.05, respectively). EGCG reduces the development of experimental non-alcoholic steatohepatitis induced by a high fat diet. It seems to exercise this effect through its effect on lipid metabolism and antioxidant characteristics.

Isolation, characterization and antihyperlipidemic activity of secoisolariciresinol diglucoside in poloxamer-407-induced experimental hyperlipidemia.

PubMed

Zanwar, Anand A; Hegde, Mahabaleshwar V; Rojatkar, Supada R; Sonawane, Kiran B; Rajamohanan, P R; Bodhankar, Subhash L

2014-09-01

Linum usitatissimum L. (Linaceae), commonly known as flaxseed, is a good source of dietary fiber and lignans. Earlier we reported cardioprotective, antihyperlipidemic, and in vitro antioxidant activity of flax lignan concentrate (FLC) obtained from flaxseed. To isolate secoisolariciresinol diglucoside (SDG) from FLC and to evaluate the antihyperlipidemic activity of SDG in poloxamer-407 (P-407)-induced hyperlipidaemic mice. FLC was subjected to column chromatography and further subjected to preparative HPTLC to isolate SDG. The chemical structure of the isolated compound was elucidated by UV, IR, (1)H NMR, (13)C NMR, DEPT, COSY, HSQC, HMBC, ROESY, MS, and specific optical rotation was recorded. Further, we have investigated the antihyperlipidaemic effect of SDG (20 mg/kg) in P-407-induced hyperlipidaemic rats. Hyperlipidaemia was induced by intraperitoneal administration of P-407 (30% w/v). Serum lipid parameters such as total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) levels were measured. The structure and stereochemistry of the isolated compound were confirmed on the basis of 1D and 2D spectral data and characterized as SDG. Finally, isolated pure SDG was screened using a P-407-induced mice model for its antihyperlipidemic action using serum lipid parameters. The isolated SDG (20 mg/kg) significantly reduced serum cholesterol, triglyceride (p < 0.001), very low-density lipoprotein (p < 0.05), and non-significantly increased HDL-C. Finally, it was concluded unequivocally that SDG showed antihyperlipidaemic effects in P-407-induced hyperlipidaemic mice. Isolated pure SDG confirms that SDG is beneficial in the prevention of experimental hyperlipidemia in laboratory animals.

Acid-induced changes in DOC quality in an experimental whole-lake manipulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donahue, W.F.; Schindler, D.W.; Page, S.J.

1998-10-01

Fluorescence analyses of archived water samples were used to typify dissolved organic carbon (DOC) quality in experimentally acidified lakes and reference lakes at the Experimental Lakes Area, in northwestern Ontario. Carbon-specific DOC fluorescence (CSF) during peak acidification was 40--50% of that for a high-DOC reference lake and similar to a low-DOC reference lake. Reference lakes showed similar but smaller decreases in CSF during several years of prolonged drought in the late 1980s. During the 1990s, recovery from acidification resulted in increased CSF, whereas reference lakes remained unchanged during the same time period. In addition to causing decreased [DOC], acidification causesmore » changes in fluorescence-peak geometry that indicate a switch in DOC quality from allochthonous to autochthonous-like during acidification. The acid-induced change in DOC quality was likely due to increased chemical oxidation or precipitation of the UV-absorbent aromatic portions of allochthonous DOC molecules, leaving more UV-transparent aliphatic chains. The change in the nature of DOC following acidification and drought may have an important role in physical, biological, and chemical processes within these lakes. With recovery from acidification, DOC quality has also recovered.« less

Left Ventricular Thrombus as a Complication of Clozapine-Induced Cardiomyopathy: A Case Report and Brief Literature Review.

PubMed

Malik, Shahbaz A; Malik, Sarah; Dowsley, Taylor F; Singh, Balwinder

2015-01-01

A 48-year-old male with history of schizoaffective disorder on clozapine presented with chest pain, dyspnea, and new left bundle branch block. He underwent coronary angiography, which revealed no atherosclerosis. The patient's workup was unrevealing for a cause for the cardiomyopathy and thus it was thought that clozapine was the offending agent. The patient was taken off clozapine and started on guideline directed heart failure therapy. During the course of hospitalization, he was also discovered to have a left ventricular (LV) thrombus for which he received anticoagulation. To our knowledge, this is the first case report of clozapine-induced cardiomyopathy complicated by a LV thrombus.

Oral Administration of Ginseng Ameliorates Cyclosporine-Induced Pancreatic Injury in an Experimental Mouse Model

PubMed Central

Lim, Sun Woo; Doh, Kyoung Chan; Jin, Long; Piao, Shang Guo; Heo, Seong Beom; Zheng, Yu Fen; Bae, Soo Kyung; Chung, Byung Ha; Yang, Chul Woo

2013-01-01

Background This study was performed to investigate whether ginseng has a protective effect in an experimental mouse model of cyclosporine-induced pancreatic injury. Methods Mice were treated with cyclosporine (30 mg/kg/day, subcutaneously) and Korean red ginseng extract (0.2 or 0.4 g/kg/day, oral gavage) for 4 weeks while on a 0.01% salt diet. The effect of ginseng on cyclosporine-induced pancreatic islet dysfunction was investigated by an intraperitoneal glucose tolerance test and measurements of serum insulin level, β cell area, macrophage infiltration, and apoptosis. Using an in vitro model, we further examined the effect of ginseng on a cyclosporine-treated insulin-secreting cell line. Oxidative stress was measured by the concentration of 8-hydroxy-2′-deoxyguanosine in serum, tissue sections, and culture media. Results Four weeks of cyclosporine treatment increased blood glucose levels and decreased insulin levels, but cotreatment with ginseng ameliorated the cyclosporine-induced glucose intolerance and hyperglycemia. Pancreatic β cell area was also greater with ginseng cotreatment compared with cyclosporine monotherapy. The production of proinflammatory molecules, such as induced nitric oxide synthase and cytokines, and the level of apoptotic cell death also decreased in pancreatic β cell with ginseng treatment. Consistent with the in vivo results, the in vitro study showed that the addition of ginseng protected against cyclosporine-induced cytotoxicity, inflammation, and apoptotic cell death. These in vivo and in vitro changes were accompanied by decreases in the levels of 8-hydroxy-2′-deoxyguanosine in pancreatic β cell in tissue section, serum, and culture media during cotreatment of ginseng with cyclosporine. Conclusions The results of our in vivo and in vitro studies demonstrate that ginseng has a protective effect against cyclosporine-induced pancreatic β cell injury via reducing oxidative stress. PMID:24009697

Crosstalk between the angiotensin and endothelin system in the cerebrovasculature after experimental induced subarachnoid hemorrhage.

PubMed

Wanderer, Stefan; Mrosek, Jan; Vatter, Hartmut; Seifert, Volker; Konczalla, Juergen

2018-04-01

Under physiologic conditions, losartan showed a dose-dependent antagonistic effect to the endothelin-1 (ET-1)-mediated vasoconstriction. This reduced vasoconstriction was abolished after preincubation with an endothelin B 1 receptor (ET(B 1 )-receptor) antagonist. Also, an increased ET(B 1 )-receptor-dependent relaxation to sarafotoxin S6c (S6c; an ET(B 1 )-receptor agonist) was detected by preincubation with losartan. Investigations after experimental induced subarachnoid hemorrhage (SAH) are still missing. Therefore, we analyzed losartan in a further pathological setup. Cerebral vasospasm was induced by a modified double hemorrhage model. Rats were sacrificed on day 3 and isometric force of basilar artery ring segments was measured. Parallel to physiological conditions, after SAH, the ET-1-induced vasoconstriction was decreased by preincubation with losartan. This reduced contraction has been abolished after preincubation with BQ-788, an ET(B 1 )-receptor antagonist. In precontracted vessels, ET-1 induced a higher vasorelaxation under losartan and the endothelin A receptor (ET(A)-receptor) antagonist BQ-123. After SAH, losartan caused a modulatory effect on the ET(B 1 )-receptor-dependent vasorelaxation. It further induced an upregulation of the NO pathway. Under losartan, the formerly known loss of the ET(B 1 )-receptor vasomotor function was abolished and a significantly increased relaxation, accompanied with an enhanced sensitivity of the ET(B 1 )-receptor, has been detected. Also, the dose-dependent antagonistic effect to the ET-1-induced contraction can be effected by angiotensin II type 1 receptor (AT 1 -receptor) antagonism due to losartan directly via the ET(B 1 )-receptor.

[Karyometry of BBN-induced precancerosis of the urothelium : An experimental analysis].

PubMed

Dahm, H H; Lehnen-Holtum, V; Rübben, H

2016-10-01

The morphology of experimental precancerous lesions of the urinary bladder has been interpreted quite differently by various authors. The aim of this investigation was to quantify these lesions by karyometry and, thus, to gain a more reliable understanding of the process. A total of 60 Wistar rats were fed with N‑butyl-N-(4-hydroxybutyl)nitrosamine (BBN) at a concentration of 0.05 % in their drinking water to induce preneoplastic changes of the urothelium. After the second week of BBN exposition, 6 animals were killed every 2 weeks up to week 20. Smears of the scraped off urothelium of 3 urinary bladders of each group were analyzed cytologically and karyometrically. BBN exposition led to statistically significant changes of the karyometric values using the χ 2 test to differentiate the control animals from the ones that had ingested BBN and the 2‑week groups from each other. These changes consisted mainly in significant deviations of the size of the nuclear area within the different groups. Morphological and karyometrical analysis showed that biologically relevant stages in the development of chemically induced urothelial precancerous lesions could be realized much earlier than had been assumed in recent publications. Karyometric analysis offered a valid basis to describe the early morphologic alterations of carcinogenesis.

Effects of losartan on experimental varicocele-induced testicular germ cell apoptosis.

PubMed

Bolat, D; Oltulu, F; Uysal, A; Kose, T; Gunlusoy, B; Yigitturk, G; Turk, N S; Turan, T

2016-09-01

To investigate the potential protective effects of losartan on varicocele-induced germ cell apoptosis, 24 adult male Sprague Dawley rats were divided into three groups: a sham operation was performed in SHAM group, and experimental left varicocele was created in VAR and VAR + LOS groups. Additionally, in VAR + LOS group, losartan was administered for 30 days starting on the day of surgery. At the end of 30 days, all animals were sacrificed and left orchiectomy was performed. Testicular injury and spermatogenesis were evaluated according to Johnsen scoring system. To assess the nitrosative stress, immunohistochemical staining for endothelial nitric oxide synthase was used and evaluated by H-score and apoptotic index (AI) of germ cells was analysed by TUNEL method. A significant decrease in the mean Johnsen score (JS) was observed in VAR group compared with SHAM (p < .001). The mean H-score and AI were significantly higher in VAR group compared with SHAM (p < .001). After losartan administration, mean JS was significantly increased (p < .001) and mean H-score and AI were significantly decreased compared with VAR group (p < .001 and .01, respectively). Findings of this suggest that losartan acts as a potent protective agent against varicocele-induced germ cell apoptosis. © 2016 Blackwell Verlag GmbH.

Drug-Induced by Systemic Lupus Erythematosus Presenting as Recurrent Pericardial Effusion After Mitral Valve Repair.

PubMed

Haydari, Aghigh; Sabzi, Feridoun; Dabiri, Samsam; Poormotaabed, Alireza

2017-09-01

We report a patient presented with recurrent pericardial effusion caused by drug-induced systemic lupus Erythematosus (SLE) following mitral valve repair. The surgery was complicated by hemiparesis and convulsion in early postoperative period. The patient had been received carbamazepine for a paroxysmal seizure that occurred following mitral valve repair. The post operative computed tomography showed embolic stroke and its sequel (seizure) that treated with carbamazepine. In the 3rd month of follow-up, however, hemiparesis recovered by physiotherapy but carbamazepine was not discontinued as by request of neurologist. In the 6th month of surgery, the patient admitted by dyspnea and massive pericardial effusion that treated by subxiphoid drainage. This event was re occurred in two times in a short time frame and each event treated by surgical approach. The serologic exam in the last admission revealed drug-induced lupus erythematosus. The carbamazepine as an anti convulsive drug has been described to cause LE like disease in multiple case reports. Laboratory exam exhibited the possibility of carbamazepine-induced lupus in our case, with the extremely rare presentation of recurrent massive pericardial effusion.

RhoA/ROCK may involve in cardiac hypertrophy induced by experimental hyperthyroidism.

PubMed

Na, Wang; Peng, Guan; Jianping, Zhang; Yanzhong, Chang; Shengjiang, Guan; Li, Chu

2012-10-01

In this study, the role of the RhoA/Rho-kinase (RhoA/ROCK)-signaling pathway in cardiovascular dysfunction associated with hyperthyroidism was examined with the use of fasudil, a Rho-kinase inhibitor. Male Spraque-Dawley rats were treated with l-thyroxine (T(4)) alone, T(4) + low-dose fasudil (2 mg/kg/day) or T(4) + high-dose fasudil (10 mg/kg/day) and compared with control animals. Rats in the T(4) group showed an increase in the ratio of heart weight to body weight, which was ameliorated by fasudil at both low and high doses. Morphometric and hemodynamic parameters were also evaluated and confirmed that fasudil attenuated the cardiac hypertrophy induced by T(4). The extent of phosphorylation of the myosin phosphatase targeting subunit was quantified by Western blotting to evaluate the activity of Rho-kinase in the heart tissue. Both Western blotting and reverse transcriptase-polymerase chain reaction analyses revealed enhancement of Rho-kinase and activator protein 1 activity and reduction of c-FLIP(L) expression in the T(4) group, and this response was inhibited by fasudil in a dose-dependent manner. Furthermore, fasudil inhibited apoptosis induced by T(4) as evidenced by the detection of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and the expressions of bax and bcl-2. These results suggested that the RhoA/ROCK pathway is involved in the cardiac hypertrophy induced by experimental hyperthyroidism. The antagonism of this pathway may thus be useful as an alternative target in the treatment of hyperthyroid heart disease.

Experimental evaluation of the pressure and temperature dependence of ion-induced nucleation.

PubMed

Munir, Muhammad Miftahul; Suhendi, Asep; Ogi, Takashi; Iskandar, Ferry; Okuyama, Kikuo

2010-09-28

An experimental system for the study of ion-induced nucleation in a SO(2)/H(2)O/N(2) gas mixture was developed, employing a soft x-ray at different pressure and temperature levels. The difficulties associated with these experiments included the changes in physical properties of the gas mixture when temperature and pressure were varied. Changes in the relative humidity (RH) as a function of pressure and temperature also had a significant effect on the different behaviors of the mobility distributions of particles. In order to accomplish reliable measurement and minimize uncertainties, an integrated on-line control system was utilized. As the pressure decreased in a range of 500-980 hPa, the peak concentration of both ions and nanometer-sized particles decreased, which suggests that higher pressure tended to enhance the growth of particles nucleated by ion-induced nucleation. Moreover, the modal diameters of the measured particle size distributions showed a systematic shift to larger sizes with increasing pressure. However, in the temperature range of 5-20 °C, temperature increases had no significant effects on the mobility distribution of particles. The effects of residence time, RH (7%-70%), and SO(2) concentration (0.08-6.7 ppm) on ion-induced nucleation were also systematically investigated. The results show that the nucleation and growth were significantly dependent on the residence time, RH, and SO(2) concentration, which is in agreement with both a previous model and previous observations. This research will be inevitable for a better understanding of the role of ions in an atmospheric nucleation mechanism.

Assessing potential abiotic and biotic complications of crayfish-induced gravel transport in experimental streams

NASA Astrophysics Data System (ADS)

Statzner, Bernhard; Peltret, Odile

2006-03-01

Biogeomorphology adds the element "biological dynamics" (of populations or communities) to chemical and physical geomorphic factors and thus complicates the framework of geomorphic processes. Such biological complications of the animal-induced transport of solids in streams should be particularly important in crayfish, as crayfish affect this transport through their overall activity and intraspecific aggression levels, which could be modified by shelter availability or the establishment of dominance hierarchies among individuals not knowing each other. Using experimental streams, we tested these hypotheses by measuring how shelter availability or residential crayfish group invasion by unknown individuals affected the impact of the crayfish Orconectes limosus on the (i) transport of gravel at baseflow (during 12 experimental days); (ii) sediment surface characteristics (after 12 days); and (iii) critical shear stress causing incipient gravel motion during simulated floods (after 12 days). The two potentially important factors shelter availability or residential group invasion negligibly affected the crayfish impact on gravel sediments, suggesting that habitat unfamiliarity (a third potentially important factor affecting crayfish activity) should increase the crayfish-induced sediment transport. Because habitat unfamiliarity is associated with sporadic long-distance migrations of a few crayfish individuals, this third factor should play a minor role in real streams, where crayfish biomass should be a key factor in relations with crayfish effects on sediments. Therefore, we combined the results of this study with those of previous crayfish experiments to assess how crayfish biomass could serve in modelling the gravel transport. Crayfish biomass explained 47% of the variability in the baseflow gravel transport and, in combination with the coefficient of variation of the bed elevation and algal cover, 72% of the variability in the critical gravel shear stress. These

[Experimental study on TCRbeta idiotypic antigenic determinants DNA vaccine to induce anti-lymphoma antibodies].

PubMed

Zhang, Yeping; Zhu, Ping; Shi, Yongjin; Liu, Jihua; Pu, Dingfang; Cao, Xianghong; Zhu, Qiang; Wang, Yijia; Ma, Mingxin; Yu, Jiren

2002-02-01

To investigate the anti-human CEM lymphoma cell activities induced by TCR idiotypic DNA vaccine containing different antigen determinants in BALB/c mice. The specific rearranged gene fragment encoding TCRVbeta region of CEM cell line was obtained by RT-PCR technique. The PCR product was cloned into eukaryocytic expression vector pcDNA3, which was used as DNA vaccine and template for PCR amplifying different antigen determinant. Gene fragments encoding different antigen determinant were amplified and cloned into pcDNA3, separately. The experimental mice were immunized by intramuscular injection of the DNA vaccines. The specific anti-idiotype antibodies were detected by indirect immunofluorescence assay. TCRbetaV of CEM cell line contains five antigen determinants. Specific anti-idiotype antibody was detected in all of the six mice immunized with DNA vaccine containing all the five determinants (the highest titer was 1:480). Although the antibody could also be detected in four of the six mice immunized with DNA vaccine containing four of the five antigen determinants, the antibody titer was lower (the highest titer was 1:80). DNA vaccine containing two of the five determinants could not induce the specific antibody. The idiotypic DNA vaccine containing the whole TCRbetaV five antigen determinants could induce the specific anti-lymphoma idiotypic antibody in BALB/c mice.

Protective effect of Corchorus olitorius leaves on sodium arsenite-induced toxicity in experimental rats.

PubMed

Das, Anup K; Bag, Sujit; Sahu, Ranabir; Dua, Tarun K; Sinha, Mohit K; Gangopadhyay, Moumita; Zaman, Kamaruz; Dewanjee, Saikat

2010-01-01

The present study was undertaken to evaluate the protective effect of aqueous extract of Corchorus olitorius leaves (AECO) against sodium arsenite-induced toxicity in experimental rats. The animals exposed to sodium arsenite at a dose of 10mg/kg body weight p.o. for 10days exhibited a significant inhibition (p<0.01) of hepatic and renal antioxidant enzymes namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase and glutathione reductase. In addition, arsenic intoxication significantly decreased (p<0.01) the level of reduced glutathione and increased (p<0.01) the levels of oxidized glutathione and thiobarbituric acid reactive substances in selected tissues. Treatment with AECO at doses of 50 and 100mg/kg body weight p.o. for 15days prior to arsenic intoxication significantly improved hepatic and renal antioxidant markers in a dose dependant manner. AECO treatment also significantly reduced the arsenic-induced DNA fragmentation of hepatic and renal tissues. Histological studies on the ultrastructural changes of liver and kidney supported the protective activity of the AECO. The results concluded that the treatment with AECO prior to arsenic intoxication has significant role in protecting animals from arsenic-induced hepatic and renal toxicity. Copyright 2009 Elsevier Ltd. All rights reserved.

Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization.

PubMed

Lee, Jung Eun; Kim, Koung Li; Kim, Danbi; Yeo, Yeongju; Han, Hyounkoo; Kim, Myung Goo; Kim, Sun Hwa; Kim, Hyuncheol; Jeong, Ji Hoon; Suh, Wonhee

2017-01-01

Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders.

Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization

PubMed Central

Lee, Jung Eun; Kim, Koung Li; Kim, Danbi; Yeo, Yeongju; Han, Hyounkoo; Kim, Myung Goo; Kim, Sun Hwa; Kim, Hyuncheol; Jeong, Ji Hoon; Suh, Wonhee

2017-01-01

Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders. PMID:28740387

Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

PubMed Central

Mohd Sairazi, Nur Shafika; Sirajudeen, K. N. S.; Asari, Mohd Asnizam; Muzaimi, Mustapha; Mummedy, Swamy; Sulaiman, Siti Amrah

2015-01-01

Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS). In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA). KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration. PMID:26793262

Antiinflammatory effects of Cordia myxa fruit on experimentally induced colitis in rats.

PubMed

Al-Awadi, F M; Srikumar, T S; Anim, J T; Khan, I

2001-05-01

Products of certain species of Cordia are reported to have antiinflammatory properties. In the present study we examined the effects of Cordia myxa fruit on experimentally induced colitis in rats. Colitis was induced by intrarectal administration of 4% acetic acid. Colitic, normal, and corresponding control animals were included. Body weight was recorded daily. All the animals were sacrificed 4 days after the fruit treatment. Colitis was monitored histologically and by activity of myeloperoxidase. Glutathione peroxidase, superoxide dismutase, as well as total antioxidant status and concentrations of zinc, copper, manganese, selenium, and iron were assayed in plasma, liver, and colon using standard methods. Histology of the colon of colitic rats showed acute colitis that was confirmed by a significant increase in the myeloperoxidase activity. Colitis was associated with significant decreases in the tissue activities of glutathione peroxidase and superoxide dismutase and lower concentrations of trace elements. Histologic examination and myeloperoxidase activity showed that the fruit treatment reversed the above findings in the inflamed colon, and in liver and plasma of colitic rats. The present results suggest that the observed antiinflammatory effect of the Cordia myxa may be attributed partly to its antioxidant property and to restoration of the levels of trace elements in the inflamed colon, liver, and plasma.

[Case of loxoprofen sodium-induced eosinophilic pneumonia that occurred ipsilaterally after VATS lobectomy for lung cancer].

PubMed

Izumo, Takehiro; Kondo, Mitsuko; Mae, Masahiro; Onizawa, Shigemitsu; Nagara, Naoki; Nozu, Tomoko; Tamaoki, Jun; Ohnuki, Takamasa; Nagai, Atsushi

2007-10-01

A 76-year-old man was admitted because of dry cough and dyspnea two weeks after VATS lobectomy for lung cancer. Chest radiographs and computed tomography showed interstitial shadows in the only operative lung side. Although antibiotic drugs were given because we believed it to be postoperative pneumonia, abnormal shadows on chest radiographs increased. A bronchoalveolar lavage fluid (BALF) study performed on the 21" day after operation showed that the proportions of eosinophils, basophils and mast cells had increased, and the CD4/CD8 ratio was 4.42. The drug lymphocyte stimulation test for loxoprofen sodium was positive. Based on the clinical course, laboratory data and BALF study, we arrived at a diagnosis of drug-induced pneumonia caused by loxoprofen sodium. Treatment with corticosteroid resulted in marked improvement of the chest radiographs and clinical findings. Drug-induced pneumonia usually occurs bilaterally, but it occurred only on the operative side in this case. Although rare, it is important to recognize that unilateral drug-induced pneumonia is one of the differential diagnose of postoperative pneumonia.

Experimental Assessment and Enhancement of Planar Laser-Induced Fluorescence Measurements of Nitric Oxide in an Inverse Diffusion Flame

NASA Technical Reports Server (NTRS)

Partridge, William P.; Laurendeau, Normand M.

1997-01-01

We have experimentally assessed the quantitative nature of planar laser-induced fluorescence (PLIF) measurements of NO concentration in a unique atmospheric pressure, laminar, axial inverse diffusion flame (IDF). The PLIF measurements were assessed relative to a two-dimensional array of separate laser saturated fluorescence (LSF) measurements. We demonstrated and evaluated several experimentally-based procedures for enhancing the quantitative nature of PLIF concentration images. Because these experimentally-based PLIF correction schemes require only the ability to make PLIF and LSF measurements, they produce a more broadly applicable PLIF diagnostic compared to numerically-based correction schemes. We experimentally assessed the influence of interferences on both narrow-band and broad-band fluorescence measurements at atmospheric and high pressures. Optimum excitation and detection schemes were determined for the LSF and PLIF measurements. Single-input and multiple-input, experimentally-based PLIF enhancement procedures were developed for application in test environments with both negligible and significant quench-dependent error gradients. Each experimentally-based procedure provides an enhancement of approximately 50% in the quantitative nature of the PLIF measurements, and results in concentration images nominally as quantitative as LSF point measurements. These correction procedures can be applied to other species, including radicals, for which no experimental data are available from which to implement numerically-based PLIF enhancement procedures.

Influence of sildenafil and donepezil administration on the serum redox balance in experimentally induced lower limb critical ischemia.

PubMed

Constantinescu, Mihaela Ioana; Constantinescu, Dan Petru; Andercou, Aurel; Mironiuc, Ion Aurel

2013-01-01

Chronic lower limb ischemia (CLLI) leads to endothelial cell dysfunctions and endothelial lesions. The use of substances that release nitric oxide and activate endothelial nitric oxide synthase has proved to be useful in increasing angiogenesis and arteriogenesis under critical ischemia conditions. To investigate the therapeutic effect of Sildenafil and Donepezil with a vasodilating action in experimentally induced CLLI and on serum redox homeostasis. The research was performed in 3 groups of rats (n=10 animals/group) with experimentally induced CLLI: group I - control group; group II - animals treated postoperatively with a therapeutic dose of sildenafil, and group III - animals treated postoperatively with a therapeutic dose of donepezil. Oxidative stress (OS) indicators (malondialdehyde - MDA, protein carbonyls - PC), antioxidant (AO) defense indicators (reduced glutathione - GSH and oxidized glutathione - GSSH), and ceruloplasmin (CP) were determined on days 7, 14, 21 and 30. Statistical processing was performed using the Excel application (Microsoft Office 2007), with the StatsDirect v.2.7.2 software. Changes in OS were evidenced in all groups on account of a decrease in MDA and PC. The greatest OS decrease in all groups was on day 30. AO defence changes were represented by decreased levels of GSH and GSSG in all groups, at the studied moments. Intracellular AO defense in the cytosol, nucleus and mitochondria was similar in all groups, (decreased GSH, GSSG and GSH/GSSG ratio). We found increased extracellular levels of GSH, GSSG, and CP and increased extracellular GSH/GSSG ratio at level compared to values on day 7. 1) The administration of sildenafil (group II) and donepezil (group III) has favorable effects on reducing OS in experimentally induced CLLI. 2) Sildenafil and Donepezil administration stimulates extracellular AO defense on account of CP. 3) Sildenafil and Donepezil administration influences intracellular redox homeostasis on account of the GSH

Schistosoma mansoni Tegument (Smteg) Induces IL-10 and Modulates Experimental Airway Inflammation.

PubMed

Marinho, Fábio Vitarelli; Alves, Clarice Carvalho; de Souza, Sara C; da Silva, Cintia M G; Cassali, Geovanni D; Oliveira, Sergio C; Pacifico, Lucila G G; Fonseca, Cristina T

2016-01-01

Previous studies have demonstrated that S. mansoni infection and inoculation of the parasite eggs and antigens are able to modulate airways inflammation induced by OVA in mice. This modulation was associated to an enhanced production of interleukin-10 and to an increased number of regulatory T cells. The S. mansoni schistosomulum is the first stage to come into contact with the host immune system and its tegument represents the host-parasite interface. The schistosomula tegument (Smteg) has never been studied in the context of modulation of inflammatory disorders, although immune evasion mechanisms take place in this phase of infection to guarantee the persistence of the parasite in the host. The aim of this study was to evaluate the Smteg ability to modulate inflammation in an experimental airway inflammation model induced by OVA and to characterize the immune factors involved in this modulation. To achieve the objective, BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with OVA aerosol after Smteg intraperitoneal inoculation. Protein extravasation and inflammatory cells were assessed in bronchoalveolar lavage and IgE levels were measured in serum. Additionally, lungs were excised for histopathological analyses, cytokine measurement and characterization of the cell populations. Inoculation with Smteg led to a reduction in the protein levels in bronchoalveolar lavage (BAL) and eosinophils in both BAL and lung tissue. In the lung tissue there was a reduction in inflammatory cells and collagen deposition as well as in IL-5, IL-13, IL-25 and CCL11 levels. Additionally, a decrease in specific anti-OVA IgE levels was observed. The reduction observed in these inflammatory parameters was associated with increased levels of IL-10 in lung tissues. Furthermore, Smteg/asthma mice showed high percentage of CD11b+F4/80+IL-10+ and CD11c+CD11b+IL-10+ cells in lungs. Taken together, these findings demonstrate that S. mansoni schistosomula tegument can modulates

Experimental validation of tunable features in laser-induced plasma resonators

NASA Astrophysics Data System (ADS)

Colón Quiñones, Roberto A.; Cappelli, Mark A.

2017-08-01

Measurements are presented which examine the use of gaseous plasma elements as highly-tunable resonators. The resonator considered here is a laser-induced plasma kernel generated by focusing the fundamental output from a Q-switched Nd:YAG laser through a lens and into a gas at constant pressure. The near-ellipsoidal plasma element interacts with incoming microwave radiation through excitation of low-order, electric-dipole resonances similar to those seen in metallic spheres. The tunability of these elements stems from the dispersive nature of plasmas arising from their variable electron density, electron momentum transfer collision frequency, and the concomitant e↵ect of these properties on the excited surface plasmon resonance. Experiments were carried out in the Ku band of the microwave spectrum to characterize the scattering properties of these resonators for di↵erent values of electron density. The experimental results are compared with results from theoretical approximations and finite element method electromagnetic simulations. The described tunable resonators have the potential to be used as the building blocks in a new class of all-plasma metamaterials with fully three-dimensional structural flexibility.

Experimental autoimmune prostatitis induces microglial activation in the spinal cord.

PubMed

Wong, Larry; Done, Joseph D; Schaeffer, Anthony J; Thumbikat, Praveen

2015-01-01

The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host's immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S14-S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain. Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF. Our data show that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain. © 2014 Wiley Periodicals, Inc.

Experimental autoimmune prostatitis induces microglial activation in the spinal cord

PubMed Central

Wong, Larry; Done, Joseph D.; Schaeffer, Anthony J.; Thumbikat, Praveen

2014-01-01

Background The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host’s immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. Methods Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S4–S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain. Results Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF. Conclusion Our data shows that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain. PMID:25263093

Cost-effectiveness of quantitative pretest probability intended to reduce unnecessary medical radiation exposure in emergency department patients with chest pain and dyspnea.

PubMed

Troyer, Jennifer L; Jones, Alan E; Shapiro, Nathan I; Mitchell, Alice M; Hewer, Ian; Kline, Jeffrey A

2015-05-01

Quantitative pretest probability (qPTP) incorporated into a decision support tool with advice can reduce unnecessary diagnostic testing among patients with symptoms suggestive of acute coronary syndrome (ACS) and pulmonary embolism (PE), reducing 30-day costs without an increase in 90-day adverse outcomes. This study estimates long-term (beyond 90-day) costs and outcomes associated with qPTP. The authors hypothesized that qPTP reduces lifetime costs and improves outcomes in low-risk patients with symptoms suggestive of ACS and PE. This was a cost-effectiveness analysis of a multicenter, randomized controlled trial of adult emergency patients with dyspnea and chest pain, in which a clinician encountering a low-risk patient with symptoms suggestive of ACS or PE conducted either the intervention (qPTP for ACS and PE with advice) or the sham (no qPTP and no advice). Effect of the intervention over a patient's lifetime was assessed using a Markov microsimulation model. Short-term costs and outcomes were from the trial; long-term outcomes and costs were from the literature. Outcomes included lifetime transition to PE, ACS, and intracranial hemorrhage (ICH); mortality from cancer, ICH, PE, ACS, renal failure, and ischemic stroke; quality-adjusted life-years (QALYs); and total medical costs compared between simulated intervention and sham groups. Markov microsimulation for a 40-year-old patient receiving qPTP found lifetime cost savings of $497 for women and $528 for men, associated with small gains in QALYs (2 and 6 days, respectively) and lower rates of cancer mortality in both sexes, but a reduction in ICH only in males. Sensitivity analysis for patients aged 60 years predicted that qPTP would continue to save costs and also reduce mortality from both ICH and cancer. Use of qPTP significantly reduced the lifetime probability of PE diagnosis, with lower probability of death from PE in both sexes aged 40 to 60 years. However, use of qPTP reduced the rate of ACS

Mechanisms controlling the oxygen consumption in experimentally induced hypochloremic alkalosis in calves.

PubMed

Cambier, Carole; Clerbaux, Thierry; Amory, Hélène; Detry, Bruno; Florquin, Sandra; Marville, Vincent; Frans, Albert; Gustin, Pascal

2002-01-01

. It may be concluded that, despite reduced oxygen delivery, oxygen consumption is maintained during experimentally induced hypochloremic alkalosis in healthy 10-30 day old calves.

Evaluation of anti-urolithiatic activity of Pashanabhedadi Ghrita against experimentally induced renal calculi in rats

PubMed Central

Gupta, Sanjay Kumar; Baghel, Madhav Singh; Bhuyan, Chaturbhuja; Ravishankar, B.; Ashok, B. K.; Patil, Panchakshari D.

2012-01-01

Population in an industrialized world is afflicted by urinary stone disease. Kidney stones are common in all kinds of urolithiasis. One distinguished formulation mentioned by Sushruta for management of Ashmari (urolithiasis) is Pashanabhedadi Ghrita (PBG), which is in clinical practice since centuries. Validation of drug is the requirement of time through the experimental study. In this study, trial of PBG has been made against ammonium oxalate rich diet and gentamicin injection induced renal calculi in albino rats. The calculi were induced by gentamicin injection and ammonium oxalate rich diet. Test drug was administered concomitantly in the dose of 900 mg/kg for 15 consecutive days. Rats were sacrificed on the 16th day. Parameters like kidney weight, serum biochemical, kidney tissue and histopathology of kidney were studied. Concomitant treatment of PBG attenuates blood biochemical parameters non-significantly, where as it significantly attenuated lipid peroxidation and enhanced glutathione and glutathione peroxidase activities. It also decreased crystal deposition markedly into the renal tubules in number as well as size and prevented damage to the renal tubules. The findings showed that PBG is having significant anti-urolithiatic activities against ammonium oxalate rich diet plus gentamicine injection induced urolithiasis in rats. PMID:23723654

Evaluation of anti-urolithiatic activity of Pashanabhedadi Ghrita against experimentally induced renal calculi in rats.

PubMed

Gupta, Sanjay Kumar; Baghel, Madhav Singh; Bhuyan, Chaturbhuja; Ravishankar, B; Ashok, B K; Patil, Panchakshari D

2012-07-01

Population in an industrialized world is afflicted by urinary stone disease. Kidney stones are common in all kinds of urolithiasis. One distinguished formulation mentioned by Sushruta for management of Ashmari (urolithiasis) is Pashanabhedadi Ghrita (PBG), which is in clinical practice since centuries. Validation of drug is the requirement of time through the experimental study. In this study, trial of PBG has been made against ammonium oxalate rich diet and gentamicin injection induced renal calculi in albino rats. The calculi were induced by gentamicin injection and ammonium oxalate rich diet. Test drug was administered concomitantly in the dose of 900 mg/kg for 15 consecutive days. Rats were sacrificed on the 16(th) day. Parameters like kidney weight, serum biochemical, kidney tissue and histopathology of kidney were studied. Concomitant treatment of PBG attenuates blood biochemical parameters non-significantly, where as it significantly attenuated lipid peroxidation and enhanced glutathione and glutathione peroxidase activities. It also decreased crystal deposition markedly into the renal tubules in number as well as size and prevented damage to the renal tubules. The findings showed that PBG is having significant anti-urolithiatic activities against ammonium oxalate rich diet plus gentamicine injection induced urolithiasis in rats.

EXPERIMENTALLY INDUCED CHANGES IN NASAL MUCOUS SECRETORY SYSTEMS AND THEIR EFFECT ON VIRUS INFECTION IN CHICKENS

PubMed Central

Bang, Betsy G.; Bang, Frederik B.

1969-01-01

The domestic chicken was used as an experimental model in which to demonstrate morphological and functional relationships of nasal organ systems, principally of mucous systems. Mucous secretions of olfactory, respiratory, lacrimal, and accessory areas were found to have clear histochemical differences, yet were sufficiently miscible in normal circumstances to form an unbroken, synchronously moving sheet. Changes induced experimentally in host physiology did not all affect the mucous components of given areas in the same way or to the same degree. Mucosal changes were produced by the following methods: Topically administered cocaine 20%, in a single application, temporarily paralyzed the cilia, and the consequently reduced traction apparently held mucus in the acini and effected a temporary lag in mucus excretion. Three successive applications caused acute acinar depletion and ciliary paralysis. Hexylcaine chloride 5% immediately desquamated all intranasal epithelia, damaged the proximal portion of the acini, and induced acinar exhaustion and mucosal inflammation—effects not overcome within 5½ days. Internal dehydration produced progressively viscous mucus, severe acinar gaping with mucus anchored in the acini, a heavy surface sheet, and deceleration or arrest of mucociliary flow. Avitaminosis A induced reduction in the height (about 50%) of all mucosae and acini, especially the inner lining of the maxillary concha, caused an actual 50% reduction in the number of cells per acinus, and retarded the mucociliary flow rate about 50%. Pilocarpine induced initial hypersecretion, later exhaustion, and, still later, slow production of densely staining mucus in the acinar cells; also acinar gaping. Breeding in a germfree environment produced a greatly reduced mucosal depth throughout the nasal fossa, an extraordinary reduction in the number of cells per acinus, relative reduction in the number of acinar neck cells, and concomitant increase in ciliated cells in that region

Minocycline attenuates experimental colitis in mice by blocking expression of inducible nitric oxide synthase and matrix metalloproteinases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, T.-Y.; Division of Gastroenterology and Hepatology, Tri-Service General Hospital, Taipei, Taiwan; Chu, H.-C.

2009-05-15

In addition to its antimicrobial activity, minocycline exerts anti-inflammatory effects in several disease models. However, whether minocycline affects the pathogenesis of inflammatory bowel disease has not been determined. We investigated the effects of minocycline on experimental colitis and its underlying mechanisms. Acute and chronic colitis were induced in mice by treatment with dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS), and the effect of minocycline on colonic injury was assessed clinically and histologically. Prophylactic and therapeutic treatment of mice with minocycline significantly diminished mortality rate and attenuated the severity of DSS-induced acute colitis. Mechanistically, minocycline administration suppressed inducible nitricmore » oxide synthase (iNOS) expression and nitrotyrosine production, inhibited proinflammatory cytokine expression, repressed the elevated mRNA expression of matrix metalloproteinases (MMPs) 2, 3, 9, and 13, diminished the apoptotic index in colonic tissues, and inhibited nitric oxide production in the serum of mice with DSS-induced acute colitis. In DSS-induced chronic colitis, minocycline treatment also reduced body weight loss, improved colonic histology, and blocked expression of iNOS, proinflammatory cytokines, and MMPs from colonic tissues. Similarly, minocycline could ameliorate the severity of TNBS-induced acute colitis in mice by decreasing mortality rate and inhibiting proinflammatory cytokine expression in colonic tissues. These results demonstrate that minocycline protects mice against DSS- and TNBS-induced colitis, probably via inhibition of iNOS and MMP expression in intestinal tissues. Therefore, minocycline is a potential remedy for human inflammatory bowel diseases.« less

Establishment of a novel experimental protocol for drug-induced seizure liability screening based on a locomotor activity assay in zebrafish.

PubMed

Koseki, Naoteru; Deguchi, Jiro; Yamashita, Akihito; Miyawaki, Izuru; Funabashi, Hitoshi

2014-08-01

As drug-induced seizures have severe impact on drug development, evaluating seizure induction potential of candidate drugs at the early stages of drug discovery is important. A novel assay system using zebrafish has attracted interest as a high throughput toxicological in vivo assay system, and we tried to establish an experimental method for drug-induced seizure liability on the basis of locomotor activity in zebrafish. We monitored locomotor activity at high-speed movement (> 20 mm/sec) for 60 min immediately after exposure, and assessed seizure liability potential in some drugs using locomotor activity. However this experimental procedure was not sufficient for predicting seizures because the potential of several drugs with demonstrated seizure potential in mammals was not detected. We, therefore, added other parameters for locomotor activity such as extending exposure time or conducting flashlight stimulation (10 Hz) which is a known seizure induction stimulus, and these additional parameters improved seizure potential detection in some drugs. The validation study using the improved methodology was used to assess 52 commercially available drugs, and the prediction rate was approximately 70%. The experimental protocol established in this present study is considered useful for seizure potential screening during early stages of drug discovery.

Cell therapy with bone marrow mononuclear cells in elastase-induced pulmonary emphysema.

PubMed

Longhini-Dos-Santos, Nathalia; Barbosa-de-Oliveira, Valter Abraão; Kozma, Rodrigo Heras; Faria, Carolina Arruda de; Stessuk, Talita; Frei, Fernando; Ribeiro-Paes, João Tadeu

2013-04-01

Emphysema is characterized by destruction of alveolar walls with loss of gas exchange surface and consequent progressive dyspnea. This study aimed to evaluate the efficiency of cell therapy with bone marrow mononuclear cells (BMMC) in an animal model of elastase-induced pulmonary emphysema. Emphysema was induced in C57Bl/J6 female mice by intranasal instillation of elastase. After 21 days, the mice received bone marrow mononuclear cells from EGFP male mice with C57Bl/J6 background. The groups were assessed by comparison and statistically significant differences (p < 0.05) were observed among the groups treated with BMMC and evaluated after 7, 14 and 21 days. Analysis of the mean linear intercept (Lm) values for the different groups allowed to observe that the group treated with BMMC and evaluated after 21 days showed the most significant result. The group that received no treatment showed a statistically significant difference when compared to other groups, except the group treated and evaluated after 21 days, evidencing the efficacy of cell therapy with BMMC in pulmonary emphysema.

The impact of naloxegol on anal sphincter function - Using a human experimental model of opioid-induced bowel dysfunction.

PubMed

Grønlund, Debbie; Poulsen, Jakob L; Krogh, Klaus; Brock, Christina; Liao, Donghua; Gregersen, Hans; Drewes, Asbjørn M; Olesen, Anne E

2018-05-30

Opioid treatment interferes with anal sphincter function and its regulation during defecation. This may result in straining, incomplete evacuation, and contribute to opioid-induced bowel dysfunction (OIBD). Employing an experimental model of oxycodone-induced OIBD, we hypothesized that co-administration of the peripherally acting μ-opioid antagonist naloxegol would improve anal sphincter function in comparison to placebo. In a double-blind randomized crossover trial, 24 healthy males were assigned to a six-day treatment of oral oxycodone 15 mg twice daily in combination with either oral naloxegol 25 mg once daily or placebo. At baseline and at day 6, anal resting pressure and the recto-anal inhibitory reflex (RAIR) were evaluated using manometry and rectal balloon distension. Furthermore, the functional lumen imaging probe was used to measure distensibility of the anal canal. Gastrointestinal symptoms were assessed with the Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire and the Bristol Stool Form Scale. During oxycodone treatment, naloxegol improved RAIR-induced sphincter relaxation by 15% (-45.9 vs -38.8 mm Hg; P < 0.01). No differences in anal resting pressure and anal canal distensibility were found between treatments (all P > 0.5). Naloxegol improved PAC-SYM symptoms (mean score over days; 2.6 vs 4.5, P < 0.001) and improved stool consistency scores (mean score over days; 3.3 vs 2.9, P < 0.01). In this experimental model of OIBD, naloxegol improved the RAIR and reduced gastrointestinal symptoms. Hence, in contrast to conventional laxatives, naloxegol may regulate opioid-induced anal sphincter dysfunction and facilitate the defecation process. Copyright © 2018 Elsevier B.V. All rights reserved.

Experimental study of microwave-induced thermoacoustic imaging

NASA Astrophysics Data System (ADS)

Jacobs, Ryan T.

Microwave-Induced Thermoacoustic Imaging (TAI) is a noninvasive hybrid modality which improves contrast by using thermoelastic wave generation induced by microwave absorption. Ultrasonography is widely used in medical practice as a low-cost alternative and supplement to magnetic resonance imaging (MRI). Although ultrasonography has relatively high image resolution (depending on the ultrasonic wavelength at diagnostic frequencies), it suffers from low image contrast of soft tissues. In this work samples are irradiated with sub-microsecond electromagnetic pulses inducing acoustic waves in the sample that are then detected with an unfocused transducer. The advantage of this hybrid modality is the ability to take advantage of the microwave absorption coefficients which provide high contrast in tissue samples. This in combination with the superior spatial resolution of ultrasound waves is important to providing a low-cost alternative to MRI and early breast cancer detection methods. This work describes the implementation of a thermoacoustic experiment using a 5 kW peak power microwave source.

Differential cholinoceptor modulation of nitric oxide isoforms in experimentally-induced inflammation of dental pulp tissue.

PubMed

De Couto Pita, A; Passafaro, D; Ganzinelli, S; Borda, E; Sterin-Borda, L

2009-06-01

The aim of the study was to investigate the role of muscarinic acetylcholine receptor (mAChR) activity in the regulation of endothelial (e), neuronal (n) and inducible (i) nitric oxide synthase (NOS) activity and expression in experimentally induced inflammation of rat dental pulp tissue. Inflammation was induced by application of bacterial lipopolysaccharide (LPS) to the pulp. Extirpated pulp-tissue samples were incubated in saline solution until the various experiments were performed. Saline-treated pulp and healthy pulp tissues were used as controls. NOS activity was measured by the production of [U-(14)C]-citrulline from [U-(14)C]-arginine. Nitrite/nitrate assay was evaluated by the conversion of nitrate to nitrite in the presence of nicotinamide adenine dinucleotide phosphate. i-nos, e-nos and n-nos mRNA levels were measured using reverse-transcriptase polymerase chain reaction by co-amplification of target cDNA with a single set of primers. Application of LPS to the pulp increased NOS activity and nitrate production (P < 0.001), generated by iNOS over-activity and expression. Pilocarpine acting on mAChRs triggered a biphasic action on NOS activity and NO accumulation. At low concentrations, pilocarpine induced a negative effect associated with a decrease in i-nos mRNA level, whilst at high concentration, it produced a positive effect associated with increased e-nos and n-nos mRNA levels. In control pulp tissue, only the positive effect of pilocarpine was observed. Irreversible pulpitis changes mAChR conformation increasing its efficiency of coupling to transducing molecules that in turn induce activate iNOS. The capacity of pilocarpine to prevent NO accumulation and iNOS activity, by acting on mAChR mutation induced by pulpitis, might be useful therapeutically as a local treatment.

Porphyromonas gingivalis Peptidylarginine Deiminase, a Key Contributor in the Pathogenesis of Experimental Periodontal Disease and Experimental Arthritis

PubMed Central

Gully, Neville; Bright, Richard; Marino, Victor; Marchant, Ceilidh; Cantley, Melissa; Haynes, David; Butler, Catherine; Dashper, Stuart; Reynolds, Eric; Bartold, Mark

2014-01-01

Objectives To investigate the suggested role of Porphyromonas gingivalis peptidylarginine deiminase (PAD) in the relationship between the aetiology of periodontal disease and experimentally induced arthritis and the possible association between these two conditions. Methods A genetically modified PAD-deficient strain of P. gingivalis W50 was produced. The effect of this strain, compared to the wild type, in an established murine model for experimental periodontitis and experimental arthritis was assessed. Experimental periodontitis was induced following oral inoculation with the PAD-deficient and wild type strains of P. gingivalis. Experimental arthritis was induced via the collagen antibody induction process and was monitored by assessment of paw swelling and micro-CT analysis of the radio-carpal joints. Experimental periodontitis was monitored by micro CT scans of the mandible and histological assessment of the periodontal tissues around the mandibular molars. Serum levels of anti-citrullinated protein antibodies (ACPA) and P. gingivalis were assessed by ELISA. Results The development of experimental periodontitis was significantly reduced in the presence of the PAD-deficient P. gingivalis strain. When experimental arthritis was induced in the presence of the PAD-deficient strain there was less paw swelling, less erosive bone damage to the joints and reduced serum ACPA levels when compared to the wild type P. gingivalis inoculated group. Conclusion This study has demonstrated that a PAD-deficient strain of P. gingivalis was associated with significantly reduced periodontal inflammation. In addition the extent of experimental arthritis was significantly reduced in animals exposed to prior induction of periodontal disease through oral inoculation of the PAD-deficient strain versus the wild type. This adds further evidence to the potential role for P. gingivalis and its PAD in the pathogenesis of periodontitis and exacerbation of arthritis. Further studies are now

Polymer-coated compliant receivers for intact laser-induced forward transfer of thin films: experimental results and modelling

NASA Astrophysics Data System (ADS)

Feinaeugle, Matthias; Horak, Peter; Sones, Collin L.; Lippert, Thomas; Eason, Rob W.

2014-09-01

In this study, we investigate both experimentally and numerically laser-induced forward transfer (LIFT) of thin films to determine the role of a thin polymer layer coating the receiver with the aim of modifying the rate of deceleration and reduction of material stress preventing intact material transfer. A numerical model of the impact phase during LIFT shows that such a layer reduces the modelled stress. The evolution of stress within the transferred deposit and the substrate as a function of the thickness of the polymer layer, the transfer velocity and the elastic properties of the polymer are evaluated. The functionality of the polymer layer is verified experimentally by LIFT printing intact 1- m-thick bismuth telluride films and polymeric light-emitting diode pads onto a layer of 12-m-thick polydimethylsiloxane and 50-nm-thick poly(3,4-ethylenedioxythiophene) blended with poly(styrenesulfonate) (PEDOT:PSS), respectively. Furthermore, it is demonstrated experimentally that the introduction of such a compliant layer improves adhesion between the deposit and its substrate.

Chronic stress induced disruption of the peri-infarct neurovascular unit following experimentally induced photothrombotic stroke.

PubMed

Zhao, Zidan; Ong, Lin Kooi; Johnson, Sarah; Nilsson, Michael; Walker, Frederick R

2017-12-01

How stress influences brain repair is an issue of considerable importance, as patients recovering from stroke are known to experience high and often unremitting levels of stress post-event. In the current study, we investigated how chronic stress modified the key cellular components of the neurovascular unit. Using an experimental model of focal cortical ischemia in male C57BL/6 mice, we examined how exposure to a persistently aversive environment, induced by the application of chronic restraint stress, altered the cortical remodeling post-stroke. We focused on systematically investigating changes in the key components of the neurovascular unit (i.e. neurons, microglia, astrocytes, and blood vessels) within the peri-infarct territories using both immunohistochemistry and Western blotting. The results from our study indicated that exposure to chronic stress exerted a significant suppressive effect on each of the key cellular components involved in neurovascular remodeling. Co-incident with these cellular changes, we observed that chronic stress was associated with an exacerbation of motor impairment 42 days post-event. Collectively, these results highlight the vulnerability of the peri-infarct neurovascular unit to the negative effects of chronic stress.

Effects of drug treatment on inflammation and hyperreactivity of airways and on immune variables in cats with experimentally induced asthma.

PubMed

Reinero, Carol R; Decile, Kendra C; Byerly, Jenni R; Berghaus, Roy D; Walby, William E; Berghaus, Londa J; Hyde, Dallas M; Schelegle, Edward S; Gershwin, Laurel J

2005-07-01

To compare the effects of an orally administered corticosteroid (prednisone), an inhaled corticosteroid (flunisolide), a leukotriene-receptor antagonist (zafirlukast), an antiserotonergic drug (cyproheptadine), and a control substance on the asthmatic phenotype in cats with experimentally induced asthma. 6 cats with asthma experimentally induced by the use of Bermuda grass allergen (BGA). A randomized, crossover design was used to assess changes in the percentage of eosinophils in bronchoalveolar lavage fluid (BALF); airway hyperresponsiveness; blood lymphocyte phenotype determined by use of flow cytometry; and serum and BALF content of BGA-specific IgE, IgG, and IgA determined by use of ELISAs. Mean +/- SE eosinophil percentages in BALF when cats were administered prednisone (5.0 +/- 2.3%) and flunisolide (2.5 +/- 1.7%) were significantly lower than for the control treatment (33.7 +/- 11.1%). We did not detect significant differences in airway hyperresponsiveness or lymphocyte surface markers among treatments. Content of BGA-specific IgE in serum was significantly lower when cats were treated with prednisone (25.5 +/- 5.4%), compared with values for the control treatment (63.6 +/- 12.9%); no other significant differences were observed in content of BGA-specific immunoglobulins among treatments. Orally administered and inhaled corticosteroids decreased eosinophilic inflammation in airways of cats with experimentally induced asthma. Only oral administration of prednisone decreased the content of BGA-specific IgE in serum; no other significant local or systemic immunologic effects were detected among treatments. Inhaled corticosteroids can be considered as an alternate method for decreasing airway inflammation in cats with asthma.

In vitro and in vivo experimental studies on trabecular meshwork degeneration induced by benzalkonium chloride (an American Ophthalmological Society thesis).

PubMed

Baudouin, Christophe; Denoyer, Alexandre; Desbenoit, Nicolas; Hamm, Gregory; Grise, Alice

2012-12-01

Long-term antiglaucomatous drug administration may cause irritation, dry eye, allergy, subconjunctival fibrosis, or increased risk of glaucoma surgery failure, potentially due to the preservative benzalkonium chloride (BAK), whose toxic, proinflammatory, and detergent effects have extensively been shown experimentally. We hypothesize that BAK also influences trabecular meshwork (TM) degeneration. Trabecular specimens were examined using immunohistology and reverse transcriptase-polymerase chain reaction. A trabecular cell line was stimulated by BAK and examined for apoptosis, oxidative stress, fractalkine and SDF-1 expression, and modulation of their receptors. An experimental model was developed with BAK subconjunctival injections to induce TM degeneration. Mass spectrometry (MS) imaging assessed BAK penetration after repeated instillations in rabbit eyes. Trabecular specimens showed extremely low densities of trabecular cells and presence of cells expressing fractalkine and fractalkine receptor and their respective mRNAs. Benzalkonium in vitro induced apoptosis, oxidative stress, and fractalkine expression and inhibited the protective chemokine SDF-1 and Bcl2, also inducing a sustained intraocular pressure (IOP) increase, with dramatic apoptosis of trabecular cells and reduction of aqueous outflow. MS imaging showed that BAK could access the TM at measurable levels after repeated instillations. BAK enhances all characteristics of TM degeneration typical of glaucoma-trabecular apoptosis, oxidative stress, induction of inflammatory chemokines-and causes degeneration in acute experimental conditions, potentially mimicking long-term accumulation. BAK was also shown to access the TM after repeated instillations. These findings support the hypothesis that antiglaucoma medications, through toxicity of their preservative, may cause further long-term trabecular degeneration and therefore enhance outflow resistance, reducing the impact of IOP-lowering agents.

GM-CSF-Induced Regulatory T cells Selectively Inhibit Anti-Acetylcholine Receptor-Specific Immune Responses in Experimental Myasthenia Gravis

PubMed Central

Sheng, Jian Rong; Muthusamy, Thiruppathi; Prabahakar, Bellur S.; Meriggioli, Matthew N.

2011-01-01

We and others have demonstrated the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) to suppress autoimmunity by increasing the number of CD4+CD25+ regulatory T cells (Tregs). In the current study, we have explored the critical role of induced antigen specific Tregs in the therapeutic effects of GM-CSF in murine experimental autoimmune myasthenia gravis (EAMG). Specifically, we show that Tregs from GM-CSF treated EAMG mice (GM-CSF/AChR-induced-Tregs) adoptively transferred into animals with EAMG suppressed clinical disease more potently than equal numbers of Tregs from either GM-CSF untreated EAMG mice or healthy mice treated with GM-CSF. In addition, GM-CSF/AChR-induced-Tregs selectively suppressed antigen specific T cell proliferation induced by AChR relative to that induced by an irrelevant self antigen, (thyroglobulin) and failed to significantly alter T cell proliferation in response to an exogenous antigen (ovalbumin). These results are consistent with the hypothesized mechanism of action of GM-CSF involving the mobilization of tolerogenic dendritic cell precursors which, upon antigen (AChR) capture, suppress the anti-AChR immune response through the induction/expansion of AChR-specific Tregs. PMID:22099723

Microscopic evaluation of induced tooth movement after subluxation trauma: an experimental study in rats

PubMed Central

Busato, Mauro Carlos Agner; Pereira, Alex Luiz Pozzobon; Sonoda, Celso Koogi; Cuoghi, Osmar Aparecido; de Mendonça, Marcos Rogério

2014-01-01

Objective The objective of this study was to assess the histological alterations that occurred in the periodontal area of rat molars submitted to induced tooth movement (ITM) right after an intentional trauma (subluxation). Methods Forty adult male Wistar rats (Rattus norvegicus albinus) were selected. The animals were divided into eight groups (n = 5), according to the combination of variables: Group 1 - control (neither trauma nor ITM); Group 2 - ITM; Groups 3, 4, 5 and 6 - dentoalveolar trauma groups corresponding, respectively, to 1, 3, 8 and 10 days after trauma; Groups 7 and 8 - the animals' molars were subjected to a 900 cN impact and, one and three days after the trauma event, tooth movement was induced. The rats' maxillary first molars were mesially moved during seven days with a closed coil (50 cN). After the experimental period of each group, the animals were sacrificed by anesthetic overdose and the right maxillas were removed and processed for histological analysis under light microscopy. Results In the animals of group 3, 4, 5 and 6, the histological alterations were not very significant. Consequently, the effect of induced tooth movement right after a subluxation event (groups 7 and 8) was very similar to those described for Group 2. Conclusion There was no difference in the quality of periodontal repair when ITM was applied to teeth that had suffered a subluxation trauma. PMID:24713565

Evaluation of liposome-encapsulated butorphanol tartrate for alleviation of experimentally induced arthritic pain in green-cheeked conures (Pyrrhura molinae)

PubMed Central

Paul-Murphy, Joanne R.; Krugner-Higby, Lisa A.; Tourdot, Renee L.; Sladky, Kurt K.; Klauer, Julia M.; Keuler, Nicholas S.; Brown, Carolyn S.; Heath, Timothy D.

2014-01-01

Objective To evaluate injection of microcrystalline sodium urate (MSU) for inducing articular pain in green-cheeked conures (Pyrrhura molinae) and the analgesic efficacy of liposome-encapsulated butorphanol tartrate (LEBT) by use of weight load data, behavioral scores, and fecal corticosterone concentration. Animals 8 conures. Procedures In a crossover study, conures were randomly assigned to receive LEBT (15 mg/kg) or liposomal vehicle subsequent to experimental induction of arthritis or sham injection. The MSU was injected into 1 tibiotarsal-tarsometatarsal (intertarsal) joint to induce arthritis (time 0). Weight-bearing load and behavioral scores were determined at 0, 2, 6, 26, and 30 hours. Results MSU injection into 1 intertarsal joint caused a temporary decrease in weight bearing on the affected limb. Treatment of arthritic conures with LEBT resulted in significantly more weight bearing on the arthritic limb than treatment with vehicle. Administration of vehicle to arthritic conures caused a decrease in activity and feeding behaviors during the induction phase of arthritis, but as the arthritis resolved, there was a significant increase in voluntary activity at 30 hours and feeding behaviors at 26 and 30 hours, compared with results for LEBT treatment of arthritic birds. Treatment with LEBT or vehicle in conures without arthritis resulted in similar measurements for weight bearing and voluntary and motivated behaviors. Conclusions and Clinical Relevance Experimental induction of arthritis in conures was a good method for evaluating tonic pain. Weight-bearing load was the most sensitive measure of pain associated with induced arthritis. Pain associated with MSU-induced arthritis was alleviated by administration of LEBT. PMID:19795935

Analytical and experimental study of mean flow and turbulence characteristics inside the passages of an axial flow inducer

NASA Technical Reports Server (NTRS)

Gorton, C. A.; Lakshminarayana, B.

1980-01-01

The inviscid and viscid effects existing within the passages of a three bladed axial flow inducer operating at a flow coefficient of 0.065 are investigated. The blade static pressure and blade limiting streamline angle distributions were determined and the three components of mean velocity, turbulence intensities, and turbulence stresses were measured at locations inside the inducer blade passage utilizing a rotating three sensor hotwire probe. Applicable equations were derived for the hotwire data reduction analysis and solved numerically to obtain the appropriate flow parameters. The three dimensional inviscid flow in the inducer was predicted by numerically solving the exact equations of motion, and the three dimensional viscid flow was predicted by incorporating the dominant viscous terms into the exact equations. The analytical results are compared with the experimental measurements and design values where appropriate. Radial velocities are found to be of the same order as axial velocities within the inducer passage, confirming the highly three dimensional characteristic of inducer flow. Total relative velocity distribution indicate a substantial velocity deficiency near the tip at mid-passage which expands significantly as the flow proceeds toward the inducer trailing edge. High turbulence intensities and turbulence stresses are concentrated within this core region. Considerable wake diffusion occurs immediately downstream of the inducer trailing edge to decay this loss core. Evidence of boundary layer interactions, blade blockage effects, radially inward flows, annulus wall effects, and backflows are all found to exist within the long, narrow passages of the inducer.

Morphological and immunobiochemical analysis of the liver in L-arginine induced experimental chronic pancreatitis.

PubMed

Hu, Na; Shen, Yicong; Liu, Fengyu; Wu, Jiuping; Yuan, Feng; Tian, Liwei; Wu, Bo; Chen, Guoqing; Zhang, Jianming; Wang, Jun

Clinical evidence indicates that hepatic abnormalities in patients with chronic pancreatitis are not uncommon. Here we aimed to study the possible association between liver and pancreatic damage in a recently described experimental mouse model of CP. The severity of the damage to pancreas, liver and other organs was assessed by biochemical markers and histopathology. The methods applied included Hematoxylin Eosin staining, electron microscope examination, biochemical measurements, RT-PCR, ELISA, and the correlations among some of the parameters contributing to these changes were statistically analyzed. The hepatic aberrations were mainly represented by mild infiltration of inflammatory cells in portal triad and congestion of central vein of liver, and the main features of drug-induced hepatotoxicity could not be observed. Severe fibrosis of pancreatic tissue was noticed in experimental group, and the existence of multiple organ injuries was also seen under the microscope. Hepatic pathologic scores were positively correlated with those from the corresponding pancreatic specimens (r = 0.72, P < 0.01). TGF-β1 protein levels significantly elevated both in the test pancreas and liver (P < 0.05) and these values were positively correlated (r = 0.86, P < 0.01). The level of interleukin-1β was increased in the serum and tissue of the liver. In addition, cardiac troponin (Tn-I) level not only significantly increased in myocardial homogenates (P < 0.05) but also was positively correlated with the corresponding pathologic score of the liver (r = 0.88, P < 0.01). The liver aberrations might be associated with L-arginine induced chronic pancreatitis. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Autoantibody profile in the experimental model of scleroderma induced by type V human collagen

PubMed Central

Callado, Maria R M; Viana, Vilma S T; Vendramini, Margarete B G; Leon, Elaine P; Bueno, Cleonice; Velosa, Ana P P; Teodoro, Walcy R; Yoshinari, Natalino H

2007-01-01

The aim of this study is to evaluate the humoral autoimmune response in the experimental model of systemic sclerosis (SSc) induced by human type V collagen (huCol V). New Zealand rabbits were immunized with huCol V in Freund's complete adjuvant (FCA) and boosted twice with 15 days intervals with huCol V in Freund's incomplete adjuvant. Control groups included animals injected only with FCA or bovine serum albumin. Bleeding was done at days 0, 30, 75 and 120. Tissue specimens were obtained for histopathological investigation. Serological analysis included detection of antibodies against huCol V and anti-topoisomerase I (Anti-Scl70) by enzyme-linked immunosorbent assay, antinuclear antibodies (ANA) by indirect immunofluorescence, and rheumatoid factor (RF) by a latex agglutination test. Target antigens were characterized by immunoblot. Histological analysis revealed extracellular matrix remodeling with fibrosis and vasculitis. Anti-Scl70 and ANA were detected as early as 30 days in all huCol V animals. The universal ANA staining pattern was Golgi-like. This serum reactivity was not abolished by previous absorption with huCol V. Characterization of the target antigen by immunoblot revealed two major protein fractions of 175 000 and 220 000 MW. Similarly to ANA, there was a gradual increase of reactivity throughout the immunization and also it was not abolished by preincubation of serum samples with huCol V. RF testing was negative in hyperimmune sera. Conclusion: The production of autoantibodies, including anti-Scl70, a serological marker for SSc associated with histopathological alterations, validates huCol V induced-experimental model and brings out its potential for understanding the pathophysiology of SSc. PMID:17442023

Immunologic and hematologic responses in ponies with experimentally induced Strongylus vulgaris infection.

PubMed

Bailey, M; Martin, S C; Lloyd, S

1989-08-01

Immunologic and hematologic responses were examined in 4 ponies with experimentally induced Strongylus vulgaris infection and in 5 helminth-free ponies. Two ponies were inoculated with 200 larvae and 2 were inoculated with 700 larvae of S vulgaris and then were reinoculated with the same numbers of larvae 34 weeks later. Initial response of the ponies inoculated with S vulgaris was S vulgaris antigen-induced lymphocyte response that developed 1.5 to 3 weeks after inoculation and did not persist. Development of antigen-reactive lymphocytes was followed sequentially by a biphasic complement-fixing antibody response, then biphasic eosinophilia. Antibody titer to S vulgaris antigen was higher in ponies inoculated with 700 larvae, compared with that in ponies given 200 larvae of S vulgaris. Also, the second peak in antibody titer and in absolute number of eosinophils was observed earlier in ponies inoculated with 700 larvae, compared with ponies inoculated with 200 S vulgaris larvae, and subsided before or from about 24 weeks after inoculation. The prepatent period for S vulgaris infection was 24 to 25 weeks. After reinoculation with S vulgaris, a degree of increased lymphocyte responsiveness was apparent but, by 17 weeks after reinoculation, only the primary peak in the absolute number of eosinophils indicated an anamnestic response. Essentially, antibody was not detectable after reinoculation.

Could Perinatal Asphyxia Induce a Synaptopathy? New Highlights from an Experimental Model

PubMed Central

Herrera, María Inés; Udovin, Lucas Daniel; Kusnier, Carlos; Kölliker-Frers, Rodolfo; de Souza, Wanderley

2017-01-01

Birth asphyxia also termed perinatal asphyxia is an obstetric complication that strongly affects brain structure and function. Central nervous system is highly susceptible to oxidative damage caused by perinatal asphyxia while activation and maturity of the proper pathways are relevant to avoiding abnormal neural development. Perinatal asphyxia is associated with high morbimortality in term and preterm neonates. Although several studies have demonstrated a variety of biochemical and molecular pathways involved in perinatal asphyxia physiopathology, little is known about the synaptic alterations induced by perinatal asphyxia. Nearly 25% of the newborns who survive perinatal asphyxia develop neurological disorders such as cerebral palsy and certain neurodevelopmental and learning disabilities where synaptic connectivity disturbances may be involved. Accordingly, here we review and discuss the association of possible synaptic dysfunction with perinatal asphyxia on the basis of updated evidence from an experimental model. PMID:28326198

Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain.

PubMed

Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H; Porreca, Frank

2017-12-01

Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients.

Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain

PubMed Central

Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H.; Porreca, Frank

2017-01-01

Gabapentin is a first-line therapy for neuropathic pain but its mechanisms and sites of action remain uncertain. We investigated gabapentin-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal gabapentin reversed evoked mechanical hypersensitivity, produced conditioned place preference (CPP) and dopamine release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal gabapentin also significantly inhibited dorsal horn wide dynamic range (WDR) neuronal responses to a range of evoked stimuli in SNL rats. In contrast, gabapentin microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP and elicited NAc dopamine release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on WDR neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous gabapentin-induced CPP and NAc dopamine release but failed to block its inhibition of tactile allodynia. Gabapentin therefore can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from non-opioid analgesics, gabapentin requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of gabapentin’s analgesic effects in patients. PMID:28832395

Experimentally induced thyrotoxicosis leads to increased connectivity in temporal lobe structures: a resting state fMRI study.

PubMed

Göttlich, Martin; Heldmann, Marcus; Göbel, Anna; Dirk, Anna-Luise; Brabant, Georg; Münte, Thomas F

2015-06-01

Adult onset hyperthyroidism may impact on different cognitive domains, including attention and concentration, memory, perceptual function, language and executive function. Previous PET studies implicated changed functionality of limbic regions, the temporal and frontal lobes in hyperthyroidism, whereas it is unknown whether cognitive effects of hyperthyroidism may be due to changed brain connectivity. This study aimed to investigate the effect of experimentally induced short-term hyperthyroidism thyrotoxicosis on resting-state functional connectivity using functional magnetic resonance imaging. Twenty-nine healthy male right-handed subjects were examined twice, once prior and once after 8 weeks of oral administration of 250 μg levothyroxine per day. Resting-state fMRI was subjected to graph-theory based analysis methods to investigate whole-brain intrinsic functional connectivity. Despite a lack of subjective changes noticed by the subjects significant thyrotoxicosis was confirmed in all subjects. This induced a significant increase in resting-state functional connectivity specifically in the rostral temporal lobes (0.05 FDR corrected at the cluster level), which is caused by an increased connectivity to the cognitive control network. The increased connectivity between temporal poles and the cognitive control network shown here under experimental conditions supports an important function of thyroid hormones in the regulation of paralimbic structures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Experimental investigation of a supersonic swept ramp injector using laser-induced iodine fluorescence

NASA Technical Reports Server (NTRS)

Hartfield, Roy J.; Hollo, Steven D.; Mcdaniel, James C.

1990-01-01

Planar measurements of injectant mole fraction and temperature have been conducted in a nonreacting supersonic combustor configured with underexpanded injection in the base of a swept ramp. The temperature measurements were conducted with a Mach 2 test section inlet in streamwise planes perpendicular to the test section wall on which the ramp was mounted. Injection concentration measurements, conducted in cross flow planes with both Mach 2 and Mach 2.9 free stream conditions, dramatically illustrate the domination of the mixing process by streamwise vorticity generated by the ramp. These measurements, conducted using a nonintrusive optical technique (laser-induced iodine fluorescence), provide an accurate and extensive experimental data base for the validation of computation fluid dynamic codes for the calculation of highly three-dimensional supersonic combustor flow fields.

Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic-pituitary-adrenal axis.

PubMed

Johnson, Elizabeth O; Kamilaris, Themis C; Calogero, Aldo E; Gold, Philip W; Chrousos, George P

2005-07-01

Previous studies on the effects of altered thyroid function on the secretion and metabolism of adrenocortical hormones suggest a degree of adrenocortical hyperactivity in hyperthyroidism. We have previously shown that experimentally-induced hyperthyroidism is associated with significant alterations in pituitary-adrenal responsiveness to synthetic ovine corticotropin-releasing hormone (oCRH) that are contingent upon the duration of the altered thyroid function. The purpose of this study was to assess the time-dependent effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis by in vivo stimulation of the hypothalamic CRH neuron and adrenal cortex. The functional integrity of the HPA axis was examined in vivo in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given 50 mug of thyroxine every day for 7 or 60 days. Responses to insulin-induced hypoglycemia and IL-1alpha stimulation were used to assess the hypothalamic CRH neuron. Adrenocortical reserve was assessed in response to low-dose adrenocorticotropic hormone (ACTH), following suppression of the HPA axis with dexamethasone. Adrenal and thymus tissue weight, in addition to basal plasma ACTH, corticosterone and thyroid indices were also determined. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days, cerebrospinal fluid (CSF) corticosterone levels were significantly increased. Basal plasma ACTH levels were similar to controls. Although plasma ACTH responses to hypoglycemic stress and IL-1alpha administration in both short- and long-term hyperthyroidism were normal, corticosterone responses to the ACTH release during the administration of these stimuli were significantly increased. The adrenal reserve was significantly elevated in short-term hyperthyroidsim. Long-term hyperthyroidism, however, was associated

The effect of spinal manipulative therapy on experimentally induced pain: a systematic literature review

PubMed Central

2012-01-01

Background Although there is evidence that spinal manipulative therapy (SMT) can reduce pain, the mechanisms involved are not well established. There is a need to review the scientific literature to establish the evidence-base for the reduction of pain following SMT. Objectives To determine if SMT can reduce experimentally induced pain, and if so, if the effect is i) only at the level of the treated spinal segment, ii) broader but in the same general region as SMT is performed, or iii) systemic. Design A systematic critical literature review. Methods A systematic search was performed for experimental studies on healthy volunteers and people without chronic syndromes, in which the immediate effect of SMT was tested. Articles selected were reviewed blindly by two authors. A summary quality score was calculated to indicate level of manuscript quality. Outcome was considered positive if the pain-reducing effect was statistically significant. Separate evidence tables were constructed with information relevant to each research question. Results were interpreted taking into account their manuscript quality. Results Twenty-two articles were included, describing 43 experiments, primarily on pain produced by pressure (n = 27) or temperature (n = 9). Their quality was generally moderate. A hypoalgesic effect was shown in 19/27 experiments on pressure pain, produced by pressure in 3/9 on pain produced by temperature and in 6/7 tests on pain induced by other measures. Second pain provoked by temperature seems to respond to SMT but not first pain. Most studies revealed a local or regional hypoalgesic effect whereas a systematic effect was unclear. Manipulation of a “restricted motion segment” (“manipulable lesion”) seemed not to be essential to analgesia. In relation to outcome, there was no discernible difference between studies with higher vs. lower quality scores. Conclusions These results indicate that SMT has a direct local/regional hypoalgesic effect on

Effects of melatonin on lipid peroxidation and anti-oxidant enzyme activity in rats with experimentally induced hyperthyroidism.

PubMed

Baydas, Burhanettin; Meral, Ismail

2005-07-01

1. The present study was designed to investigate the effects of high-dose melatonin on lipid peroxidation and anti-oxidant enzyme activity in rats with experimentally induced hyperthyroidism. 2. Twenty-four albino male rats, weighing 240-260 g, were randomly allotted into one of three experimental groups (control, hyperthyroid and hyperthyroid + melatonin treatment), with each group containing eight animals. Hyperthyroidism was induced by a daily with i.p. injection of 200 microg l-thyroxine for 30 days. In addition to l-thyroxin treatment, rats in the hyperthyroid + melatonin treatment group were also given daily i.p. injections of 10 mg/kg melatonin on the last 10 days of l-thyroxine treatment. Control animals received injections of an equivalent volume of saline solution. Rats received the last injection 24 h before being killed. 3. At the end of the experiment, rats in all three groups were fasted for 12 h and killed by cardiac puncture under ether anaesthesia. Blood samples were taken for the determination of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) levels and concentrations of tri-iodothyronine (T(3)) and thyroxine (T(4)). 4. It was found that MDA and SOD levels and concentrations of T(3) and T(4) were higher and the GSH level was lower in rats with hyperthyroidism compared with controls. Melatonin treatment decreased the elevated MDA and SOD levels and increased the lowered GSH level to control levels in rats with hyperthyroidism, but did not ameliorate the concentrations of T(3) and T(4). 5. It was concluded that high-dose melatonin treatment may decrease the hyperthyroidism-induced disturbances of lipid peroxidation and anti-oxidant enzyme activity and oxidative damage.

Toll-like receptors-2 and 4 are overexpressed in an experimental model of particle-induced osteolysis.

PubMed

Valladares, Roberto D; Nich, Christophe; Zwingenberger, Stefan; Li, Chenguang; Swank, Katherine R; Gibon, Emmanuel; Rao, Allison J; Yao, Zhenyu; Goodman, Stuart B

2014-09-01

Aseptic loosening secondary to particle-associated periprosthetic osteolysis remains a major cause of failure of total joint replacements (TJR) in the mid- and long term. As sentinels of the innate immune system, macrophages are central to the recognition and initiation of the inflammatory cascade, which results in the activation of bone resorbing osteoclasts. Toll-like receptors (TLRs) are involved in the recognition of pathogen-associated molecular patterns and danger-associated molecular patterns. Experimentally, polymethylmethacrylate and polyethylene (PE) particles have been shown to activate macrophages via the TLR pathway. The specific TLRs involved in PE particle-induced osteolysis remain largely unknown. We hypothesized that TLR-2, -4, and -9 mediated responses play a critical role in the development of PE wear particle-induced osteolysis in the murine calvarium model. To test this hypothesis, we first demonstrated that PE particles caused observable osteolysis, visible by microCT and bone histomorphometry when the particles were applied to the calvarium of C57BL/6 mice. The number of TRAP positive osteoclasts was significantly greater in the PE-treated group when compared to the control group without particles. Finally, using immunohistochemistry, TLR-2 and TLR-4 were highly expressed in PE particle-induced osteolytic lesions, whereas TLR-9 was downregulated. TLR-2 and -4 may represent novel therapeutic targets for prevention of wear particle-induced osteolysis and accompanying TJR failure. © 2013 Wiley Periodicals, Inc.

Experimental system for the control of surgically induced infections, operating and maintenance instructions D203613-004

NASA Technical Reports Server (NTRS)

Tevebaugh, M. D.

1971-01-01

An experimental portable system used to control surgically induced infections is described. The system consists of a portable clean room comprised of a laminar flow filter system consistent with Federal standards; a helmet-shoulder pad assembly; a communication system; a helmet ventilation system; a transparent walled enclosure; and surgical gowns. Guidelines for the set up and operation of such equipment are given along with corrective steps to use in case of system malfunctions. Cleaning procedures, maintenance requirements, and disassembly and transfer particulars are included.

In Vitro and in Vivo Experimental Studies on Trabecular Meshwork Degeneration Induced by Benzalkonium Chloride (An American Ophthalmological Society Thesis)

PubMed Central

Baudouin, Christophe; Denoyer, Alexandre; Desbenoit, Nicolas; Hamm, Gregory; Grise, Alice

2012-01-01

Purpose: Long-term antiglaucomatous drug administration may cause irritation, dry eye, allergy, subconjunctival fibrosis, or increased risk of glaucoma surgery failure, potentially due to the preservative benzalkonium chloride (BAK), whose toxic, proinflammatory, and detergent effects have extensively been shown experimentally. We hypothesize that BAK also influences trabecular meshwork (TM) degeneration. Methods: Trabecular specimens were examined using immunohistology and reverse transcriptase–polymerase chain reaction. A trabecular cell line was stimulated by BAK and examined for apoptosis, oxidative stress, fractalkine and SDF-1 expression, and modulation of their receptors. An experimental model was developed with BAK subconjunctival injections to induce TM degeneration. Mass spectrometry (MS) imaging assessed BAK penetration after repeated instillations in rabbit eyes. Results: Trabecular specimens showed extremely low densities of trabecular cells and presence of cells expressing fractalkine and fractalkine receptor and their respective mRNAs. Benzalkonium in vitro induced apoptosis, oxidative stress, and fractalkine expression and inhibited the protective chemokine SDF-1 and Bcl2, also inducing a sustained intraocular pressure (IOP) increase, with dramatic apoptosis of trabecular cells and reduction of aqueous outflow. MS imaging showed that BAK could access the TM at measurable levels after repeated instillations. Conclusion: BAK enhances all characteristics of TM degeneration typical of glaucoma—trabecular apoptosis, oxidative stress, induction of inflammatory chemokines—and causes degeneration in acute experimental conditions, potentially mimicking long-term accumulation. BAK was also shown to access the TM after repeated instillations. These findings support the hypothesis that antiglaucoma medications, through toxicity of their preservative, may cause further long-term trabecular degeneration and therefore enhance outflow resistance, reducing the

Mycobacterium tuberculosis Coinfection Has No Impact on Plasmodium berghei ANKA-Induced Experimental Cerebral Malaria in C57BL/6 Mice.

PubMed

Blank, Jannike; Behrends, Jochen; Jacobs, Thomas; Schneider, Bianca E

2016-02-01

Cerebral malaria (CM) is the most severe complication of human infection with Plasmodium falciparum. The mechanisms predisposing to CM are still not fully understood. Proinflammatory immune responses are required for the control of blood-stage malaria infection but are also implicated in the pathogenesis of CM. A fine balance between pro- and anti-inflammatory immune responses is required for parasite clearance without the induction of host pathology. The most accepted experimental model to study human CM is Plasmodium berghei ANKA (PbANKA) infection in C57BL/6 mice that leads to the development of a complex neurological syndrome which shares many characteristics with the human disease. We applied this model to study the outcome of PbANKA infection in mice previously infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. Tuberculosis is coendemic with malaria in large regions in the tropics, and mycobacteria have been reported to confer some degree of unspecific protection against rodent Plasmodium parasites in experimental coinfection models. We found that concomitant M. tuberculosis infection did not change the clinical course of PbANKA-induced experimental cerebral malaria (ECM) in C57BL/6 mice. The immunological environments in spleen and brain did not differ between singly infected and coinfected animals; instead, the overall cytokine and T cell responses in coinfected mice were comparable to those in animals solely infected with PbANKA. Our data suggest that M. tuberculosis coinfection is not able to change the outcome of PbANKA-induced disease, most likely because the inflammatory response induced by the parasite rapidly dominates in mice previously infected with M. tuberculosis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

May cannabinoids prevent the development of chemotherapy-induced diarrhea and intestinal mucositis? Experimental study in the rat.

PubMed

Abalo, R; Uranga, J A; Pérez-García, I; de Andrés, R; Girón, R; Vera, G; López-Pérez, A E; Martín-Fontelles, M I

2017-03-01

The antineoplastic drug 5-fluoruracil (5-FU) is a pirimidine analog, which frequently induces potentially fatal diarrhea and mucositis. Cannabinoids reduce gastrointestinal motility and secretion and might prevent 5-FU-induced gut adverse effects. Here, we asked whether cannabinoids may prevent diarrhea and mucositis induced by 5-FU in the rat. Male Wistar rats received vehicle or the non-selective cannabinoid agonist WIN 55,212-2 (WIN; 0.5 mg kg -1 injection -1 , 1 injection day -1 , 4 consecutive days) by intraperitoneal (ip) route; on the first 2 days, animals received also saline or 5-FU (150 mg kg -1 injection -1 , cumulative dose of 300 mg kg -1 ). Gastrointestinal motor function was radiographically studied after barium contrast intragastric administration on experimental days 1 and 4. Structural alterations of the stomach, small intestine and colon were histologically studied on day 4. PAS staining and immunohistochemistry for Ki67, chromogranin A and CD163 were used to detect secretory, proliferating, and endocrine cells, and activated macrophages respectively. As shown radiographically, 5-FU induced significant gastric emptying delay (on days 1 and 4) and diarrhea (on day 4). WIN did not significantly alter the motility curves obtained for either control or 5-FU-treated animals but tended to reduce the severity of 5-FU-induced diarrhea and increased permanence of barium from day 1 to the beginning of day 4 in 5-FU-treated animals. 5-FU-induced mucositis was severe and not counteracted by WIN. 5-FU-induced diarrhea, but not mucositis, was partly prevented by WIN at a low dose. Cannabinoids might be useful to prevent chemotherapy-induced diarrhea. © 2016 John Wiley & Sons Ltd.

The role of periodontal ASIC3 in orofacial pain induced by experimental tooth movement in rats.

PubMed

Gao, Meiya; Long, Hu; Ma, Wenqiang; Liao, Lina; Yang, Xin; Zhou, Yang; Shan, Di; Huang, Renhuan; Jian, Fan; Wang, Yan; Lai, Wenli

2016-12-01

This study aimed to clarify the roles of Acid-sensing ion channel 3 (ASIC3) in orofacial pain following experimental tooth movement. Sixty male Sprague-Dawley rats were divided into the experimental group (40g, n = 30) and the sham group (0g, n = 30). Closed coil springs were ligated between maxillary incisor and molars to achieve experimental tooth movement. Rat grimace scale (RGS) scores were assessed at 0, 1, 3, 5, 7, and 14 days after the placement of the springs. ASIC3 immunostaining was performed and the expression levels of ASIC3 were measured through integrated optical density/area in Image-Pro Plus 6.0. Moreover, 18 rats were divided into APETx2 group (n = 6), amiloride group (n = 6), and vehicle group (n = 6), and RGS scores were obtained compared among them to verify the roles of ASIC3 in orofacial pain following tooth movement. ASIC3 expression levels became significantly higher in the experimental group than in sham group on 1, 3, and 5 days and became similar on 7 and 14 days. Pain levels (RGS scores) increased in both groups and were significantly higher in the experimental group on 1, 3, 5, and 7 days and were similar on 14 days. Periodontal ASIC3 expression levels were correlated with orofacial pain levels following experimental tooth movement. Periodontal administrations of ASIC3 antagonists (APETx2 and amiloride) could alleviate pain. This study needs to be better evidenced by RNA interference of ASIC3 in periodontal tissues in rats following experimental tooth movement. Moreover, we hope further studies would concentrate on the pain perception of ASIC3 knockout (ASIC3 -/- ) mice. Our results suggest that periodontal ASIC3 plays an important role in orofacial pain induced by experimental tooth movement. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Visually induced analgesia in a deep tissue experimental pain model: A randomised crossover experiment.

PubMed

van Selm, M J; Gibson, W I; Travers, M J; Moseley, G L; Hince, D; Wand, B M

2018-04-20

Visualizing one's own painful body part appears to have an effect on reported pain intensity. Furthermore, it seems that manipulating the size of the viewed image can determine the direction and extent of this phenomenon. When visual distortion has been applied to clinical populations, the analgesic effects have been in opposition to those observed in some experimental pain models. To help resolve this problem, we explored the effect of visualisation and magnification of the visual image on reported pain using a delayed onset muscle soreness (DOMS) pain model. We induced DOMS in the quadriceps of 20 healthy volunteers. Forty-eight hours later, participants performed a series of painful contractions of the DOMS-affected muscle under four randomised conditions: (1) Viewing the injured thigh; (2) Viewing the contralateral thigh; (3) Viewing a neutral object; and (4) Viewing the injured thigh through magnifying glasses. For each condition, participants rated their pain intensity during a series of painful contractions. We observed that direct visualisation of the injured thigh had no effect on pain intensity when compared to viewing the contralateral thigh or neutral object. However, magnification of the DOMS-affected leg during the performance of painful contractions caused participants to report more pain than when viewing the injured thigh normally. These results further demonstrate that the effect of visualisation varies between different pain conditions. These results may have implications for the integration of visual feedback into clinical practice. We present delayed onset muscle soreness as a model for exploring visually induced analgesia. Our findings suggest that this phenomenon is expressed differently in exogenous and endogenous experimental pain models. Further exploration may offer a potential pathway for the integration of visual analgesia into the management of clinical pain. © 2018 European Pain Federation - EFIC®.

Effects of sevoflurane on ventilator induced lung injury in a healthy lung experimental model.

PubMed

Romero, A; Moreno, A; García, J; Sánchez, C; Santos, M; García, J

2016-01-01

Ventilator-induced lung injury (VILI) causes a systemic inflammatory response in tissues, with an increase in IL-1, IL-6 and TNF-α in blood and tissues. Cytoprotective effects of sevoflurane in different experimental models are well known, and this protective effect can also be observed in VILI. The objective of this study was to assess the effects of sevoflurane in VILI. A prospective, randomized, controlled study was designed. Twenty female rats were studied. The animals were mechanically ventilated, without sevoflurane in the control group and sevoflurane 3% in the treated group (SEV group). VILI was induced applying a maximal inspiratory pressure of 35 cmH2O for 20 min without any positive end-expiratory pressure for 20 min (INJURY time). The animals were then ventilated 30 min with a maximal inspiratory pressure of 12 cmH2O and 3 cmH2O positive end-expiratory pressure (time 30 min POST-INJURY), at which time the animals were euthanized and pathological and biomarkers studies were performed. Heart rate, invasive blood pressure, pH, PaO2, and PaCO2 were recorded. The lung wet-to-dry weight ratio was used as an index of lung edema. No differences were found in the blood gas analysis parameters or heart rate between the 2 groups. Blood pressure was statistically higher in the control group, but still within the normal clinical range. The percentage of pulmonary edema and concentrations of TNF-α and IL-6 in lung tissue in the SEV group were lower than in the control group. Sevoflurane attenuates VILI in a previous healthy lung in an experimental subclinical model in rats. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Pumped storage system model and experimental investigations on S-induced issues during transients

NASA Astrophysics Data System (ADS)

Zeng, Wei; Yang, Jiandong; Hu, Jinhong

2017-06-01

Because of the important role of pumped storage stations in the peak regulation and frequency control of a power grid, pump turbines must rapidly switch between different operating modes, such as fast startup and load rejection. However, pump turbines go through the unstable S region in these transition processes, threatening the security and stability of the pumped storage station. This issue has mainly been investigated through numerical simulations, while field experiments generally involve high risks and are difficult to perform. Therefore, in this work, the model test method was employed to study S-induced security and stability issues for a pumped storage station in transition processes. First, a pumped storage system model was set up, including the piping system, model units, electrical control systems and measurement system. In this model, two pump turbines with different S-shaped characteristics were installed to determine the influence of S-shaped characteristics on transition processes. The model platform can be applied to simulate any hydraulic transition process that occurs in real power stations, such as load rejection, startup, and grid connection. On the experimental platform, the S-shaped characteristic curves were measured to be the basis of other experiments. Runaway experiments were performed to verify the impact of the S-shaped characteristics on the pump turbine runaway stability. Full load rejection tests were performed to validate the effect of the S-shaped characteristics on the water-hammer pressure. The condition of one pump turbine rejecting its load after another defined as one-after-another (OAA) load rejection was performed to validate the possibility of S-induced extreme draft tube pressure. Load rejection experiments with different guide vane closing schemes were performed to determine a suitable scheme to adapt the S-shaped characteristics. Through these experiments, the threats existing in the station were verified, the

Protective effects of D-002 on experimentally induced gastroesophageal reflux in rats.

PubMed

Zamora, Zullyt; Molina, Vivian; Mas, Rosa; Ravelo, Yazmin; Perez, Yohany; Oyarzabal, Ambar

2014-02-28

To investigate the effects of beeswax alcohols (D-002) on the esophageal damage induced by gastroesophageal reflux (GER) in rats. Sixty male rats were randomized into six groups (10 rats/group): a negative control and five groups with experimentally induced GER: a positive vehicle control, three treated with D-002 (25, 100 and 200 mg/kg, respectively), and one with omeprazole 10 mg/kg. All treatments were given by gastric gavage. One hour after dosing, GER was produced by simultaneous ligation of the pyloric end and the forestomach. Esophageal lesions index (ELI), gastric secretion volume and acidity, and esophageal malondialdehyde (MDA) and sulfhydryl (SH) group concentrations were measured. Statistical significance was considered at P < 0.05. As compared to the negative control, the positive control group exhibited increased ELI (5.2 ± 0.33 vs 0 ± 0, P = 0.0003), gastric secretion volume (2.69 ± 0.09 vs 0.1 ± 0.0, P = 0.0003) and acidity (238 ± 19.37 vs 120.0 ± 5.77, P = 0.001), and esophageal concentrations of MDA (2.56 ± 0.1 vs 1.76 ± 0.28, P = 0.001) and SH groups (1.02 ± 0.05 vs 0.56 ± 0.08, P = 0.0003). D-002 (25, 100 and 200 mg/kg) reduced ELI (3.36 ± 0.31, 2.90 ± 0.46 and 2.8 ± 0.23, respectively) vs the positive control (5.2 ± 0.33) (P = 0.004; P = 0.002; P = 0.001, respectively). There were no significant changes in acidity with D-002 treatment, and only the highest dose reduced the volume of the gastric secretion (1.92 ± 0.25) vs the positive control (2.69 ± 0.09, P = 0.013). D-002 (25, 100 and 200 mg/kg) lowered the esophageal MDA (2.05 ± 0.16, 1.98 ± 0.22 and 1.93 ± 0.22, respectively) (P = 0.01; P = 0.03; P = 0.03, respectively) and SH group concentration (0.87 ± 0.06, 0.79 ± 0.08 and 0.77 ± 0.06, respectively) (P = 0.04; P = 0.04; P = 0.02) vs the positive control (2.56 ± 0.10 and 1.02 ± 0.05, respectively). Omeprazole decreased ELI (2.54 ± 0.47), gastric secretion volume (1.97 ± 0.14) and acidity (158.5 ± 22

Experimental and Computational Induced Aerodynamics from Missile Jet Reaction Controls at Angles of Attack to 75 Degrees

NASA Technical Reports Server (NTRS)

Capone, Francis J.; Ashbury, Scott C.; Deere, Karen A.

1996-01-01

An investigation was conducted in the Langley 16-Foot Transonic Tunnel to determine induced aerodynamic effects from jet reaction controls of an advanced air-to-air missile concept. The 75-percent scale model featured independently controlled reaction jets located near the nose and tail of the model. Aerodynamic control was provided by four fins located near the tail of the model. This investigation was conducted at Mach numbers of 0.35 and 0.60, at angles of attack up to 75 deg and at nozzle pressure ratios up to 90. Jet-reaction thrust forces were not measured by the force balance but jet-induced forces were. In addition, a multiblock three-dimensional Navier-Stokes method was used to calculate the flowfield of the missile at angles of attack up to 40 deg. Results indicate that large interference effects on pitching moment were induced from operating the nose jets with the the off. Excellent correlation between experimental and computational pressure distributions and pitching moment were obtained a a Mach number of 0.35 and at angles of attack up to 40 deg.

Exercise-induced pulmonary artery hypertension in a patient with compensated cardiac disease: hemodynamic and functional response to sildenafil therapy.

PubMed

Nikolaidis, Lazaros; Memon, Nabeel; O'Murchu, Brian

2015-02-01

We describe the case of a 54-year-old man who presented with exertional dyspnea and fatigue that had worsened over the preceding 2 years, despite a normally functioning bioprosthetic aortic valve and stable, mild left ventricular dysfunction (left ventricular ejection fraction, 0.45). His symptoms could not be explained by physical examination, an extensive biochemical profile, or multiple cardiac and pulmonary investigations. However, abnormal cardiopulmonary exercise test results and a right heart catheterization-combined with the use of a symptom-limited, bedside bicycle ergometer-revealed that the patient's exercise-induced pulmonary artery hypertension was out of proportion to his compensated left heart disease. A trial of sildenafil therapy resulted in objective improvements in hemodynamic values and functional class.

Experimental Demonstration of a Resonator-Induced Phase Gate in a Multiqubit Circuit-QED System

NASA Astrophysics Data System (ADS)

Paik, Hanhee; Mezzacapo, A.; Sandberg, Martin; McClure, D. T.; Abdo, B.; Córcoles, A. D.; Dial, O.; Bogorin, D. F.; Plourde, B. L. T.; Steffen, M.; Cross, A. W.; Gambetta, J. M.; Chow, Jerry M.

2016-12-01

The resonator-induced phase (RIP) gate is an all-microwave multiqubit entangling gate that allows a high degree of flexibility in qubit frequencies, making it attractive for quantum operations in large-scale architectures. We experimentally realize the RIP gate with four superconducting qubits in a three-dimensional circuit-QED architecture, demonstrating high-fidelity controlled-z (cz) gates between all possible pairs of qubits from two different 4-qubit devices in pair subspaces. These qubits are arranged within a wide range of frequency detunings, up to as large as 1.8 GHz. We further show a dynamical multiqubit refocusing scheme in order to isolate out 2-qubit interactions, and combine them to generate a 4-qubit Greenberger-Horne-Zeilinger state.

Neurogenic mediators contribute to local edema induced by Micrurus lemniscatus venom

PubMed Central

2017-01-01

Background/Aims Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema formation, have been described in patients bitten by different species of Micrurus. Thus, we investigated the ability of Micrurus lemniscatus venom (MLV) to induce local edema. We also explored mechanisms underlying this effect, focusing on participation of neuropeptides and mast cells. Methodology/Principal findings Intraplantar injection of MLV (1–10 μg/paw) in rats caused dose- and time-dependent edema with a peak between 15 min and 1 h after injection. MLV also induced degranulation of peritoneal mast cells (MCs). MC depletion by compound 48/80 markedly reduced MLV-induced edema. Pre-treatment (30 min) of rats with either promethazine a histamine H1 receptor antagonist or methysergide, a nonselective 5-HT receptor antagonist, reduced MLV-induced edema. However, neither thioperamide, a histamine H3/H4 receptor antagonist, nor co-injection of MLV with HOE-140, a BK2 receptor antagonist, altered the response. Depletion of neuropeptides by capsaicin or treatment of animals with NK1- and NK2-receptor antagonists (SR 140333 and SR 48968, respectively) markedly reduced MLV-induced edema. Conclusions/Significance In conclusion, MLV induces paw edema in rats by mechanisms involving activation of mast cells and substance P-releasing sensory C-fibers. Tachykinins NKA and NKB, histamine, and serotonin are major mediators of the MLV-induced edematogenic response. Targeting mast cell- and sensory C-fiber-derived mediators should be considered as potential therapeutic approaches to interrupt development of local edema induced by Micrurus venoms. PMID:29161255

Rodent models of insomnia: a review of experimental procedures that induce sleep disturbances.

PubMed

Revel, Florent G; Gottowik, Juergen; Gatti, Sylvia; Wettstein, Joseph G; Moreau, Jean-Luc

2009-06-01

Insomnia, the most common sleep disorder, is characterized by persistent difficulty in falling or staying asleep despite adequate opportunity to sleep, leading to daytime fatigue and mental dysfunction. As sleep is a sophisticated physiological process generated by a network of neuronal systems that cannot be reproduced in-vitro, pre-clinical development of hypnotic drugs requires in-vivo investigations. Accordingly, this review critically evaluates current and putative rodent models of insomnia which could be used to screen novel hypnotics. Only few valid insomnia models are currently available, although many experimental conditions lead to disturbance of physiological sleep. We categorized these conditions as a function of the procedure used to induce perturbation of sleep, and we discuss their respective advantages and pitfalls with respect to validity, feasibility and translational value to human research.

IP-10 protects while MIP-2 promotes experimental anesthetic hapten - induced hepatitis

PubMed Central

Njoku, Dolores B.; Li, Zhaoxia; Mellerson, Jenelle L; Sharma, Rajni; Talor, Monica V.; Barat, Nicole; Rose, Noel R.

2009-01-01

MIP-2 and IFN-γ inducible protein-10 (IP-10) and their respective receptors, CXCR2 and CXCR3, modulate tissue inflammation by recruiting neutrophils or T cells from the spleen or bone marrow. Yet, how these chemokines modulate diseases such as immune-mediated drug-induced liver injury (DILI) is essentially unknown. To investigate how chemokines modulate experimental DILI in our model we used susceptible BALB/c (WT) and IL-4−/− (KO) mice that develop significantly reduced hepatitis and splenic T cell priming to anesthetic haptens and self proteins following TFA-S100 immunizations. We detected CXCR2+ splenic granulocytes in all mice two weeks following immunizations; by 3 weeks, MIP-2 levels (p<0.001) and GR1+ cells were elevated in WT livers, suggesting MIP-2-recruited granulocytes. Elevated splenic CXCR3+ CD4+T cells were identified after 2 weeks in KO mice indicating elevated IP-10 levels which were confirmed during T cell priming. This result suggested that IP-10 reduced T cell priming to critical DILI antigens. Increased T cell proliferation following co-culture of TFA-S100-primed WT splenocytes with anti-IP-10 (p<0.05) confirmed that IP-10 reduced T cell priming to CYP2E1 and TFA. We propose that MIP-2 promotes and IP-10 protects against the development of hepatitis and T cell priming in this murine model. PMID:19131211

B-type natriuretic peptide-guided management and outcome in patients with obesity and dyspnea--results from the BASEL study.

PubMed

Noveanu, Markus; Breidthardt, Tobias; Cayir, Sevgi; Potocki, Mihael; Laule, Kirsten; Mueller, Christian

2009-09-01

Obesity may reduce diagnostic accuracy of B-type natriuretic peptide (BNP) and affect long-term outcome. This study evaluated patients included in the BASEL study (N = 452). We compared BNP levels in patients with (n = 86) and without (n = 366) obesity (body mass index <30 and >30 kg/m(2)) and determined sensitivities and specificities of BNP in both patient groups by receiver-operating characteristic analysis. Impact of BNP measurements on patient management and outcome in obesity, as well as 360-day mortality, was assessed. The BNP levels were lower in obese patients (172 pg/mL [interquartile range 31-515] vs 306 [interquartile range 75-1,040]). The optimal BNP cut-point to detect heart failure was 182 pg/mL in obese patients and 298 pg/mL nonobese patients. Obese patients had lower in-hospital mortality (3.5% vs 8.5%, P = .045) and 360-day mortality (15% vs 30%, P = .001). In obese patients, the determination of BNP levels reduced time to initiation of the appropriate treatment (96 +/- 98 vs 176 +/- 230, P < .05) without impacting other end points. Adjustment of BNP values in the assessment of obese patients presenting with acute dyspnea seems necessary to improve diagnostic accuracy and patient management. Obese patients had half the short- and long-term mortality of nonobese patients, independent of their final discharge diagnosis.

Radiation induced currents in mineral-insulated cables and in pick-up coils: model calculations and experimental verification in the BR1 reactor

NASA Astrophysics Data System (ADS)

Vermeeren, Ludo; Leysen, Willem; Brichard, Benoit

2018-01-01

Mineral-insulated (MI) cables and Low-Temperature Co-fired Ceramic (LTCC) magnetic pick-up coils are intended to be installed in various position in ITER. The severe ITER nuclear radiation field is expected to lead to induced currents that could perturb diagnostic measurements. In order to assess this problem and to find mitigation strategies models were developed for the calculation of neutron-and gamma-induced currents in MI cables and in LTCC coils. The models are based on calculations with the MCNPX code, combined with a dedicated model for the drift of electrons stopped in the insulator. The gamma induced currents can be easily calculated with a single coupled photon-electron MCNPX calculation. The prompt neutron induced currents requires only a single coupled neutron-photon-electron MCNPX run. The various delayed neutron contributions require a careful analysis of all possibly relevant neutron-induced reaction paths and a combination of different types of MCNPX calculations. The models were applied for a specific twin-core copper MI cable, for one quad-core copper cable and for silver conductor LTCC coils (one with silver ground plates in order to reduce the currents and one without such silver ground plates). Calculations were performed for irradiation conditions (neutron and gamma spectra and fluxes) in relevant positions in ITER and in the Y3 irradiation channel of the BR1 reactor at SCK•CEN, in which an irradiation test of these four test devices was carried out afterwards. We will present the basic elements of the models and show the results of all relevant partial currents (gamma and neutron induced, prompt and various delayed currents) in BR1-Y3 conditions. Experimental data will be shown and analysed in terms of the respective contributions. The tests were performed at reactor powers of 350 kW and 1 MW, leading to thermal neutron fluxes of 1E11 n/cm2s and 3E11 n/cm2s, respectively. The corresponding total radiation induced currents are ranging from

Transforming growth factor beta induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis.

PubMed

Fantini, M C; Becker, C; Tubbe, I; Nikolaev, A; Lehr, H A; Galle, P; Neurath, M F

2006-05-01

The imbalance between effector and regulatory T cells plays a central role in the pathogenesis of inflammatory bowel diseases. In addition to the thymus, CD4+CD25+ regulatory T cells can be induced in the periphery from a population of CD25- T cells by treatment with transforming growth factor beta (TGF-beta). Here, we analysed the in vivo function of TGF-beta induced regulatory T (Ti-Treg) cells in experimental colitis. Ti-Treg cells were generated in cell culture in the presence or absence of TGF-beta and tested for their regulatory potential in experimental colitis using the CD4+CD62L+ T cell transfer model. Ti-Treg cells significantly suppressed Th1 mediated colitis on CD4+CD62L+ T cell transfer in vivo, as shown by high resolution endoscopy, histology, immunohistochemistry, and cytokine analysis. Further analysis of in vivo and in vitro expanded Ti-Treg cells showed that exogenous interleukin 2 (IL-2) was crucial for survival and expansion of these cells. Our data suggest that regulatory Ti-Treg cells expand by TGF-beta and exogenous IL-2 derived from effector T cells at the site of inflammation. In addition to Tr1 and thymic CD4+CD25+ T cells, peripheral Ti-Treg cells emerge as a class of regulatory T cells with therapeutic potential in T cell mediated chronic intestinal inflammation.

Hepatoprotective effect of Solanum xanthocarpum fruit extract against CCl4 induced acute liver toxicity in experimental animals.

PubMed

Gupta, Ramesh K; Hussain, Talib; Panigrahi, G; Das, Avik; Singh, Gireesh Narayan; Sweety, K; Faiyazuddin, Md; Rao, Chandana Venkateswara

2011-12-01

To investigate the hepatoprotective potential of Solanum xanthocarpum (Solanaceae) (S. xanthocarpum) in experimental rats to validate its traditional claim. 50% ethanolic fruit extract of S. xanthocarpum (SXE, 100, 200 or 400 mg/kg body weight) was administered daily for 14 days in experimental animals. Liver injury was induced chemically, by CCl(4) administration (1 mL/kg i. p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), Serum alkaline phosphatise (SALP) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were screened along with histopathological studies. Obtained results demonstrated that the treatment with SXE significantly (P<0.05-<0.001) and dose-dependently prevented chemically induced increase in serum levels of hepatic enzymes. Furthermore, SXE significantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and catalase towards normal levels. Histopathology of the liver tissue showed that SXE attenuated the hepatocellular necrosis and led to reduction of inflammatory cells inflltration. The results of this study strongly indicate the protective effect of SXE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scientifically support its traditional use. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Experimental Exploration on Rainfall-induced Mass Re-mobilization after Giant Earthquake: A case study in Wenchuan earthquake hit region, China

NASA Astrophysics Data System (ADS)

Yang, Zongji; Bogaard, Thom. A.; Qiao, Jianping; Jiang, Yuanjun

2015-04-01

Prevention and mitigation of rainfall induced geological hazards after the Ms=8 Wenchuan earthquake on May 12th, 2008 were gained more significance for the rebuild of earthquake hit regions in China. After the Wenchuan earthquake, there were thousands of slopes failure, which were much more susceptible to subsequent heavy rainfall and many even transformed into potential debris flows. An typical example can be found in the catastrophic disaster occurred in Zhongxing County, Chengdu City on 10th July, 2013 in which the unknown fractured slope up the mountain was triggered by a downpour and transformed into subsequent debris flow which wiped the community downstream, about 200 victims were reported in that tragic event. The transform patterns of rainfall-induced mass re-mobilization was categorized into three major type as the erosion of fractured slopes, initiate on loosen deposit and outbreak of landslide (debris flow) dams according to vast field investigation in the earthquake hit region. Despite the widespread and hidden characters,the complexity of the process also demonstrated in the transforms of the mass re-mobilized by the erosion of both gravity and streams in the small watersheds which have never been reported before the giant Wenchuan Earthquake in many regions. As a result, an increasing number of questions for disaster relief and mitigation were proposed including the threshold of early warning and measurement of the volume for the design of mitigation measures on rainfall-induced mass re-mobilization in debris flow gullies. This study is aimed for answer the essential questions about the threshold and amount of mass initiation triggered by the subsequent rainfall in post earthquake time. In this study, experimental tests were carried out for simulating the failure of the rainfall-induced mass re-mobilization in respectively in a natural co-seismic fractured slope outside and the debris flow simulation platform inside the laboratory. A natural

A Systematic Review of Relaxation, Meditation, and Guided Imagery Strategies for Symptom Management in Heart Failure.

PubMed

Kwekkeboom, Kristine L; Bratzke, Lisa C

2016-01-01

Pain, dyspnea, fatigue, and sleep disturbance are prevalent and distressing symptoms in persons with advanced heart failure. Although many lifestyle and self-care interventions have been developed to control heart failure progression, very few studies have explored treatments exclusively for symptom palliation. Cognitive-behavioral strategies may be effective treatment for these symptoms in advanced heart failure. A systemic review was conducted to describe the effect of cognitive-behavioral strategies on pain, dyspnea, fatigue, and sleep disturbance in patients with heart failure. CINAHL, Medline, and PsychINFO were searched from inception through December 2014. Articles were selected for inclusion if they tested a cognitive-behavioral strategy using a quasi-experimental or experimental design, involved a sample of adults with heart failure, and measured pain, dyspnea, fatigue, sleep disturbance, or symptom-related quality of life. The 2 authors evaluated study quality, abstracted data elements from each study, and synthesized findings. Thirteen articles describing 9 unique studies met criteria and were included in the review. Five studies tested relaxation strategies, 3 tested meditation strategies, and 1 tested a guided imagery strategy. Of the 9 studies, 7 demonstrated some improvement in symptom outcomes. Relaxation, meditation, guided imagery, or combinations of these strategies resulted in less dyspnea and better sleep compared with attention control or usual care conditions and reduced pain, dyspnea, fatigue, and sleep disturbance within treatment groups (pretreatment to posttreatment). Symptom-related quality of life was improved with meditation compared with attention control and usual care conditions and improved pre- to post-guided imagery. Studies exploring cognitive-behavioral symptom management strategies in heart failure vary in quality and report mixed findings but indicate potential beneficial effects of relaxation, meditation, and guided imagery

A Systematic Review of Relaxation, Meditation, and Guided Imagery Strategies for Symptom Management in Heart Failure

PubMed Central

Kwekkeboom, Kristine L.; Bratzke, Lisa C.

2015-01-01

Background Pain, dyspnea, fatigue, and sleep disturbance are prevalent and distressing symptoms in persons with advanced heart failure. Although many lifestyle and self-care interventions have been developed to control heart failure progression, very few studies have explored treatments exclusively for symptom palliation. Cognitive-behavioral strategies may be effective treatment for these symptoms in advanced heart failure. Objective A systemic review was conducted to describe the effect of cognitive-behavioral strategies on pain, dyspnea, fatigue, and sleep disturbance in patients with heart failure. Methods CINAHL, Medline, and PsychINFO were searched from inception through December 2014. Articles were selected for inclusion if they tested a cognitive-behavioral strategy using a quasi-experimental or experimental design, involved a sample of adults with heart failure, and measured pain, dyspnea, fatigue, sleep disturbance, or symptom-related quality of life (QoL). The two authors evaluated study quality, abstracted data elements from each study, and synthesized findings. Results Thirteen articles describing nine unique studies met criteria and were included in the review. Five studies tested relaxation strategies, three tested meditation strategies, and one tested a guided imagery strategy. Seven of the nine studies demonstrated some improvement in symptom outcomes. Relaxation, meditation, guided imagery, or combinations of these strategies resulted in less dyspnea and better sleep compared to attention control or usual care conditions, and reduced pain, dyspnea, fatigue and sleep disturbance within treatment groups (pre- to post-treatment). Symptom-related QoL was improved with meditation compared to attention control and usual care conditions, and improved pre- to post-guided imagery. Conclusions Studies exploring cognitive-behavioral symptom management strategies in heart failure vary in quality and report mixed findings, but indicate potential beneficial

An Experimental Model of Diet-Induced Metabolic Syndrome in Rabbit: Methodological Considerations, Development, and Assessment.

PubMed

Arias-Mutis, Óscar Julián; Genovés, Patricia; Calvo, Conrado J; Díaz, Ana; Parra, Germán; Such-Miquel, Luis; Such, Luis; Alberola, Antonio; Chorro, Francisco Javier; Zarzoso, Manuel

2018-04-20

In recent years, obesity and metabolic syndrome (MetS) have become a growing problem for public health and clinical practice, given their increased prevalence due to the rise of sedentary lifestyles and unhealthy eating habits. Thanks to animal models, basic research can investigate the mechanisms underlying pathological processes such as MetS. Here, we describe the methods used to develop an experimental rabbit model of diet-induced MetS and its assessment. After a period of acclimation, animals are fed a high-fat (10% hydrogenated coconut oil and 5% lard), high-sucrose (15% sucrose dissolved in water) diet for 28 weeks. During this period, several experimental procedures were performed to evaluate the different components of MetS: morphological and blood pressure measurements, glucose tolerance determination, and the analysis of several plasma markers. At the end of the experimental period, animals developed central obesity, mild hypertension, pre-diabetes, and dyslipidemia with low HDL, high LDL, and an increase of triglyceride (TG) levels, thus reproducing the main components of human MetS. This chronic model allows new perspectives for understanding the underlying mechanisms in the progression of the disease, the detection of preclinical and clinical markers that allow the identification of patients at risk, or even the testing of new therapeutic approaches for the treatment of this complex pathology.

Specificity of the femoral slump test for the assessment of experimentally induced anterior knee pain.

PubMed

Lai, Weng-Hang; Shih, Yi-Fen; Lin, Pei-Ling; Chen, Wen-Yin; Ma, Hsiao-Li

2012-12-01

To assess the specificity of the femoral slump test (FST) when assessing experimentally induced anterior knee pain. Cross-sectional, exploratory study. Research laboratory. Asymptomatic subjects (N=12; 6 men; 6 women) for the study. An experimental pain model was used to simulate anterior knee pain by injecting .25 mL of hypertonic saline solution (5% NaCl) into the medial infrapatellar fat pad. Not applicable. The changes in pain intensity and diameter after applying the structure differential maneuver (neck flexion/extension) during the FST were recorded and analyzed. Results revealed that the structure differential maneuver of the FST did not alter the pain intensity or diameter in 9 (neck extension) and 10 (neck flexion) out of 12 subjects, which meant that the FST provided appropriate testing responses in 75% to 83% cases when the anterior knee pain did not originate in neural tissues. The FST had a specificity of more than .75 when detecting nerve mechanosensitivity problems of anterior knee pain. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Methotrexate-induced pneumonitis in Crohn's disease. Case report and review of the literature

PubMed Central

2010-01-01

Methotrexate (MTX) is a folate-antagonist used in several neoplastic and inflammatory diseases. Reports of pulmonary complications in patients given low-dose MTX therapy are increasing. Pulmonary toxicity from MTX has a variable frequency and can present with different forms. Most often MTX-induced pneumonia in patients affected by rheumatoid arthritis (RA) is reported. In this paper we describe a case of MTX-related pneumonitis in a relatively young woman affected by Crohn's disease who presented non-productive cough, fever and dyspnea on exercise. Chest X-ray demonstrated bilateral interstitial infiltrates and at computed tomography (CT) ground-glass opacities appeared in both lungs. At spirometry an obstructive defect was demonstrated. A rapid improvement of symptoms and the regression of radiographic and spirometric alterations was achieved through MTX withdrawal and the introduction of corticosteroid therapy. PMID:22958737

Vibration-induced particle formation during yogurt fermentation - Industrial vibration measurements and development of an experimental setup.

PubMed

Körzendörfer, Adrian; Temme, Philipp; Nöbel, Stefan; Schlücker, Eberhard; Hinrichs, Jörg

2016-07-01

The aim of the study was to investigate the effects of vibrations during yogurt fermentation. Machinery such as pumps and switching valves generate vibrations that may disturb the gelation by inducing large particles. Oscillation measurements on an industrial yogurt production line showed that oscillations are transferred from pumps right up to the fermentation tanks. An experimental setup (20L) was developed to study the effect of vibrations systematically. The fermenters were decoupled with air springs to enable reference fermentations under idle conditions. A vibration exciter was used to stimulate the fermenters. Frequency sweeps (25-1005Hz, periodic time 10s) for 20min from pH5.4 induced large particles. The number of visible particles was significantly increased from 35±4 (reference) to 89±9 particles per 100g yogurt. Rheological parameters of the stirred yogurt samples were not influenced by vibrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inclusion body disease of cranes: comparison of pathologic findings in cranes with acquired vs. experimentally induced disease

USGS Publications Warehouse

Schuh, J.C.; Sileo, L.; Siegfried, Lynne M.; Yuill, Thomas M.

1986-01-01

Inclusion body disease of cranes was the cause of death in 17 immature and mature cranes of 5 different species in Wisconsin. A herpesvirus of unknown origin was the apparent cause. An isolate of this herpesvirus was used to experimentally infect 3 species of cranes. Macroscopic and microscopic lesions associated with naturally acquired and experimentally induced disease were essentially identical. Multifocal hepatic and splenic necrosis was found in all cranes evaluated. Necrosis of the gastrointestinal tract, thymus, and bursa of Fabricius also was seen in some of the cranes. Eosinophilic intranuclear inclusion bodies often were commonly associated with hepatic lesions, sometimes with the splenic lesions, and rarely with the thymic or gastrointestinal tract lesions. The lesions of this inclusion body disease were similar to those reported for cranes in Austria from which a crane herpesvirus was isolated.

The Protective Role of Dexpanthenol on the Endometrial Implants in an Experimentally Induced Rat Endometriosis Model.

PubMed

Soylu Karapinar, Oya; Pinar, Neslihan; Özgür, Tümay; Özcan, Oğuzhan; Bayraktar, H Suphi; Kurt, Raziye Keskin; Nural, Orhan

2017-02-01

Dexpanthenol (Dxp), antioxidant and anti-inflammatory agent, plays an important role in the repair systems against oxidative stress and inflammatory response. The objective of this study is to determine the effect of Dxp on experimental endometriosis model. A prospective experimental study was conducted in Experimental Animal Laboratory of Mustafa Kemal University, Hatay. Twenty nonpregnant female Wistar albino rats, in which experimental model of endometriosis was surgically induced, were randomly divided into 2 groups. Group 1 was administered 500 mg/kg/d Dxp intraperitoneally for 14 days, and group 2 was given the same amount of saline solution. After 2 weeks of medication, the rats were killed and implant volumes, histopathologic scores; and levels of serum total antioxidant status, total oxidant status (TOS), and oxidative stress index (OSI) were evaluated. Plasma and peritoneal fluid levels of tumor necrosis factor α (TNF-α) were analyzed. The endometriotic implant volumes, histopathologic scores, and serum TOS and OSI values were significantly decreased ( P < .05) in the Dxp group compared to the control group. Plasma and peritoneal fluid TNF-α levels were significantly decreased ( P < .05) in the Dxp group compared to the control group. Dexpanthenol has free radical scavenger effects, and antioxidant properties has significantly regressed endometriotic implant volumes, histopathologic scores, and serum TOS and OSI values. Serum and peritoneal fluid TNF-α levels were significantly decreased in the Dxp group. So Dxp decreased oxidative stress.

Experimental characterization of fire-induced response of rigid polyurethane foam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chu, T.Y.; Gill, W.; Moore, J.W.

1995-12-31

Reported is the result of an experimental investigation of fire-induced response of a 96 kg/m{sup 3} closed cell rigid polyurethane foam. The specimen is 0.37 m in diameter, and 152 mm thick, placed in a cylindrical test vessel. The fire condition is simulated by heating the bottom of the test vessel to 1283 K using a radiant heat source. Real-time x-ray shows that the degradation process involves the progression of a charring front into the virgin material. The charred region has a regular and graded structure consisting of a packed bubble outer layer and successive layers of thin shells. Themore » layer-to-layer permeability appears to be poor. There are indications that gas vents laterally. The shell-like structure might be the result of lateral venting. Although the foam degradation process is quite complicated, the in-depth temperature responses in the uncharted foam appear to be consistent with steady state ablation. The measured temperature responses are well represented by the exponential distribution for steady state ablation. An estimate of the thermal diffusivity of the foam is obtained from the ablation model. The experiment is part of a more comprehensive program to develop material response models of foams and encapsulants.« less

Therapeutics effect of N-acetyl cysteine on mustard gas exposed patients: evaluating clinical aspect in patients with impaired pulmonary function test.

PubMed

Shohrati, Majid; Aslani, Jafar; Eshraghi, Mehdi; Alaedini, Farshid; Ghanei, Mostafa

2008-03-01

Long-term prescription of N-acetyl cysteine (NAC) may be effective in diseases caused by active radicals of oxygen species. The aim of this study was to determine the effect of 2- and 4-month administration of NAC (1800 mg daily) on mustard induced bronchiolitis obliterans. In a double blind clinical trial, 144 patients with bronchiolitis obliterans due to sulfur mustard in bronchiolitis obliterans syndrome (BOS) classes 1 and 2, randomly entered Group 1 (n=72, NAC) and Group 2 (n=72, placebo). Dyspnea, wake-up dyspnea, cough, and sputum were measured after 4 months. Spirometric findings were measured at the beginning of the trial, 2 months after and after 4 months of prescription of 1800 mg/day in three doses of NAC or placebo. Dyspnea, cough, sputum, and wake-up dyspnea improved after 4 months of NAC compared to the control group. After 4 months, spirometric components were significantly improved in NAC group compared to placebo group. Fourth months administration of NAC (1800 mg daily) can improve clinical conditions and spirometric findings in mustard exposed in BOS class 1 or 2.

Strong protection induced by an experimental DIVA subunit vaccine against bluetongue virus serotype 8 in cattle.

PubMed

Anderson, Jenna; Hägglund, Sara; Bréard, Emmanuel; Riou, Mickaël; Zohari, Siamak; Comtet, Loic; Olofson, Ann-Sophie; Gélineau, Robert; Martin, Guillaume; Elvander, Marianne; Blomqvist, Gunilla; Zientara, Stéphan; Valarcher, Jean Francois

2014-11-20

Bluetongue virus (BTV) infections in ruminants pose a permanent agricultural threat since new serotypes are constantly emerging in new locations. Clinical disease is mainly observed in sheep, but cattle were unusually affected during an outbreak of BTV seroype 8 (BTV-8) in Europe. We previously developed an experimental vaccine based on recombinant viral protein 2 (VP2) of BTV-8 and non-structural proteins 1 (NS1) and NS2 of BTV-2, mixed with an immunostimulating complex (ISCOM)-matrix adjuvant. We demonstrated that bovine immune responses induced by this vaccine were as good or superior to those induced by a classic commercial inactivated vaccine. In this study, we evaluated the protective efficacy of the experimental vaccine in cattle and, based on the detection of VP7 antibodies, assessed its DIVA compliancy following virus challenge. Two groups of BTV-seronegative calves were subcutaneously immunized twice at a 3-week interval with the subunit vaccine (n=6) or with adjuvant alone (n=6). Following BTV-8 challenge 3 weeks after second immunization, controls developed viremia and fever associated with other mild clinical signs of bluetongue disease, whereas vaccinated animals were clinically and virologically protected. The vaccine-induced protection was likely mediated by high virus-neutralizing antibody titers directed against VP2 and perhaps by cellular responses to NS1 and NS2. T lymphocyte responses were cross-reactive between BTV-2 and BTV-8, suggesting that NS1 and NS2 may provide the basis of an adaptable vaccine that can be varied by using VP2 of different serotypes. The detection of different levels of VP7 antibodies in vaccinated animals and controls after challenge suggested a compliancy between the vaccine and the DIVA companion test. This BTV subunit vaccine is a promising candidate that should be further evaluated and developed to protect against different serotypes. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Experimental Induction of Genome Chaos.

PubMed

Ye, Christine J; Liu, Guo; Heng, Henry H

2018-01-01

Genome chaos, or karyotype chaos, represents a powerful survival strategy for somatic cells under high levels of stress/selection. Since the genome context, not the gene content, encodes the genomic blueprint of the cell, stress-induced rapid and massive reorganization of genome topology functions as a very important mechanism for genome (karyotype) evolution. In recent years, the phenomenon of genome chaos has been confirmed by various sequencing efforts, and many different terms have been coined to describe different subtypes of the chaotic genome including "chromothripsis," "chromoplexy," and "structural mutations." To advance this exciting field, we need an effective experimental system to induce and characterize the karyotype reorganization process. In this chapter, an experimental protocol to induce chaotic genomes is described, following a brief discussion of the mechanism and implication of genome chaos in cancer evolution.

Drug-Induced Inhibition of Angiotensin Converting Enzyme and Dipeptidyl Peptidase 4 Results in Nearly Therapy Resistant Bradykinin Induced Angioedema: A Case Report

PubMed Central

Hahn, Janina; Trainotti, Susanne; Hoffmann, Thomas K.; Greve, Jens

2017-01-01

Patient: Female, 83 Final Diagnosis: Angioedema Symptoms: Edema Medication: Ramipril Clinical Procedure: — Specialty: Otolaryngology Objective: Unusual clinical course Background: Bradykinin is an underestimated mediator of angioedema. One subgroup of bradykinin induced angioedema is angioedema triggered by treatment with angiotensin converting enzyme (ACE) inhibitors. Due to its localization in the head and neck region and its unpredictable course, it is a possibly life-threatening condition. There is not an officially approved treatment for ACE inhibitor induced angioedema. Case Report: We present a case of an 83-year-old woman, who presented to our ENT department because of acute swelling of the tongue. On admission, there was no pharyngeal or laryngeal edema and no dyspnea. Treatment with glucocorticoids and antihistamines had no response. The patient had ramipril as regular medication, so we assumed ACE inhibitor induced angioedema and treated consequently with C1-inhibitor (human) 1,500 IU. Nevertheless, swelling was progressive and required intubation. Even after the second specific treatment with icatibant, her angioedema subsided extremely slowly. The patient also had regular treatment with saxagliptin, a dipeptidyl peptidase 4 inhibitor, so we assumed that the simultaneous inhibition of two bradykinin degrading enzymes led to a treatment-refractory course of angioedema. Conclusions: General awareness for bradykinin induced angioedema due to regular medication is limited. Our case demonstrated the importance of improving awareness and knowledge about this side effect. We need a better understanding of the pathomechanism to aid in more precise clinical diagnosis. Securing the patient’s airway as well as administration of an officially approved therapy is of utmost importance. As the number of patients simultaneously treated with antihypertensive and antidiabetic drugs is likely to increase, the incidence of bradykinin mediated drug induced angioedema is

Experimental Demonstration of a Resonator-Induced Phase Gate in a Multiqubit Circuit-QED System.

PubMed

Paik, Hanhee; Mezzacapo, A; Sandberg, Martin; McClure, D T; Abdo, B; Córcoles, A D; Dial, O; Bogorin, D F; Plourde, B L T; Steffen, M; Cross, A W; Gambetta, J M; Chow, Jerry M

2016-12-16

The resonator-induced phase (RIP) gate is an all-microwave multiqubit entangling gate that allows a high degree of flexibility in qubit frequencies, making it attractive for quantum operations in large-scale architectures. We experimentally realize the RIP gate with four superconducting qubits in a three-dimensional circuit-QED architecture, demonstrating high-fidelity controlled-z (cz) gates between all possible pairs of qubits from two different 4-qubit devices in pair subspaces. These qubits are arranged within a wide range of frequency detunings, up to as large as 1.8 GHz. We further show a dynamical multiqubit refocusing scheme in order to isolate out 2-qubit interactions, and combine them to generate a 4-qubit Greenberger-Horne-Zeilinger state.

Accelerated bone formation on photo-induced hydrophilic titanium implants: an experimental study in the dog mandible.

PubMed

Hirakawa, Yuko; Jimbo, Ryo; Shibata, Yasuaki; Watanabe, Ikuya; Wennerberg, Ann; Sawase, Takashi

2013-08-01

The purpose of this study was to investigate the effect of photo-induced hydrophilic titanium dioxide (TiO₂) on serum fibronectin (sFN) attachment, and further to evaluate initial osseointegration responses in the dog mandibles. To apply the anatase TiO₂ film, plasma source ion implantation (PSII) method followed by annealing was employed for the titanium disks and implants, which were then illuminated with UV-A for 24 h for the experimental groups. Non-deposited titanium disks and implants were prepared for the control group. Surface characterization was performed using the interferometer and contact angle analyzer. The attachments of sFN were evaluated using fluorescence emission analysis. Thereafter both groups of implants were placed in the mandible of six beagle dogs. Bone response was investigated with histological and histomorphometrical analyses after periods of 2 and 4 weeks. The experimental groups exhibited strong hydrophilicity under UV-A illumination and showed significant improvement in sFN attachment. And further, the experimental implants enhanced the bone formation with the bone-to-implant contact of 42.7% after 2 weeks of healing (control: 28.4%). The combined applications of plasma fibronectin and PSII to produce hydrophilic titanium surfaces could accelerate early osseointegration. © 2012 John Wiley & Sons A/S.

Concentrations of cysteinyl leukotrienes in urine and bronchoalveolar lavage fluid of cats with experimentally induced asthma.

PubMed

Norris, Carol R; Decile, Kendra C; Berghaus, Londa J; Berghaus, Roy D; Walby, William F; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

2003-11-01

To evaluate changes in cysteinyl leukotriene (LT) concentrations in urine and bronchoalveolar lavage fluid (BALF) in cats with experimentally induced asthma. 19 cats with experimentally induced asthma and 5 control cats. Cats were sensitized to Bermuda grass or house dust mite allergen, and phenotypic features of asthma were confirmed with intradermal skin testing, evaluation of BALF eosinophil percentages, and pulmonary function testing. A competitive ELISA kit for LTC4, LTD4, and LTE4 was used for quantitative analysis of LTs. Urinary creatinine concentrations and BALF total protein (TP) concentrations were measured, and urinary LT-to-creatinine ratios and BALF LT-to-TP ratios were calculated. Mean urinary LT-to-creatinine ratios did not differ significantly between control cats and allergen-sensitized cats before or after sensitization and challenge exposure with saline (0.9% NaCl) solution or allergen, respectively. In BALF the mean LT-to-TP ratio of control cats did not differ significantly before or after sensitization and challenge exposure with saline. Asthmatic cats had BALF LT-to-TP ratios that were significantly lower than control cats at all time points, whereas ratios for asthmatic cats did not differ significantly among the various time points. Although LTs were readily detectable in urine, no significant increases in urinary LT concentrations were detected after challenge in allergen-sensitized cats. Spot testing of urinary LT concentrations appears to have no clinical benefit for use in monitoring the inflammatory asthmatic state in cats. The possibility that cysteinyl LTs bind effectively to their target receptors in BALF and, thus, decrease free LT concentrations deserves further study.

Interstitial Lung Disease Induced by Osimertinib for Epidermal Growth Factor Receptor (EGFR) T790M-positive Non-small Cell Lung Cancer.

PubMed

Matsumoto, Yoshiya; Kawaguchi, Tomoya; Yamamoto, Norio; Sawa, Kenji; Yoshimoto, Naoki; Suzumura, Tomohiro; Watanabe, Tetsuya; Mitsuoka, Shigeki; Asai, Kazuhisa; Kimura, Tatsuo; Yoshimura, Naruo; Kuwae, Yuko; Hirata, Kazuto

2017-09-01

A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration. We diagnosed the patient to have interstitial lung disease induced by osimertinib.

Dietary medium-chain triglycerides prevent chemically induced experimental colitis in rats.

PubMed

Kono, Hiroshi; Fujii, Hideki; Ishii, Kenichi; Hosomura, Naohiro; Ogiku, Masahito

2010-03-01

The effects of dietary medium-chain triglycerides (MCTs) on experimental colitis induced by 2,4,6-trinitrobenzene sulphonic acid (TNBS) were investigated in rats. Male Wistar rats were given an intracolonic injection of TNBS and were then fed liquid diets containing MCTs or corn oil (AIN93) as controls. Serum and tissue samples were collected 1 week after TNBS enema. The severity of colitis was evaluated pathologically, and tissue myeloperoxidase (MPO) activity was measured. Furthermore, messenger RNA (mRNA) and protein levels for inflammatory cytokines and a chemokine were assessed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. In another set of experiments, the protein expression of Toll-like receptor (TLR)-4 in the colon was measured 1 week after feeding of liquid diets. To investigate the effects of MCTs on macrophages, RAW246.7 macrophages were incubated with media containing albumin conjugated with MCT or linoleic acid, which is the major component of corn oil. Then, the production of tumor necrosis factor-alpha (TNF-alpha) was measured. Dietary MCTs blunted significantly the protein levels of TLR-4 in the colon. Furthermore, the expression of TLR-4 was significantly blunted in RAW264.7 cells incubated with MCTs compared with cells incubated with linoleic acid. Induction of interleukin 1beta (IL-1beta), TNF-alpha, and macrophage inflammatory protein-2 (MIP-2) in the colon was attenuated by dietary MCT. Furthermore, MPO activities in the colonic tissue were significantly blunted in animals fed the MCT diets compared with those fed the control diets. As a result, dietary MCTs improved chemically induced colitis significantly. MCTs most likely are useful for the therapy of inflammatory bowel disease as an anti-inflammatory immunomodulating nutrient. Copyright 2010 Mosby, Inc. All rights reserved.

Apigenin Attenuates Inflammation in Experimentally Induced Acute Pancreatitis-Associated Lung Injury.

PubMed

Basios, Neofitos; Lampropoulos, Pavlos; Papalois, Apostolos; Lambropoulou, Maria; Pitiakoudis, Michael K; Kotini, Athanasia; Simopoulos, Constantinos; Tsaroucha, Alexandra K

2016-06-01

Acute pancreatitis is associated with acute lung injury. The aim of the present study is to evaluate alterations of lungs in an experimental model of acute pancreatitis (AP) following both bilio-pancreatic duct obstruction close to the duodenum. Acute pancreatitis is a common disease with significant mortality. This situation makes the need of finding protective factors for the lung parenchyma, imperative. In the present study there is an effort to clarify the role of apigenin, a substance which is well known for its antioxidant and anti-inflammatory effects, on lung injury, following acute pancreatitis in rats. In the present study, 126 male Wistar-type rats 3-4 months old and 220-350 g weight were used. At time 0 we randomly assigned the following groups: Group Sham: Rats were subjected to virtual surgery. Group Control: Rats were subjected to surgery for induction of acute pancreatitis. Group Apigenin: Rats were subjected to surgery for induction of acute pancreatitis and enteral feeding with apigenin. Immunochemistry for TNF-α and IL-6 as well as MPO activity were measured at predetermined time intervals 6, 12, 24, 48, and 72 h, in order to evaluate architectural disturbances of the lung tissue. From the pathological reports we realized that comparing the control group with the apigenin group, there is an improvement of lung tissue damage following apigenin administration, with statistical significance. Apigenin reduces most histopathological alterations of the pulmonary tissue, reduces MPO and TNF-α activity at 48 hours and, furthermore, reduces IL-6 activity at 72 hours post-administration. Oral Apigenin administration in rats, following experimental induced acute pancreatitis, seems to be protective on the lung tissue. Apigenin administration to humans could potentially ameliorate acute lung injuries. However, special caution is required for humans' use, as more detailed studies are needed.

Proton-induced accelerated decay of the fungicide, vinclozolin, on TiO2 surface under solar irradiation: Experimental and DFT study.

PubMed

Osipov, Ivan; Gorbachev, Mikhail Y; Gorinchoy, Natalia N

2018-04-03

The photochemical degradation of vinclozolin by addition of titanium dioxide on silica support has been examined both experimental and quantum-chemically. Solar irradiation of vinclozolin on silica with and without addition of titanium dioxide for 6 h resulted in 21% and 97.8% vinclozolin residues, respectively. In both these cases, phototransformation leads to the formation of (3,5-dichlorophenyl isocyanate) and (3,5-dichloroaniline). The presence of the intermediary product resulted from opening of the 2,4-oxazolidine-dione ring is also confirmed by GS-MS and LC-MS chromatography. The proton-induced mechanism of vinclozolin decay at the above experimental conditions is clarified on the base of DFT calculations.

Bone Marrow-Derived Mononuclear Cell Therapy in Papain-Induced Experimental Pulmonary Emphysema

PubMed Central

Machado, Mariana N.; Mazzoli-Rocha, Flavia; Casquilho, Natália V.; Maron-Gutierrez, Tatiana; Ortenzi, Victor H.; Morales, Marcelo M.; Fortunato, Rodrigo S.; Zin, Walter A.

2018-01-01

Murine papain-induced emphysema is a model that reproduces many of the features found in patients. Bone marrow-derived mononuclear cells (BMMC) have already been used to repair the alveolar epithelium in respiratory diseases, but not in the papain model. Thus, we hypothesized that BMMC could prevent the pathophysiological processes in papain-induced experimental emphysema. Female BALB/c mice received intratracheal instillation of 50 μL of saline (S groups) or papain (P groups, 10 IU/50 μl of saline) on days 1 and 7 of the experimental protocol. On the 14th day, 2 × 106 BMMC of male BALB/c mice (SC21 and PC21) or saline (SS21 and PS21) were injected by the jugular vein. Analyses were done on days 14 (S14 and P14) and 21 (SS21, PS21, SC21, and PC21) of the protocol. qPCR evaluated the presence of the Y chromosome in the lungs of BMMC recipient animals. Functional residual capacity (FRC), alveolar diameter, cellularity, elastic fiber content, concentrations of TNF-α, IL-1β, IL-6, MIP-2, KC, IFN-γ, apoptosis, mRNA expression of the dual oxidase (DUOX1 and DUOX2), production of H2O2 and DUOX activity were evaluated in lung tissue. We did not detect the Y chromosome in recipients' lungs. FRC, alveolar diameter, polymorphonuclear cells (PMN) and levels of KC, MIP-2, and IFN-γ increased in P14 and PS21 groups; the changes in the latter were reverted by BMMC. TNF-α, IL-1β e IL-6 were similar in all groups. The amount of elastic fibers was smaller in P14 and PS21 than in other groups, and BMMC did not increase it in PC21 mice. PS21 animals showed increased DUOX activity and mRNA expression for DUOX1 and 2. Cell therapy reverted the activity of DUOX and mRNA expression of DUOX1. BMMC reduced mRNA expression of DUOX2. Apoptosis index was elevated in PS21 mice, which was reduced by cell therapy in PC21. Static compliance, viscoelastic component of elastance and pressure to overcome viscoelasticity were increased in P14 and PS21 groups. These changes and the high

Recruitment of 99m-technetium- or 111-indium-labelled polymorphonuclear leucocytes in experimentally induced pyogranulomas in lambs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guilloteau, L.; Pepin, M.; Pardon, P.

1990-10-01

The recruitment of polymorphonuclear leucocytes (PMNs) during the development of experimental pyogranulomas induced by Corynebacterium pseudotuberculosis was followed in nine male lambs by scintigraphic examination. Autologous blood PMNs were labelled with 99m-technetium or 111-indium and were re-injected intravenously into infected lambs. The functional properties of the labelled cells were monitored (1) in vitro by measuring their phagocytic and bactericidal activity against C. pseudotuberculosis and their chemotaxis under agarose, and (2) in vivo by following scintigraphically their capacity to accumulate in an inflammatory focus induced by intradermal injection of latex beads coated with Salmonella abortus equi lipopolysaccharide. Following inoculation of corynebacteriamore » into the right ear of lambs, radioactive foci were observed to be localized in the right ear and in the draining lymph nodes during the 4 days following inoculation. Histopathological examination performed 32 h after inoculation confirmed the intense accumulation of PMNs at these sites. With the exception of one animal, which presented visible foci in the neck 14 days postinoculation, no radioactive foci were observed during the later phases of experimental infection, despite the presence of multiple pyogranulomas which were confirmed by bacteriological examination after necropsy of the lambs. Histopathological examination of these lesions revealed layers of fibroblasts, lymphocytes, and macrophages surrounding a necrotic centre. The results of these studies suggest that the contribution of PMNs during the chronic phase of inflammation is considerably reduced in comparison with the acute inflammatory phase of the infectious process.« less

Experimental evidence for drought induced alternative stable states of soil moisture

NASA Astrophysics Data System (ADS)

Robinson, David. A.; Jones, Scott B.; Lebron, Inma; Reinsch, Sabine; Domínguez, María T.; Smith, Andrew R.; Jones, Davey L.; Marshall, Miles R.; Emmett, Bridget A.

2016-01-01

Ecosystems may exhibit alternative stable states (ASS) in response to environmental change. Modelling and observational data broadly support the theory of ASS, however evidence from manipulation experiments supporting this theory is limited. Here, we provide long-term manipulation and observation data supporting the existence of drought induced alternative stable soil moisture states (irreversible soil wetting) in upland Atlantic heath, dominated by Calluna vulgaris (L.) Hull. Manipulated repeated moderate summer drought, and intense natural summer drought both lowered resilience resulting in shifts in soil moisture dynamics. The repeated moderate summer drought decreased winter soil moisture retention by ~10%. However, intense summer drought, superimposed on the experiment, that began in 2003 and peaked in 2005 caused an unexpected erosion of resilience and a shift to an ASS; both for the experimental drought manipulation and control plots, impairing the soil from rewetting in winter. Measurements outside plots, with vegetation removal, showed no evidence of moisture shifts. Further independent evidence supports our findings from historical soil moisture monitoring at a long-term upland hydrological observatory. The results herald the need for a new paradigm regarding our understanding of soil structure, hydraulics and climate interaction.

Experimental evidence for drought induced alternative stable states of soil moisture

PubMed Central

Robinson, David. A.; Jones, Scott B.; Lebron, Inma; Reinsch, Sabine; Domínguez, María T.; Smith, Andrew R.; Jones, Davey L.; Marshall, Miles R.; Emmett, Bridget A.

2016-01-01

Ecosystems may exhibit alternative stable states (ASS) in response to environmental change. Modelling and observational data broadly support the theory of ASS, however evidence from manipulation experiments supporting this theory is limited. Here, we provide long-term manipulation and observation data supporting the existence of drought induced alternative stable soil moisture states (irreversible soil wetting) in upland Atlantic heath, dominated by Calluna vulgaris (L.) Hull. Manipulated repeated moderate summer drought, and intense natural summer drought both lowered resilience resulting in shifts in soil moisture dynamics. The repeated moderate summer drought decreased winter soil moisture retention by ~10%. However, intense summer drought, superimposed on the experiment, that began in 2003 and peaked in 2005 caused an unexpected erosion of resilience and a shift to an ASS; both for the experimental drought manipulation and control plots, impairing the soil from rewetting in winter. Measurements outside plots, with vegetation removal, showed no evidence of moisture shifts. Further independent evidence supports our findings from historical soil moisture monitoring at a long-term upland hydrological observatory. The results herald the need for a new paradigm regarding our understanding of soil structure, hydraulics and climate interaction. PMID:26804897

An experimental approach to improve the Monte Carlo modelling of offline PET/CT-imaging of positron emitters induced by scanned proton beams

NASA Astrophysics Data System (ADS)

Bauer, J.; Unholtz, D.; Kurz, C.; Parodi, K.

2013-08-01

We report on the experimental campaign carried out at the Heidelberg Ion-Beam Therapy Center (HIT) to optimize the Monte Carlo (MC) modelling of proton-induced positron-emitter production. The presented experimental strategy constitutes a pragmatic inverse approach to overcome the known uncertainties in the modelling of positron-emitter production due to the lack of reliable cross-section data for the relevant therapeutic energy range. This work is motivated by the clinical implementation of offline PET/CT-based treatment verification at our facility. Here, the irradiation induced tissue activation in the patient is monitored shortly after the treatment delivery by means of a commercial PET/CT scanner and compared to a MC simulated activity expectation, derived under the assumption of a correct treatment delivery. At HIT, the MC particle transport and interaction code FLUKA is used for the simulation of the expected positron-emitter yield. For this particular application, the code is coupled to externally provided cross-section data of several proton-induced reactions. Studying experimentally the positron-emitting radionuclide yield in homogeneous phantoms provides access to the fundamental production channels. Therefore, five different materials have been irradiated by monoenergetic proton pencil beams at various energies and the induced β+ activity subsequently acquired with a commercial full-ring PET/CT scanner. With the analysis of dynamically reconstructed PET images, we are able to determine separately the spatial distribution of different radionuclide concentrations at the starting time of the PET scan. The laterally integrated radionuclide yields in depth are used to tune the input cross-section data such that the impact of both the physical production and the imaging process on the various positron-emitter yields is reproduced. The resulting cross-section data sets allow to model the absolute level of measured β+ activity induced in the investigated

Comparison of histological effects of polydeoxyribonucleic acid and hyaluronic acid in experimentally induced osteoarthritis of the knee joints of rats

PubMed Central

Karahan, Nazım; Arslan, İlyas; Orak, Müfit; Midi, Ahmet; Yücel, İstemi

2017-01-01

Aim: The histological effects of intra-articular polydeoxyribonucleic acid and hyaluronic acid in experimentally induced osteoarthritis of the knee joints of rats were investigated. Methods: Thirty rats were divided into three groups, i.e. polydeoxyribonucleic acid group, hyaluronic acid group and saline group. Osteoarthritis of the knee joints of the rats were induced by acl- transection. The polydeoxyribonucleic group was injected with 100 µg (0.05 cc) polydeoxyribonucleic acid. The hyaluronic acid group was injected with 100 µg (0.05 cc) hyaluronic acid, and the saline group was injected with 50 µl (0.05 cc) of 0.9% sodium chloride solution. All of the rats were sacrificed on day 29 and the right knee joints were prepared, and evaluated histologically by Mankin classification. Findings: The differences in total Mankin scores between the three groups were statistically significant (P < 0.01). The differences in total Mankin scores between the polydeoxyribonucleic acid group and the hyaluronic acid group were statistically significant (P < 0.01). The differences in total Mankin scores between hyaluronic acid group and saline group were statistically significant (P < 0.01). Tidemark continuity in all the specimens of the polydeoxyribonucleic acid group was noteworthy. Conclusion: The present study shows that more chondroprotective effect and less degeneration was observed with intra-articularly delivered polydeoxyribonucleic acid compared to hyaluronic acid and saline solution in the experimentally induced osteoarthritis of the knee joints of rats.

[Usefullness of Beta-blocker for Hemodynamic Changes Induced by Uterotonic Drug in a Patient with Hypertrophic Obstructive Cardiomyopathy Undergoing Elective Cesarean Section].

PubMed

Tsukano, Yuri; Sugita, Michiko; Ikuta, Yoshihiro; Yamamoto, Tatsuo

2015-06-01

Combined spinal-epidural anesthesia (CSEA) was given to a 27-year-old woman with hypertrophic obstructive cardiomyopathy (HOCM) for a selective cesarean section. After the injection of uterotonic drug via uterine muscle and a vein after delivery, the patient developed dyspnea, tachycardia, ST-change on elecrocardiogram and hypotension. It is important in HOCM patients to control heart rate and left ventricular contractile force. We started to infuse beta-blocker (landiolol, 10 μg x kg(-1) x min(-1)) and improved these symptoms of the patient. This case demonstrates that CSEA is safe for HOCM patients and beta-blocker is effective to improve hemodynamic changes induced by uterotonic drug in these patients.

Experimental cross-sections for proton induced nuclear reactions on mercury up to 65 MeV

NASA Astrophysics Data System (ADS)

Hermanne, A.; Tárkányi, F.; Takács, S.; Ditrói, F.; Szücs, Z.; Brezovcsik, K.

2016-07-01

Cross-sections for formation of activation products induced by protons on natural mercury targets were measured. Results for 196m,196g,197g(cum), 198m,198g,199g(cum), 200g(cum), 201,202Tl, 194g(cum), 195g(cum), 196g(cum), 198m,199g(cum) Au and 195m,197m,203Hg are presented up to 65 MeV incident particle energy, many of these for the first time. The experimental data are compared with literature values and with the predictions of the TALYS 1.6 code (results taken from TENDL-2015 on-line library), thick target yields were derived and possible applications in biomedical sciences are discussed.

[Oxidative stress experimental model of rat with stria vascularis marginal cells injury induced by hydrogen peroxide in vitro].

PubMed

Li, Jun; Kong, Wei-jia; Zhao, Xue-yan; Hu, Yu-juan

2008-11-01

To set up the oxidative stress experimental model of rat cochlea with stria vascularis marginal cells injury induced by hydrogen peroxide in vitro. Cultured marginal cells of rat were treated by 200, 300, 400, 600 and 800 micromol/L hydrogen peroxide (H(2)O(2)) for 0.5, 1, 2, 4, 16 and 24 hours, respectively. Cell viability was assessed by the CCK-8 assay. The content of the lipid peroxidation production malondialdehyde (MDA) were detected in H(2)O(2) induced marginal cells injury with different concentration H(2)O(2). Apoptosis was assessed by flow cytometry by propidium sodium staining. The expression of the cleaved-caspase-3 was assessed by Western blot. Being exposed to H(2)O(2), marginal cells displayed nuclear pyknosis and margination, cytoplasmic condensation, cell shrinkage and formation of membrane and bounded apoptotic bodies. A time-dependent and dose-dependent decrease of cellular viability was detected with the treatment of H(2)O(2). Cellular maleic dialdehyde was generated in proportion to the concentration of H(2)O(2) at 2 hours and the number of apoptotic cells increased significantly (P < 0. 05). Western blot showed the expression of the cleaved-caspase-3 increased when 200 micromol/L, 300 micromol/L and 400 micromol/L H(2)O(2) treated cultured marginal cells. Thereafter the expression of the cleaved-caspase-3 decreased with 600 micromol/L H(2)O(2) and with 800 micromol/L H(2)O(2) the expression of cleaved-caspase-3 was weak. The findings indicated that the experimental model can be established successfully using cultured cells exposed to H(2)O(2) and activation of caspase-3 is associated with hydrogen peroxide induced rat marginal cells the oxidative stress injury.

Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat.

PubMed

Koromilas, Christos; Tsakiris, Stylianos; Kalafatakis, Konstantinos; Zarros, Apostolos; Stolakis, Vasileios; Kimpizi, Despoina; Bimpis, Alexios; Tsagianni, Anastasia; Liapi, Charis

2015-02-01

Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent

Mouse Experimental Myopia Has Features of Primate Myopia

PubMed Central

Tkatchenko, Tatiana V.; Shen, Yimin

2010-01-01

Purpose. Several recent studies have suggested that experimental myopia can be induced in mice. However, it is not clear what role the photopic visual input plays in this process and whether mouse myopia is similar to human myopia. The purpose of this study was to carry out an in vivo high-resolution analysis of changes in ocular components and refractive state of the eye upon induction of experimental myopia in mice. Methods. A high-resolution small animal MRI system and a high-resolution automated eccentric infrared photorefractor were used to analyze changes of the refractive state and ocular components in C57BL/6J mice associated with experimental myopia induced by diffusers and −25 D lenses under photopic conditions. Results. The authors found that both diffusers and −25 D lenses induce myopia in C57BL/6J mice under photopic conditions (continuous light, 200 ± 15 lux). The extent of myopic shift induced by −25 D lenses was greater than the shift induced by diffusers (−15.2 ± 0.7 D, lenses; −12.0 ± 1.4 D, diffusers). Myopia in mice is attributed to an increase in size of the postequatorial segment of the eye. Experimental myopia in mice can be induced only during the susceptible period in postnatal development, which ends around postnatal day 67. Conclusions. Both diffusers and spectacle lenses induce myopia in mice under photopic conditions, during the susceptible period in postnatal development. Myopia in mice is associated with elongation of the vitreous chamber of the eye, as in humans and nonhuman primates. PMID:19875658

Protective Effect of Selenium Against Cisplatin-Induced Ototoxicity in an Experimental Design.

PubMed

Doğan, Sedat; Yazici, Hasmet; Yalçinkaya, Esin; Erdoğdu, Halil Ibrahim; Tokgöz, Sibel Alicura; Sarici, Furkan; Namuslu, Mehmet; Sarikaya, Yasin

2016-10-01

Cisplatin is an effective chemotherapeutic agent in the treatment of several types of malignant solid tumors but its clinical use is associated with ototoxicity. In the present study, we investigated the effect of selenium administration on lipid peroxidation (malondialdehyde [MDA]) and cisplatin-induced ototoxicity in rats. Healthy wistar albino rats (n = 21) were randomly divided into 3 groups: control (C), cisplatin (Cis), cisplatin and selenium (Cis+Se). Cisplatin was administered for 3 days to Cis and Cis+Se groups. Cis+Se group received selenium 5 days before cisplatin injection and continued for 11 consecutive days. Hearing thresholds and lipid peroxidation (MDA) levels of the rats were recorded before injections and at the end of experimental protocol. The cochleas of animals were harvested for histologic and immunuhistochemical examinations. In biochemichal analyses, pretreatment with selenium prevented the elevation of MDA levels in Cis+Se group rats. Moreover, animals in Cis+Se group had better hearing threshold levels than animals in cis group. Samples obtained from the animals in Cis group revealed extensive loss of the normal microarchitecture of the organ of Corti. On the other hand, animals in Cis+Se group exhibited a preservation of the morphology of the organ of Corti and outer hair cells. In the immunohistochemical examinations of cochlear tissues stained with anti-caspase-3, a higher degree of immunopositivity was found in the Cis group. When Cis+Se group and Cis group were compared, significantly less immunopositivity occurred in the Cis+Se group (P < 0.05). Thus, it appears that pretreatment with selenium may reduce cisplatin-induced ototoxicity in rats.

Assessment of contrast-enhanced ultrasonography of the hepatic vein for detection of hemodynamic changes associated with experimentally induced portal hypertension in dogs.

PubMed

Morishita, Keitaro; Hiramoto, Akira; Michishita, Asuka; Takagi, Satoshi; Hoshino, Yuki; Itami, Takaharu; Lim, Sue Yee; Osuga, Tatsuyuki; Nakamura, Sayuri; Ochiai, Kenji; Nakamura, Kensuke; Ohta, Hiroshi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi

2017-04-01

OBJECTIVE To assess the use of contrast-enhanced ultrasonography (CEUS) of the hepatic vein for the detection of hemodynamic changes associated with experimentally induced portal hypertension in dogs. ANIMALS 6 healthy Beagles. PROCEDURES A prospective study was conducted. A catheter was surgically placed in the portal vein of each dog. Hypertension was induced by intraportal injection of microspheres (10 to 15 mg/kg) at 5-day intervals via the catheter. Microsphere injections were continued until multiple acquired portosystemic shunts were created. Portal vein pressure (PVP) was measured through the catheter. Contrast-enhanced ultrasonography was performed before and after establishment of hypertension. Time-intensity curves were generated from the region of interest in the hepatic vein. Perfusion variables measured for statistical analysis were hepatic vein arrival time, time to peak, time to peak phase (TTPP), and washout ratio. The correlation between CEUS variables and PVP was assessed by use of simple regression analysis. RESULTS Time to peak and TTPP were significantly less after induction of portal hypertension. Simple regression analysis revealed a significant negative correlation between TTPP and PVP. CONCLUSIONS AND CLINICAL RELEVANCE CEUS was useful for detecting hemodynamic changes associated with experimentally induced portal hypertension in dogs, which was characterized by a rapid increase in the intensity of the hepatic vein. Furthermore, TTPP, a time-dependent variable, provided useful complementary information for predicting portal hypertension. IMPACT FOR HUMAN MEDICINE Because the method described here induced presinusoidal portal hypertension, these results can be applied to idiopathic portal hypertension in humans.

Role of Epithelial–Mesenchymal Transition in Repair of the Lacrimal Gland after Experimentally Induced Injury

PubMed Central

You, Samantha; Avidan, Orna; Tariq, Ayesha; Ahluwalia, Ivy; Stark, Paul C.; Kublin, Claire L.

2012-01-01

Purpose. Ongoing studies demonstrate that the murine lacrimal gland is capable of repair after experimentally induced injury. It was recently reported that repair of the lacrimal gland involved the mobilization of mesenchymal stem cells (MSCs). These cells expressed the type VI intermediate filament protein nestin whose expression was upregulated during the repair phase. The aim of the present study was to investigate the roles of vimentin, a type III intermediate filament protein and a marker of epithelial–mesenchymal transition (EMT) in repair of the lacrimal gland. Methods. Injury was induced by direct injection of interleukin (IL)-1 into the exorbital lacrimal gland. MSCs were prepared from injured glands using tissue explants. Expression of vimentin and the transcription factor Snai1, a master regulator of EMT, was determined by RT-PCR, Western blotting analysis, and immunofluorescence. Results. These data show that vimentin expression, at both the mRNA and the protein levels, was upregulated during the repair phase (2–3 days postinjury) and returned to the control level when repair ended. Temporal expression of Snai1 mirrored that of vimentin and was localized in cell nuclei. Cultured MSCs isolated from injured lacrimal glands expressed Snai1 and vimentin alongside nestin and alpha smooth muscle actin (another biomarker of EMT). There was a strong positive correlation between Snai1 expression and vimentin expression. Conclusions. It was found that EMT is induced during repair of the lacrimal gland to generate MSCs to initiate repair, and that mesenchymal–epithelial transition is then activated to form acinar and ductal epithelial cells. PMID:22025566

[Comparative study of the antiglaucomatous activity of Glauplex 2 and pilocarpine nitrate on alpha-chymotrypsin-induced experimental glaucoma].

PubMed

Andermann, G; de Burlet, G; Cannet, C

1982-01-01

The antiglaucomatous effects of Glauplex 2 and pilocarpine nitrate on alpha-chymotrypsine-induced experimental glaucoma were studied in 8 rabbits. Changes in intraocular pressure were measured over a period of 12 hours after a single instillation of Glauplex 2 or two instillations of 2.6 p. cent pilocarpine nitrate at t = 0 and t = 6 hours. The antihypertensive effect of a single instillation of Glauplex 2 was shown to be approximately equivalent to that of two instillations of 2.6 p. cent pilocarpine nitrate.

The smell of "anxiety": Behavioral modulation by experimental anosmia in zebrafish.

PubMed

Abreu, Murilo S; Giacomini, Ana C V V; Kalueff, Allan V; Barcellos, Leonardo J G

2016-04-01

Olfaction is strongly involved in the regulation of fish behavior, including reproductive, defensive, social and migration behaviors. In fish, anosmia (the lack of olfaction) can be induced experimentally, impairing their ability to respond to various olfactory stimuli. Here, we examine the effects of experimental lidocaine-induced anosmia on anxiety-like behavior and whole-body cortisol levels in adult zebrafish (Danio rerio). We show that experimentally-induced anosmia reduces anxiolytic-like behavioral effects of fluoxetine and seems to interact with anxiogenic effect of stress also paralleling cortisol responses in zebrafish. These findings provide first experimental evidence that temporary anosmia modulates anxiety-like behaviors and physiology in adult zebrafish. Copyright © 2016 Elsevier Inc. All rights reserved.

Anti-inflammatory and immunomodulatory effects of Spirulina platensis in comparison to Dunaliella salina in acetic acid-induced rat experimental colitis.

PubMed

Abdel-Daim, Mohamed M; Farouk, Sameh M; Madkour, Fedekar F; Azab, Samar S

2015-04-01

Spirulina platensis (SP) is used as a source of protein and vitamin supplement in humans without any significant side-effects. Dunaliella salina (DS) is also regarded as one of the richest natural producers of carotenoid, thus used as a source of antioxidants to protect cells from oxidative damage. The aim of the present study is to compare the ameliorative effect of Spirulina and Dunaliella in experimental colitis. Spirulina and Dunaliella were investigated at the same dose of 500 mg/kg body weight for their modulatory effect against acetic-acid induced ulcerative colitis (UC) in rats. The colonic lesion was analyzed by examining macroscopic damage, bloody diarrhea scores, colon weight/length and change in body weight of tested rats. Colon lipid peroxidation and oxidative stress markers were examined by evaluating malondialdehyde (MDA), protein carbonyl (PCO), catalase (CAT), reduced glutathione (GSH) and superoxide dismutase (SOD). Colon inflammatory markers; myeloperoxidase (MPO) and prostaglandin (PGE2) as well as proinflammatory cytokines; tumor necrosis factor (TNF-α) and interleukins (IL-1β, IL-6) were also studied. The colonic mucosal injury, biochemical and histopathologic results suggest that both SP and DS exhibit significant modulatory effect on acetic acid-induced colitis in rats, which may be due to a significant increase of antioxidant enzymes activity and significant inhibition of lipid peroxidation and inflammation markers. Results showed that in comparison to Sulfasalazine, SP exhibited better therapeutic and safety profile than DS against acetic acid-induced UC. This study suggests potential benefits of SP and DS in an experimental model of colitis.

An Experimental Visualization and Image Analysis of Electrohydrodynamically Induced Vapor-Phase Silicon Oil Flow under DC Corona Discharge

NASA Astrophysics Data System (ADS)

Ohyama, Ryu-Ichiro; Fukumoto, Masaru

A DC corona discharge induced electrohydrodynamic (EHD) flow phenomenon for a multi-phase fluid containing a vapor-phase dielectric liquid in the fresh air was investigated. The experimental electrode system was a simple arrangement of needle-plate electrodes for the corona discharges and high-resistivity silicon oil was used as the vapor-phase liquid enclosure. The qualitative observation of EHD flow patterns was conducted by an optical processing on computer tomography and the time-series of discharge current pulse generations at corona discharge electrode were measured simultaneously. These experimental results were analyzed in relationship between the EHD flow motions and the current pulse generations in synchronization. The current pulses and the EHD flow motions from the corona discharge electrode presented a continuous mode similar to the ionic wind in the fresh air and an intermittent mode. In the intermittent mode, the observed EHD flow motion was synchronized with the separated discharge pulse generations. From these experimental results, it was expected that the existence of silicon oil vapor trapped charges gave an occasion to the intermittent generations of the discharge pulses and the secondary EHD flow.

Experimental study of fs-laser induced sub-100-nm periodic surface structures on titanium.

PubMed

Nathala, Chandra S R; Ajami, Ali; Ionin, Andrey A; Kudryashov, Sergey I; Makarov, Sergey V; Ganz, Thomas; Assion, Andreas; Husinsky, Wolfgang

2015-03-09

In this work the formation of laser-induced periodic surface structures (LIPSS) on a titanium surface upon irradiation by linearly polarized femtosecond (fs) laser pulses with a repetition rate of 1 kHz in air environment was studied experimentally. In particular, the dependence of high-spatial-frequency-LIPSS (HSFL) characteristics on various laser parameters: fluence, pulse number, wavelength (800 nm and 400 nm), pulse duration (10 fs - 550 fs), and polarization was studied in detail. In comparison with low-spatial-frequency-LIPSS (LSFL), the HSFL emerge at a much lower fluence with orientation perpendicular to the ridges of the LSFL. It was observed that these two types of LIPSS demonstrate different fluence, shot number and wavelength dependencies, which suggest their origin is different. Therefore, the HSFL formation mechanism cannot be described by the widely accepted interference model developed for describing LSFL formation.

Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations.

PubMed

Das, Jharana; Singh, Rameshwar; Sharma, Deepak

2017-05-01

Traumatic epilepsy is defined by episodes of recurring seizures secondary to severe brain injury. Though drugs are found effective to control seizures, their long-term use have been observed to increase reactive oxygen species in animals. Flavonoid fisetin, a natural bioactive phytonutrient reported to exert anticonvulsive effect in experimental seizure models. But, trauma-induced seizures could not be prevented by anticonvulsants was reported in some clinical studies. To study the effect of fisetin on epileptiform electrographic activity in iron-induced traumatic epilepsy and also the probable reason behind the effect in rats. Fisetin pretreatment (20 mg/kg body wt., p.o.) of rats for 12 weeks were chosen followed by injecting iron (5 µl, 100 mM) stereotaxically to generate iron-induced epilepsy. Experimental design include electrophysiological study (electroencephalograph in correlation with multiple unit activity (MUA) in the cortex and CA1 subfield of the hippocampus; spectral analysis of seizure and seizure-associated behavioral study (Morris water maze for spatial learning, open-field test for anxiety) and biochemical study (lipid peroxidation, Na + ,K + -ATPase activity) in both the cortex and the hippocampus. Fisetin pretreatment was found to prevent the development of iron-induced electrical seizure and decrease the corresponding MUA in the cortex (*P˂0.05) as well as in the hippocampus (***P˂0.001). Fisetin pretreatment decreased the lipid peroxides (*P˂0.05) and retained the Na + ,K + -ATPase activity (*P˂0.05) which was found altered in the epileptic animals and also found to attenuate the seizure-associated cognitive dysfunctions. This study demonstrated the antiepileptic action of fisetin in iron-induced model of epileptic rats by inhibiting oxidative stress.

Computational and experimental analysis of TMS-induced electric field vectors critical to neuronal activation

NASA Astrophysics Data System (ADS)

Krieg, Todd D.; Salinas, Felipe S.; Narayana, Shalini; Fox, Peter T.; Mogul, David J.

2015-08-01

Objective. Transcranial magnetic stimulation (TMS) represents a powerful technique to noninvasively modulate cortical neurophysiology in the brain. However, the relationship between the magnetic fields created by TMS coils and neuronal activation in the cortex is still not well-understood, making predictable cortical activation by TMS difficult to achieve. Our goal in this study was to investigate the relationship between induced electric fields and cortical activation measured by blood flow response. Particularly, we sought to discover the E-field characteristics that lead to cortical activation. Approach. Subject-specific finite element models (FEMs) of the head and brain were constructed for each of six subjects using magnetic resonance image scans. Positron emission tomography (PET) measured each subject’s cortical response to image-guided robotically-positioned TMS to the primary motor cortex. FEM models that employed the given coil position, orientation, and stimulus intensity in experimental applications of TMS were used to calculate the electric field (E-field) vectors within a region of interest for each subject. TMS-induced E-fields were analyzed to better understand what vector components led to regional cerebral blood flow (CBF) responses recorded by PET. Main results. This study found that decomposing the E-field into orthogonal vector components based on the cortical surface geometry (and hence, cortical neuron directions) led to significant differences between the regions of cortex that were active and nonactive. Specifically, active regions had significantly higher E-field components in the normal inward direction (i.e., parallel to pyramidal neurons in the dendrite-to-axon orientation) and in the tangential direction (i.e., parallel to interneurons) at high gradient. In contrast, nonactive regions had higher E-field vectors in the outward normal direction suggesting inhibitory responses. Significance. These results provide critical new

Experimental, theoretical, and device application development of nanoscale focused electron-beam-induced deposition

NASA Astrophysics Data System (ADS)

Randolph, Steven Jeffrey

Electron-beam-induced deposition (EBID) is a highly versatile nanofabrication technique that allows for growth of a variety of materials with nanoscale precision and resolution. While several applications and studies of EBID have been reported and published, there is still a significant lack of understanding of the complex mechanisms involved in the process. Consequently, EBID process control is, in general, limited and certain common experimental results regarding nanofiber growth have yet to be fully explained. Such anomalous results have been addressed in this work both experimentally and by computer simulation. Specifically, a correlation between SiOx nanofiber deposition observations and the phenomenon of electron beam heating (EBH) was shown by comparison of thermal computer models and experimental results. Depending on the beam energy, beam current, and nanostructure geometry, the heat generated can be substantial and may influence the deposition rate. Temperature dependent EBID growth experiments qualitatively verified the results of the EBH model. Additionally, EBID was used to produce surface image layers for maskless, direct-write lithography (MDL). A single layer process used directly written SiOx features as a masking layer for amorphous silicon thin films. A bilayer process implemented a secondary masking layer consisting of standard photoresist into which a pattern---directly written by EBID tungsten---was transferred. The single layer process was found to be extremely sensitive to the etch selectivity of the plasma etch. In the bilayer process, EBID tungsten was written onto photoresist and the pattern transferred by means of oxygen plasma dry development following a brief refractory descum. Conditions were developed to reduce the spatial spread of electrons in the photoresist layer and obtain ˜ 35 nm lines. Finally, an EBID-based technique for field emitter repair was applied to the Digital Electrostatically focused e-beam Array Lithography (DEAL

Interstitial Lung Disease Induced by Osimertinib for Epidermal Growth Factor Receptor (EGFR) T790M-positive Non-small Cell Lung Cancer

PubMed Central

Matsumoto, Yoshiya; Kawaguchi, Tomoya; Yamamoto, Norio; Sawa, Kenji; Yoshimoto, Naoki; Suzumura, Tomohiro; Watanabe, Tetsuya; Mitsuoka, Shigeki; Asai, Kazuhisa; Kimura, Tatsuo; Yoshimura, Naruo; Kuwae, Yuko; Hirata, Kazuto

2017-01-01

A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration. We diagnosed the patient to have interstitial lung disease induced by osimertinib. PMID:28794368

Comparison of the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

PubMed

Yamane, Tsuyoshi; Fujii, Yoko; Orito, Kensuke; Osamura, Kaori; Kanai, Takao; Wakao, Yoshito

2008-12-01

To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis. 24 Beagles. 18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographically and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated. After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups. Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

Experimental Type 2 Diabetes Induces Enzymatic Changes in Isolated Rat Enterocytes

PubMed Central

Martínez, Isabel M.; Morales, Inmaculada; García-Pino, Guadalupe; Campillo, José E.

2003-01-01

Diabetes in humans and in experimental animals produces changes in the function and structure of the small intestine. The authors determined the activity of intestinal disaccharidases (maltase and sucrase) and of 6-phosphofructo-1-kinase (PFK-1) in enterocytes isolated from the small intestine of male Wistar rats (2.5 to 3 months old) with experimental nonobese type 2 diabetes, induced by streptozotocin (STZ) injection on the day of birth (n0-STZ) or on the 5th day of life (n5-STZ), with different degrees of hyperglycemia and insulinemia (n0-STZ and n5-STZ models). The glycemia (mmol/L) of the diabetic rats (n0-STZ: 8.77 ± 0.47; n5-STZ: 20.83 ± 0.63) was higher (P < .01) than that of the nondiabetic (ND) rats (5.99 ± 0.63); on the contrary, the insulinemia (ng/mL) was significantly lower in both n0-STZ (1.74 ± 0.53; P < .05) and n5-STZ (1.12 ± 0.44; P < .01) diabetic rats than in normal rats (3.77 ± 0.22). The sucrase and maltase activities (U/g protein) in diabetic rats (n0-STZ: 89 ± 9 and 266 ± 12; n5-STZ: 142 ± 23 and 451 ± 57) were significantly higher than those in the ND group (66 ± 5 and 228 ± 22). The PFK-1 activities (mU/mg protein) in the diabetic models (n0-STZ: 14.89 ± 1.51; n5-STZ: 13.35 ± 3.12) were significantly lower (P < .05) than in ND rats (20.54 ± 2.83). The data demonstrated enzymatic alterations in enterocytes isolated fromthe small intestine of n0-STZ rats that are greater (P < .05) than in the more hyperglycemic and hypoinsulinemic n5-STZ animals. The results also show that nonobese type 2–like diabetes in the rat produces modifications that favor an increase in glucose absorption rates. PMID:14630573

Excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in experimental approaches of Parkinsonism.

PubMed

Fernández-Espejo, Emilio; Bis-Humbert, Cristian

2018-06-06

3-iodo-l-tyrosine might play a role in Parkinson's disease since this molecule is able, at high concentration, to inhibit tyrosine-hydroxylase activity, the rate-limiting enzyme in dopamine biosynthesis. The possible Parkinson-like effects of 3-iodo-l-tyrosine were tested on three experimental approaches in mice: cultured substantia nigra neurons, the enteric nervous system of the jejunum after intra-peritoneal infusions, and the nigrostriatal system following unilateral intrabrain injections. 3-iodo-l-tyrosine, a physiological molecule, was used at concentrations higher than its serum levels in humans. Parkinson-like signs were evaluated through abnormal aggregation of α-synuclein and tyrosine-hydroxylase, loss of tyrosine-hydroxylase-expressing and striatum-projecting neurons and fibers, reduced tyrosine-hydroxylase density, and Parkinson-like motor and non-motor deficits. The retrograde tracer FluoroGold was used in the brain model. The findings revealed that excess amounts of 3-iodo-l-tyrosine induce Parkinson-like effects in the three experimental approaches. Thus, culture neurons of substantia nigra show, after 3-iodo-l-tyrosine exposure, intracytoplasmic inclusions that express α-synuclein and tyrosine-hydroxylase. Intra-peritoneal infusions of 3-iodo-l-tyrosine cause, in the long-term, α-synuclein aggregation, thicker α-synuclein-positive fibers, and loss of tyrosine-hydroxylase-positive cells and fibers in intramural plexuses and ganglia of the jejunum. Infusion of 3-iodo-l-tyrosine into the left dorsal striata of mice damages the nigrostriatal system, as revealed through lower striatal tyrosine-hydroxylase density, reduced number of tyrosine-hydroxylase-expressing and striatum-projecting neurons in the left substantia nigra, as well as the emergence of Parkinson-like behavioral deficits such as akinesia, bradykinesia, motor disbalance, and locomotion directional bias. In conclusion, excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in

Treatment of experimentally induced pneumonic pasteurellosis of young calves with tilmicosin.

PubMed Central

Morck, D W; Merrill, J K; Gard, M S; Olson, M E; Nation, P N

1997-01-01

concentrations of the antibiotic were comparatively high, even at 72 h post-infection (6.50 +/- 0.75 ppm). Lung tissue concentrations at 72 h were significantly higher in experimentally infected calves than in non-infected tilmicosin-treated animals (P < 0.05). These data demonstrate that tilmicosin was effective in treating experimentally-induced pneumonic pasteurellosis as determined by alleviation of clinical signs, pathological findings at post mortem, and presence of viable bacteria from the lung. Concentrations substantially above MIC for P. haemolytica were present in lung tissue even at 72 h following a single subcutaneous injection of 10 mg tilmicosin per kg body weight. Images Figure 2A. Figure 2B. PMID:9242998

Descending antinociception induced by secondary somatosensory cortex stimulation in experimental neuropathy: role of the medullospinal serotonergic pathway

PubMed Central

Sagalajev, Boriss; Viisanen, Hanna; Wei, Hong

2017-01-01

Stimulation of the secondary somatosensory cortex (S2) has attenuated pain in humans and inflammatory nociception in animals. Here we studied S2 stimulation-induced antinociception and its underlying mechanisms in an experimental animal model of neuropathy induced by spinal nerve ligation (SNL). Effect of S2 stimulation on heat-evoked limb withdrawal latency was assessed in lightly anesthetized rats that were divided into three groups based on prior surgery and monofilament testing before induction of anesthesia: 1) sham-operated group and 2) hypersensitive and 3) nonhypersensitive (mechanically) SNL groups. In a group of hypersensitive SNL animals, a 5-HT1A receptor agonist was microinjected into the rostroventromedial medulla (RVM) to assess whether autoinhibition of serotonergic cell bodies blocks antinociception. Additionally, effect of S2 stimulation on pronociceptive ON-cells and antinociceptive OFF-cells in the RVM or nociceptive spinal wide dynamic range (WDR) neurons were assessed in anesthetized hypersensitive SNL animals. S2 stimulation induced antinociception in hypersensitive but not in nonhypersensitive SNL or sham-operated animals. Antinociception was prevented by a 5-HT1A receptor agonist in the RVM. Antinociception was associated with decreased duration of heat-evoked response in RVM ON-cells. In spinal WDR neurons, heat-evoked discharge was delayed by S2 stimulation, and this antinociceptive effect was prevented by blocking spinal 5-HT1A receptors. The results indicate that S2 stimulation suppresses nociception in SNL animals if SNL is associated with tactile allodynia-like hypersensitivity. In hypersensitive SNL animals, S2 stimulation induces antinociception mediated by medullospinal serotonergic pathways acting on the spinal 5-HT1A receptor, and partly through reduction of the RVM ON-cell discharge. NEW & NOTEWORTHY Stimulation of S2 cortex, but not that of an adjacent cortical area, induced descending heat antinociception in rats with the

Anti-inflammatory and anti-oxidative effects of alpha-lipoic acid in experimentally induced acute otitis media.

PubMed

Tatar, A; Korkmaz, M; Yayla, M; Gozeler, M S; Mutlu, V; Halici, Z; Uslu, H; Korkmaz, H; Selli, J

2016-07-01

To investigate the anti-inflammatory, anti-oxidative and tissue protective effects, as well as the potential therapeutic role, of alpha-lipoic acid in experimentally induced acute otitis media. Twenty-five guinea pigs were assigned to one of five groups: a control (non-otitis) group, and otitis-induced groups treated with saline, penicillin G, alpha-lipoic acid, or alpha-lipoic acid plus penicillin G. Tissue samples were histologically analysed, and oxidative parameters in tissue samples were measured and compared between groups. The epithelial integrity was better preserved, and histological signs of inflammation and secretory metaplasia were decreased, in all groups compared to the saline treated otitis group. In the alpha-lipoic acid plus penicillin G treated otitis group, epithelial integrity was well preserved and histological findings of inflammation were significantly decreased compared to the saline, penicillin G and alpha-lipoic acid treated otitis groups. The most favourable oxidative parameters were observed in the control group, followed by the alpha-lipoic acid plus penicillin G treated otitis group. Alpha-lipoic acid, with its antioxidant, anti-inflammatory and tissue protective properties, may decrease the clinical sequelae and morbidity associated with acute otitis media.

The effects of prednisolone and serum malondialdehyde levels in puppies with experimentally induced meconium aspiration syndrome.

PubMed

Kirimi, E; Tuncer, O; Kösem, M; Ceylan, E; Tas, A; Tasal, I; Balahoroğlu, R; Caksen, H

2003-01-01

The aim of this study was to investigate the effect of different doses of prednisolone in puppies experimentally induced with meconium aspiration syndrome (MAS). Meconium was collected from human babies in the first day of life and was released into the trachea of 11 newborn puppies to induce MAS. Puppies were treated with 2 mg/kg prednisolone (standard dose), 30 mg/kg prednisolone (megadose) or 0.9% saline, all administered intravenously. The study ended 20 h after meconium aspiration and the lungs were then scored for histopathology. Animals not treated with prednisolone deteriorated after 8 h while respiration rate, oxygenation, pH and partial pressure of carbon dioxide values were better in the prednisolone-treated groups. Histopathology scores were better in the treatment groups compared with the control group, with megadose giving the best result. At the end of the study, serum malondialdehyde levels were significantly higher in the megadose prednisolone group compared with the other two groups. In conclusion, we determined that prednisolone reduced physiological and histological changes in puppies with MAS and that a 30 mg/kg dose was more effective than 2 mg/kg.

An Experimental and Numerical Study of Roughness-Induced Instabilities in a Mach 3.5 Boundary Layer

NASA Technical Reports Server (NTRS)

Kegerise, Michael A.; King, Rudolph A.; Owens, Lewis R.; Choudhari, Meelan M.; Norris, Andrew T.; Li, Fei; Chang, Chau-Layn

2012-01-01

Progress on a joint experimental and numerical study of laminar-to-turbulent transition induced by an isolated roughness element in a high-speed laminar boundary layer is reported in this paper. The numerical analysis suggests that transition is driven by the instability of high- and low-speed streaks embedded in the wake of the isolated roughness element. In addition, spatial stability analysis revealed that the wake flow supports multiple modes (even and odd) of convective instabilities that experience strong enough growth to cause transition. The experimental measurements, which included hot-wire and pitot-probe surveys, confirmed the existence of embedded high- and low-speed streaks in the roughness wake. Furthermore, the measurements indicate the presence of both even and odd modes of instability, although their relative magnitude depends on the specifics of the roughness geometry and flow conditions (e.g., the value of Re(sub kk) or k/delta. For the two test cases considered in the measurements (Re(sub kk) values of 462 and 319), the even mode and the odd mode were respectively dominant and appear to play a primary role in the transition process.

Repair of experimental plaque-induced periodontal disease in dogs.

PubMed

Shoukry, M; Ben Ali, L; Abdel Naby, M; Soliman, A

2007-09-01

Forty mongrel dogs were used in this study for induction of periodontal disease by placing subgingival silk ligatures affecting maxillary and mandibular premolar teeth during a 12-month period. Experimental premolar teeth received monthly clinical, radiographic, and histometric/pathologic assessments. The results demonstrated significant increases in scores and values of periodontal disease parameters associated with variable degrees of alveolar bone loss. The experimental maxillary premolar teeth exhibited more severe and rapid rates of periodontal disease compared with mandibular premolar teeth. Histometric analysis showed significant reduction in free and attached gingiva of the experimental teeth. Histopathological examination of buccolingual sections from experimental premolar teeth showed the presence of rete pegs within the sulcular epithelium with acanthosis and erosive changes, widening of the periodontal ligament, and alveolar bone resorption. Various methods for periodontal repair were studied in 194 experimental premolar teeth exhibiting different degrees of periodontal disease. The treatment plan comprised non-surgical (teeth scaling, root planing, and oral hygiene) and surgical methods (closed gingival curettage, modified Widman flap, and reconstructive surgery using autogenous bone marrow graft and canine amniotic membrane). The initial non-surgical treatment resulted in a periodontal recovery rate of 37.6% and was found effective for treatment of early periodontal disease based on resolution of gingivitis and reduction of periodontal probing depths. Surgical treatment by closed gingival curettage to eliminate the diseased pocket lining resulted in a recovery rate of 48.8% and proved effective in substantially reducing deep periodontal pockets. Open root planing following flap elevation resulted in a recovery rate of 85.4% and was effective for deep and refractory periodontal pockets. Autogenous bone graft implantation combined with canine amniotic

Effect of combination of thalidomide and sulfasalazine in experimentally induced inflammatory bowel disease in rats.

PubMed

Prakash, O; Medhi, B; Saikia, U N; Pandhi, P

2011-09-01

Thalidomide provided significant protection against tri nitro benzene sulfonic acid induced colitis. Combination therapy also reduced colonic inflammation and all the biochemical parameters (myeloperoxidase assay, malondialdehyde assay and tumor necrosis factor-alpha, estimation) were significant as compared to control as well as thalidomide alone treated group. Combination therapy showed additive effect of thalidomide which restored lipid peroxidation as well as reduced myeloperoxidase and TNF-a towards the normal levels. Morphological and histological scores were significantly reduced in combination groups. In experimental model of colitis, oral administration of thalidomide (150 mg/kg) alone as well as its combination with sulfasalazine (360 mg/kg) significantly reduced the colonic inflammation. The results indicate the additive effect of thalidomide with sulfasalazine in rat colitis model which requires further confirmation in human studies.

Effects of experimentally induced low back pain on the sit-to-stand movement and electroencephalographic contingent negative variation

PubMed Central

Jacobs, Jesse V.; Yaguchi, Chie; Kaida, Chizuru; Irei, Mariko; Naka, Masami; Henry, Sharon M.; Fujiwara, Katsuo

2011-01-01

It is becoming increasingly evident that people with chronic, recurrent low back pain (LBP) exhibit changes in cerebrocortical activity that associate with altered postural coordination, suggesting a need for a better understanding of how the experience of LBP alters postural coordination and cerebrocortical activity. To characterize changes in postural coordination and pre-movement cerebrocortical activity related to the experience of acutely induced LBP, 14 healthy participants with no history of LBP performed sit-to-stand movements in 3 sequential conditions: (1) without experimentally induced LBP; NoPain1, (2) with movement-associated LBP induced by electrocutaneous stimulation; Pain, and (3) again without induced LBP; NoPain2. The Pain condition elicited altered muscle activation and redistributed forces under the seat and feet prior to movement, decreased peak vertical force exerted under the feet during weight transfer, longer movement times, as well as decreased and earlier peak hip extension. Stepwise regression models demonstrated that electroencephalographic amplitudes of contingent negative variation during the Pain condition significantly correlated with the participants’ change in sit-to-stand measures between the NoPain1 and Pain conditions, as well as with the subsequent difference in sit-to-stand measures between the NoPain1 and NoPain2 conditions. The results, therefore, identify the contingent negative variation as a correlate for the extent of an individual’s LBP-related movement modifications and to the subsequent change in movement patterns from before to after the experience of acutely induced LBP, thereby providing a direction for future studies aimed to understand the neural mechanisms underlying the development of altered movement patterns with LBP. PMID:21952791

Peroxisome proliferator-activated receptors γ/mitochondrial uncoupling protein 2 signaling protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus

PubMed Central

2012-01-01

Background Status epilepticus induces subcellular changes that may lead to neuronal cell death in the hippocampus. However, the mechanism of seizure-induced neuronal cell death remains unclear. The mitochondrial uncoupling protein 2 (UCP2) is expressed in selected regions of the brain and is emerged as an endogenous neuroprotective molecule in many neurological disorders. We evaluated the neuroprotective role of UCP2 against seizure-induced hippocampal neuronal cell death under experimental status epilepticus. Methods In Sprague–Dawley rats, kainic acid (KA) was microinjected unilaterally into the hippocampal CA3 subfield to induce prolonged bilateral seizure activity. Oxidized protein level, translocation of Bcl-2, Bax and cytochrome c between cytosol and mitochondria, and expression of peroxisome proliferator-activated receptors γ (PPARγ) and UCP2 were examined in the hippocampal CA3 subfield following KA-induced status epilepticus. The effects of microinjection bilaterally into CA3 area of a PPARγ agonist, rosiglitazone or a PPARγ antagonist, GW9662 on UCP2 expression, induced superoxide anion (O2· -) production, oxidized protein level, mitochondrial respiratory chain enzyme activities, translocation of Bcl-2, Bax and cytochrome c, and DNA fragmentation in bilateral CA3 subfields were examined. Results Increased oxidized proteins and mitochondrial or cytosol translocation of Bax or cytochrome c in the hippocampal CA3 subfield was observed 3–48 h after experimental status epilepticus. Expression of PPARγ and UCP2 increased 12–48 h after KA-induced status epilepticus. Pretreatment with rosiglitazone increased UCP2 expression, reduced protein oxidation, O2· - overproduction and dysfunction of mitochondrial Complex I, hindered the translocation of Bax and cytochrome c, and reduced DNA fragmentation in the CA3 subfield. Pretreatment with GW9662 produced opposite effects. Conclusions Activation of PPARγ upregulated mitochondrial UCP2 expression

Breathing Maneuvers as a Vasoactive Stimulus for Detecting Inducible Myocardial Ischemia – An Experimental Cardiovascular Magnetic Resonance Study

PubMed Central

Fischer, Kady; Guensch, Dominik P; Shie, Nancy; Lebel, Julie; Friedrich, Matthias G

2016-01-01

Background Breathing maneuvers can elicit a similar vascular response as vasodilatory agents like adenosine; yet, their potential diagnostic utility in the presence of coronary artery stenosis is unknown. The objective of the study is to investigate if breathing maneuvers can non-invasively detect inducible ischemia in an experimental animal model when the myocardium is imaged with oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR). Methods and Findings In 11 anesthetised swine with experimentally induced significant stenosis (fractional flow reserve <0.75) of the left anterior descending coronary artery (LAD) and 9 control animals, OS-CMR at 3T was performed during two different breathing maneuvers, a long breath-hold; and a combined maneuver of 60s of hyperventilation followed by a long breath-hold. The resulting change of myocardial oxygenation was compared to the invasive measurements of coronary blood flow, blood gases, and oxygen extraction. In control animals, all breathing maneuvers could significantly alter coronary blood flow as hyperventilation decreased coronary blood flow by 34±23%. A long breath-hold alone led to an increase of 97±88%, while the increase was 346±327% (p<0.001), when the long breath-hold was performed after hyperventilation. In stenosis animals, the coronary blood flow response was attenuated after both hyperventilation and the following breath-hold. This was matched by the observed oxygenation response as breath-holds following hyperventilation consistently yielded a significant difference in the signal of the MRI images between the perfusion territory of the stenosis LAD and remote myocardium. There was no difference between the coronary territories during the other breathing maneuvers or in the control group at any point. Conclusion In an experimental animal model, the response to a combined breathing maneuver of hyperventilation with subsequent breath-holding is blunted in myocardium subject to significant coronary

Protective effect of IGF-1 on experimental liver cirrhosis-induced common bile duct ligation.

PubMed

Cantürk, Nuh Zafer; Cantürk, Zeynep; Ozden, Meltem; Dalçik, Hakki; Yardimoglu, Melda; Tülübas, Feti

2003-01-01

The causes of malnutrition in liver cirrhosis are multifactorial. Levels of IGF-1 (insulin like growth factor-1) that is a crucial regulator of intermediary metabolism decreases. The aim of this study was to analyze the effect of IGF-1 supplementation during liver cirrhosis induced by common bile duct ligation. Rats were divided into five different groups: One sham and four experimental groups. Rats in three of four groups were treated with 2 micrograms/day IGF-1 with a different time of experiment in each group. Blood biochemical parameters, tissue malondialdehyde, glutathione levels and the activity of tissue antioxidant enzymes and conventional and immunohistochemical analysis of liver samples were studied for each group. Serum albumin, total protein, fibrinogen levels decreased and prothrombin time was prolonged in the bile duct ligated and transected experimental group but not in the IGF-I treated rats compared with the rats in sham group. Liver malondialdehyde levels significantly increased in control group but not in IGF-1 treated groups. The activities of antioxidant enzymes were decreased compared with the other groups. Histopathology findings of liver biopsy demonstrated intense degree fibrosis and overexpression of fibroblast growth factor and desmin in the control group but a lesser degree of those in the IGF-1 treated groups. IGF-1 treatment improves liver function and decreases oxidative liver damage and histopathological findings. Further studies are required to delineate the mechanisms of protective effects of IGF-1.

Hydrogen-rich saline alleviates experimental noise-induced hearing loss in guinea pigs.

PubMed

Zhou, Y; Zheng, H; Ruan, F; Chen, X; Zheng, G; Kang, M; Zhang, Q; Sun, X

2012-05-03

NS+NOISE groups than the HS+NOISE group (P<0.01). Hydrogen-rich saline can alleviate experimental noise-induced hearing loss in guinea pigs, partially by preventing the death of cochlear hair cells after intensive noise exposure. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Esculin ameliorates cognitive impairment in experimental diabetic nephropathy and induces anti-oxidative stress and anti-inflammatory effects via the MAPK pathway.

PubMed

Song, Yu; Wang, Xiaochun; Qin, Shengkai; Zhou, Siheng; Li, Jiaolun; Gao, Yue

2018-05-01

Esculin is a derivative of coumarin, which is also an active ingredient of ash bark, and has antibacterial, anti-inflammatory, anti‑allergy and skin protective effects. The underlying mechanism and protective effects of esculin on cognitive impairment in experimental diabetic nephropathy (DN) was investigated in the present study. Male C57BL/6J 6‑week‑old mice were injected intravenously with a single dose of streptozotocin (STZ; 30 mg/kg). At 2 weeks after the STZ injection, mice received intravenous injection with 5, 10 or 20 mg/kg esculin for 2 weeks. In the present study, the results of the Morris water maze test demonstrated that esculin significantly improved behavior and recognition memory in STZ‑induced diabetic rats. Furthermore, treatment of STZ‑induced diabetic rats with esculin significantly inhibited tumor necrosis factor‑α, interleukin‑6, malondialdehyde, monocyte chemoattractant protein‑1 and intracellular adhesion molecule‑1 activity levels, and increased the activity of superoxide dismutase, in the kidney, which was determined by ELISA. In addition, esculin treatment significantly suppressed the renal protein expression of activator protein 1, phosphorylated (p)‑p38 mitogen activated protein kinase (MAPK) and p‑c‑Jun N‑terminal kinase, and increased p‑extracellular signal regulated kinase 1/2 protein expression, in STZ‑induced diabetic rats, as determined by western blotting. These results indicate that esculin may ameliorate cognitive impairment in experimental DN, and exert anti‑oxidative stress and anti‑inflammatory effects, via the MAPK signaling pathway. Thus, it may serve as a potential target for cognitive impairment of DN in the future.

The role of inspiratory muscle training in the management of asthma and exercise-induced bronchoconstriction.

PubMed

Shei, Ren-Jay; Paris, Hunter L R; Wilhite, Daniel P; Chapman, Robert F; Mickleborough, Timothy D

2016-11-01

Asthma is a pathological condition comprising of a variety of symptoms which affect the ability to function in daily life. Due to the high prevalence of asthma and associated healthcare costs, it is important to identify low-cost alternatives to traditional pharmacotherapy. One of these low cost alternatives is the use of inspiratory muscle training (IMT), which is a technique aimed at increasing the strength and endurance of the diaphragm and accessory muscles of respiration. IMT typically consists of taking voluntary inspirations against a resistive load across the entire range of vital capacity while at rest. In healthy individuals, the most notable benefits of IMT are an increase in diaphragm thickness and strength, a decrease in exertional dyspnea, and a decrease in the oxygen cost of breathing. Due to the presence of expiratory flow limitation in asthma and exercise-induced bronchoconstriction, dynamic lung hyperinflation is common. As a result of varying operational lung volumes, due in part to hyperinflation, the respiratory muscles may operate far from the optimal portion of the length-tension curve, and thus may be forced to operate against a low pulmonary compliance. Therefore, the ability of these muscles to generate tension is reduced, and for any given level of ventilation, the work of breathing is increased as compared to non-asthmatics. Evidence that IMT is an effective treatment for asthma is inconclusive, due to limited data and a wide variation in study methodologies. However, IMT has been shown to decrease dyspnea, increase inspiratory muscle strength, and improve exercise capacity in asthmatic individuals. In order to develop more concrete recommendations regarding IMT as an effective low-cost adjunct in addition to traditional asthma treatments, we recommend that a standard treatment protocol be developed and tested in a placebo-controlled clinical trial with a large representative sample.

Protective effect of gallic acid in experimental model of ketamine-induced psychosis: possible behaviour, biochemical, neurochemical and cellular alterations.

PubMed

Yadav, Monu; Jindal, Deepak Kumar; Dhingra, Mamta Sachdeva; Kumar, Anil; Parle, Milind; Dhingra, Sameer

2018-04-01

Gallic acid has been reported to possess a number of psychopharmacological activities. These activities are attributed to the antioxidant potential due to the presence of phenolic moeity. The present study was carried out to investigate the protective effects of gallic acid in an experimental model of ketamine-induced psychosis in mice. Ketamine (50 mg/kg, i.p.) was used to induce stereotyped psychotic behavioural symptoms in mice. Behavioural studies (locomotor activity, stereotype behaviour, immobility duration and memory retention) were carried out to investigate the protective of gallic acid on ketamine-induced psychotic symptoms, followed by biochemical and neurochemical changes and cellular alterations in the brain. Chronic treatment with gallic acid for 15 consecutive days significantly attenuated stereotyped behavioural symptoms in mice. Biochemical estimations revealed that gallic acid reduced the lipid peroxidation and restored the total brain proteins. Furthermore, gallic acid remarkably reduced the dopamine levels, AChE activity and inflammatory surge (serum TNF-α), and increased the levels of GABA and increased glutathione in mice. The study revealed that gallic acid could ameliorate psychotic symptoms and biochemical changes in mice, indicating protective effects in psychosis.

Experimental Contact Lens to Prevent Glaucoma-Induced Blindness

MedlinePlus

... By Sharon Reynolds Posted January 23, 2014 An experimental contact lens design releases a glaucoma medicine at a steady rate ... materials. Other designs have most often used a pre-made lens dipped in a drug solution, which ...

[Acute alveolitis after using a waterproofing aerosol: apropos of 2 cases].

PubMed

Testud, F; Gabrielle, L; Paquin, M L; Descotes, J

1998-04-01

Waterproofing sprays for leather clothing have seldom been involved in severe accidents. In some circumstances, their pulmonary toxicity is marked, as shown by two case reports and a review of the literature. Acute alveolitis is described in two young adults without previous respiratory illness, following the use of a waterproofing spray for leather clothing. Clinical features typical of a flu-like reaction (malaise, fever and chills) were associated with dyspnea and with hemoptysis in one patient. X-ray examination evidenced lesional edema which quickly resolved after symptomatic treatment. The toxic mechanism is debated, but experimental data and clinical findings suggest the causative role of recently introduced fluoropolymers. Waterproofing sprays for leather clothing may induce severe respiratory illness after massive inhalation in confined area. Treatment is supportive.

Assessment of IgE binding to native and hydrolyzed soy protein in serum obtained from dogs with experimentally induced soy protein hypersensitivity.

PubMed

Serra, Montserrat; Brazís, Pilar; Fondati, Alessandra; Puigdemont, Anna

2006-11-01

To assess binding of IgE to native, whole hydrolyzed, and separated hydrolyzed fractions of soy protein in serum obtained from dogs with experimentally induced soy protein hypersensitivity. 8 naïve Beagles (6 experimentally sensitized to native soy protein and 2 control dogs). 6 dogs were sensitized against soy protein by administration of allergens during a 90-day period. After the sensitization protocol was completed, serum concentrations of soy-specific IgE were measured and intradermal skin tests were performed in all 6 dogs to confirm that the dogs were sensitized against soy protein. Serum samples from each sensitized and control dog underwent western blot analysis to assess the molecular mass band pattern of the different allergenic soy fractions and evaluate reactivities to native and hydrolyzed soy protein. In sera from sensitized dogs, a characteristic band pattern with 2 major bands (approx 75 and 50 kd) and 2 minor bands (approx 31 and 20 kd) was detected, whereas only a diffuse band pattern associated with whole hydrolyzed soy protein was detected in the most reactive dog. Reactivity was evident only for the higher molecular mass peptide fraction. In control dogs, no IgE reaction to native or hydrolyzed soy protein was detected. Data suggest that the binding of soy-specific IgE to the hydrolyzed soy protein used in the study was significantly reduced, compared with binding of soy-specific IgE to the native soy protein, in dogs with experimentally induced soy hypersensitivity.

Regulation of adenosine deaminase (ADA) on induced mouse experimental autoimmune uveitis (EAU) ‡

PubMed Central

Liang, Dongchun; Zuo, Aijun; Zhao, Ronglan; Shao, Hui; Kaplan, Henry J.; Sun, Deming

2016-01-01

Adenosine is an important regulator of the immune response and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies have shown that adenosine receptor (AR) agonists can be either anti- or pro-inflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1–20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8–14 days post-immunization, shortly before EAU expression, but ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses and this effect was γδ T cell-dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help improve the design of ADA- and AR-targeted therapies. PMID:26856700

Anti-thymocyte globulin induces neoangiogenesis and preserves cardiac function after experimental myocardial infarction.

PubMed

Lichtenauer, Michael; Mildner, Michael; Werba, Gregor; Beer, Lucian; Hoetzenecker, Konrad; Baumgartner, Andrea; Hasun, Matthias; Nickl, Stefanie; Mitterbauer, Andreas; Zimmermann, Matthias; Gyöngyösi, Mariann; Podesser, Bruno Karl; Klepetko, Walter; Ankersmit, Hendrik Jan

2012-01-01

Acute myocardial infarction (AMI) followed by ventricular remodeling is the major cause of congestive heart failure and death in western world countries. Of relevance are reports showing that infusion of apoptotic leucocytes or anti-lymphocyte serum after AMI reduces myocardial necrosis and preserves cardiac function. In order to corroborate this therapeutic mechanism, the utilization of an immunosuppressive agent with a comparable mechanism, such as anti-thymocyte globulin (ATG) was evaluated in this study. AMI was induced in rats by ligation of the left anterior descending artery. Initially after the onset of ischemia, rabbit ATG (10 mg/rat) was injected intravenously. In vitro and in vivo experiments showed that ATG induced a pronounced release of pro-angiogenic and chemotactic factors. Moreover, paracrine factors released from ATG co-incubated cell cultures conferred a down-regulation of p53 in cardiac myocytes. Rats that were injected with ATG evidenced higher numbers of CD68+ macrophages in the ischemic myocardium. Animals injected with ATG evidenced less myocardial necrosis, showed a significant reduction of infarct dimension and an improvement of post-AMI remodeling after six weeks (infarct dimension 24.9% vs. 11.4%, p<0.01). Moreover, a higher vessel density in the peri-infarct region indicated a better collateralization in rats that were injected with ATG. These data indicate that ATG, a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53. This might have raised the resistance against apoptotic cell death during ischemia. The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI.

Prevention of antipsychotic-induced hyperglycaemia by vitamin D: a data mining prediction followed by experimental exploration of the molecular mechanism.

PubMed

Nagashima, Takuya; Shirakawa, Hisashi; Nakagawa, Takayuki; Kaneko, Shuji

2016-05-20

Atypical antipsychotics are associated with an increased risk of hyperglycaemia, thus limiting their clinical use. This study focused on finding the molecular mechanism underlying antipsychotic-induced hyperglycaemia. First, we searched for drug combinations in the FDA Adverse Event Reporting System (FAERS) database wherein a coexisting drug reduced the hyperglycaemia risk of atypical antipsychotics, and found that a combination with vitamin D analogues significantly decreased the occurrence of quetiapine-induced adverse events relating diabetes mellitus in FAERS. Experimental validation using mice revealed that quetiapine acutely caused insulin resistance, which was mitigated by dietary supplementation with cholecalciferol. Further database analysis of the relevant signalling pathway and gene expression predicted quetiapine-induced downregulation of Pik3r1, a critical gene acting downstream of insulin receptor. Focusing on the phosphatidylinositol 3-kinase (PI3K) signalling pathway, we found that the reduced expression of Pik3r1 mRNA was reversed by cholecalciferol supplementation in skeletal muscle, and that insulin-stimulated glucose uptake into C2C12 myotube was inhibited in the presence of quetiapine, which was reversed by concomitant calcitriol in a PI3K-dependent manner. Taken together, these results suggest that vitamin D coadministration prevents antipsychotic-induced hyperglycaemia and insulin resistance by upregulation of PI3K function.

Diet shifts and population dynamics of estuarine foraminifera during ecosystem recovery after experimentally induced hypoxia crises

NASA Astrophysics Data System (ADS)

Brouwer, G. M.; Duijnstee, I. A. P.; Hazeleger, J. H.; Rossi, F.; Lourens, L. J.; Middelburg, J. J.; Wolthers, M.

2016-03-01

This study shows foraminiferal dynamics after experimentally induced hypoxia within the wider context of ecosystem recovery. 13C-labeled bicarbonate and glucose were added to the sediments to examine foraminiferal diet shifts during ecosystem recovery and test-size measurements were used to deduce population dynamics. Hypoxia-treated and undisturbed patches were compared to distinguish natural (seasonal) fluctuations from hypoxia-induced responses. The effect of timing of disturbance and duration of recovery were investigated. The foraminiferal diets and population dynamics showed higher fluctuations in the recovering patches compared to the controls. The foraminiferal diet and population structure of Haynesina germanica and Ammonia beccarii responded differentially and generally inversely to progressive stages of ecosystem recovery. Tracer inferred diet estimates in April and June and the two distinctly visible cohorts in the test-size distribution, discussed to reflect reproduction in June, strongly suggest that the ample availability of diatoms during the first month of ecosystem recovery after the winter hypoxia was likely profitable to A. beccarii. Enhanced reproduction itself was strongly linked to the subsequent dietary shift to bacteria. The distribution of the test dimensions of H. germanica indicated that this species had less fluctuation in population structure during ecosystem recovery but possibly reproduced in response to the induced winter hypoxia. Bacteria seemed to consistently contribute more to the diet of H. germanica than diatoms. For the diet and test-size distribution of both species, the timing of disturbance seemed to have a higher impact than the duration of the subsequent recovery period.

BDNF and VEGF in the pathogenesis of stress-induced affective diseases: an insight from experimental studies.

PubMed

Nowacka, Marta; Obuchowicz, Ewa

2013-01-01

Stress is known to play an important role in etiology, development and progression of affective diseases. Especially, chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis (HPA), neurotransmission and the immune system, acts as a trigger for affective diseases. It has been reported that the rise in the concentration of pro-inflammatory cytokines and persistent up-regulation of glucocorticoid expression in the brain and periphery increases the excitotoxic effect on CA3 pyramidal neurons in the hippocampus resulting in dendritic atrophy, apoptosis of neurons and possibly inhibition of neurogenesis in adult brain. Stress was observed to disrupt neuroplasticity in the brain, and growing evidence demonstrates its role in the pathomechanism of affective disorders. Experimental studies indicate that a well-known brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) which have recently focused increasing attention of neuroscientists, promote cell survival, positively modulate neuroplasticity and hippocampal neurogenesis. In this paper, we review the alterations in BDNF and VEGF pathways induced by chronic and acute stress, and their relationships with HPA axis activity. Moreover, behavioral effects evoked in rodents by both above-mentioned factors and the effects consequent to their deficit are presented. Biochemical as well as behavioral findings suggest that BDNF and VEGF play an important role as components of cascade of changes in the pathomechanism of stress-induced affective diseases. Further studies on the mechanisms regulating their expression in stress conditions are needed to better understand the significance of trophic hypothesis of stress-induced affective diseases.

Axisymmetric and non-axisymmetric exhaust jet induced effects on a V/STOL vehicle design. Part 3: Experimental technique

NASA Technical Reports Server (NTRS)

Schnell, W. C.

1982-01-01

The jet induced effects of several exhaust nozzle configurations (axisymmetric, and vectoring/modulating varients) on the aeropropulsive performance of a twin engine V/STOL fighter design was determined. A 1/8 scale model was tested in an 11 ft transonic tunnel at static conditions and over a range of Mach Numbers from 0.4 to 1.4. The experimental aspects of the static and wind-on programs are discussed. Jet effects test techniques in general, fow through balance calibrations and tare force corrections, ASME nozzle thrust and mass flow calibrations, test problems and solutions are emphasized.

An acidic polysaccharide of Panax ginseng ameliorates experimental autoimmune encephalomyelitis and induces regulatory T cells.

PubMed

Hwang, Insun; Ahn, Ginnae; Park, Eunjin; Ha, Danbee; Song, Jie-Young; Jee, Youngheun

2011-08-30

An acidic polysaccharide of Panax ginseng (APG), so called ginsan, is a purified polysaccharide. APG has multiple immunomodulatory effects of stimulating natural killer (NK) and T cells and producing a variety of cytokines that proved to diminish the proinflammatory response, and protect from septic lethality. To determine APG's role in the autoimmune demyelinating disease, we tested whether APG can regulate inflammatory and encephalitogenic response in experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS). Here, we demonstrate the therapeutic efficacy of the APG which induces the suppression of an encephalitogenic response during EAE. APG significantly ameliorates the progression of EAE by inhibiting the proliferation of autoreactive T cells and the production of inflammatory cytokines such as IFN-γ, IL-1β and IL-17. More importantly, APG promotes the generation of immunosuppressive regulatory T cells (Tregs) through the activation of transcription factor, Foxp3. Furthermore, the depletion of CD25+ cells from APG-treated EAE mice abrogates the beneficial effects of EAE. The capacity of APG to induce clinically beneficial effects furthers our understanding of the basis for its therapeutic immunosuppression of EAE and, possibly, MS. Thus, our results suggest that APG may serve as an effective therapy for MS and other autoimmune diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

Inhibition of the NLRP3 inflammasome reduces the severity of experimentally-induced acute pancreatitis in obese mice

PubMed Central

York, Jason M; Castellanos, Karla J; Cabay, Robert J; Fantuzzi, Giamila

2014-01-01

Acute pancreatitis (AP), while most often a mild and self-limiting inflammatory disease, worsens to a characteristically necrotic severe acute pancreatitis (SAP) in about 20% of cases. Obesity, affecting more than a third of American adults, is a risk factor for the development of SAP, but the exact mechanism of this association has not been identified. Coincidental with chronic low-grade inflammation, activation of the NLRP3 inflammasome increases with obesity. Lean mice genetically deficient for specific components of the NLRP3 inflammasome are protected from experimentally-induced AP, indicating a direct involvement of this pathway in AP pathophysiology. We hypothesized that inhibition of the NLRP3 inflammasome with the sulfonylurea drug glyburide would reduce disease severity in obese mice with cerulein-induced SAP. Treatment with glyburide led to significantly reduced relative pancreatic mass and water content and less pancreatic damage and cell death in genetically obese ob/ob mice with SAP compared to vehicle-treated obese SAP mice. Glyburide administration in ob/ob mice with cerulein induced SAP also resulted in significantly reduced serum levels of interleukin-6, lipase and amylase, and led to lower production of LPS-stimulated IL-1β release in cultured peritoneal cells, compared to vehicle treated ob/ob mice with SAP. Together, these data indicate involvement of the NLRP3 inflammasome in obesity-associated SAP, and expose the possible utility of its inhibition in prevention or treatment of SAP in obese individuals. PMID:25152324

TVP1022 attenuates cardiac remodeling and kidney dysfunction in experimental volume overload-induced congestive heart failure.

PubMed

Abassi, Zaid A; Barac, Yaron D; Kostin, Sawa; Roguin, Ariel; Ovcharenko, Elena; Awad, Hoda; Blank, Ayelet; Bar-Am, Orit; Amit, Tamar; Schaper, Jutta; Youdim, Moussa; Binah, Ofer

2011-07-01

Despite the availability of many pharmacological and mechanical therapies, the mortality rate among patients with congestive heart failure (CHF) remains high. We tested the hypothesis that TVP1022 (the S-isomer of rasagiline; Azilect), a neuroprotective and cytoprotective molecule, is also cardioprotective in the settings of experimental CHF in rats. In rats with volume overload-induced CHF, we investigated the therapeutic efficacy of TVP1022 (7.5 mg/kg) on cardiac function, structure, biomarkers, and kidney function. Treatment with TVP1022 for 7 days before CHF induction prevented the increase in left ventricular end-diastolic area and end-systolic area, and the decrease in fractional shortening measured 14 days after CHF induction. Additionally, TVP1022 pretreatment attenuated CHF-induced cardiomyocyte hypertrophy, fibrosis, plasma and ventricular B-type natriuretic peptide levels, and reactive oxygen species expression. Further, in CHF rats, TVP1022 decreased cytochrome c and caspase 3 expression, thereby contributing to the cardioprotective efficacy of the drug. TVP1022 also enhanced the urinary Na(+) excretion and improved the glomerular filtration rate. Similar cardioprotective effects were obtained when TVP1022 was given to rats after CHF induction. TVP1022 attenuated the adverse functional, structural, and molecular alterations in CHF, rendering this drug a promising candidate for improving cardiac and renal function in this disease state.

Hemodynamic changes as a diagnostic tool in acute heart failure--a pilot study.

PubMed

Engineer, Rakesh S; Benoit, Justin L; Hicks, Caitlin W; Kolattukudy, Sunny J; Burkhoff, Daniel; Peacock, W Frank

2012-01-01

To examine whether posturally induced changes in cardiac output differentiate patients presenting with dyspnea to the emergency department (ED) with acute heart failure (AHF) from other causes. This was an observational study of patients presenting to the ED with dyspnea. Exclusion criteria included ischemic chest pain, electrocardiographic changes diagnostic of acute myocardial infarction, pericardial effusion or chest wall deformities causing dyspnea, or heart transplant. Hemodynamic variables of cardiac index (CI), total peripheral resistance index, and thoracic fluid content (TFC) were determined in upright seated and supine positions 3 minutes apart using bioreactance technology (Cheetah Medical Inc, Portland, Ore). Acute heart failure was defined as either B-type natriuretic peptide 100 to 500 pg/mL and discharge diagnosis of AHF or a B-type natriuretic peptide greater than 500 pg/mL. Of 92 patients, 25 had AHF, 23 had asthma/chronic obstructive pulmonary disease (COPD), and 44 had dyspnea related to other conditions; 41 (44.1%) were male, 56 (60.2%) were African American, and the mean age was 58 ± 15.0 years. Mean baseline TFC was higher in AHF vs asthma/COPD (59.3 ± 26.0 vs 39.7 ± 14.8 1/kW, P = .003) and trended higher compared to other patients with dyspnea (49.2 ± 22.0, P = .10). Postural changes in mean CI were lower in AHF (-0.20 ± 0.84 L min(-1) m(-2)) vs asthma/COPD (1.20 ± 1.23 L min(-1) m(-2); P = .002) and other dyspnea patients (0.82 ± 0.91 L min(-1) m(-2); P = .007). Patients with AHF have greater TFC but lower CI responses to postural changes compared to patients with asthma and COPD. Knowledge of these changes may help rapidly differentiate AHF from asthma and COPD in the ED. Copyright © 2012 Elsevier Inc. All rights reserved.

Discrepancies between modified Medical Research Council dyspnea score and COPD assessment test score in patients with COPD

PubMed Central

Rhee, Chin Kook; Kim, Jin Woo; Hwang, Yong Il; Lee, Jin Hwa; Jung, Ki-Suck; Lee, Myung Goo; Yoo, Kwang Ha; Lee, Sang Haak; Shin, Kyeong-Cheol; Yoon, Hyoung Kyu

2015-01-01

Background and objective According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, either a modified Medical Research Council (mMRC) dyspnea score of ≥2 or a chronic obstructive pulmonary disease (COPD) assessment test (CAT) score of ≥10 is considered to represent COPD patients who are more symptomatic. We aimed to identify the ideal CAT score that exhibits minimal discrepancy with the mMRC score. Methods A receiver operating characteristic curve of the CAT score was generated for an mMRC scores of 1 and 2. A concordance analysis was applied to quantify the association between the frequencies of patients categorized into GOLD groups A–D using symptom cutoff points. A κ-coefficient was calculated. Results For an mMRC score of 2, a CAT score of 15 showed the maximum value of Youden’s index with a sensitivity and specificity of 0.70 and 0.66, respectively (area under the receiver operating characteristic curve [AUC] 0.74; 95% confidence interval [CI], 0.70–0.77). For an mMRC score of 1, a CAT score of 10 showed the maximum value of Youden’s index with a sensitivity and specificity of 0.77 and 0.65, respectively (AUC 0.77; 95% CI, 0.72–0.83). The κ value for concordance was highest between an mMRC score of 1 and a CAT score of 10 (0.66), followed by an mMRC score of 2 and a CAT score of 15 (0.56), an mMRC score of 2 and a CAT score of 10 (0.47), and an mMRC score of 1 and a CAT score of 15 (0.43). Conclusion A CAT score of 10 was most concordant with an mMRC score of 1 when classifying patients with COPD into GOLD groups A–D. However, a discrepancy remains between the CAT and mMRC scoring systems. PMID:26316736

RF Ablation of Giant Hemangiomas Inducing Acute Renal Failure: A Report of Two Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tilborg, Aukje A. J. M. van, E-mail: a.vantilborg@vumc.nl; Dresselaars, Helena F.; Scheffer, Hester J.

ObjectiveIn patients that require treatment for hepatic giant cavernous hemangiomas (GCH), radiofrequency ablation (RFA) has been suggested to represent a safe and effective alternative to invasive surgery. In a recent report of bipolar RFA, using two expandable needle electrodes, was uneventfully performed in patients with large GCH (>10 cm). The objective of this report is to present two cases in which bipolar RFA of symptomatic GCH was complicated by acute kidney injury.Materials and methodsIn 2015 we treated two patients for very large symptomatic GCH (15.7 and 25.0 cm) with bipolar RFA during open laparotomy.ResultsIn both patients the urine showed a red–brown discolorationmore » directly after the ablation. They became anuric and presented with progressive dyspnea, tachypnea, and tachycardia, requiring hemodialysis for a period of 1 month in one case. Lab results revealed hemepigment-induced acute kidney. Both patients fully recovered and both showed a complete relief of symptoms at 3 months following the procedure.ConclusionRFA for large GCHs can cause hemepigment-induced acute kidney injury due to massive intravascular hemolysis. The presented cases suggest that caution is warranted and advocate an upper limit regarding the volume of GCHs that can be safely ablated.« less

Experimental analysis on viscoelasticity-induced migration of RBCs using digital holographic microscopy

NASA Astrophysics Data System (ADS)

Go, Taesik; Byeon, Hyeokjun; Lee, Sang Joon

2016-11-01

Migration of particles in viscoelastic fluids has recently received large attention, because the generated elastic forces in viscoelastic fluids give rise to a simple focusing pattern over a wide range of flow rates. In this study, the vertical focusing and alignment of rigid spherical particles, normal and hardened RBCs in a viscoelastic fluid were experimentally investigated by employing a digital in-line holographic microscopy (DIHM). By the elastic forces, the three different particles are pushed away from the walls and concentrated in the midplane of the rectangular microchannel. Furthermore, most of both RBCs maintain face-on orientation in the microchannel. The effects of deformability of RBC on the viscoelasticity-induced migration and orientation in the channel were also examined. In contrary to non-deformable particles, normal RBCs are dispersed as flow rate increases. In the region near side wall of the microchannel, normal RBCs have edge-on orientation with a large angle of inclination, compared to hardened RBCs. These findings have a strong potential in the design of microfluidic devices for deformability-based separation of cells in viscoelastic fluid flows and label-free diagnoses of certain hematological diseases. This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIP) (No. 2008-0061991).

Experimental protocol for manipulating plant-induced soil heterogeneity.

PubMed

Brandt, Angela J; del Pino, Gaston A; Burns, Jean H

2014-03-13

Coexistence theory has often treated environmental heterogeneity as being independent of the community composition; however biotic feedbacks such as plant-soil feedbacks (PSF) have large effects on plant performance, and create environmental heterogeneity that depends on the community composition. Understanding the importance of PSF for plant community assembly necessitates understanding of the role of heterogeneity in PSF, in addition to mean PSF effects. Here, we describe a protocol for manipulating plant-induced soil heterogeneity. Two example experiments are presented: (1) a field experiment with a 6-patch grid of soils to measure plant population responses and (2) a greenhouse experiment with 2-patch soils to measure individual plant responses. Soils can be collected from the zone of root influence (soils from the rhizosphere and directly adjacent to the rhizosphere) of plants in the field from conspecific and heterospecific plant species. Replicate collections are used to avoid pseudoreplicating soil samples. These soils are then placed into separate patches for heterogeneous treatments or mixed for a homogenized treatment. Care should be taken to ensure that heterogeneous and homogenized treatments experience the same degree of soil disturbance. Plants can then be placed in these soil treatments to determine the effect of plant-induced soil heterogeneity on plant performance. We demonstrate that plant-induced heterogeneity results in different outcomes than predicted by traditional coexistence models, perhaps because of the dynamic nature of these feedbacks. Theory that incorporates environmental heterogeneity influenced by the assembling community and additional empirical work is needed to determine when heterogeneity intrinsic to the assembling community will result in different assembly outcomes compared with heterogeneity extrinsic to the community composition.

Antihypertensive effects of inducible nitric oxide synthase inhibition in experimental pre-eclampsia.

PubMed

Amaral, Lorena M; Pinheiro, Lucas C; Guimaraes, Danielle A; Palei, Ana C T; Sertório, Jonas T; Portella, Rafael L; Tanus-Santos, Jose E

2013-10-01

Upregulation of inducible nitric oxide synthase (iNOS) has been reported in both experimental and clinical hypertension. However, although pro-inflammatory cytokines that up-regulate iNOS contribute to pre-eclampsia, no previous study has tested the hypothesis that a selective iNOS inhibitor (1400 W) could exert antihypertensive effects associated with decreased iNOS expression and nitrosative stress in pre-eclampsia. This study examined the effects of 1400 W in the reduced uteroplacental perfusion pressure (RUPP) placental ischaemia animal model and in normal pregnant rats. Sham-operated and RUPP rats were treated with daily vehicle or 1 mg/kg/day N-[3-(Aminomethyl) benzyl] acetamidine (1400 W) subcutaneously for 5 days. Plasma 8-isoprostane levels, aortic reactive oxygen species (ROS) levels and nicotinamide adenine dinucleotide phosphate (NADPH)-dependent ROS production were evaluated by ELISA, dihydroethidium fluorescence microscopy and lucigenin chemiluminescence respectively. Inducible nitric oxide synthase expression was assessed by western blotting analysis and aortic nitrotyrosine was evaluated by immunohistochemistry. Mean arterial blood pressure increased by ~30 mmHg in RUPP rats, and 1400 W attenuated this increase by ~50% (P < 0.05). While RUPP increased plasma 8-isoprostane levels, aortic ROS levels, and NADPH-dependent ROS production (P < 0.05), treatment with 1400 W blunted these alterations (P < 0.05). Moreover, while RUPP increased iNOS expression and aortic nitrotyrosine levels (P < 0.05), treatment with 1400 W blunted these alterations (P < 0.05). These results clearly implicate iNOS in the hypertension associated with RUPP. Our findings may suggest that iNOS inhibitors could be clinically useful in the therapy of pre-eclampsia, especially in particular groups of patients genetically more prone to express higher levels of iNOS. This issue deserves further confirmation. © 2013 The Authors. Journal of Cellular and Molecular

Effects of histidine and n-acetylcysteine on experimental lesions induced by doxorubicin in sciatic nerve of rats.

PubMed

Farshid, Amir Abbas; Tamaddonfard, Esmaeal; Najafi, Sima

2015-10-01

In this study, the effect of separate and combined intraperitoneal (i.p.) injections of histidine and n-acetylcysteine were investigated on experimental damage induced by doxorubicin (DOX) in sciatic nerve of rats. DOX was i.p. injected at a dose of 4 mg/kg once weekly for four weeks. Histidine and n-acetylcysteine were i.p. injected at a same dose of 20 mg/kg. Cold and mechanical allodynia were recorded using acetone spray and von Frey filaments tests, respectively. The sciatic nerve damage was evaluated by light microscopy. Plasma levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured. Histidine and especially n-acetylcysteine at a same dose of 20 mg/kg suppressed cold and mechanical allodynia, improved sciatic nerve lesions and reversed MDA and TAC levels in DOX-treated groups. Combination treatment with histidine and n-acetylcysteine showed better responses when compared with them used alone. The results of the present study showed peripheral neuroprotective effects for histidine and n-acetylcysteine. Reduction of free radical-induced toxic effects may have a role in neuroprotective properties of histidine and n-acetylcysteine.

Anti-myelin antibodies play an important role in the susceptibility to develop proteolipid protein-induced experimental autoimmune encephalomyelitis

PubMed Central

Marín, N; Eixarch, H; Mansilla, M J; Rodríguez-Martín, E; Mecha, M; Guaza, C; Álvarez-Cermeño, J C; Montalban, X; Villar, L M; Espejo, C

2014-01-01

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is an autoimmune disorder in which activated T cells cross the blood–brain barrier (BBB) to initiate an inflammatory response that leads to demyelination and axonal damage. The key mechanisms responsible for disease initiation are still unknown. We addressed this issue in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. It is widely known that EAE manifests only in certain strains when immunized with myelin proteins or peptides. We studied the differential immune responses induced in two mouse strains that are susceptible or resistant to EAE induction when they are immunized with the 139–151 peptide of proteolipid protein, an encephalitogenic peptide capable of inducing EAE in the susceptible strain. The adequate combination of major histocompatibility complex alleles and myelin peptides triggered in susceptible mice a T helper type 17 (Th17) response capable of inducing the production of high-affinity anti-myelin immunoglobulin (Ig)G antibodies. These were not detected in resistant mice, despite immunization with the encephalitogenic peptide in junction with complete Freund's adjuvant and pertussis toxin, which mediate BBB disruption. These data show the pivotal role of Th17 responses and of high-affinity anti-myelin antibodies in EAE induction and that mechanisms that prevent their appearance can contribute to resistance to EAE. PMID:24188195

Cynodon dactylon extract as a preventive and curative agent in experimentally induced nephrolithiasis.

PubMed

Atmani, F; Sadki, C; Aziz, M; Mimouni, M; Hacht, B

2009-04-01

Cynodon dactylon (Poaceae family) decoction was used in the treatment of kidney stones. However, no scientific study was undertaken so far to demonstrate the beneficial effect of the plant. Thus, the aim of the current study is to evaluate the effect of Cynodon aqueous extract as a preventive and curative agent in experimentally induced nephrolithiasis in a rat model. Ethylene glycol (EG) was used in the experiment to induce calcium oxalate (CaOx) deposition into kidneys. In preventive protocol, Cynodon decoction was administered in the same day with EG to evaluate the ability of the extract to prevent crystal deposition. However, in curative protocol, rats were first rendered nephrolithiasic and then the extract was administered to assess the ability of the plant to eliminate the pre-existing crystal deposition. In both protocols, urinary biochemical and other variables were measured during the course of the study. Crystalluria and renal histology were examined as well. The results showed that, in both protocols, all measured variables were similar for both the rat groups. Nevertheless, urinary biochemical analysis was apparently unaffected by the extract except oxalate in preventive protocol, and calcium, sodium, and potassium in curative protocol which were significantly highly excreted in treated rats compared to untreated animals. Crystalluria was characterized mostly by the presence of large quantities of CaOx monohydrate and CaOx dihydrate particles in untreated rats. However, crystalluria was mainly dominated by the presence of CaOx dihydrate particles with reduced size. The most apparent beneficial effect of Cynodon extract was seen in kidney tissues where reduced levels of CaOx deposition have been noticed especially in medullary and papillary sections from treated rats. We concluded that C. dactylon extract has beneficial effect in preventing and eliminating CaOx deposition into kidneys. Such findings provide a scientific explanation for its use in the

Enolate-Forming Phloretin Pharmacophores: Hepatoprotection in an Experimental Model of Drug-Induced Toxicity.

PubMed

Geohagen, Brian C; Vydyanathan, Amaresh; Kosharskyy, Boleslav; Shaparin, Naum; Gavin, Terrence; LoPachin, Richard M

2016-06-01

Drug-induced toxicity is often mediated by electrophilic metabolites, such as bioactivation of acetaminophen (APAP) to N-acetyl-p-benzoquinone imine (NAPQI). We have shown that APAP hepatotoxicity can be prevented by 2-acetylcyclopentanone (2-ACP). This 1,3-dicarbonyl compound ionizes to form an enolate nucleophile that scavenges NAPQI and other electrophilic intermediates. In this study, we expanded our investigation of enolate-forming compounds to include analyses of the phloretin pharmacophores, 2',4',6'-trihydroxyacetophenone (THA) and phloroglucinol (PG). Studies in a mouse model of APAP overdose showed that THA provided hepatoprotection when given either by intraperitoneal injection or oral administration, whereas PG was hepatoprotective only when given intraperitoneally. Corroborative research characterized the molecular pharmacology (efficacy, potency) of 2-ACP, THA, and PG in APAP-exposed isolated mouse hepatocytes. For comparative purposes, N-acetylcysteine (NAC) cytoprotection was also evaluated. Measurements of multiple cell parameters (e.g., cell viability, mitochondrial membrane depolarization) indicated that THA and, to a lesser extent, PG provided concentration-dependent protection against APAP toxicity, which exceeded that of 2-ACP or NAC. The enolate-forming compounds and NAC truncated ongoing APAP exposure and thereby returned intoxicated hepatocytes toward normal viability. The superior ability of THA to protect is related to multifaceted modes of action that include metal ion chelation, free radical trapping, and scavenging of NAPQI and other soft electrophiles involved in oxidative stress. The rank order of potency for the tested cytoprotectants was consistent with that determined in a parallel mouse model. These data suggest that THA or a derivative might be useful in treating drug-induced toxicities and other conditions that involve electrophile-mediated pathogenesis. Copyright © 2016 by The American Society for Pharmacology and

Experimentally induced hyperchloremic and DL-lactic acidosis in calves: an attempt to study the effects of oral rehydration on acid-base status.

PubMed

Schwedhelm, L; Kirchner, D; Klaus, B; Bachmann, L

2013-04-01

Many diarrheic calves suffer from metabolic acidosis, which is commonly treated by oral rehydration therapy. Oral rehydration solutions can be prepared in water, milk, or milk replacer. Therefore, the aim of the study was to verify dietary effects of water- or milk replacer-based oral rehydration solutions on parameters of acid-base balance in calves with experimentally induced hyperchloremic and dl-lactate acidosis. In 12 calves, hyperchloremic or dl-lactate acidosis was induced by HCl or dl-lactic acid infusions according to protocols outlined in previous literature. Immediately after induction, the calves were fed with milk replacer or water- or milk replacer-based oral rehydration solutions, or remained fasting, respectively. Blood samples were taken to monitor acid-base status over an experimental period of 4h. Using the protocols, all calves revealed a manifest hyperchloremic or dl-lactate acidosis. Because of high infusion volumes, plasma volume was expanded and effects of feeding regimens on blood parameters were rare. Unexpected clinical aberrations occurred after repeated induction of dl-lactate acidosis: all calves developed a thrombophlebitis of the jugular vein, whereas HCl infusion had no effect on endothelium. Induction of acidosis via infusion is not suitable to study dietary effects. A protocol to induce acidosis and dehydration simultaneously is required to duplicate the metabolic conditions of diarrheic calves. In further investigations, attention should be focused on effects of d-lactate or its metabolites on endothelial tissue. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Acute selenium toxicosis induced in baby pigs by parenteral administration of selenium-vitamin E preparations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Vleet, J.F.; Meyer, K.B.; Olander, H.J.

1974-09-15

Acute selenium (Se) toxicosis was induced in baby pigs by intramuscular (IM) injection of Se, as selenite, using commercially available selenium-vitamin E (Se-E) preparations. Graded amounts of Se were given to 26 pigs from a herd that had not experienced losses from Se-E deficiency and to 136 pigs from a herd that had continual losses from Se-E deficiency. Of the 2 groups of pigs, those from the Se-E-deficient herd were more susceptible to acute Se toxicosis. Clinical signs of toxicosis were vomiting, anorexia, depression, dyspnea, weakness, and coma, with death occurring 24 to 48 hours after injection. Pathologic alterations observedmore » grossly and histologically included pulmonary edema, skeletal myodegeneration, hepatic degeneration and necrosis, transudation into body cavities, and widespread circulatory disturbances. Mean tissue Se concentrations in 20 pigs with acute toxicosis 24 to 48 hours after injection were 12.44 ppm in liver, 1.31 ppm in kidney, and 0.32 ppm in skeletal muscle.« less

Influence of serial electrical stimulations of perifornical and posterior hypothalamic orexin-containing neurons on regulation of sleep homeostasis and sleep-wakefulness cycle recovery from experimental comatose state and anesthesia-induced deep sleep.

PubMed

Chijavadze, E; Chkhartishvili, E; Babilodze, M; Maglakelidze, N; Nachkebia, N

2013-11-01

The work was aimed for the ascertainment of following question - whether Orexin-containing neurons of dorsal and lateral hypothalamic, and brain Orexinergic system in general, are those cellular targets which can speed up recovery of disturbed sleep homeostasis and accelerate restoration of sleep-wakefulness cycle phases during some pathological conditions - experimental comatose state and/or deep anesthesia-induced sleep. Study was carried out on white rats. Modeling of experimental comatose state was made by midbrain cytotoxic lesions at intra-collicular level.Animals were under artificial respiration and special care. Different doses of Sodium Ethaminal were used for deep anesthesia. 30 min after comatose state and/or deep anesthesia induced sleep serial electrical stimulations of posterior and/or perifornical hypothalamus were started. Stimulation period lasted for 1 hour with the 5 min intervals between subsequent stimulations applied by turn to the left and right side hypothalamic parts.EEG registration of cortical and hippocampal electrical activity was started immediately after experimental comatose state and deep anesthesia induced sleep and continued continuously during 72 hour. According to obtained new evidences, serial electrical stimulations of posterior and perifornical hypothalamic Orexin-containing neurons significantly accelerate recovery of sleep homeostasis, disturbed because of comatose state and/or deep anesthesia induced sleep. Speed up recovery of sleep homeostasis was manifested in acceleration of coming out from comatose state and deep anesthesia induced sleep and significant early restoration of sleep-wakefulness cycle behavioral states.

Mucosal tolerance induced by an immunodominant peptide from rat alpha3(IV)NC1 in established experimental autoimmune glomerulonephritis.

PubMed

Reynolds, John; Abbott, Danielle S; Karegli, Julieta; Evans, David J; Pusey, Charles D

2009-06-01

Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture's disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the noncollagenous domain of the alpha 3 chain of type IV collagen, alpha3(IV)NC1. Recent studies have identified an immunodominant peptide, pCol (24-38), from the N-terminus of rat alpha3(IV)NC1; this peptide contains the major B- and T-cell epitopes in EAG and can induce crescentic nephritis. In this study, we investigated the mechanisms of mucosal tolerance in EAG by examining the effects of the nasal administration of this peptide after the onset of disease. A dose-dependent effect was observed: a dose of 300 microg had no effect, a dose of 1000 microg resulted in a moderate reduction in EAG severity, and a dose of 3000 microg produced a marked reduction in EAG severity accompanied by diminished antigen-specific, T-cell proliferative responses. These results demonstrate that mucosal tolerance in EAG can be induced by nasal administration of an immunodominant peptide from the N-terminus of alpha3(IV)NC1 and should be of value in designing new therapeutic strategies for patients with Goodpasture's disease and other autoimmune disorders.

Curative effect of Terminalia chebula extract on acetic acid-induced experimental colitis: role of antioxidants, free radicals and acute inflammatory marker.

PubMed

Gautam, M K; Goel, Shalini; Ghatule, R R; Singh, A; Nath, G; Goel, R K

2013-10-01

The present study has evaluated the healing effects of extract of dried fruit pulp of Terminalia chebula (TCE) on acetic acid (AA)-induced colitis in rats. TCE (600 mg/kg) showed healing effects against AA-induced colonic damage score and weight when administered orally daily for 14 days. TCE was further studied for its effects on various physical (mucus/blood in stool and stool frequency, food and water intake and body weight changes), histology, antibacterial activity and free radicals (NO and LPO), antioxidants (SOD, CAT and GSH) and myeloperoxidase in colonic tissue. Intra-colonic AA administration increased colonic mucosal damage and inflammation, mucus/bloody diarrhoea, stool frequency, but decreased body weight which were reversed by TCE and sulfasalazine (SS, positive control) treatments. TCE showed antibacterial activity and both TCE and SS enhanced the antioxidants, but decreased free radicals and myeloperoxidase activities affected in acetic acid-induced colitis. TCE indicated the presence of active principles with proven antioxidants, anti-inflammatory, immunomodulatory, and free radical scavenging and healing properties. Thus, TCE seemed to be safe and effective in healing experimental colitis.

Temporal changes of oxidative stress markers in Escherichia coli K1-induced experimental meningitis in a neonatal rat model.

PubMed

Giridharan, Vijayasree V; Simões, Lutiana R; Dagostin, Valdemira S; Generoso, Jaqueline S; Rezin, Gislaine T; Florentino, Drielly; Muniz, Jhonata P; Collodel, Allan; Petronilho, Fabricia; Quevedo, Joao; Barichello, Tatiana

2017-07-13

Despite advances in antimicrobial therapy and advanced critical care neonatal bacterial meningitis has a mortality rate of over 10% and induces neurological sequelae in 20-50% of cases. Escherichia coli K1 (E. coli K1) is the most common gram-negative organism causing neonatal meningitis and is the second most common cause behind group B streptococcus. We previously reported that an E. coli K1 experimental meningitis infection in neonatal rats resulted in habituation and aversive memory impairment and a significant increase in cytokine levels in adulthood. In this present study, we investigated the oxidative stress profile including malondialdehyde (MDA) levels, carbonyl protein formation, myeloperoxidase activity (MPO) activity, superoxide dismutase (SOD) activity and catalase (CAT) activity 6, 12, 24, 48, 72 and 96h after E. coli K1 experimental meningitis infection. In addition, sulfhydryl groups, nitrite and nitrate levels and activity of the mitochondrial respiratory chain enzymes were also measured in the frontal cortex and hippocampus of neonatal rats. The results from this study demonstrated a significant increase in MDA, protein carbonyls and MPO activity and a simultaneous decrease in SOD activity in the hippocampus of the neonatal meningitis survivors but the same was not observed in frontal cortex. In addition, we also observed a significant increase in complex IV activity in the hippocampus and frontal cortex of meningitis survivor rats. Thus, the results from this study reaffirmed the possible role of oxidative stress, nitric oxide and its related compounds in the complex pathophysiology of E. coli K1-induced bacterial meningitis. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical and hematologic variables in ponies with experimentally induced equine ehrlichial colitis (Potomac horse fever).

PubMed

Ziemer, E L; Whitlock, R H; Palmer, J E; Spencer, P A

1987-01-01

The clinical and hematologic variables of 10 ponies with experimentally induced equine ehrlichial colitis (EEC; syn: Potomac horse fever) were studied for a 30-day period (6 ponies) or until death (4 ponies). The earliest clinical sign indicative of EEC was fever (rectal temperature exceeding 39 C). All ponies became depressed (CNS) at various times during the disease, and 90% of the ponies developed diarrhea between 9 and 15 days after infection was induced. The most significant hematologic change was an increase in plasma protein concentration after the onset of fever (P less than 0.05). The PCV in all ponies became increased above base line during the diarrheic phase of EEC. Forty percent of the ponies developed anemia (PCV less than or equal to 23%) during the study. White blood cell counts were highly variable, with 80% of the ponies developing leukopenia (WBC less than 5,000/microliters) during the illness and 60% of the ponies developing leukocytosis (WBC greater than 14,000/microliters) after leukopenia was observed. Differential WBC changes varied widely and included neutropenia with a left shift, lymphopenia, and eosinopenia. Serial thrombocyte counts, which were done for only 1 pony, identified the development of marked thrombocytopenia. Some hematologic changes in ponies with EEC were similar to those reported in canine monocytic and equine granulocytic ehrlichioses. These data are discussed in the context of the pathogenesis and differential diagnosis of EEC.

Helichrysum plicatum DC. subsp. plicatum extract as a preventive agent in experimentally induced urolithiasis model.

PubMed

Bayir, Yasin; Halici, Zekai; Keles, Mevlut Sait; Colak, Suat; Cakir, Ahmet; Kaya, Yusuf; Akçay, Fatih

2011-11-18

Since ancient times, various herbal preparations have been used in treatment of urolithiasis, which is basically formation of calcium oxalate stones in kidney. The aim of our study is to assess the effects of Helichrysum plicatum DC. subsp. plicatum (HP) as a preventive agent in experimentally induced urolithiasis model in rats. The efficacy of 125, 250, and 500 mg/kg HP extract was studied in 1% ethylene glycol and 1% ammonium chloride-induced urolithiasis for 21 days in rats. The weight difference and the levels of calcium, magnesium, phosphorus, urea nitrogen, creatinine and uric acid in both serum and 24h-urine were measured. The calcium oxalate (CaOx) and pH were defined in urine. Histo-pathological analyses in kidneys were also performed. The rats' weights were higher in HP groups than urolithiasis group. Urolithiasis caused a significant increase in both serum and urine biochemical parameters compared to healthy rats. HP extract decreased levels of these parameters. Urine CaOx level was high in urolithiasis rats, whereas it was decreased by HP extract. Histopathological examinations revealed extensive intratubular crystal depositions and degenerative tubular structures in urolithiasis group, but not in HP treatment groups. More studies will be necessary to elucidate the antiurolithiatic activity of HP. Nonetheless, having a beneficial effect in preventing and eliminating CaOx deposition into kidneys, HP extract may be a potential drug for urolithiasis treatment. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Protective effects of black cumin (Nigella sativa) oil on TNBS-induced experimental colitis in rats.

PubMed

Isik, F; Tunali Akbay, Tugba; Yarat, A; Genc, Z; Pisiriciler, R; Caliskan-Ak, E; Cetinel, S; Altıntas, A; Sener, G

2011-03-01

The pathogenesis and treatment of ulcerative colitis remain poorly understood. The aim of the present study is to investigate the effects of black cumin (Nigella sativa) oil on rats with colitis. Experimental colitis was induced with 1 mL trinitrobenzene sulfonic acid (TNBS) in 40% ethanol by intracolonic administration with 8-cm-long cannula under ether anesthesia to rats in colitis group and colitis + black cumin oil group. Rats in the control group were given saline at the same volume by intracolonic administration. Black cumin oil (BCO, Origo "100% natural Black Cumin Seed Oil," Turkey) was given to colitis + black cumin oil group by oral administration during 3 days, 5 min after colitis induction. Saline was given to control and colitis groups at the same volume by oral administration. At the end of the experiment, macroscopic lesions were scored and the degree of oxidant damage was evaluated by colonic total protein, sialic acid, malondialdehyde, and glutathione levels, collagen content, and tissue factor, superoxide dismutase, and myeloperoxidase activities. Tissues were also examined by histological and cytological analysis. Proinflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6], lactate dehydrogenase activity, and triglyceride and cholesterol levels were analyzed in blood samples. We found that black cumin oil decreased the proinflammatory cytokines, lactate dehydrogenase, triglyceride, and cholesterol, which were increased in colitis. BCO, by preventing inflammatory status in the blood, partly protected colonic tissue against experimental ulcerative colitis.

Determination of ultra-short laser induced damage threshold of KH{sub 2}PO{sub 4} crystal: Numerical calculation and experimental verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Jian; Department of Physics, The Ohio State University, 191 W. Woodruff Ave, Columbus, OH 43210; Chen, Mingjun, E-mail: chenmj@hit.edu.cn, E-mail: chowdhury.24@osu.edu

Rapid growth and ultra-precision machining of large-size KDP (KH{sub 2}PO{sub 4}) crystals with high laser damage resistance are tough challenges in the development of large laser systems. It is of high interest and practical significance to have theoretical models for scientists and manufacturers to determine the laser-induced damage threshold (LIDT) of actually prepared KDP optics. Here, we numerically and experimentally investigate the laser-induced damage on KDP crystals in ultra-short pulse laser regime. On basis of the rate equation for free electron generation, a model dedicated to predicting the LIDT is developed by considering the synergistic effect of photoionization, impact ionizationmore » and decay of electrons. Laser damage tests are performed to measure the single-pulse LIDT with several testing protocols. The testing results combined with previously reported experimental data agree well with those calculated by the model. By taking the light intensification into consideration, the model is successfully applied to quantitatively evaluate the effect of surface flaws inevitably introduced in the preparation processes on the laser damage resistance of KDP crystals. This work can not only contribute to further understanding of the laser damage mechanisms of optical materials, but also provide available models for evaluating the laser damage resistance of exquisitely prepared optical components used in high power laser systems.« less

THE COURSE OF EXPERIMENTAL HEMOTHORAX IN RADIATION SICKNESS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, C.C.

1957-05-01

Experimental hemothorax induced by injecting 10 to 12 ml of autogenous blood into the pleural cavity of healthy rabbits was borne well without any marked general reaction. Rabbits irradiated with 600 r were more affected by experimental hemothorax. Instead of absorption, exudation accumulated in the pleural cavity. In rabbits irradiated with 600 r, experimental hemothorax markediy shortened the latent period of radiation sickness and hastened its climax. (C.H.)

Induced Cannibalism in Experimental Populations of the Forensic Indicator Chrysomya putoria Wiedemann (Diptera: Calliphoridae).

PubMed

Botteon, V W; Fernandes, F S; Godoy, W A C

2016-04-01

We analyzed the behavior of third-instars of Chrysomya putoria as potential cannibals in experimental populations. Cannibalism rates were evaluated in three settings observed for 3, 6, 9, and 24 h, placing injured and uninjured larvae of C. putoria together. Our data heavily support that C. putoria larvae behave as cannibals when induced by a wound in another larva, and also after starving for 24 h. The probability of cannibalism increased as a function of time, both in no-choice and in choice experiments evidencing that time is a determining factor for cannibalism induction in C. putoria. However, the treatment combining injured with uninjured larvae showed the highest probability of cannibalism. These results suggest that C. putoria larvae may cannibalize under scarcity of food over long time or the presence of injured larvae. This study is useful to understand the behavior of C. putoria feeding on ephemeral substrates such as carrion or corpses and brings relevant and significant contribution to population ecology of blowflies and also forensic entomology.

Drug-induced lung injury associated with sorafenib: analysis of all-patient post-marketing surveillance in Japan.

PubMed

Horiuchi-Yamamoto, Yuka; Gemma, Akihiko; Taniguchi, Hiroyuki; Inoue, Yoshikazu; Sakai, Fumikazu; Johkoh, Takeshi; Fujimoto, Kiminori; Kudoh, Shoji

2013-08-01

Sorafenib is a multi-kinase inhibitor currently approved in Japan for unresectable and/or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma. Although drug-induced lung injury has recently been the focus of interest in Japanese patients treated with molecular targeting agents, the clinical features of patients receiving sorafenib remain to be completely investigated. All-patient post-marketing surveillance data was obtained within the frame of Special Drug Use Investigation; between April 2008 and March 2011, we summarized the clinical information of 62 cases with drug-induced lung injury among approximately 13,600 sorafenib-treated patients in Japan. In addition, we summarized the results of evaluation by a safety board of Japanese experts in 34 patients in whom pulmonary images were available. For the calculation of reporting frequency, interim results of Special Drug Use Investigation were used. In the sets of completed reports (2,407 in renal cell carcinoma and 647 in hepatocellular carcinoma), the reporting frequency was 0.33 % (8 patients; fatal, 4/8) and 0.62 % (4 patients; fatal, 2/4), respectively. Major clinical symptoms included dyspnea, cough, and fever. Evaluation of the images showed that 18 cases out of 34 patients had a pattern of diffuse alveolar damage. The patients with hepatocellular carcinoma showed a greater incidence and earlier onset of lung injury than those with renal cell carcinoma. Although the overall reporting frequency of sorafenib-induced lung injury is not considered high, the radiological diffuse alveolar damage pattern led to a fatal outcome. Therefore, early recognition of sorafenib-induced lung injury is crucial for physicians and patients.

Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Constantinou, Maria A.; Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75, Mikras Asias str., 11527 Athens; Theocharis, Stamatios E.

2007-01-01

Metabonomics has already been used to discriminate different pathological states in biological fields. The metabolic profiles of chronic experimental fibrosis and cirrhosis induction in rats were investigated using {sup 1}H NMR spectroscopy of liver extracts and serum combined with pattern recognition techniques. Rats were continuously administered with thioacetamide (TAA) in the drinking water (300 mg TAA/L), and sacrificed on 1st, 2nd, and 3rd month of treatment. {sup 1}H NMR spectra of aqueous and lipid liver extracts, together with serum were subjected to Principal Component Analysis (PCA). Liver portions were also subjected to histopathological examination and biochemical determination of malondialdehyde (MDA).more » Liver fibrosis and cirrhosis were progressively induced in TAA-treated rats, verified by the histopathological examination and the alterations of MDA levels. TAA administration revealed a number of changes in the {sup 1}H NMR spectra compared to control samples. The performance of PCA in liver extracts and serum, discriminated the control samples from the fibrotic and cirrhotic ones. Metabolic alterations revealed in NMR spectra during experimental liver fibrosis and cirrhosis induction, characterize the stage of fibrosis and could be illustrated by subsequent PCA of the spectra. Additionally, the PCA plots of the serum samples presented marked clustering during fibrosis progression and could be extended in clinical diagnosis for the management of cirrhotic patients.« less

Experimental intrauterine growth retardation.

PubMed

van Marthens, E; Harel, S; Zamenshof, S

1975-01-01

The effects of experimental intrauterine growth retardation on subsequent fetal development, especially with respect to brain development, were studied in a new animal model. The rabbit was chosen since it has a perinatal pattern of brain development similar to that of the human. Experimental ischemia was induced during the last trimester by ligation of spiral arterioles and the differential effects on fetal development at term (30th gestational day) are reported. Specific brain regions were examined for wet weight, total cell number (DNA) and total protein content. Highly significant decreases in all these parameters were found in both the cortex and cerebellum following experimental intrauterine growth retardation; these two organs were differentially affected. The prospects and advantages of using this animal model for the study of the postnatal "catch-up growth" are discussed.

Experimental validation of a numerical model for subway induced vibrations

NASA Astrophysics Data System (ADS)

Gupta, S.; Degrande, G.; Lombaert, G.

2009-04-01

This paper presents the experimental validation of a coupled periodic finite element-boundary element model for the prediction of subway induced vibrations. The model fully accounts for the dynamic interaction between the train, the track, the tunnel and the soil. The periodicity or invariance of the tunnel and the soil in the longitudinal direction is exploited using the Floquet transformation, which allows for an efficient formulation in the frequency-wavenumber domain. A general analytical formulation is used to compute the response of three-dimensional invariant or periodic media that are excited by moving loads. The numerical model is validated by means of several experiments that have been performed at a site in Regent's Park on the Bakerloo line of London Underground. Vibration measurements have been performed on the axle boxes of the train, on the rail, the tunnel invert and the tunnel wall, and in the free field, both at the surface and at a depth of 15 m. Prior to these vibration measurements, the dynamic soil characteristics and the track characteristics have been determined. The Bakerloo line tunnel of London Underground has been modelled using the coupled periodic finite element-boundary element approach and free field vibrations due to the passage of a train at different speeds have been predicted and compared to the measurements. The correspondence between the predicted and measured response in the tunnel is reasonably good, although some differences are observed in the free field. The discrepancies are explained on the basis of various uncertainties involved in the problem. The variation in the response with train speed is similar for the measurements as well as the predictions. This study demonstrates the applicability of the coupled periodic finite element-boundary element model to make realistic predictions of the vibrations from underground railways.

Experimental study on impact-induced seismic wave propagating through quartz sand simulating asteroid regolith

NASA Astrophysics Data System (ADS)

Matsue, Kazuma; Arakawa, Masahiko; Yasui, Minami; Matsumoto, Rie; Tsujido, Sayaka; Takano, Shota; Hasegawa, Sunao

2015-08-01

Introduction: Recent spacecraft surveys clarified that asteroid surfaces were covered with regolith made of boulders and pebbles such as that found on the asteroid Itokawa. It was also found that surface morphologies of asteroids formed on the regolith layer were modified. For example, the high-resolution images of the asteroid Eros revealed the evidence of the downslope movement of the regolith layer, then it could cause the degradation and the erasure of small impact crater. One possible process to explain these observations is the regolith layer collapse caused by seismic vibration after projectile impacts. The impact-induced seismic wave might be an important physical process affecting the morphology change of regolith layer on asteroid surfaces. Therefore, it is significant for us to know the relationship between the impact energy and the impact-induced seismic wave. So in this study, we carried out impact cratering experiments in order to observe the seismic wave propagating through the target far from the impact crater.Experimental method: Impact cratering experiments were conducted by using a single stage vertical gas gun set at Kobe Univ and a two-stage vertical gas gun set at ISAS. We used quartz sands with the particle diameter of 500μm, and the bulk density of 1.48g/cm3. The projectile was a ball made of polycarbonate with the diameter of 4.75mm and aluminum, titan, zirconia, stainless steel, cupper, tungsten carbide projectile with the diameter of 2mm. These projectiles were launched at the impact velocity from 0.2 to 7km/s. The target was set in a vacuum chamber evacuated below 10 Pa. We measured the seismic wave by using a piezoelectric uniaxial accelerometer.Result: The impact-induced seismic wave was measured to show a large single peak and found to attenuate with the propagation distance. The maximum acceleration of the seismic wave was recognized to have a good relationship with the normalized distance x/R, where x is the propagation distance

Effects of intravenous hyperosmotic sodium bicarbonate on arterial and cerebrospinal fluid acid-base status and cardiovascular function in calves with experimentally induced respiratory and strong ion acidosis.

PubMed

Berchtold, Joachim F; Constable, Peter D; Smith, Geoffrey W; Mathur, Sheerin M; Morin, Dawn E; Tranquilli, William J

2005-01-01

The objectives of this study were to determine the effects of hyperosmotic sodium bicarbonate (HSB) administration on arterial and cerebrospinal fluid (CSF) acid-base balance and cardiovascular function in calves with experimentally induced respiratory and strong ion (metabolic) acidosis. Ten healthy male Holstein calves (30-47 kg body weight) were instrumented under halothane anesthesia to permit cardiovascular monitoring and collection of blood samples and CSE Respiratory acidosis was induced by allowing the calves to spontaneously ventilate, and strong ion acidosis was subsequently induced by i.v. administration of L-lactic acid. Calves were then randomly assigned to receive either HSB (8.4% NaHCO3; 5 ml/kg over 5 minutes, i.v.; n=5) or no treatment (controls, n=5) and monitored for 1 hour. Mixed respiratory and strong ion acidosis was accompanied by increased heart rate, cardiac index, mean arterial pressure, cardiac contractility (maximal rate of change of left ventricular pressure), and mean pulmonary artery pressure. Rapid administration of HSB immediately corrected the strong ion acidosis, transiently increased arterial partial pressure of carbon dioxide (P(CO2)), and expanded the plasma volume. The transient increase in arterial P(CO2) did not alter CSF P(CO2) or induce paradoxical CSF acidosis. Compared to untreated control calves, HSB-treated calves had higher cardiac index and contractility and a faster rate of left ventricular relaxation for 1 hour after treatment, indicating that HSB administration improved myocardial systolic function. We conclude that rapid i.v. administration of HSB provided an effective and safe method for treating strong ion acidosis in normovolemic halothane-anesthetized calves with experimentally induced respiratory and strong ion acidosis. Fear of inducing paradoxical CSF acidosis is not a valid reason for withholding HSB administration in calves with mixed respiratory and strong ion acidosis.

Extension of the energy range of experimental activation cross-sections data of deuteron induced nuclear reactions on indium up to 50MeV.

PubMed

Tárkányi, F; Ditrói, F; Takács, S; Hermanne, A; Ignatyuk, A V

2015-11-01

The energy range of our earlier measured activation cross-sections data of longer-lived products of deuteron induced nuclear reactions on indium were extended from 40MeV up to 50MeV. The traditional stacked foil irradiation technique and non-destructive gamma spectrometry were used. No experimental data were found in literature for this higher energy range. Experimental cross-sections for the formation of the radionuclides (113,110)Sn, (116m,115m,114m,113m,111,110g,109)In and (115)Cd are reported in the 37-50MeV energy range, for production of (110)Sn and (110g,109)In these are the first measurements ever. The experimental data were compared with the results of cross section calculations of the ALICE and EMPIRE nuclear model codes and of the TALYS 1.6 nuclear model code as listed in the on-line library TENDL-2014. Copyright © 2015 Elsevier Ltd. All rights reserved.

Glycyrrhizin ameliorates metabolic syndrome-induced liver damage in experimental rat model.

PubMed

Sil, Rajarshi; Ray, Doel; Chakraborti, Abhay Sankar

2015-11-01

Glycyrrhizin, a major constituent of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate insulin resistance, hyperglycemia, dyslipidemia, and obesity in rats with metabolic syndrome. Liver dysfunction is associated with this syndrome. The objective of this study is to investigate the effect of glycyrrhizin treatment on metabolic syndrome-induced liver damage. After induction of metabolic syndrome in rats by high fructose (60%) diet for 6 weeks, the rats were treated with glycyrrhizin (50 mg/kg body weight, single intra-peritoneal injection). After 2 weeks of treatment, rats were sacrificed to collect blood samples and liver tissues. Compared to normal, elevated activities of serum alanine transaminase, alkaline phosphatase and aspartate transaminase, increased levels of liver advanced glycation end products, reactive oxygen species, lipid peroxidation, protein carbonyl, protein kinase Cα, NADPH oxidase-2, and decreased glutathione cycle components established liver damage and oxidative stress in fructose-fed rats. Activation of nuclear factor κB, mitogen-activated protein kinase pathways as well as signals from mitochondria were found to be involved in liver cell apoptosis. Increased levels of cyclooxygenase-2, tumor necrosis factor, and interleukin-12 proteins suggested hepatic inflammation. Metabolic syndrome caused hepatic DNA damage and poly-ADP ribose polymerase cleavage. Fluorescence-activated cell sorting using annexin V/propidium iodide staining confirmed the apoptotic hepatic cell death. Histology of liver tissue also supported the experimental findings. Treatment with glycyrrhizin reduced oxidative stress, hepatic inflammation, and apoptotic cell death in fructose-fed rats. The results suggest that glycyrrhizin possesses therapeutic potential against hepatocellular damage in metabolic syndrome.

Experimental evaluation of neural probe’s insertion induced injury based on digital image correlation method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Wenguang, E-mail: zhwg@sjtu.edu.cn; Ma, Yakun; Li, Zhengwei

Purpose: The application of neural probes in clinic has been challenged by probes’ short lifetime when implanted into brain tissue. The primary goal is to develop an evaluation system for testing brain tissue injury induced by neural probe’s insertion using microscope based digital image correlation method. Methods: A brain tissue phantom made of silicone rubber with speckle pattern on its surface was fabricated. To obtain the optimal speckle pattern, mean intensity gradient parameter was used for quality assessment. The designed testing system consists of three modules: (a) load module for simulating neural electrode implantation process; (b) data acquisition module tomore » capture micrographs of speckle pattern and to obtain reactive forces during the insertion of the probe; (c) postprocessing module for extracting tissue deformation information from the captured speckle patterns. On the basis of the evaluation system, the effects of probe wedge angle, insertion speed, and probe streamline on insertion induced tissue injury were investigated. Results: The optimal quality speckle pattern can be attained by the following fabrication parameters: spin coating rate—1000 r/min, silicone rubber component A: silicone rubber component B: softener: graphite = 5 ml: 5 ml: 2 ml: 0.6 g. The probe wedge angle has a significant effect on tissue injury. Compared to wedge angle 40° and 20°, maximum principal strain of 60° wedge angle was increased by 40.3% and 87.5%, respectively; compared with a relatively higher speed (500 μm/s), the maximum principle strain within the tissue induced by slow insertion speed (100 μm/s) was increased by 14.3%; insertion force required by probe with convex streamline was smaller than the force of traditional probe. Based on the experimental results, a novel neural probe that has a rounded tip covered by a biodegradable silk protein coating with convex streamline was proposed, which has both lower insertion and micromotion induced

Resveratrol protects from lipopolysaccharide-induced inflammation in the uterus and prevents experimental preterm birth.

PubMed

Bariani, María Victoria; Correa, Fernando; Leishman, Emma; Domínguez Rubio, Ana Paula; Arias, Andreína; Stern, Aníbal; Bradshaw, Heather B; Franchi, Ana María

2017-08-01

pregnant BALB/c mice with resveratrol prevented the LPS-induced preterm birth in 64% of the cases, whereas only 15% of mice with LPS alone escaped preterm birth. Treatment with resveratrol resulted in a reduced NOS activity (P < 0.05) in the uterus of LPS-treated mice. Similarly, resveratrol reduced the expression of LPS-induced pro-inflammatory agents such as iNOS (P < 0.05), COX-2 (P < 0.05), prostaglandin E2 (PGE2) (P < 0.05) and anandamide (AEA) (P < 0.05). Moreover, resveratrol administration resulted in changes in the uterine endocannabinoid profiling altered by LPS. N/A. Since our experimental design involves the use of mice, the extrapolation of the results presented here to humans is limited. Our findings provide evidence for the tocolytic effects of resveratrol. Dr Ana María Franchi was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2013/0097) and by Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 2012/0061). Dr Heather B. Bradshaw was funded by NIH (DA006668). The authors have no competing interests. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Platelet-rich plasma to treat experimentally-induced skin wounds in animals: A systematic review and meta-analysis.

PubMed

Tambella, Adolfo Maria; Attili, Anna Rita; Dupré, Gilles; Cantalamessa, Andrea; Martin, Stefano; Cuteri, Vincenzo; Marcazzan, Sabrina; Del Fabbro, Massimo

2018-01-01

The objective of the study was to review current literature to determine whether the topical application of platelet-rich plasma (PRP) promotes healing in experimentally-induced full-thickness skin wounds in animals. The hypothesis was that the adjunct of PRP has a positive effect on wound healing. An electronic search was carried out on the following databases: Web of Science, Cochrane Library, PubMed, Research Gate, Cochrane Wounds Group, Veterinary Information Network. No publication date nor language restrictions were applied. Randomised and not randomised controlled clinical trials comparing PRP with placebo or with other treatments were included. The reduction of open wound area in PRP-treated (test) wounds compared to control wounds was the primary outcome. Secondary outcomes were healing time and number of healed cases in test group compared to control. The following effect sizes were calculated: the Hedges' g for continuous variables; the odds ratio for binary data. Eighteen controlled clinical trials were included in the qualitative and quantitative synthesis, with a total of 661 wounds. All studies were published in the period 2007-2016. Eight studies were carried out on rodent/lagomorph mammals and 10 on non-rodent/lagomorph mammals. In all included studies, control wounds underwent placebo or were left untreated. The PRP group showed a better healing performance than the control group in each outcome. The effect size was statistically significant considering the primary outcome and the overall aggregation of the three outcomes. The effect size, although in favour of the treatment with PRP, was not significant considering the healing time and the number of healings. The overall heterogeneity was mild or moderate. Five studies reported a high risk of selection bias. The publication bias was always mild or absent. The results support the hypothesis of the positive effects of the PRP when compared to control groups in the treatment of experimentally-induced

Platelet-rich plasma to treat experimentally-induced skin wounds in animals: A systematic review and meta-analysis

PubMed Central

Attili, Anna Rita; Dupré, Gilles; Cantalamessa, Andrea; Martin, Stefano; Cuteri, Vincenzo; Marcazzan, Sabrina; Del Fabbro, Massimo

2018-01-01

The objective of the study was to review current literature to determine whether the topical application of platelet-rich plasma (PRP) promotes healing in experimentally-induced full-thickness skin wounds in animals. The hypothesis was that the adjunct of PRP has a positive effect on wound healing. An electronic search was carried out on the following databases: Web of Science, Cochrane Library, PubMed, Research Gate, Cochrane Wounds Group, Veterinary Information Network. No publication date nor language restrictions were applied. Randomised and not randomised controlled clinical trials comparing PRP with placebo or with other treatments were included. The reduction of open wound area in PRP-treated (test) wounds compared to control wounds was the primary outcome. Secondary outcomes were healing time and number of healed cases in test group compared to control. The following effect sizes were calculated: the Hedges’ g for continuous variables; the odds ratio for binary data. Eighteen controlled clinical trials were included in the qualitative and quantitative synthesis, with a total of 661 wounds. All studies were published in the period 2007–2016. Eight studies were carried out on rodent/lagomorph mammals and 10 on non-rodent/lagomorph mammals. In all included studies, control wounds underwent placebo or were left untreated. The PRP group showed a better healing performance than the control group in each outcome. The effect size was statistically significant considering the primary outcome and the overall aggregation of the three outcomes. The effect size, although in favour of the treatment with PRP, was not significant considering the healing time and the number of healings. The overall heterogeneity was mild or moderate. Five studies reported a high risk of selection bias. The publication bias was always mild or absent. The results support the hypothesis of the positive effects of the PRP when compared to control groups in the treatment of experimentally-induced

Gastroprotective Efficacy and Safety Evaluation of Scoparone Derivatives on Experimentally Induced Gastric Lesions in Rodents

PubMed Central

Son, Dong Ju; Lee, Gyung Rak; Oh, Sungil; Lee, Sung Eun; Choi, Won Sik

2015-01-01

This study investigated the gastroprotective efficacy of synthesized scoparone derivatives on experimentally induced gastritis and their toxicological safety. Six scoparone derivatives were synthesized and screened for gastroprotective activities against HCl/ethanol- and indomethacin-induced gastric ulcers in rats. Among these compounds, 5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin were found to have gastroprotective activity greater than the standard drug rebamipide; 6-methoxy-7,8-methylenedioxycoumarin, 6-methoxy-7,8-(1-methoxy)-methylenedioxycoumarin, 6,7-methylenedioxycoumarin, and 6,7-(1-methoxy)-methylenedioxycoumarin were found to be equipotent or less potent that of rebamipide. Pharmacological studies suggest that the presence of a methoxy group at position C-5 or C-8 of the scoparone’s phenyl ring significantly improves gastroprotective activity, whereas the presence of a dioxolane ring at C-6, C-7, or C-8 was found to have decreased activity. In order to assess toxicological safety, two of the potent gastroprotective scoparone derivatives—5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin—were examined for their acute toxicity in mice as well as their effect on cytochrome P450 (CYP) enzyme activity. These two compounds showed low acute oral toxicity in adult male and female mice, and caused minimal changes to CYP3A4 and CYP2C9 enzyme activity. These results indicate that compared to other scoparone derivatives, 5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin can improve gastroprotective effects, and they have low toxicity and minimal effects on drug-metabolizing enzymes. PMID:25781220

In vitro and in vivo studies on antitumor effects of gossypol on human stomach adenocarcinoma (AGS) cell line and MNNG induced experimental gastric cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunassekaran, G.R., E-mail: gunassekaran@yahoo.co.in; Kalpana Deepa Priya, D.; Gayathri, R.

2011-08-12

Highlights: {yields} Gossypol is a well known polyphenolic compound used for anticancer studies but we are the first to report that gossypol has antitumor effect on MNNG induced gastric cancer in experimental animal models. {yields} Our study shows that gossypol inhibits the proliferation of AGS (human gastric adenocarcinoma) cell line. {yields} In animal models, gossypol extends the survival of cancer bearing animals and also protects the cells from carcinogenic effect. {yields} So we suggest that gossypol would be a potential chemotherapeutic and chemopreventive agent for gastric cancer. -- Abstract: The present study has evaluated the chemopreventive effects of gossypol onmore » N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis and on human gastric adenocarcinoma (AGS) cell line. Gossypol, C{sub 30}H{sub 30}O{sub 8}, is a polyphenolic compound that has anti proliferative effect and induces apoptosis in various cancer cells. The aim of this work was to delineate in vivo and in vitro anti-initiating mechanisms of orally administered gossypol in target (stomach) tissues and in human gastric adenocarcinoma (AGS) cell line. In vitro results prove that gossypol has potent cytotoxic effect and inhibit the proliferation of adenocarcinoma (AGS) cell line. In vivo results prove gossypol to be successful in prolonging the survival of MNNG induced cancer bearing animals and in delaying the onset of tumor in animals administrated with gossypol and MNNG simultaneously. Examination of the target (stomach) tissues in sacrificed experimental animals shows that administration of gossypol significantly reduces the level of tumor marker enzyme (carcino embryonic antigen) and pepsin. The level of Nucleic acid contents (DNA and RNA) significantly reduces, and the membrane damage of glycoprotein subsides, in the target tissues of cancer bearing animals, with the administration of gossypol. These data suggest that gossypol may create a beneficial effect in

Epidermal growth factor receptor inhibition with erlotinib ameliorates anti-Thy 1.1-induced experimental glomerulonephritis.

PubMed

Rintala, Jukka M; Savikko, Johanna; Rintala, Sini E; Palin, Niina; Koskinen, Petri K

2016-06-01

Mesangial proliferative glomerulonephritis is a common glomerular disorder that may lead to end-stage renal disease. Epidermal growth factor (EGF) plays an important role in the regulation of cell growth, proliferation, and differentiation and in the pathology of various renal diseases. Erlotinib is a novel, oral, highly selective tyrosine kinase inhibitor of the EGF receptor. It is clinically used to treat non-small cell lung and pancreatic cancers. Here, we investigated the effect of erlotinib on the progression of mesangioproliferative glomerulonephritis in an experimental model. Mesangial glomerulonephritis was induced with anti-rat Thy-1.1 antibody in male Wistar rats weighing 150-160 g. Rats were treated with erlotinib (10 mg/kg/day p.o.) or vehicle only (polyethylene glycol). Native Wistar rat kidneys were used as histological controls. Serum creatinine levels were measured at day 7. Kidneys were harvested 7 days after antibody administration for histology. Native controls showed no histological signs of glomerular pathology. In the vehicle group, intense glomerular inflammation developed after 7 days and prominent mesangial cell proliferation and glomerular matrix accumulation was seen. Erlotinib was well tolerated and there were no adverse effects during the follow-up period. Erlotinib significantly prevented progression of the glomerular inflammatory response and glomerular mesangial cell proliferation as well as matrix accumulation when compared with the vehicle group. Erlotinib also preserved renal function. These results indicate that erlotinib prevents the early events of experimental mesangial proliferative glomerulonephritis. Therefore, inhibition of the EGF receptor with erlotinib could prevent the progression of glomerulonephritis also in clinical nephrology.

[The value of transbronchial lung biopsy findings in the diagnosis of a case of TS-1-induced pulmonary toxicity].

PubMed

Ito, Shunsuke; Yamaguchi, Tomoyoshi; Morisue, Ryo; Ogaw, Yukari; Munakata, Kazuo; Fukuda, Yuh

2011-12-01

We report the case of a 67-year-old man with a diagnosis of stage IV stomach cancer in May 2010 who was treated with outpatient chemotherapy using TS-1, paclitaxel and lentinan. Dyspnea and coughing developed after drug administration in November and the patient was hospitalized on day 5 after the appearance of symptoms due to hypoxemia and the presence of ground-glass opacities in the right middle and lower lung fields. On the same day, bronchoscopy was performed for differentiation from infection and lymphangitic carcinomatosis. A transbronchial lung biopsy suggested drug-induced pulmonary toxicity, and a drug lymphocyte stimulation test was highly positive for TS-1. Discontinuation of TS-1 alone improved his respiratory status and imaging findings. TS-1 is available only in Japan, and because it is administered orally and its toxicity is minimal, its use has been expanded to treat a variety of malignancies. Drug-induced pulmonary toxicity due to TS-1 occurs in only 0.03% of all cases, and there are few reports regarding the histopathological findings of TS-1-related pulmonary toxicity. Although it can be difficult to diagnose drug-induced pulmonary toxicity because it demonstrates a variety of imaging findings, the present case suggests that it is important to proactively perform transbronchial lung biopsy at the early stage of diagnosis and promptly determine a course of treatment.

Protective effect of Calendula officinalis Linn. flowers against 3-nitropropionic acid induced experimental Huntington's disease in rats.

PubMed

Shivasharan, B D; Nagakannan, Pandian; Thippeswamy, Boreddy Shivanandappa; Veerapur, Veeresh Prabakar; Bansal, Punit; Unnikrishnan, Mazhuvancherry K

2013-10-01

Oxidative stress (OS) and nitric oxide mechanisms have been recently proposed in 3-nitropropionic acid (3-NP)-induced neurotoxicity. The compounds, having antioxidant, anti-inflammatory and estrogenic effects, have been suggested for neuroprotection in different experimental models. Calendula officinalis Linn. flower extract (COE) is known for its potent antioxidant, anti-inflammatory, estrogenic and neuroprotective activities. Hence, the present study was designed to evaluate the neuroprotective effect of COE on 3-NP-induced neurotoxicity in rats by observing behavioral changes, OS and striatal damage in rat brain. Adult female Wistar rats were pretreated with vehicle or COE (100 and 200 mg/kg) for 7 days, followed by cotreatment with 3-NP (15 mg/kg, intraperitoneally) for the next 7 days. At the end of the treatment schedule, rats were evaluated for alterations in sensory motor functions and short-term memory. Animals were sacrificed and brain homogenates were used for the estimation of lipid peroxidation (LPO), glutathione, total thiols, glutathione S-transferase, catalase and nitrite. A set of brain slices was used for the evaluation of neuronal damage in the striatal region of the brain. 3-NP caused significant alterations in animal behavior, oxidative defense system evidenced by raised levels of LPO and nitrite concentration, and depletion of antioxidant levels. It also produced a loss of neuronal cells in the striatal region. Treatment with COE significantly attenuated behavioral alterations, oxidative damage and striatal neuronal loss in 3-NP-treated animals. The present study shows that COE is protective against 3-NP-induced neurotoxicity in rats. The antioxidant, anti-inflammatory and estrogenic properties of COE may be responsible for its neuroprotective action.

A Systematic Review of Experimental and Clinical Acupuncture in Chemotherapy-Induced Peripheral Neuropathy

PubMed Central

Franconi, Giovanna; Schröder, Sven; Marchetti, Paolo; Robinson, Nicola

2013-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect that can be very disabling and can limit or delay the dose of chemotherapy that can be administered. Acupuncture may be effective for treating peripheral neuropathy. The aim of this study was to review the available literature on the use of acupuncture for CIPN. The systematic literature search was performed using MEDLINE, Google Scholar, Cochrane Database, CINHAL, and ISI Proceedings. Hand searching was conducted, and consensus was reached on all extracted data. Only papers in the English language were included, irrespective of study design. From 3989 retrieved papers, 8 relevant papers were identified. One was an experimental study which showed that electroacupuncture suppressed CIPN pain in rats. In addition, there were 7 very heterogeneous clinical studies, 1 controlled randomised study using auricular acupuncture, 2 randomized controlled studies using somatic acupuncture, and 3 case series/case reports which suggested a positive effect of acupuncture in CIPN. Conclusions. Only one controlled randomised study demonstrated that acupuncture may be beneficial for CIPN. All the clinical studies reviewed had important methodological limitations. Further studies with robust methodology are needed to demonstrate the role of acupuncture for treating CIPN resulting from cancer treatment. PMID:23983788

Immunologic responses against hydrolyzed soy protein in dogs with experimentally induced soy hypersensitivity.

PubMed

Puigdemont, Anna; Brazís, Pilar; Serra, Montserrat; Fondati, Alessandra

2006-03-01

To assess whether dogs with experimentally induced type I hypersensitivity against soy protein would respond to soy hydrolysate and develop cutaneous or gastrointestinal tract reactions after intradermal and oral challenge exposure. 12 naïve Beagle pups (9 sensitized and 3 control dogs). 9 dogs were sensitized against soy protein by administration of allergens during a 90-day period. After the sensitization period, serum concentrations of soy-specific IgE were determined and an intradermal test was performed to confirm the dogs were sensitized against soy protein. An intradermal challenge test and an oral challenge test with native and hydrolyzed soy protein were conducted on 6 sensitized and 2 control dogs. High serum concentrations of soy-specific IgE and positive results for the intradermal test were observed for the 9 sensitized dogs after completion of the sesitization process. Sensitized dogs challenge exposed with hydrolyzed soy protein had a reduced inflammatory response after intradermal injection and no clinical response after an oral challenge exposure, compared with responses after intradermal and oral challenge exposure with native soy protein. Soy-sensitized dogs did not respond to oral administration of hydrolyzed soy protein. Thus, hydrolyzed soy protein may be useful in diets formulated for the management of dogs with adverse reactions to food.

Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis

PubMed Central

Nighot, Prashant; Al-Sadi, Rana; Guo, Shuhong; Watterson, D. Martin; Ma, Thomas

2015-01-01

Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9−/− mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9−/− mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9−/− mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK−/− mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9−/− mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK. PMID:26514773

Experimental investigation of localized stress-induced leakage current distribution in gate dielectrics using array test circuit

NASA Astrophysics Data System (ADS)

Park, Hyeonwoo; Teramoto, Akinobu; Kuroda, Rihito; Suwa, Tomoyuki; Sugawa, Shigetoshi

2018-04-01

Localized stress-induced leakage current (SILC) has become a major problem in the reliability of flash memories. To reduce it, clarifying the SILC mechanism is important, and statistical measurement and analysis have to be carried out. In this study, we applied an array test circuit that can measure the SILC distribution of more than 80,000 nMOSFETs with various gate areas at a high speed (within 80 s) and a high accuracy (on the 10-17 A current order). The results clarified that the distributions of localized SILC in different gate areas follow a universal distribution assuming the same SILC defect density distribution per unit area, and the current of localized SILC defects does not scale down with the gate area. Moreover, the distribution of SILC defect density and its dependence on the oxide field for measurement (E OX-Measure) were experimentally determined for fabricated devices.

Electromagnetically induced absorption in detuned stub waveguides: a simple analytical and experimental model

NASA Astrophysics Data System (ADS)

Mouadili, A.; El Boudouti, E. H.; Soltani, A.; Talbi, A.; Djafari-Rouhani, B.; Akjouj, A.; Haddadi, K.

2014-12-01

We give an analytical and experimental demonstration of a classical analogue of the electromagnetic induced absorption (EIA) in a simple photonic device consisting of two stubs of lengths d1 and d2 grafted at the same site along a waveguide. By detuning the lengths of the two stubs (i.e. δ = d2 - d1) we show that: (i) the amplitudes of the electromagnetic waves in the two stubs can be written following the two resonators model where each stub plays the role of a radiative resonator with low Q factor. The destructive interference between the waves in the two stubs may give rise to a sharp resonance peak with high Q factor in the transmission as well as in the absorption. (ii) The transmission coefficient around the resonance induced by the stubs can be written following a Fano-like form. In particular, we give an explicit expression of the position, width and Fano parameter of the resonances as a function of δ. (iii) By taking into account the loss in the waveguides, we show that at the transmission resonance, the transmission (reflection) increases (decreases) as a function of δ. Whereas the absorption goes through a maximum around 0.5 for a threshold value δth which depends on the attenuation in the system and then falls to zero. (iv) We give a comparison between the phase of the determinant of the scattering matrix, the so-called Friedel phase and the phase of the transmission amplitude. (v) The effect of the boundary conditions at the end of the resonators on the EIA resonance is also discussed. The analytical results are obtained by means of the Green's function method, whereas the experiments are carried out using coaxial cables in the radio-frequency regime. These results should have important consequences for designing integrated devices such as narrow-frequency optical or microwave filters and high-speed switches.

Exercise-induced Pulmonary Hypertension

PubMed Central

Vanderpool, Rebecca; Dhakal, Bishnu P.; Saggar, Rajeev; Saggar, Rajan; Vachiery, Jean-Luc; Lewis, Gregory D.

2013-01-01

Exercise stresses the pulmonary circulation through increases in cardiac output (Q.) and left atrial pressure. Invasive as well as noninvasive studies in healthy volunteers show that the slope of mean pulmonary artery pressure (mPAP)–flow relationships ranges from 0.5 to 3 mm Hg⋅min⋅L−1. The upper limit of normal mPAP at exercise thus approximates 30 mm Hg at a Q. of less than 10 L⋅min−1 or a total pulmonary vascular resistance at exercise of less than 3 Wood units. Left atrial pressure increases at exercise with an average upstream transmission to PAP in a close to one-for-one mm Hg fashion. Multipoint PAP–flow relationships are usually described by a linear approximation, but present with a slight curvilinearity, which is explained by resistive vessel distensibility. When mPAP is expressed as a function of oxygen uptake or workload, plateau patterns may be observed in patients with systolic heart failure who cannot further increase Q. at the highest levels of exercise. Exercise has to be dynamic to avoid the increase in systemic vascular resistance and abrupt changes in intrathoracic pressure that occur with resistive exercise and can lead to unpredictable effects on the pulmonary circulation. Postexercise measurements are unreliable because of the rapid return of pulmonary vascular pressures and flows to the baseline resting state. Recent studies suggest that exercise-induced increase in PAP to a mean higher than 30 mm Hg may be associated with dyspnea-fatigue symptomatology. PMID:23348976

Time course of Paclitaxel-induced apoptosis in an experimental model of virus-induced breast cancer.

PubMed

Erba, Paola A; Manfredi, Chiara; Lazzeri, Elena; Minichilli, Fabrizio; Pauwels, Ernest K J; Sbrana, Alberto; Strauss, H William; Mariani, Giuliano

2010-05-01

Early assessment of the efficacy of treatment is important in patients with breast cancer, whose routine adjuvant regimen frequently includes chemotherapy. Irrespective of the exact mechanisms involved in induction, the common early phenotypic marker of apoptosis is the expression on the outer cell membrane surface of phosphatidylserine, which avidly binds annexin V. (99m)Tc-labeled annexin V has been proposed for in vivo scintigraphic detection of apoptosis, albeit with contradicting results. This study was performed to define the time course of apoptosis induced by the chemotherapeutic agent paclitaxel in a model of virus-induced murine breast cancer. The RIII virus induces an estrogen-dependent, slow-growing breast cancer; BALB-c/cRIII female mice with breast tumors averaging 10 mm were studied, both in baseline conditions and at various times after the intravenous administration of paclitaxel (equivalent to a human dose of 20 mg/70 kg of body weight). The biodistribution of (99m)Tc-annexin V was evaluated at baseline and then at 1, 3, 6, and 24 h after paclitaxel administration. Apoptotic and antiapoptotic markers were also evaluated in tumor samples obtained at the same time points: DNA breaks (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling [TUNEL]), active caspase-3, apoptosis-inducing factor, and Bcl-2 protein. Baseline uptake of (99m)Tc-annexin V in breast tumors was about 2-fold higher than the uptake in normal breast tissue (demonstrating some ongoing apoptosis); tracer uptake increased at 1 and 3 h after paclitaxel administration (to almost double the baseline value) and then declined to levels even lower than baseline. Although no activation of the apoptosis-inducing factor mechanism was detected, a peak in TUNEL-positive tumor cells was reached 3 h after paclitaxel administration (to more than 6-fold the baseline level). The antiapoptotic marker Bcl-2 exhibited a biphasic pattern, with a maximum drop at 3 h, followed by return

Astigmatism in Monkeys with Experimentally Induced Myopia or Hyperopia

PubMed Central

KEE, CHEA-SU; HUNG, LI-FANG; QIAO-GRIDER, YING; RAMAMIRTHAM, RAMKUMAR; SMITH, EARL L.

2006-01-01

Purpose Astigmatism is the most common ametropia found in humans and is often associated with large spherical ametropias. However, little is known about the etiology of astigmatism or the reason(s) for the association between spherical and astigmatic refractive errors. This study examines the frequency and characteristics of astigmatism in infant monkeys that developed axial ametropias as a result of altered early visual experience. Methods Data were obtained from 112 rhesus monkeys that experienced a variety of lens-rearing regimens that were intended to alter the normal course of emmetropization. These visual manipulations included form deprivation (n = 13); optically imposed defocus (n = 48); and continuous ambient lighting with (n = 6) or without optically imposed defocus (n = 6). In addition, data from 19 control monkeys and 39 infants reared with an optically imposed astigmatism were used for comparison purposes. The lens-rearing period started at approximately 3 weeks of age and ended by 4 to 5 months of age. Refractive development for all monkeys was assessed periodically throughout the treatment and subsequent recovery periods by retinoscopy, keratometry, and A-scan ultrasonography. Results In contrast to control monkeys, the monkeys that had experimentally induced axial ametropias frequently developed significant amounts of astigmatism (mean refractive astigmatism = 0.37 ± 0.33 D [control] vs. 1.24 ± 0.81 D [treated]; two-sample t-test, p < 0.0001), especially when their eyes exhibited relative hyperopic shifts in refractive error. The astigmatism was corneal in origin (Pearson’s r; p < 0.001 for total astigmatism and the JO and J45 components), and the axes of the astigmatism were typically oblique and bilaterally mirror symmetric. Interestingly, the astigmatism was not permanent; the majority of the monkeys exhibited substantial reductions in the amount of astigmatism at or near the end of the lens-rearing procedures. Conclusions In infant monkeys

Clinician gestalt estimate of pretest probability for acute coronary syndrome and pulmonary embolism in patients with chest pain and dyspnea.

PubMed

Kline, Jeffrey A; Stubblefield, William B

2014-03-01

Pretest probability helps guide diagnostic testing for patients with suspected acute coronary syndrome and pulmonary embolism. Pretest probability derived from the clinician's unstructured gestalt estimate is easier and more readily available than methods that require computation. We compare the diagnostic accuracy of physician gestalt estimate for the pretest probability of acute coronary syndrome and pulmonary embolism with a validated, computerized method. This was a secondary analysis of a prospectively collected, multicenter study. Patients (N=840) had chest pain, dyspnea, nondiagnostic ECGs, and no obvious diagnosis. Clinician gestalt pretest probability for both acute coronary syndrome and pulmonary embolism was assessed by visual analog scale and from the method of attribute matching using a Web-based computer program. Patients were followed for outcomes at 90 days. Clinicians had significantly higher estimates than attribute matching for both acute coronary syndrome (17% versus 4%; P<.001, paired t test) and pulmonary embolism (12% versus 6%; P<.001). The 2 methods had poor correlation for both acute coronary syndrome (r(2)=0.15) and pulmonary embolism (r(2)=0.06). Areas under the receiver operating characteristic curve were lower for clinician estimate compared with the computerized method for acute coronary syndrome: 0.64 (95% confidence interval [CI] 0.51 to 0.77) for clinician gestalt versus 0.78 (95% CI 0.71 to 0.85) for attribute matching. For pulmonary embolism, these values were 0.81 (95% CI 0.79 to 0.92) for clinician gestalt and 0.84 (95% CI 0.76 to 0.93) for attribute matching. Compared with a validated machine-based method, clinicians consistently overestimated pretest probability but on receiver operating curve analysis were as accurate for pulmonary embolism but not acute coronary syndrome. Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

Light-induced noncentrosymmetry in acceptor-donor-substituted azobenzene solutions

NASA Astrophysics Data System (ADS)

Zhao, Jiang; Si, Jinhai; Wang, Yougui; Ye, Peixian; Fu, Xingfa; Qiu, Ling; Shen, Yuquan

1995-10-01

Light-induced noncentrosymmetry was achieved experimentally in acceptor-donor-substituted azobenzene solutions and observed by phase-matched nondegenerate six-wave mixing. The microscopic origin of the induced noncentrosymmetry was found to be orientational hole burning, which was distinguished directly with net orientation of molecules by experimental observations. The decay time of the induced noncentrosymmetry depended on the rotational orientation time of the sample's molecule, which varied linearly with the viscosity of the solvent.

Alterations in the lenticular protein profile in experimental selenite-induced cataractogenesis and prevention by ellagic acid.

PubMed

Sakthivel, Muniyan; Geraldine, Pitchairaj; Thomas, Philip A

2011-08-01

Accumulating evidence suggests that oxidative stress underlies age-related formation of cataract, and that antioxidants retard cataractogenesis. This study aimed to evaluate whether ellagic acid, a natural polyphenol with antioxidant properties, prevents alterations in the lenticular protein profile in an experimental model of selenite cataract. Alterations in lenticular protein were determined by two-dimensional electrophoresis (2DE) and image analysis. Eluted αA-crystallin spots were analyzed by mass spectrometry. Western blot analysis was also performed to confirm the differential expression of certain crystallins and cytoskeletal proteins. In cataractous lenses, 2DE and image analysis revealed approximately 45 and 60 prominent spots in soluble and insoluble protein fractions respectively. Analysis of the pI and molecular weight of protein spots revealed differences in the expression of crystallin proteins in soluble and insoluble fractions. Western blot analysis confirmed changes in the expression of αA- and βB1- crystallins in both soluble and insoluble protein fractions, while mass spectrometry confirmed the degradation of αA-crystallin in selenite cataractous lenses. Western blot analysis also confirmed the occurrence of altered expression of certain cytoskeletal proteins in insoluble fractions. However, the lenticular protein profile in lenses from selenite-challenged, ellagic acid-treated rats was essentially similar to that noted in lenses from normal rats. The present study confirms the importance of structural and cytoskeletal proteins in the maintenance of lenticular transparency; the results also suggest that ellagic acid prevents lenticular protein alterations induced by selenite in an experimental setting.

Piracetam Facilitates the Anti-Amnesic but not Anti-Diabetic Activity of Metformin in Experimentally Induced Type-2 Diabetic Encephalopathic Rats.

PubMed

Pandey, Shruti; Garabadu, Debapriya

2017-07-01

Piracetam exhibits anti-amnesic activity in several animal models of dementia. However, its anti-amnesic potential has yet to be evaluated in type-2 diabetes mellitus (T2DM)-induced encephalopathy. Therefore, in the present study, piracetam (25, 50 and 100 mg/kg) was screened for anti-amnesic and anti-diabetic activity in T2DM-induced encephalopathic male rats. Subsequently, anti-amnesic and anti-diabetic activities were evaluated for piracetam, metformin and their combination in T2DM-induced encephalopathic animals. Rats received streptozotocin (45 mg/kg) and nicotinamide (110 mg/kg) injections on day-1 (D-1) of the experimental schedule and were kept undisturbed for 35 days to exhibit T2DM-induced encephalopathy. All drug treatments were continued from D-7 to D-35 in both experiments. Piracetam (100 mg/kg) attenuated loss in learning and memory in terms of increase in escape latency on D-4 (D-34) and decrease in time spent in the target quadrant on D-5 (D-35) of Morris water maze test protocol, and spatial memory in terms of reduced spontaneous alternation behavior in Y-maze test of encephalopathic rats. Additionally, piracetam attenuated altered levels of fasting plasma glucose and insulin, HOMA-IR and HOMA-B in encephalopathic animals, comparatively lesser than metformin. In the next experiment, combination of piracetam and metformin exhibited better anti-amnesic but not anti-diabetic activity than respective monotherapies in encephalopathic rats. Further, the combination attenuated reduced acetylcholine level and increased acetylcholinesterase activity, increased glycogen synthase kinase-3β level and decreased brain-derived neurotropic factor level in hippocampus and pre-frontal cortex of encephalopathic animals. Thus, piracetam could be used as an adjuvant to metformin in the management of dementia in T2DM-induced encephalopathy.

Comparative study of the effects of experimentally induced hypothyroidism and hyperthyroidism in some brain regions in albino rats.

PubMed

El-Bakry, A M; El-Gareib, A W; Ahmed, R G

2010-08-01

Thyroid hormones (THs) play a crucial role in the development and physiological functioning of different body organs especially the brain. Therefore, the objective of this study was to show the histopathological effects of the different thyroid states on some brain regions (cerebrum and cerebellum) and the skeletal features of their newborns during the postnatal development from the 1st to 3rd week. The female white albino rats were allocated into 3 groups as follows: the experimental hypothyroidism group is induced by 0.02% methimazole (MMI) (w/v) in drinking water, while the experimental hyperthyroidism group is performed by exogenous T4 [from 50 to 200microg/kg body weight intragastric administration beside adding 0.002% T4 (w/v) to the drinking water] from the gestation day 1 to lactation day 21 and control group which received tap water. As well, both maternal hypo- and hyperthyroidism caused some malformation and developmental defects in the cerebellar and cerebral cortex of their newborns along the duration of the experiment. These degenerative symptoms became more prominent and widely spread at the 3rd postnatal week. Concomitantly, there were some degeneration, deformation and severe growth retardation in neurons of these regions in both treated groups throughout the experimental period. Moreover, the skeletal features of these newborns were accelerated in hyperthyroid group while these maturations were delayed partially in hypothyroid ones during the examined periods. These alterations, on both treated groups, were age and dose dependent. Thus, further studies need to be done to emphasize this concept. Published by Elsevier Ltd.

A Chemically Modified Curcumin (CMC 2.24) Inhibits Nuclear Factor κB Activation and Inflammatory Bone Loss in Murine Models of LPS-Induced Experimental Periodontitis and Diabetes-Associated Natural Periodontitis.

PubMed

Elburki, Muna S; Rossa, Carlos; Guimarães-Stabili, Morgana R; Lee, Hsi-Ming; Curylofo-Zotti, Fabiana A; Johnson, Francis; Golub, Lorne M

2017-08-01

The purpose of this study was to assess the effect of a novel chemically modified curcumin (CMC 2.24) on NF-κB and MAPK signaling and inflammatory cytokine production in two experimental models of periodontal disease in rats. Experimental model I: Periodontitis was induced by repeated injections of LPS into the gingiva (3×/week, 3 weeks); control rats received vehicle injections. CMC 2.24, or the vehicle, was administered by daily oral gavage for 4 weeks. Experimental model II: Diabetes was induced in adult male rats by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC 2.24, or the vehicle, was administered by oral gavage daily for 3 weeks to the diabetics. Hemimaxillae and gingival tissues were harvested, and bone loss was assessed radiographically. Gingival tissues were pooled according to the experimental conditions and processed for the analysis of matrix metalloproteinases (MMPs) and bone-resorptive cytokines. Activation of p38 MAPK and NF-κB signaling pathways was assessed by western blot. Both LPS and diabetes induced an inflammatory process in the gingival tissues associated with excessive alveolar bone resorption and increased activation of p65 (NF-κB) and p38 MAPK. In both models, the administration of CMC 2.24 produced a marked reduction of inflammatory cytokines and MMPs in the gingival tissues, decreased bone loss, and decreased activation of p65 (NF-κB) and p38 MAPK. Inhibition of these cell signaling pathways by this novel tri-ketonic curcuminoid (natural curcumin is di-ketonic) may play a role in its therapeutic efficacy in locally and systemically associated periodontitis.

Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sabatino, María Eugenia; Sosa, Liliana del Valle; Petiti, Juan Pablo

Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophsmore » taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of