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Sample records for acute phase immunodominant

  1. Immunodominant CD4+ T-cell epitope within nonstructural protein 3 in acute hepatitis C virus infection

    NARCIS (Netherlands)

    Diepolder, H. M.; Gerlach, J. T.; Zachoval, R.; Hoffmann, R. M.; Jung, M. C.; Wierenga, E. A.; Scholz, S.; Santantonio, T.; Houghton, M.; Southwood, S.; Sette, A.; Pape, G. R.

    1997-01-01

    In acute hepatitis C virus infection, 50 to 70% of patients develop chronic disease. Considering the low rate of spontaneous viral clearance during chronic hepatitis C infection, the first few months of interaction between the patient's immune system and the viral population seem to be crucial in

  2. Immunodomination during peripheral vaccinia virus infection.

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    Leon C W Lin

    Full Text Available Immunodominance is a fundamental property of CD8(+ T cell responses to viruses and vaccines. It had been observed that route of administration alters immunodominance after vaccinia virus (VACV infection, but only a few epitopes were examined and no mechanism was provided. We re-visited this issue, examining a panel of 15 VACV epitopes and four routes, namely intradermal (i.d., subcutaneous (s.c., intraperitoneal (i.p. and intravenous (i.v. injection. We found that immunodominance is sharpened following peripheral routes of infection (i.d. and s.c. compared with those that allow systemic virus dissemination (i.p. and i.v.. This increased immunodominance was demonstrated with native epitopes of VACV and with herpes simplex virus glycoprotein B when expressed from VACV. Responses to some subdominant epitopes were altered by as much as fourfold. Tracking of virus, examination of priming sites, and experiments restricting virus spread showed that priming of CD8(+ T cells in the spleen was necessary, but not sufficient to broaden responses. Further, we directly demonstrated that immunodomination occurs more readily when priming is mainly in lymph nodes. Finally, we were able to reduce immunodominance after i.d., but not i.p. infection, using a VACV expressing the costimulators CD80 (B7-1 and CD86 (B7-2, which is notable because VACV-based vaccines incorporating these molecules are in clinical trials. Taken together, our data indicate that resources for CD8(+ T cell priming are limiting in local draining lymph nodes, leading to greater immunodomination. Further, we provide evidence that costimulation can be a limiting factor that contributes to immunodomination. These results shed light on a possible mechanism of immunodomination and highlight the need to consider multiple epitopes across the spectrum of immunogenicities in studies aimed at understanding CD8(+ T cell immunity to viruses.

  3. Acute-phase proteins: As diagnostic tool

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    Sachin Jain

    2011-01-01

    Full Text Available The varied reactions of the host to infection, inflammation, or trauma are collectively known as the acute-phase response and encompass a wide range of pathophysiological responses such as pyrexia, leukocytosis, hormone alterations, and muscle protein depletion combining to minimize tissue damage while enhancing the repair process. The mechanism for stimulation of hepatic production of acute-phase proteins is by proinflammatory cytokines. The functions of positive acute-phase proteins (APP are regarded as important in optimization and trapping of microorganism and their products, in activating the complement system, in binding cellular remnants like nuclear fractions, in neutralizing enzymes, scavenging free hemoglobin and radicals, and in modulating the host′s immune response. APP can be used as diagnostic tool in many diseases like bovine respiratory syncytial virus, prostate cancer, bronchopneumonia, multiple myeloma, mastitis, Streptococcus suis infection, starvation, or lymphatic neoplasia. Thus, acute-phase proteins may provide an alternative means of monitoring animal health.

  4. Acute phase protein response during acute ruminal acidosis in cattle

    DEFF Research Database (Denmark)

    Danscher, A. M.; Thoefner, M. B.; Heegaard, Peter M. H.

    2011-01-01

    The aim of the study was to describe the acute phase protein and leukocyte responses in dairy heifers during acute, oligofructose-induced ruminal acidosis. The study included 2 trials involving oral oligofructose overload (17g/kg BW) to nonpregnant Danish Holstein heifers. Trial 1 included 12...... performed.Heifers receiving oligofructose developed a profound ruminal and systemic acidosis (in Trial 1 and 2 lowest ruminal pH was 4.3±0.2 and 3.8±0.02, respectively, and minimum SBE was −9.3±4.1 and −8.9±2.8, respectively). In Trial 1, SAA concentrations were higher than baseline concentrations on all...... than control heifers at 18 and 24h after overload (max. 13.7±4.3 billions/L). Feeding had no effect on plasma fibrinogen concentrations or WBC in Trial 1.Acute ruminal and systemic acidosis caused by oligofructose overload resulted in distinct acute phase protein and leukocyte responses in dairy...

  5. Management of pemphigus vulgaris during acute phase

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    Kar P

    2003-03-01

    Full Text Available We present our experience with 21 patients of pemphigus vulgaris seen over a period of 10 years managed in service hospitals during acute phase of the disease. Age groups of patients ranged from 25-45 years. Eighteen (85.7% were young adults, 30-40 years of age. Fifteen (71.4% were men and 6(28.6% were women. All the cases were hospitalized in ICU, till the acute phase of the disease subsided. Complete hematological profile, urinalysis, serum biochemistry and repeated bacterial cultures from the skin were carried out in all patients at the time of admission and thereafter weekly. The treatment comprised of potassium permanganate lotion bath (1:10000 and 1 framycetin gauze dressing of the denuded areas, maintenance of fluid and electrolyte balance. All suspected infections and septicemia were treated with appropriate antibiotics. The corticosteroids were usually administered as a single dose of prednisolone 1 mg/kg/day. Cyclophosphamide was given at an initial dose of 50mg/day and the dose was escalated to 100mg/day. Once the bulk of the lesions were healed, the dose of corticosteroids was gradually lowered by approximately 50% every two weeks and cyclophosphamide was continued till patients were symptomfree. Out of 21 patients receiving corticosteroids, cyclophosphamide and other supportive therapy, 20(95% had undergone clinical resolution of the disease. During follow up study 15(71.4% patients remained symptom-free and undergone clinical remission. Five patients (23.8% had relapse, out of which 4(19% remained symptom free, after subsequent treatment. There was one death (4.7% in our study.

  6. Neuropsychological intervention in the acute phase

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    Norup, Anne; Siert, Lars; Mortensen, Erik Lykke

    2013-01-01

    This pilot study investigated the effects of acute neuropsychological intervention for relatives of patients with severe brain injury. Participants were enrolled in an intervention group comprising 39 relatives, and a control group comprising 47 relatives. The intervention consisted of supportive......-acute rehabilitation. Outcome measures included selected scales from the Symptom Checklist Revised 90 (SCL-90-R), the Short Form 36 (SF-36), and a visual analogue quality of life scale. The intervention group showed a significant decrease in anxiety scores from the acute to the sub-acute setting (= 2.70 = 0.......0100.30), but also significantly lower Role Emotional scores (= 2.12 = 0.043, = 0.40). In the sub-acute setting, an analysis of covariance model showed a borderline significant difference between the intervention and the control group on the anxiety scale (= 0.066 = 0.59). Any effects of the acute neuropsychological...

  7. Variable processing and cross-presentation of HIV by dendritic cells and macrophages shapes CTL immunodominance and immune escape.

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    Jens Dinter

    2015-03-01

    Full Text Available Dendritic cells (DCs and macrophages (Møs internalize and process exogenous HIV-derived antigens for cross-presentation by MHC-I to cytotoxic CD8⁺ T cells (CTL. However, how degradation patterns of HIV antigens in the cross-presentation pathways affect immunodominance and immune escape is poorly defined. Here, we studied the processing and cross-presentation of dominant and subdominant HIV-1 Gag-derived epitopes and HLA-restricted mutants by monocyte-derived DCs and Møs. The cross-presentation of HIV proteins by both DCs and Møs led to higher CTL responses specific for immunodominant epitopes. The low CTL responses to subdominant epitopes were increased by pretreatment of target cells with peptidase inhibitors, suggestive of higher intracellular degradation of the corresponding peptides. Using DC and Mø cell extracts as a source of cytosolic, endosomal or lysosomal proteases to degrade long HIV peptides, we identified by mass spectrometry cell-specific and compartment-specific degradation patterns, which favored the production of peptides containing immunodominant epitopes in all compartments. The intracellular stability of optimal HIV-1 epitopes prior to loading onto MHC was highly variable and sequence-dependent in all compartments, and followed CTL hierarchy with immunodominant epitopes presenting higher stability rates. Common HLA-associated mutations in a dominant epitope appearing during acute HIV infection modified the degradation patterns of long HIV peptides, reduced intracellular stability and epitope production in cross-presentation-competent cell compartments, showing that impaired epitope production in the cross-presentation pathway contributes to immune escape. These findings highlight the contribution of degradation patterns in the cross-presentation pathway to HIV immunodominance and provide the first demonstration of immune escape affecting epitope cross-presentation.

  8. Neuropsychological intervention in the acute phase

    DEFF Research Database (Denmark)

    Norup, Anne; Siert, Lars; Mortensen, Erik Lykke

    2013-01-01

    This pilot study investigated the effects of acute neuropsychological intervention for relatives of patients with severe brain injury. Participants were enrolled in an intervention group comprising 39 relatives, and a control group comprising 47 relatives. The intervention consisted of supportive.......0100.30), but also significantly lower Role Emotional scores (= 2.12 = 0.043, = 0.40). In the sub-acute setting, an analysis of covariance model showed a borderline significant difference between the intervention and the control group on the anxiety scale (= 0.066 = 0.59). Any effects of the acute neuropsychological...

  9. The acute phase response and exercise: court and field sports

    Science.gov (United States)

    Fallon, K; Fallon, S; Boston, T

    2001-01-01

    Objective—To determine the presence or absence of an acute phase response after training for court and field sports. Participants—All members of the Australian women's soccer team (n = 18) and all members of the Australian Institute of Sport netball team (n = 14). Methods—Twelve acute phase reactants (white blood cell count, neutrophil count, platelet count, serum iron, ferritin, and transferrin, percentage transferrin saturation, α1 antitrypsin, caeruloplasmin, α2 acid glycoprotein, C reactive protein, and erythrocyte sedimentation rate) were measured during a rest period and after moderate and heavy training weeks in members of elite netball and women's soccer teams. Results—Responses consistent with an acute phase response were found in five of 24 tests in the soccer players, and in three of 24 tests in the netball players. Responses in the opposite direction were found in seven of 24 tests in the soccer players and two of 24 tests in the netballers. The most sensitive reactant measured, C reactive protein, did not respond in a manner typical of an acute phase response. Conclusion—An acute phase response does not seem to occur as a consequence of the levels of training typical of elite female netball and soccer teams. This has implications for the interpretation of biochemical variables in these groups. Key Words: acute phase response; iron; plasma proteins; inflammation PMID:11375875

  10. Application of acute phase protein measurements in veterinary clinical chemistry

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    Petersen, Henning; Nielsen, J. P.; Heegaard, Peter M. H.

    2004-01-01

    The body's early defence in response to trauma, inflammation or infection, the acute phase response, is a complex set of systemic reactions seen shortly after exposure to a triggering event. One of the many components is an acute phase protein response in which increased hepatic synthesis leads t...... A and their possible use as non-specific indicators of health in large animal veterinary medicine such as in the health status surveillance of pigs at the herd level, for the detection of mastitis in dairy cattle and for the prognosis of respiratory diseases in horses....

  11. Acute exercise does not induce an acute phase response (APR) in Standardbred trotters

    DEFF Research Database (Denmark)

    Kristensen, Lena; Buhl, Rikke; Nostell, Katarina

    2014-01-01

    ), and iron], muscle enzymes [creatinine kinase (CK) and aspartate transaminase (AST)], and hemoglobin were assessed in 58 Standardbred trotters before and after racing. Hemoglobin levels increased and iron levels decreased 12 to 14 h after racing and haptoglobin concentrations, white blood cell counts......, and iron levels were decreased 2 and/or 7 d after racing. Concentrations of CK, AST, SAA, and fibrinogen were unaltered in response to racing. Acute strenuous exercise did not elicit an acute phase reaction. The observed acute increase in hemoglobin levels and decreases in haptoglobin and iron levels may...

  12. Effect of smoking on acute phase reactants, stress hormone ...

    African Journals Online (AJOL)

    smoking, vitamin C status, and the acute phase and stress hormone responses in ... the longest symptom for the groups of non-smokers and smokers were 6.8 and ..... N, Nestorovic V (2013) Changes in vitamin C and oxi- dative stress status ...

  13. Usefulness of acute phase proteins for monitoring development of ...

    African Journals Online (AJOL)

    Background: Serum levels of acute phase proteins (APP) have been used to diagnose and follow up treatment of liver diseases. This study was carried out to determine the usefulness of APP to predict development of hepatocellular carcinoma (HCC) among Hepatitis B virus (HBV) carriers. Study design: In a prospective ...

  14. Clinical neurological characteristics of ischemic stroke subtypes in acute phase

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    S. I. Shkrobot

    2018-02-01

    Full Text Available Objectives. The aim of the present study was to clarify clinical neurological characteristics and different ischemic stroke subtypes unfavorable course predictors in acute phase. Material and Methods. 482 patients with different ischemic stroke subtypes were observed. Among them there were 125 (25.9 % with cardioembolic infarct (CEI, 119 (24.7 % with large artery atherosclerosis (LAAS infarct, 122 (25.3 % with lacunar stroke (LAC, 116 (24.1 % with stroke of undetermined etiology (UDE. The comparative analysis of clinical picture was performed. The predictors of unfavorable course of acute phase were established. Results. We have found out that severe neurological deficit, high mortality and the worst functional outcome during the first 14 days were observed in patients with CEI and LAAS. The highest frequency of early neurological deterioration (END was detected at LAC (in 22.7 % of patients. There was a relationship between END and presence of transient ischemic attack (TIA in past medical history, the level of systolic blood pressure (SBP at the beginning of the disease and the degree of carotid arteries stenosis on the side of lesion. The patients with LAC had mild neurological deficit and better prognosis compared with other ischemic stroke subtypes. Among the clinical factors that have impact on the CEI, LAAS and UDE acute phase course were: the size of lesion, the level of consciousness on the 1st day, the baseline SBP, patient’s age. At LAAS, the presence of transient ischemic attack (TIA in past medical history and low SBP in the onset of the disease (less than140 mm Hg has an additional prognostic value for an unfavorable functional outcome. The severity of LAC in acute period depended on its localization and size. Localization of LAC in the internal capsule, thalamus and pons were characterized by the highest severity. Conclusions. Clinical neurological features of ischemic stroke depend on its subtype and have some prognostic value

  15. Acute Phase Hyperglycemia among Patients Hospitalized with Acute Coronary Syndrome: Prevalence and Prognostic Significance

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    Hameed Laftah Wanoose

    2011-03-01

    Full Text Available AbstractObjectives: Regardless of diabetes status, hyperglycemia on arrival for patients presenting with acute coronary syndrome, has been associated with adverse outcomes including death. The aim of this study is to look at the frequency and prognostic significance of acute phase hyperglycemia among patients attending the coronary care unit with acute coronary syndrome over the in-hospital admission days.Methods: The study included 287 consecutive patients in the Al- Faiha Hospital in Basrah (Southern Iraq during a one year period from December 2007 to November 2008. Patients were divided into two groups with respect to admission plasma glucose level regardless of their diabetes status (those with admission plasma glucose of <140 mg/dl (7.8 mmol/L and those equal to or more than that. Acute phase hyperglycemia was defined as a non-fasting glucose level equal to or above 140 mg/dl (7.8 mmol/L regardless of past history of diabetes.Results: Sixty one point seven percent (177 of patients were admitted with plasma glucose of ≥140 mg/dl (7.8 mmol/L. There were no differences were found between both groups regarding the mean age, qualification, and smoking status, but males were predominant in both groups. A family history of diabetes, and hypertension, were more frequent in patients with plasma glucose of ≥140 mg/dl (7.8 mmol/L. There were no differences between the two groups regarding past history of ischemic heart disease, stroke, lipid profile, troponin-I levels or type of acute coronary syndrome. Again heart failure was more common in the admission acute phase hyperglycemia group, but there was no difference regarding arrhythmia, stroke, or death. Using logistic regression with heart failure as the dependent variable we found that only the admission acute phase hyperglycemia (OR=2.1344, 95�0CI=1.0282-4.4307; p=0.0419 was independently associated with heart failure. While male gender, family history of diabetes mellitus, hypertension and

  16. Chromosome abnormalities in the acute phase of CML

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    Rowley, J D

    1978-01-01

    Additional chromosome changes are superimposed on the Ph/sup 1/ positive cell line in approximately 80% of patients in the acute phase of chronic myelogenous leukemia (CML). These changes may precede the onset of blast crisis by several months. They are nonrandom and frequently involve an extra No. 8, an isochromosome for the long arm of No. 17, an extra No. 19, and a second Ph/sup 1/ chromosome. Since such changes may occur in combination, modal numbers frequently range between 47 and 57 chromosomes. Although present evidence suggests that abnormal clones originate, or at least proliferate, in the spleen, similar changes have been observed in patients who underwent splenectomy during the chronic phase of their disease. The question of particular clinical-chromosomal correlations has been discussed in only one study. It appeared that patients whose karyotype did not change might have a longer median survival than those whose karyotype showed additional abnormalities. Tests for levels of terminal deoxynucleotidyl transferase (TDT) and response to anti-acute lymphoblastic leukemia (ALL) serum suggest that some, but not all patients react as do patients with ALL. Those who are similar to ALL have high levels of TDT and are anti-ALL serum-positive; the others have low levels of TDT and are anti-ALL serum-negative. In the future, correlations of these more sophisticated tests with the blast morphology, clinical course, and karyotype pattern should provide significant new insights into the acute phase of CML.

  17. Three-Phase Bone Scintigraphic Diagnosis of Acute Transient Synovitis

    International Nuclear Information System (INIS)

    Chung, Soo Kyo; Lee, Myung Hee; Kim, Choon Yul; Bahk, Yong Whee

    1985-01-01

    Acute transient synovitis of the hip presents clinically pain and limping. But in the majority of the cases, definite positive findings are not manifest in roentgenogram in its early phase. However radionuclide bone imaging combines with the assessment of vascularization and bone tracer uptake is of great value in solving this diagnostic problem. The materials for this study consisted of 29 children with acute transient synovitis of the hip, characterized by symptoms and physical signs of an arthritis, negative X-ray findings and disappearance of all symptoms and signs within a short period of time. They were twenty males and 9 females and age ranged from 1 to 12 years. We took pelvic roentgenogram in AP and frog-leg views. After intravenous bolus injection of 10 to 15 mCi of 99m Tc-methylene diphosphonate, 24 sequential image of the pelvis was taken at 2-second interval for blood flow study. The scintigrams were made using a gamma camera with high resolution parallel hole collimator. Blood pool imaging was obtained at 2 minutes after tracer administration. After 3 hours, static images were taken and then close-up image of the hip using pin-hole collimator was followed. The results were as follows: 1) Bone scintigram was much more sensitive than conventional roentgenogram in diagnosis of acute transient synovitis of the hip. 2) Three-phase imagings showed increased vascular activities in blood pool scintigrams in 96%. 3) Pin-hole imaging showed increased tracer uptake in the regional bones of the hip, particularly in the medial aspect of femoral head and acetabulum. 4) We confirmed that three-phase imaging reinforced with pin-hale technique were very useful in diagnose of acute transient synovitis of the hip.

  18. Hyperglycemia in nondiabetic patients during the acute phase of stroke

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    Daniel Agustin Godoy

    2012-02-01

    Full Text Available OBJECTIVE: To determine patterns of hyperglycemic (HG control in acute stroke. METHODS: Anonymous survey through Internet questionnaire. Participants included Latin-American physicians specialized in neurocritical care. RESULTS: The response rate was 74%. HG definition varied widely. Fifty per cent considered it when values were >140 mg/dL (7.8 mmol/L. Intravenous (IV regular insulin was the drug of choice for HG correction. One fifth of the respondents expressed adherence to a protocol. Intensive insulin therapy (IIT was used by 23%. Glucose levels were measured in all participants at admission. Routine laboratory test was the preferred method for monitoring. Reactive strips were more frequently used when monitoring was intensive. Most practitioners (56.7% monitored glucose more than two times daily throughout the Intensive Care Unit stay. CONCLUSIONS: There is considerable variability and heterogeneity in the management of elevated blood glucose during acute phase of stroke by the surveyed Latin-American physicians.

  19. The porcine acute phase protein response to acute clinical and subclinical experimental infection with Streptococcus suis

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    Sørensen, Nanna Skall; Tegtmeier, C.; Andresen, Lars Ole

    2006-01-01

    The pig acute phase protein (APP) response to experimental Streptococcus suis (S. suis) infection was mapped by the measurement of the positive APPs C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp) and major acute phase protein (pig-MAP) and the negative APPs albumin...... and apolipoprotein (Apo) A-I. The aim was to elucidate the differences in the acute phase behaviour of the individual APPs during a typical bacterial septicaemic, infection. Pigs were inoculated subcutaneously with live S. suis serotype 2 and blood was sampled before and on various days post inoculation (p...... the experiment with maximum levels around 10 times the day 0-levels, and pig-MAP was elevated on days 1-12 p.i. with peak levels of around seven times the day 0-levels. Apo A-I was decreased from days 1 to 8 and showed minimum levels of about 40% of day 0-levels around 1-2 days p.i. No clear pattern of changes...

  20. Acute phase proteins in cattle after exposure to complex stress

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    Lomborg, S. R.; Nielsen, L. R.; Heegaard, Peter M. H.

    2008-01-01

    Abstract Stressors such as weaning, mixing and transportation have been shown to lead to increased blood concentrations of acute phase proteins (APP), including serum amyloid A (SAA) and haptoglobin, in calves. This study was therefore undertaken to assess whether SAA and haptoglobin levels...... concentrations of SAA and haptoglobin increased significantly in response to the stressors (P...... in blood mirror stress in adult cattle. Six clinically healthy Holstein cows and two Holstein heifers were transported for four to six hours to a research facility, where each animal was housed in solitary tie stalls. Blood samples for evaluation of leukocyte counts and serum SAA and haptoglobin...

  1. Physical anhedonia in the acute phase of schizophrenia

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    Petridou Eleni

    2006-01-01

    Full Text Available Abstract Background The aim of the current study is to investigate the relationship between physical anhedonia and psychopathological parameters, pharmacological parameters or motor side-effects in a sample of inpatients with schizophrenia in an acute episode of their illness. Method Eighty one patients with schizophrenia, consecutively admitted, with an acute episode of their illness, at the Eginition Hospital, Department of Psychiatry, University of Athens, during a one-year period were investigated regarding possible relationships between physical anhedonia, social-demographic data and clinical parameters as well as motor side-effects, induced by antipsychotic agents. All patients were assessed using the Chapman Revised Physical Anhedonia Scale (RPAS, the Positive and Negative Syndrome Scale (PANSS, the Rating Scale for Extrapyramidal Side-Effects (EPSE, the Barnes Akathisia Rating Scale (BARS and the Abnormal Involuntary Movement Scale (AIMS. Simple cross tabulations were initially employed. Subsequently, multiple regression analysis was performed. Results Both positive and negative symptoms were associated with physical anhedonia. A positive association between physical anhedonia and the non-paranoid sub-category of schizophrenia was also proved. Conclusion According to these results, it seems that in the acute phase of schizophrenia, physical anhedonia may be a contributing factor to patient's psychopathology.

  2. Corticomuscular coherence in the acute and subacute phase after stroke

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    Larsen, Lisbeth Hoejkjaer; Zibrandtsen, Ivan Chrilles; Wienecke, Troels

    2017-01-01

    –6 weeks after stroke, but no change was observed in CMC or IMC. Conclusions CMC and IMC were reduced in patients in the early phase after stroke. However, changes in coherence do not appear to be an efficient marker for early recovery of hand function following stroke. Significance This is the first study......Objective Stroke is one of the leading causes of physical disability due to damage of the motor cortex or the corticospinal tract. In the present study we set out to investigate the role of adaptations in the corticospinal pathway for motor recovery during the subacute phase after stroke. Methods...... We examined 19 patients with clinically diagnosed stroke and 18 controls. The patients had unilateral mild to moderate weakness of the hand. Each patient attended two sessions at approximately 3 days (acute) and 38 days post stroke (subacute). Task-related changes in the communication between motor...

  3. Identification of common immunodominant antigens of Eimeria tenella, Eimeria acervulina and Eimeria maxima by immunoproteomic analysis.

    Science.gov (United States)

    Liu, Lianrui; Huang, Xinmei; Liu, Jianhua; Li, Wenyu; Ji, Yihong; Tian, Di; Tian, Lu; Yang, Xinchao; Xu, Lixin; Yan, Ruofeng; Li, Xiangrui; Song, Xiaokai

    2017-05-23

    Clinical chicken coccidiosis is mostly caused by simultaneous infection of several Eimeria species, and host immunity against Eimeria is species-specific. It is urgent to identify common immunodominant antigen of Eimeria for developing multivalent anticoccidial vaccines. In this study, sporozoite proteins of Eimeria tenella, Eimeria acervulina and Eimeria maxima were analyzed by two-dimensional electrophoresis (2DE). Western bot analysis was performed on the yielded 2DE gel using antisera of E. tenella E. acervulina and E. maxima respectively. Next, the detected immunodominant spots were identified by comparing the data from MALDI-TOF-MS/MS with available databases. Finally, Eimeria common antigens were identified by comparing amino acid sequence between the three Eimeria species. The results showed that analysis by 2DE of sporozoite proteins detected 629, 626 and 632 protein spots from E. tenella, E. acervulina and E. maxima respectively. Western bot analysis revealed 50 (E. tenella), 64 (E. acervulina) and 57 (E. maxima) immunodominant spots from the sporozoite 2DE gels of the three Eimeria species. The immunodominant spots were identified as 33, 27 and 25 immunodominant antigens of E. tenella, E. acervulina and E. maxima respectively. Fifty-four immunodominant proteins were identified as 18 ortholog proteins among the three Eimeria species. Finally, 5 of the 18 ortholog proteins were identified as common immunodominant antigens including elongation factor 2 (EF-2), 14-3-3 protein, ubiquitin-conjugating enzyme domain-containing protein (UCE) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In conclusion, our results not only provide Eimeria sporozoite immunodominant antigen map and additional immunodominant antigens, but also common immunodominant antigens for developing multivalent anticoccidial vaccines.

  4. Vaccination elicits a prominent acute phase response in horses.

    Science.gov (United States)

    Andersen, Susanne A; Petersen, Henrik H; Ersbøll, Annette K; Falk-Rønne, Jørgen; Jacobsen, Stine

    2012-02-01

    European and American guidelines for vaccination against tetanus and influenza in horses recommend annual and annual/semi-annual vaccinations, respectively, against the two pathogens. Too-frequent vaccination may, however, have adverse effects, among other things because an inflammatory response is elicited with subsequent alterations in homeostasis. The objective of the study was to compare the acute phase response (APR) in 10 horses following administration of two different types of vaccines, namely, an inactivated Immune Stimulating COMplex (ISCOM) vaccine and a live recombinant vector vaccine. Blood was sampled before and after vaccination to measure levels of serum amyloid A (SAA), fibrinogen, white blood cell counts (WBC) and iron. Vaccination induced a prominent APR with increased WBC, elevated blood levels of SAA and fibrinogen, and decreased serum iron concentrations. The ISCOM vaccine caused significantly (Phorse owners about convalescence after vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Acute phase proteins as diagnostic markers in horses with colic

    DEFF Research Database (Denmark)

    Pihl, Tina; Scheepers, Elrien; Sanz, Macarena

    2016-01-01

    Objective – To investigate the diagnostic potential of the concentrations of acute-phase proteins serum amyloid A (SAA), haptoglobin (Hp), and fibrinogen in blood and peritoneal fluid (PF) for differentiating horses within flammatory colic (entero-colitis and peritonitis) from those with surgical...... of the model to correctly differentiate inflammatory from surgical colic was 86% determined as area under the receiver operating characteristic curve. Adding blood parameters (WBC, PCV, total plasma protein, lactate, SAA, Hp, and fibrinogen concentrations) to the logistic model based on clinical parameters...... revealed that only WBC and SAA and fibrinogen concentrations improved the model. With SAA included in the model no additional blood parameters improved the model, and the final model had an area under the curve of 90%. Addition of PF parameters (hemolysis, total protein concentration, WBC, SAA, or Hp...

  6. Relationship between Acute Phase of Chronic Periodontitis and Meteorological Factors in the Maintenance Phase of Periodontal Treatment: A Pilot Study.

    Science.gov (United States)

    Takeuchi, Noriko; Ekuni, Daisuke; Tomofuji, Takaaki; Morita, Manabu

    2015-08-05

    The acute phase of chronic periodontitis may occur even in patients during supportive periodontal therapy. However, the details are not fully understood. Since the natural environment, including meteorology affects human health, we hypothesized that weather conditions may affect occurrence of acute phase of chronic periodontitis. The aim of this study was to investigate the relationship between weather conditions and acute phase of chronic periodontitis in patients under supportive periodontal therapy. Patients who were diagnosed with acute phase of chronic periodontitis under supportive periodontal therapy during 2011-2013 were selected for this study. We performed oral examinations and collected questionnaires and meteorological data. Of 369 patients who experienced acute phase of chronic periodontitis, 153 had acute phase of chronic periodontitis without direct-triggered episodes. When using the autoregressive integrated moving average model of time-series analysis, the independent covariant of maximum hourly range of barometric pressure, maximum hourly range of temperature, and maximum daily wind speed were significantly associated with occurrence of acute phase of chronic periodontitis (p chronic periodontitis.

  7. S-40: Acute Phase Protein Increse in High Altitude Mountaineers

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    Tolga Saka

    2017-03-01

    Full Text Available “Erciyes Tigers” are an elite group of high altitude climbers. They have been climbing ErciyesMountain (3500 m, in Kayseri, Turkey once a week at least for ten years. When they climb Erciyes in winter, they also take a snow bath. This study investigated the effects of regular high altitude climbing on the metabolic and hematological responses of mountaineers. Venous blood samples were taken to investigate hematological, biochemical parameters and some hormone values from 21 mountaineers and 16 healthy age-matched sedentary volunteers at resting condition. The neutrophil/lymphocyte (N/L ratio was calculated. The N/L was associated with an increased risk of long-term mortality and it could provide a good measure of exercise stress and subsequent recovery. Most of the hematological and biochemical parameters i.e., erythrocyte, leukocyte, hemoglobin and hematocrit values did not change significantly. The neutrophil to lymphocyte (N/L ratio was significantly (p<0.04 decreased in the mountaineer compared with the sedentary group. Total protein (p<0.000 and albumin (0.001 were lower, while ferritin (p<0.04, creatine (p<0.03 and creatine phosphokinase levels (p<0.01 were higher in mountaineers. Our results show that regular high altitude climbing increased serum levels of some acute-phase proteins and these increments were not transient.

  8. ACUTE PHASE PROTEIN INCREASE IN HIGH ALTITUDE MOUNTAINEERS

    Directory of Open Access Journals (Sweden)

    Tolga Saka

    Full Text Available ABSTRACT Introduction: Many middle-aged Turks go hiking in mountains to breathe some fresh air or to maintain fitness. Objective: This study investigated the effects of regular high altitude mountain climbing on the metabolic and hematological responses of mountaineers. Methods: Hematological and biochemical parameters were studied, as well as some hormonal values of 21 mountaineers and 16 healthy age-matched sedentary volunteers. Results: The neutrophil to lymphocyte ratio (NLR was significantly lower (p<0.04 in mountaineers compared with the sedentary group. Total protein (p<0.001 and albumin (p<0.001 were lower, while the levels of ferritin (p<0.04, creatine (p<0.03 and creatine phosphokinase (p<0.01 were higher in mountaineers. Other hematological and biochemical parameters, i.e., erythrocytes, leukocytes, hemoglobin and hematocrit, did not change significantly. Conclusion: Our results show that regular exposure to high altitude increased the serum levels of some acute phase proteins with anti-inflammatory properties.

  9. Phase II trial of vindesine in patients with acute leukemia.

    Science.gov (United States)

    Sklaroff, R B; Arlin, Z; Young, C W

    1979-01-01

    Vindesine was administered to 18 patients with acute leukemia who had failed conventional chemotherapy. Each course of therapy consisted of an iv bolus infusion at a dose of 1-2 mg/m2 given daily x 5-10 days. Of 13 patients with acute lymphoblastic leukemia, two had partial remissions which lasted 2 and 3 months and five had minor responses. One of three patients with acute nonlymphoblastic leukemia and one of two patients with blastic crisis of chronic myelogenous leukemia each had a minor response. The data suggest that vindesine has activity in the treatment of acute leukemia.

  10. Diagnostical meaning acute phase proteins in cerebrospinal liquid in children with neuroinfections

    OpenAIRE

    L. A. Alekseeva; N. V. Skripchenko; T. V. Bessonova

    2010-01-01

    In the article presented results of the examination of acute phase proteins in cerebrospinal liquid in 237 children with meningitis and encephalitis viral and bacterial etiology. The dependence between the level of acute phase proteins in cerebrospinal liquid and etiology of neuroinfectional process, the severity of brain damage and the process stage was determined. Diagnostic and prognostic efficiency of the acute phase proteins (C-reactive protein, albumin, alpha-1-antitripsin, alpha-2-macr...

  11. Acute phase proteins in the diagnosis of bovine subclinical mastitis.

    Science.gov (United States)

    Safi, Shahabeddin; Khoshvaghti, Ameneh; Jafarzadeh, Seyed Reza; Bolourchi, Mahmoud; Nowrouzian, Iradj

    2009-12-01

    The California mastitis test (CMT) and somatic cell count (SCC) are commonly used for diagnosis of subclinical mastitis in cattle. Acute phase proteins (APPs), as alternative biomarkers of mastitis, may increase in concentration in the absence of macroscopic changes in the milk, or may precede the onset of clinical signs. The aim of this study was to compare the accuracy of APPs measured in milk and in serum with bacterial culture for the diagnosis of bovine subclinical mastitis. One hundred and seventy-five Holstein cows were randomly selected from 7 dairy farms. Quarter milk and serum samples were taken from all cows. Milk samples were analyzed using a CMT and SCC, and for haptoglobin (MHp) and amyloid A (MAA) concentrations, and were also submitted for bacterial culture. Serum samples obtained concurrently were analyzed for haptoglobin (SHp) and amyloid A (SAA). Two-sample Wilcoxon (Mann-Whitney) test was used to compare SCC, MAA, MHp, SAA, and SHp concentrations between culture-positive and culture-negative animals. Receiver-operating characteristic analysis was used to assess the performance of each test using bacterial culture as the reference method. MAA concentration was the most accurate of the 5 tests, with a sensitivity of 90.6% and specificity of 98.3% at concentrations >16.4 mg/L. MAA and MHp had significantly larger areas under the curve than the respective serum proteins, SAA and SHp. The results suggest that measuring haptoglobin and amyloid A in milk is more accurate than serum analysis for the diagnosis of subclinical mastitis in Holstein cows.

  12. Acute and "chronic" phase reaction-a mother of disease.

    Science.gov (United States)

    Bengmark, Stig

    2004-12-01

    The world is increasingly threatened by a global epidemic of chronic diseases. Almost half of the global morbidity and almost two thirds of global mortality is due to these diseases-approximately 35 million die each year from chronic diseases. And they continue to increase. Increasing evidence suggest that these diseases are associated with lifestyle, stress, lack of physical exercise, over-consumption of calorie-condensed foods rich in saturated fat, sugar and starch, but also under-consumption of antioxidant-rich fruits and vegetables. As a result the function of the innate immune system is severe impaired. This review discusses the changes induced in response to mental and physical stress and their association with the subsequent development of metabolic syndrome, and its association with various chronic diseases. The endothelial cells and their function appears to be of great importance, and the function of their cellular membranes of special importance to the function of the underlying cells; their ability to obtain nutrients and antioxidants and to eliminate waste products. The abdominal adipocytes seen to play a key role, as they have the ability to in stressful situations release much of proinflammatory cytokines, PAI-1 and free fatty acids compared to elsewhere in the body. The load on the liver of these various substances in often of greater magnitude than the liver can handle. Some of the most common chronic diseases and their potential association with acute and "chronic" phase response, and with metabolic syndrome are discussed separately. The need for studies with lifestyle modifications is especially emphasized.

  13. The onset of the progression of acute phase response mechanisms induced by extreme impacts can be followed by the decrease in blood levels of positive acute phase proteins.

    Science.gov (United States)

    Larina, Olga; Bekker, Anna

    Studies performed at space flights and earth-based simulation models detected the plasma indices of acute phase reaction (APR), i.e. the increase of APR cytokine mediators and alterations in the production of blood acute phase proteins (APP) at the initial stages of adaptation to altered gravity conditions. Acute phase response is the principal constituent of the functional activity of innate immunity system. Changes in plasma APPs contents are considered to serve the restoration of homeostasis state. According to trends of their concentration shifts at the evolving of acute phase reaction APPs are denoted as positive, neutral, or negative. Plasma concentrations of positive acute phase proteins α1-acid glycoprotein (α1-AGP), α1-antitrypsin (α1-AT), and neutral α2-macroglobulin (α2-M) were measured in human study at 12-hour antiorthostatic position (AOP) with 15° head down tilt and hypoxia experiments at 14% oxygen in pressure chamber. Both of these impacts were shown to produce alterations in the APP levels indicative for acute phase response. Nevertheless, in AOP experiment noticeable decrease in α1-AGP concentration occurred by hour 12, and even more pronounced decline of α1-AGP and α1-AT were found on hypoxia hours 12 and 36. Acute phase proteins α1-AGP and α2-M possess the features of proteinase inhibitors. This function is implemented by the formation of complexes with the molecules of proteolytic enzymes which subsequently are removed from the blood flow. Transient decrease in plasma concentrations of protease inhibitors on early phases of APR development was reported to result from the growth of plasma protease activity due to cathepsin release from activated leukocytes, which had not yet been compensated by enhanced APP synthesis. Being a carrier protein for positively charged and neutral substances, α1-AGP shows pronounced elevation in its blood content during APR development. As assumed, it is required for the transportation of the increased

  14. Reassessment of HIV-1 Acute Phase Infectivity: Accounting for Heterogeneity and Study Design with Simulated Cohorts

    Science.gov (United States)

    Bellan, Steve E.; Dushoff, Jonathan; Galvani, Alison P.; Meyers, Lauren Ancel

    2015-01-01

    Background The infectivity of the HIV-1 acute phase has been directly measured only once, from a retrospectively identified cohort of serodiscordant heterosexual couples in Rakai, Uganda. Analyses of this cohort underlie the widespread view that the acute phase is highly infectious, even more so than would be predicted from its elevated viral load, and that transmission occurring shortly after infection may therefore compromise interventions that rely on diagnosis and treatment, such as antiretroviral treatment as prevention (TasP). Here, we re-estimate the duration and relative infectivity of the acute phase, while accounting for several possible sources of bias in published estimates, including the retrospective cohort exclusion criteria and unmeasured heterogeneity in risk. Methods and Findings We estimated acute phase infectivity using two approaches. First, we combined viral load trajectories and viral load-infectivity relationships to estimate infectivity trajectories over the course of infection, under the assumption that elevated acute phase infectivity is caused by elevated viral load alone. Second, we estimated the relative hazard of transmission during the acute phase versus the chronic phase (RHacute) and the acute phase duration (d acute) by fitting a couples transmission model to the Rakai retrospective cohort using approximate Bayesian computation. Our model fit the data well and accounted for characteristics overlooked by previous analyses, including individual heterogeneity in infectiousness and susceptibility and the retrospective cohort's exclusion of couples that were recorded as serodiscordant only once before being censored by loss to follow-up, couple dissolution, or study termination. Finally, we replicated two highly cited analyses of the Rakai data on simulated data to identify biases underlying the discrepancies between previous estimates and our own. From the Rakai data, we estimated RHacute = 5.3 (95% credibility interval [95% CrI]: 0

  15. Acute-phase reactants in periodontal disease: current concepts and future implications.

    Science.gov (United States)

    Archana, Vilasan; Ambili, Ranjith; Nisha, Krishnavilasam Jayakumary; Seba, Abraham; Preeja, Chandran

    2015-05-01

    Periodontal disease has been linked to adverse cardiovascular events by unknown mechanisms. C-reactive protein is a systemic marker released during the acute phase of an inflammatory response and is a prognostic marker for cardiovascular disease, with elevated serum levels being reported during periodontal disease. Studies also reported elevated levels of various other acute-phase reactants in periodontal disease. It has been reported extensively in the literature that treatment of periodontal infections can significantly lower serum levels of C-reactive protein. Therefore, an understanding of the relationship between acute-phase response and the progression of periodontal disease and other systemic health complications would have a profound effect on the periodontal treatment strategies. In view of this fact, the present review highlights an overview of acute-phase reactants and their role in periodontal disease. © 2014 Wiley Publishing Asia Pty Ltd.

  16. Targeted proteomics as a tool for porcine acute phase proteins measurements

    DEFF Research Database (Denmark)

    Marco-Ramell, Anna; Bassols, Anna; Bislev, Stine Lønnerup

    2013-01-01

    . Selected reaction monitoring (SRM), a targeted quantitative proteomic technique, may be used as an alternative to commercial kits for the measurement and validation of target proteins. Acute phase proteins (APPs) are widely recognized inflammation and infection biomarkers (Eckersall, 2010...

  17. Rapid and widely disseminated acute phase protein response after experimental bacterial infection of pigs

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Mortensen, Shila; Boye, Mette

    2009-01-01

    The acute phase protein response is a well-described generalized early host response to tissue injury, inflammation and infection, observed as pronounced changes in the concentrations of a number of circulating serum proteins. The biological function of this response and its interplay with other...... parts of innate host defence reactions remain somewhat elusive. In order to gain new insight into this early host defence response in the context of bacterial infection we studied gene expression changes in peripheral lymphoid tissues as compared to hepatic expression changes, 14-18 h after lung...... with measurements of interleukin-6 and selected acute phase proteins in serum. C-reactive protein and serum amyloid A were clearly induced 14-18 h after infection. Extrahepatic expression of acute phase proteins was found to be dramatically altered as a result of the lung infection with an extrahepatic acute phase...

  18. Reassessment of HIV-1 acute phase infectivity: accounting for heterogeneity and study design with simulated cohorts.

    Directory of Open Access Journals (Sweden)

    Steve E Bellan

    2015-03-01

    Full Text Available The infectivity of the HIV-1 acute phase has been directly measured only once, from a retrospectively identified cohort of serodiscordant heterosexual couples in Rakai, Uganda. Analyses of this cohort underlie the widespread view that the acute phase is highly infectious, even more so than would be predicted from its elevated viral load, and that transmission occurring shortly after infection may therefore compromise interventions that rely on diagnosis and treatment, such as antiretroviral treatment as prevention (TasP. Here, we re-estimate the duration and relative infectivity of the acute phase, while accounting for several possible sources of bias in published estimates, including the retrospective cohort exclusion criteria and unmeasured heterogeneity in risk.We estimated acute phase infectivity using two approaches. First, we combined viral load trajectories and viral load-infectivity relationships to estimate infectivity trajectories over the course of infection, under the assumption that elevated acute phase infectivity is caused by elevated viral load alone. Second, we estimated the relative hazard of transmission during the acute phase versus the chronic phase (RHacute and the acute phase duration (dacute by fitting a couples transmission model to the Rakai retrospective cohort using approximate Bayesian computation. Our model fit the data well and accounted for characteristics overlooked by previous analyses, including individual heterogeneity in infectiousness and susceptibility and the retrospective cohort's exclusion of couples that were recorded as serodiscordant only once before being censored by loss to follow-up, couple dissolution, or study termination. Finally, we replicated two highly cited analyses of the Rakai data on simulated data to identify biases underlying the discrepancies between previous estimates and our own. From the Rakai data, we estimated RHacute = 5.3 (95% credibility interval [95% CrI]: 0.79-57 and dacute

  19. Effects of montelukast sodium combined with pidotimod on acute phase protein and immune function in children with acute bronchitis

    Directory of Open Access Journals (Sweden)

    Jing Wang

    2017-08-01

    Full Text Available Objective: To observe the effects of montelukast sodium combined with pidotimod on acute phase protein (APP and indexes of immunologic function in pediatric acute bronchitis treatment. Methods: A total of 180 cases children with acute bronchitis acted as research objects were randomly divided into control group (n=65 and observation group (n=63. On the basis of conventional therapy, control group was treated by plus pidotimod. On this base, observation group was treated with montelukast sodium. The changes of acute phase proteins (CRP, HP, a1-AAG and CER and immune function (CD3+ , CD4+ , CD8+ and CD4+ /CD8+ levels before and after treatment were observed after 2 months. Results: Before treatment, CRP, HP, a1-AAG, CER, CD3+ , CD4+ , CD8+ and CD4+ /CD8+ levels of two groups had no statistically significant difference; CRP, HP, a1-AAG, CER, and CD8+ levels of control and observation groups decreased significantly after treatment, the decreases of observation group were more obvious than that of control group, and the levels after treatment were significantly lower than that of control groups. The levels of CD3+ , CD4+ and CD4+ /CD8+ in two groups after treatment were significantly higher than those before treatment. For observation group, the levels of CD3+ , CD4+ and CD4+ /CD8+ increased more significantly after treatment, which were significantly higher than that of the control group. Conclusion: Using Montelukast sodium combined with pidotimod can effectively reduce the children's acute phase protein levels, improve immune function, which has clinical value for the treatment of children with acute bronchitis.

  20. Intensive treadmill training in the acute phase after ischemic stroke

    DEFF Research Database (Denmark)

    Strømmen, Anna Maria; Christensen, Thomas; Jensen, Kai

    2016-01-01

    The aim of the study was to (a) assess the feasibility of intensive treadmill training in patients with acute ischemic stroke, (b) test whether physical activity of the legs during training increases with time, and (c) evaluate to what extent training sessions contribute toward the overall physical...... activity of these patients. Twenty hospitalized patients with acute ischemic stroke trained on a treadmill twice daily for 30 min for 5 days and on day 30. Physical activity was measured as activity counts (AC) from accelerometers. A total of 196 of 224 initiated training sessions were completed. Training...... with increasing number of days, with the median AC being 133% higher on day 5 than on day 1. AC in the paretic leg during 60 min of training constituted median 53% of the daytime AC. Early intensive treadmill training in acute ischemic stroke patients is thus feasible and contributes considerably toward...

  1. Interaction of an immunodominant epitope with Ia molecules in T-cell activation

    DEFF Research Database (Denmark)

    Adorini, L; Sette, A; Buus, S

    1988-01-01

    The amino acid sequence corresponding to residues 107-116 of hen egg-white lysozyme (HEL) has been identified as containing an immunodominant T-cell epitope recognized in association with the I-Ed molecule. The immunodominance of this epitope in HEL-primed H-2d mice was demonstrated by analysis o......-120)-peptide was found to be immunogenic in H-2d mice. Thus, a single semiconservative substitution drastically reduces binding capacity and abolishes immunogenicity, suggesting that a strict correlation exists between binding of a peptide to Ia molecules and its immunogenicity....

  2. MDCT of acute pancreatitis: Intraindividual comparison of single-phase versus dual-phase MDCT for initial assessment of acute pancreatitis using different CT scoring systems

    Energy Technology Data Exchange (ETDEWEB)

    Avanesov, Maxim, E-mail: m.avanesov@uke.de [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Weinrich, Julius M.; Kraus, Thomas [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Derlin, Thorsten [Department of Nuclear Medicine, Hannover Medical School (Germany); Adam, Gerhard; Yamamura, Jin [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Karul, Murat [Department of Diagnostic and Interventional Radiology, Marienkrankenhaus Hamburg (Germany)

    2016-11-15

    Objectives: The purpose of the retrospective study was to evaluate the additional value of dual-phase multidetector computed tomography (MDCT) protocols over a single-phase protocol on initial MDCT in patients with acute pancreatitis using three CT-based pancreatitis severity scores with regard to radiation dose. Methods: In this retrospective, IRB approved study MDCT was performed in 102 consecutive patients (73 males; 55years, IQR48–64) with acute pancreatitis. Inclusion criteria were CT findings of interstitial edematous pancreatitis (IP) or necrotizing pancreatitis (NP) and a contrast-enhanced dual-phase (arterial phase and portal-venous phase) abdominal CT performed at ≥72 h after onset of symptoms. The severity of pancreatic and extrapancreatic changes was independently assessed by 2 observers using 3 validated CT-based scoring systems (CTSI, mCTSI, EPIC). All scores were applied to arterial phase and portal venous phase scans and compared to score results of portal venous phase scans, assessed ≥14 days after initial evaluation. For effective dose estimation, volume CT dose index (CTDIvol) and dose length product (DLP) were recorded in all examinations. Results: In neither of the CT severity scores a significant difference was observed after application of a dual-phase protocol compared with a single-phase protocol (IP: CTSI: 2.7 vs. 2.5, p = 0.25; mCTSI: 4.0 vs. 4.0, p = 0.10; EPIC: 2.0 vs. 2.0, p = 0.41; NP: CTSI: 8.0 vs. 7.0, p = 0.64; mCTSI: 8.0 vs. 8.0, p = 0.10; EPIC: 3.0 vs. 3.0, p = 0.06). The application of a single-phase CT protocol was associated with a median effective dose reduction of 36% (mean dose reduction 31%) compared to a dual-phase CT scan. Conclusions: An initial dual-phase abdominal CT after ≥72 h after onset of symptoms of acute pancreatitis was not superior to a single-phase protocol for evaluation of the severity of pancreatic and extrapancreatic changes. However, the effective radiation dose may be reduced by 36% using a

  3. The Effects of Diesel Exhaust and Stress on the Acute Phase Response and Symptoms in the Chemically Intolerant

    National Research Council Canada - National Science Library

    Fiedler, Nancy; Leumbach, Robert; Kipen, Howard; Lioy, Paul; Zhang, Jungfeng; Lehrer, Paul

    2006-01-01

    .... The purpose of the proposed study is to test a model for chemical sensitivity in GWV in which simultaneous acute exposures to DE and psychological stress cause increased symptoms via the acute phase response (APR...

  4. The Effects of Diesel Exhaust and Stress on the Acute Phase Response and Symptoms in the Chemically Intolerant

    National Research Council Canada - National Science Library

    Fiedler, Nancy L; Laumbach, Robert; Kipen, Howard; Lioy, Paul; Zhang, Lunfeng

    2004-01-01

    Purpose: The proposed study is designed to test a model of Gulf War Illness, in which simultaneous acute exposures to DE and psychological stress cause increased symptoms via the acute phase response (APR...

  5. Regulation of urea synthesis during the acute phase response in rats

    DEFF Research Database (Denmark)

    Thomsen, Karen Louise; Jessen, Niels; Buch Møller, Andreas

    2013-01-01

    The acute-phase response is a catabolic event involving increased waste of amino-nitrogen (N) via hepatic urea synthesis, despite an increased need for amino-N incorporation into acute-phase proteins. This study aimed to clarify the regulation of N elimination via urea during different phases...... of the tumor necrosis factor-α (TNF-α)-induced acute-phase response in rats. We used four methods to study the regulation of urea synthesis: We examined urea cycle enzyme mRNA levels in liver tissue, the hepatocyte urea cycle enzyme proteins, the in vivo capacity of urea-N synthesis (CUNS), and known humoral...... regulators of CUNS at 1, 3, 24, and 72 h after TNF-α injection (25 μg/kg iv rrTNF-α) in rats. Serum acute-phase proteins and their liver mRNA levels were also measured. The urea cycle enzyme mRNA levels acutely decreased and then gradually normalized, whereas the urea cycle enzyme proteins remained...

  6. Effects of anabolic steroids on acute phase responses in intra-abdominal sepsis

    Directory of Open Access Journals (Sweden)

    K. Mealy

    1997-01-01

    Full Text Available The acute phase response is an important adaptive response to sepsis and injury. As anabolic steroids increase protein synthesis we postulated that these agents might also increase hepatic acute phase protein synthesis. Male Wistar rats were pretreated with testosterone or danazol for 48 h prior to caecal ligation and puncture (CLP. Thirty-six h following surgery the animals were killed and blood taken for full blood count, total protein, albumin, α, β and γ globulin fractions on serum electrophoresis, complement C3 and transferrin levels. Danazol increased the α1, α2 and β1 globulin serum protein fractions in comparison with no surgery and CLP alone groups. These results indicate that danazol increases plasma acute phase proteins, as measured by electrophoresis, in this model of intra-abdominal sepsis.

  7. Diagnostical meaning acute phase proteins in cerebrospinal liquid in children with neuroinfections

    Directory of Open Access Journals (Sweden)

    L. A. Alekseeva

    2010-01-01

    Full Text Available In the article presented results of the examination of acute phase proteins in cerebrospinal liquid in 237 children with meningitis and encephalitis viral and bacterial etiology. The dependence between the level of acute phase proteins in cerebrospinal liquid and etiology of neuroinfectional process, the severity of brain damage and the process stage was determined. Diagnostic and prognostic efficiency of the acute phase proteins (C-reactive protein, albumin, alpha-1-antitripsin, alpha-2-macroglobulin, gaptoglobin examination in children with neuroinfections was specified. Developed method of express diagnostics of the severity of inflammatory damage of the brain in bacterial meningitis in children by determination in cerebrospinal liquid alpha-2-macroglobulin is described.

  8. The effects of combined therapy of rheumatoid arthritis on the acute phase reactants.

    Science.gov (United States)

    Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Pllana, Ejup; Dragusha, Gani; Gashi, Masar; Rexhepi, Blerta

    2009-01-01

    The paper presents the results of studies of acute phase reactants in the 60 treated patients with rheumatoid arthritis. Patients were divided into two groups, depending on the applied treatment: group I (n = 30) was treated with methotrexate, sulfasalazine and hydroxychloroquine, and group II (n = 30) with methotrexate. The results of our study shows that there is a statistically significant reduction in the value of acute phase reactants and clinical parameters after treatment in both investigated groups of patients, and also a significant statistical difference between the first and second group of treated patients.

  9. Optimal combinations of acute phase proteins for detecting infectious disease in pigs

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Stockmarr, Anders; Piñeiro, Matilde

    2011-01-01

    The acute phase protein (APP) response is an early systemic sign of disease, detected as substantial changes in APP serum concentrations and most disease states involving inflammatory reactions give rise to APP responses. To obtain a detailed picture of the general utility of porcine APPs to detect...... gondii) and one viral (porcine respiratory and reproductive syndrome virus) infection and one aseptic inflammation. Immunochemical analyses of seven APPs, four positive (C-reactive protein (CRP), haptoglobin (Hp), pig major acute phase protein (pigMAP) and serum amyloid A (SAA)) and three negative...

  10. Immunodominant fragments of myelin basic protein initiate T cell-dependent pain

    Directory of Open Access Journals (Sweden)

    Liu Huaqing

    2012-06-01

    day post-injury is critical to the generation of tactile allodynia, neuroinflammation, and the immunodominant MBP digest peptides in nerve. These MBP peptides initiate mechanical allodynia in both a T cell-dependent and -independent manner. In the course of Wallerian degeneration, the repeated exposure of the cryptic MBP epitopes, which are normally sheltered from immunosurveillance, may induce the MBP-specific T cell clones and a self-sustaining immune reaction, which may together contribute to the transition of acute pain into a chronic neuropathic pain state.

  11. Immunodominant fragments of myelin basic protein initiate T cell-dependent pain.

    Science.gov (United States)

    Liu, Huaqing; Shiryaev, Sergey A; Chernov, Andrei V; Kim, Youngsoon; Shubayev, Igor; Remacle, Albert G; Baranovskaya, Svetlana; Golubkov, Vladislav S; Strongin, Alex Y; Shubayev, Veronica I

    2012-06-07

    , neuroinflammation, and the immunodominant MBP digest peptides in nerve. These MBP peptides initiate mechanical allodynia in both a T cell-dependent and -independent manner. In the course of Wallerian degeneration, the repeated exposure of the cryptic MBP epitopes, which are normally sheltered from immunosurveillance, may induce the MBP-specific T cell clones and a self-sustaining immune reaction, which may together contribute to the transition of acute pain into a chronic neuropathic pain state.

  12. Acute phase response and plasma carotenoid concentrations in older women: findings from the nun study.

    Science.gov (United States)

    Boosalis, M G; Snowdon, D A; Tully, C L; Gross, M D

    1996-01-01

    This cross-sectional study investigated whether the acute phase response was associated with suppressed circulating levels of antioxidants in a population of 85 Catholic sisters (nuns) ages 77-99 y. Fasting blood was drawn to determine the presence of an acute phase response, as defined by an elevation in the serum concentration of C-reactive protein. Serum concentrations of albumin, thyroxine-binding prealbumin, zinc, copper, and fibrinogen were determined as were plasma concentrations of carotenoids and alpha tocopherol. Results showed that the presence of an acute phase response was associated with (1) an expected significant decrease in the serum concentrations of albumin (p < 0.001) and thyroxine-binding prealbumin (p < 0.001); (2) an expected significant increase in copper (p < 0.001) and fibrinogen (p = 0.003); and (3) a significant decrease in the plasma concentrations of lycopene (p = 0.03), alpha carotene (p = 0.02), beta carotene (p = 0.02), and total carotenoids (p = 0.01). The acute phase response was associated with decreased plasma levels of the antioxidants lycopene, alpha carotene, and beta carotene. This decrease in circulating antioxidants may further compromise antioxidant status and increase oxidative stress and damage in elders.

  13. Relationship between Acute Phase Proteins and Serum Fatty Acid Composition in Morbidly Obese Patients

    Science.gov (United States)

    Fernandes, Ricardo; Beserra, Bruna Teles Soares; Cunha, Raphael Salles Granato; Hillesheim, Elaine; Camargo, Carolina de Quadros; Pequito, Danielle Cristina Tonello; de Castro, Isabela Coelho; Fernandes, Luiz Cláudio; Nunes, Everson Araújo; Trindade, Erasmo Benício Santos de Moraes

    2013-01-01

    Background. Obesity is considered a low-grade inflammatory state and has been associated with increased acute phase proteins as well as changes in serum fatty acids. Few studies have assessed associations between acute phase proteins and serum fatty acids in morbidly obese patients. Objective. To investigate the relationship between acute phase proteins (C-Reactive Protein, Orosomucoid, and Albumin) and serum fatty acids in morbidly obese patients. Methods. Twenty-two morbidly obese patients were enrolled in this study. Biochemical and clinical data were obtained before bariatric surgery, and fatty acids measured in preoperative serum. Results. Orosomucoid was negatively correlated with lauric acid (P = 0.027) and eicosapentaenoic acid (EPA) (P = 0.037) and positively with arachidonic acid (AA) (P = 0.035), AA/EPA ratio (P = 0.005), and n-6/n-3 polyunsaturated fatty acids ratio (P = 0.035). C-Reactive Protein (CRP) was negatively correlated with lauric acid (P = 0.048), and both CRP and CRP/Albumin ratio were negatively correlated with margaric acid (P = 0.010, P = 0.008, resp.). Albumin was positively correlated with EPA (P = 0.027) and margaric acid (P = 0.008). Other correlations were not statistically significant. Conclusion. Our findings suggest that serum fatty acids are linked to acute phase proteins in morbidly obese patients. PMID:24167354

  14. Modulation of the acute phase response in feedlot steers supplemented with Saccharomyces cerevisiae

    Science.gov (United States)

    This study was designed to determine the effect of supplementing feedlot steers with Saccharomyces cerevisiae CNCM I-1079 (SC) on the acute phase response to a lipopolysaccharide (LPS) challenge. Steers (n = 18; 266 ± 4 kilograms body weight) were separated into three treatment groups (n = 6/treatm...

  15. The effect of chronic ammonia exposure on acute phase proteins, immunoglobulin and cytokines in laying hens

    Science.gov (United States)

    Ammonia is a potential health hazard to both humans and animals, causing systemic low-grade inflammation based on its levels and durations. The objective of this study was to examine the effect of 45 weeks of exposure to 30 ppm NH3 on the concentrations of acute phase proteins, immunoglobulins and c...

  16. The bovine acute phase response to endotoxin and Gram-negative bacteria

    DEFF Research Database (Denmark)

    Jacobsen, Stine

    The overall aims of the work presented in this thesis were to characterize bovine cytokine and acute phase protein (APP) responses to lipopolysaccharide (LPS) and to investigate how LPS-induced clinical and immunoinflammatory responses differed between individual cows. Two kinds of experimental e...

  17. Acute and phase-shifting effects of ocular and extraocular light in human circadian physiology

    NARCIS (Netherlands)

    Rüger, Melanie; Gordijn, Marijke C.M.; Beersma, Domien G.M.; de Vries, Bonnie; Daan, Serge

    2003-01-01

    Light can influence physiology and performance of humans in two distinct ways. It can acutely change the level of physiological and behavioral parameters, and it can induce a phase shift in the circadian oscillators underlying variations in these levels. Until recently, both effects were thought to

  18. The acute-phase response and serum amyloid A inhibit the inflammatory response to Acinetobacter baumannii Pneumonia

    NARCIS (Netherlands)

    Renckens, Rosemarijn; Roelofs, Joris J. T. H.; Knapp, Sylvia; de Vos, Alex F.; Florquin, Sandrine; van der Poll, Tom

    2006-01-01

    BACKGROUND: Acinetobacter baumannii is an emerging pathogen in nosocomial pneumonia. Trauma and postsurgical patients display a profound acute-phase protein response and are susceptible to pneumonia. METHODS: To study the way in which the acute-phase response induced by sterile tissue injury

  19. Local and disseminated acute phase response during bacterial respiratory infection in pigs

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Mortensen, Shila; Heegaard, Peter M. H.

    2010-01-01

    The acute phase response is playing an important role, aiming to restore the healthy state after tissue injury, inflammation and infection. The biological function of this response and its interplay with other parts of innate defense reactions remain somewhat elusive. Expression of acute phase...... locations of the infected lung (necrotic areas, areas bordering on necrotic areas, and from visually unaffected areas). Expression differences was also studied in the liver and in peripheral lymphoid tissue (tracheobronchial lymph nodes, spleen, tonsils) of infected (n=10) and non-infected (n=5) pigs using......-phase proteins was found 14-18h after experimental infection with A. pleuropneumoniae. This firmly establishes that expression of APPs is widely disseminated, involving changes in the expression of APPs at a dynamic scale comparable to the hepatic response. These results suggest that many different cell...

  20. Shedding of the immunodominant P20 surface antigen of Eimeria bovis sporozoites.

    OpenAIRE

    Speer, C A; Whitmire, W M

    1989-01-01

    P20 is an immunodominant surface antigen of Eimeria bovis sporozoites. As parasites underwent merogony within cultured bovine monocytes and Madin-Darby bovine kidney (MDBK) cells, P20 appeared to be shed gradually by meronts and was absent in type 1 and 2 first-generation merozoites. Meronts of E. bovis appeared to shed P20 into the parasitophorous vacuole of bovine monocytes, whereas MDBK cells evidently released P20 into the culture medium or destroyed its antigenic determinant.

  1. Use of activated protein C has no avail in the early phase of acute pancreatitis.

    Science.gov (United States)

    Akay, Sinan; Ozutemiz, Omer; Yenisey, Cigdem; Simsek, Nilufer Genc; Yuce, Gul; Batur, Yucel

    2008-01-01

    Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancreatitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activities were collected, and blood for serum amylase, urea, creatinine, and interleukin-6 measurements was withdrawn. Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435+/-432 U/L vs. 27,426+/-118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970+/-323 pg/mL vs. 330+/-368 pg/mL, respectively). In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions.

  2. Acute phase response in two consecutive experimentally induced E. coli intramammary infections in dairy cows

    Directory of Open Access Journals (Sweden)

    Saatsi Johanna

    2008-06-01

    Full Text Available Abstract Background Acute phase proteins haptoglobin (Hp, serum amyloid A (SAA and lipopolysaccharide binding protein (LBP have suggested to be suitable inflammatory markers for bovine mastitis. The aim of the study was to investigate acute phase markers along with clinical parameters in two consecutive intramammary challenges with Escherichia coli and to evaluate the possible carry-over effect when same animals are used in an experimental model. Methods Mastitis was induced with a dose of 1500 cfu of E. coli in one quarter of six cows and inoculation repeated in another quarter after an interval of 14 days. Concentrations of acute phase proteins haptoglobin (Hp, serum amyloid A (SAA and lipopolysaccharide binding protein (LBP were determined in serum and milk. Results In both challenges all cows became infected and developed clinical mastitis within 12 hours of inoculation. Clinical disease and acute phase response was generally milder in the second challenge. Concentrations of SAA in milk started to increase 12 hours after inoculation and peaked at 60 hours after the first challenge and at 44 hours after the second challenge. Concentrations of SAA in serum increased more slowly and peaked at the same times as in milk; concentrations in serum were about one third of those in milk. Hp started to increase in milk similarly and peaked at 36–44 hours. In serum, the concentration of Hp peaked at 60–68 hours and was twice as high as in milk. LBP concentrations in milk and serum started to increase after 12 hours and peaked at 36 hours, being higher in milk. The concentrations of acute phase proteins in serum and milk in the E. coli infection model were much higher than those recorded in experiments using Gram-positive pathogens, indicating the severe inflammation induced by E. coli. Conclusion Acute phase proteins would be useful parameters as mastitis indicators and to assess the severity of mastitis. If repeated experimental intramammary

  3. Increased platelet aggregation and turnover in the acute phase of ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Jensen, Kristian Løkke Funck; Dalsgaard, Jens; Grove, Erik Lerkevang

    2013-01-01

    Newly produced platelets are present in the acute phase of ST-elevation myocardial infarction (STEMI). This may influence the antiplatelet effect of aspirin and clopidogrel administered prior to primary percutaneous coronary intervention (PPCI). The aims of this study were to investigate the anti...... turnover may partly explain the reduced efficacy of antiplatelet drugs in the acute phase of STEMI....... the antiplatelet effect of aspirin and clopidogrel and evaluate platelet turnover in the acute phase of STEMI compared to a stable phase 3 months later. In this observational follow-up study on 48 STEMI patients transferred for PPCI, loading doses of aspirin (300 mg) and clopidogrel (600 mg) were given orally...... in the ambulance. Blood samples were obtained immediately prior to PPCI, at 4 and 12 hours after administration of bolus doses and at follow-up after 3 months. Residual platelet aggregation was evaluated by Multiplate® and VerifyNow® aggregometry. Platelet turnover was evaluated by automated flow cytometry...

  4. [Echocardiographic indices related with acute coronary anatomy in acute phase of myocardial infarction: our experience].

    Science.gov (United States)

    Belluzzi, Fabio; Ciocca, Anna; Grosso Di Palma, Lucia; Cattaneo, Mattia; Conti, Caterina; Magrini, Fabio

    2011-11-01

    Inferior acute myocardial infarction (IAMI) is often associated with right ventricle involvement (RVAMI). Echocardiogram (Echo) shows the ischemic involvement of the right ventricle with an initial dilatation (RVD) and segmental cinetic abnormalities (RVSCS). During RVAMI the normal convexity of the interatrial septum (IAS) toward right atrium is inverted (IASI). 53 patients with IAMI were studied with ECG, echo and hemodinamic monitoring by a Swan-Ganz catheter. Echo was early performed and patients were subdivided into three groups: 1. IAMI with RVSCS and/or RVD with IASI (12 patients); 2. IAMI with RVSCS and/or RVD without IASI (8 patients); 3. IAMI without VSCS, RVD IASI (33 patients). ECG showed RV involvement only in A and B groups (ST-T segment elevation more than 2 mm in V3 r - V5 r). Echo-Doppler showed no statistically differences between the two groups on RV protodiastolic pression; no hemodinamic differences between the two groups (p = n.s.); no statistically differences in central venous pressure, right ventricular pressure, cardiac output, wedge pressure. Complications (arrhytmias, heart failure, ipotension, pericarditis, 3rd A-V block) were so subdivided: group A: 6 patients (50%); group B: 2 patients (24%); group C: 4 patients (12%) with statistical significance (p41 % in group A (5 patients); 20 % in group B (2 patients); 6 % in group C (2 patients), with p<0.01 between all three groups. Echo after six months showed IASI only in two patients of group A. Patients with IASI revealed complications (residual angina, ventricular ipercinetic arrytmias). IASI in patients with IAMI and RVAMI seems to identify a group with higher risk in developing complications and with a more adverse prognosis.

  5. The porcine acute phase response to infection with Actinobacillus pleuropneumoniae. Haptoglobin, C-reactive protein, major acute phase protein and serum amyloid a protein are sensitive indicators of infection

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Klausen, Joan; Nielsen, J.P.

    1998-01-01

    response peaking at around 2 days after infection. Haptoglobin, C-reactive protein (CRP), and major acute phase protein (MAP) responded with large increases in serum levels, preceding the development of specific antibodies by 4-5 days. Serum amyloid A protein (SAA) was also strongly induced. The increase......, kinetics of induction and normalization were different between these proteins. It is concluded that experimental Ap-infection by the aerosol route induces a typical acute phase reaction in the pig, and that pig Hp, CRP, MAP, and SAA are major acute phase reactants. These findings indicate the possibility...

  6. Pig-MAP, porcine acute phase proteins and standardisation of assays in Europe

    DEFF Research Database (Denmark)

    Alava, M.A.; Gonzalez-Ramon, N.; Heegaard, Peter M. H.

    1997-01-01

    The pattern of plasma proteins changes greatly following infection, inflammation or tissue injury. The concentration of some proteins referred to as acute phase proteins (APPs) significantly increases within hours or days after the onset of these processes. In contrast, the concentration of other...... during the inflammation. In addition to CRP and Hp, a serum alpha(2)-globulin was observed to be the major acute phase (MAP) protein in pigs. Pig-MAP is a new mammalian plasma protein, which is the pig counterpart of a recently cloned human serum protein denominated PK-120 or MRP. Pig-MAP shows promise...... for the presence of infectious, inflammatory and pathological lesions in animals. The ability to monitor the APP concentration in serum of pigs will improve the quality and safety of the meat produced as well as provide important diagnostic information for animal health and welfare. The serum concentration of APP...

  7. Acrolein-Induced Dyslipidemia and Acute Phase Response Independenly of HMG-CoA Reductase

    Science.gov (United States)

    Conklin, Daniel J.; Prough, Russell A.; Juvan, Peter; Rezen, Tadeja; Rozman, Damjana; Haberzettl, Petra; Srivastava, Sanjay; Bhatnagar, Aruni

    2012-01-01

    Scope Aldehydes are ubiquitous natural constituents of foods, water and beverages. Dietary intake represents the greatest source of exposure to acrolein and related aldehydes. Oral acrolein induces dyslipidemia acutely and chronically increases atherosclerosis in mice, yet the mechanisms are unknown. Because lipid synthesis and trafficking are largely under hepatic control, we examined hepatic genes in murine models of acute and chronic oral acrolein exposure. Methods and results Changes in hepatic gene expression were examined using a Steroltalk microarray. Acute acrolein feeding modified plasma and hepatic proteins and increased plasma triglycerides within 15 min. By 6h, acrolein altered hepatic gene expression including Insig1, Insig2 and Hmgcr genes and stimulated an acute phase response (APR) with up-regulation of serum amyloid A genes (Saa) and systemic hypoalbuminemia. To test if decreased HMG-CoA reductase activity could modify acrolein-induced dyslipidemia or the APR, mice were pretreated with simvastatin. Statin treatment, however, did not alter acrolein-induced dyslipidemia or hypoalbuminemia associated with an APR. Few hepatic genes were dysregulated by chronic acrolein feeding in apoE-null mice. These studies confirmed that acute acrolein exposure altered expression of hepatic genes involved with lipid synthesis and trafficking and APR, and thus, indicated a hepatic locus of acrolein-induced dyslipidemia and APR that was independent of HMG CoA-reductase. Conclusion Dietary intake of acrolein could contribute to cardiovascular disease risk by disturbing hepatic function. PMID:21812109

  8. Emergence of the acute-phase protein hemopexin in jawed vertebrates

    OpenAIRE

    Dooley, Helen; Buckingham, E. Bryan; Criscitiello, Michael F.; Flajnik, Martin F.

    2010-01-01

    When released from damaged erythrocytes free heme not only provides a source of iron for invading bacteria but is also highly toxic due to its ability to catalyze free radical formation. Hemopexin (Hx) binds free heme with very high affinity and thus protects against heme toxicity, sequesters heme from pathogens, and helps conserve valuable iron. Hx is also an acute-phase serum protein (APP), whose expression is induced by inflammation. To date Hx has been identified as far back in phylogeny ...

  9. 'Living a life in shades of grey': experiencing depressive symptoms in the acute phase after stroke.

    Science.gov (United States)

    Kouwenhoven, Siren E; Kirkevold, Marit; Engedal, Knut; Kim, Hesook S

    2012-08-01

    The aim of the present study was to describe the lived experience of stroke survivors suffering from depressive symptoms in the acute phase; addressing the following questions: (a) what is the nature of depression as experienced by post-stroke patients in the acute phase? (b) what is it like to live with depression within the first weeks following stroke? Post-stroke depression occurs in at least one quarter of stroke survivors and is linked to poorer outcomes. This qualitative study is methodologically grounded in hermeneutic phenomenology, influenced by van Manen and Ricoeur. A descriptive, qualitative design was used applying in-depth interviews as the method of data collection with nine participants. The data collection took place in 2008. The material revealed two main themes that generate the feeling and description of 'living a life in shades of grey': (a) being trapped and (b) losing oneself. 'Shades of grey' could be understood as being confined in a new life-world and losing oneself as the person one knew. The participants confirmed suffering from depressive symptoms, but depression was not seen as meaningful on its own. They related their experiences of post-stroke depression in the acute phase to the losses they experienced. Nurses ought to take into account the depth of the life changes that stroke survivors may experience. There is a need for continued empirical research on how nurses may help and support stroke survivors dealing with depressive symptoms in the acute phase after stroke and how depressive symptoms develop over time. © 2011 Blackwell Publishing Ltd.

  10. Differing results of direct and indirect solid phase radioimmunoassay for HBsAg in acute hepatitis

    International Nuclear Information System (INIS)

    Strohm, W.D.; Legler, K.; Gerlich, W.; Stamm, B.; Zimmer, S.; Biotest-Serum-Institut G.m.b.H., Frankfurt am Main; Goettingen Univ.

    1978-01-01

    In 54 patients suffering from active viral hepatitis the indirect solid phase radioimmunoassay (ind-SPRIA) for HBsAg was positive in 9 cases the direct solid phase radioimmunoassay (d-SPRIA) being negative. In 2 further cases ind-SPRIA was positive during several weeks but d-SPRIA only once. AntiHBc could be detected in 9 of these patients. In 7 patients the usual decrease of the transaminase activity was followed by a second elavation with prolongation of the disease. The unknown factor detected by ind-SPRIA suggests a special of acute hepatitis. (orig.) [de

  11. Differing results of direct and indirect solid phase radioimmunoassay for HBsAg in acute hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Strohm, W D; Legler, K; Gerlich, W; Stamm, B; Zimmer, S [Frankfurt Univ. (Germany, F.R.). Abt. fuer Gastroenterologie; Biotest-Serum-Institut G.m.b.H., Frankfurt am Main (Germany, F.R.); Goettingen Univ. (Germany, F.R.). Hygiene-Institut)

    1978-09-01

    In 54 patients suffering from active viral hepatitis the indirect solid phase radioimmunoassay (ind-SPRIA) for HBsAg was positive in 9 cases the direct solid phase radioimmunoassay (d-SPRIA) being negative. In 2 further cases ind-SPRIA was positive during several weeks but d-SPRIA only once. AntiHBc could be detected in 9 of these patients. In 7 patients the usual decrease of the transaminase activity was followed by a second elavation with prolongation of the disease. The unknown factor detected by ind-SPRIA suggests a special of acute hepatitis.

  12. Serum acute phase protein concentrations in female dogs with mammary tumors.

    Science.gov (United States)

    Tecles, Fernando; Caldín, Marco; Zanella, Anna; Membiela, Francisco; Tvarijonaviciute, Asta; Subiela, Silvia Martínez; Cerón, José Joaquín

    2009-03-01

    Acute phase proteins (APPs) are proteins whose concentrations in serum change after any inflammatory stimulus or tissue damage. The aim of the current study was to evaluate 3 positive APPs (C-reactive protein, serum amyloid A, and haptoglobin) and 1 negative APP (albumin) in female dogs with mammary neoplasia. Acute phase proteins were studied in 70 female dogs aged 8-12 years in the following groups: healthy (n = 10); mammary tumors in stages I (n = 19), II (n = 5), III (n = 6), IV (n = 5), and V (n = 7); and with mammary neoplasia plus a concomitant disease (n = 18). In animals with mammary neoplasia, significant increases of positive APPs were only detected in those that had metastasis or a neoplasm with a diameter greater than 5 cm and ulceration. Dogs with mammary neoplasia and a concomitant disease also had high C-reactive protein concentrations. Albumin concentration was decreased in animals with metastasis and with a concomitant disease. The results of the present study indicate that the acute phase response could be stimulated in female dogs with mammary gland tumors because of different factors, such as metastasis, large size of the primary mass, and ulceration or secondary inflammation of the neoplasm.

  13. The Acute Phase of Trypanosoma cruzi Infection Is Attenuated in 5-Lipoxygenase-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Adriana M. C. Canavaci

    2014-01-01

    Full Text Available In the present work we examine the contribution of 5-lipoxygenase- (5-LO- derived lipid mediators to immune responses during the acute phase of Trypanosoma cruzi infection in 5-LO gene knockout (5-LO−/− mice and wild-type (WT mice. Compared with WT mice, the 5-LO−/− mice developed less parasitemia/tissue parasitism, less inflammatory cell infiltrates, and a lower mortality. This resistance of 5-LO−/− mice correlated with several differences in the immune response to infection, including reduced PGE2 synthesis; sustained capacity of splenocytes to produce high levels of interleukin (IL-12 early in the infection; enhanced splenocyte production of IL-1β, IL-6, and IFN-γ; rapid T-cell polarization to secrete high quantities of IFN-γ and low quantities of IL-10; and greater numbers of CD8+CD44highCD62Llow memory effector T cells at the end of the acute phase of infection. The high mortality in WT mice was associated with increased production of LTB4/LTC4, T cell bias to produce IFN-γ, high levels of serum nitrite, and marked protein extravasation into the peritoneal cavity, although survival was improved by treatment with a cys-LT receptor 1 antagonist. These data also provide evidence that 5-LO-derived mediators negatively affect host survival during the acute phase of T. cruzi infection.

  14. Circulating microbial products and acute phase proteins as markers of pathogenesis in lymphatic filarial disease.

    Directory of Open Access Journals (Sweden)

    R Anuradha

    Full Text Available Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+ or without (CP Ag- active infection; with clinically asymptomatic infections (INF; and in those without infection (endemic normal [EN]. Comparisons between the two actively infected groups (CP Ag+ compared to INF and those without active infection (CP Ag- compared to EN were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein, acute phase proteins (haptoglobin and serum amyloid protein-A, and inflammatory cytokines (IL-1β, IL-12, and TNF-α are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins.

  15. Acute Phase Proteins in Response to Dictyocaulus viviparus Infection in Calves

    Directory of Open Access Journals (Sweden)

    Waller K Persson

    2004-06-01

    Full Text Available Three experiments were carried out to examine the acute phase response, as measured by the acute phase proteins (APP haptoglobin, serum amyloid A (SAA and fibrinogen, in calves infected with lungworm, Dictyocaulus vivparus. In addition, eosinophil counts were analysed. Three different dose models were used in 3 separate experiments: I 250 D. viviparus infective third stage larvae (L3 once daily for 2 consecutive days, II 100 D. viviparus L3 once daily for 5 consecutive days, and III 2000 L3 once. All 3 dose regimes induced elevated levels of haptoglobin, SAA and fibrinogen, although there was considerable variation both between and within experiments. A significant increase was observed in all 3 APP at one or several time points in experiment I and III, whereas in experiment II, the only significant elevation was observed for fibrinogen at one occasion. The eosinophil numbers were significantly elevated in all 3 experiments. The results show that lungworm infection can induce an acute phase response, which can be monitored by the selected APP. Elevated APP levels in combination with high numbers of eosinophils in an animal with respiratory disease may be used as an indicator of lung worm infection, and help the clinician to decide on treatment. However, high numbers of eosinophils and low levels of APP do not exclude a diagnosis of lungworm. Thus, lungworm infection may not be detected if measurements of APP are used to assess calf health in herds or individual animals.

  16. Trajectories of sleep changes during the acute phase of traumatic brain injury: A 7-day actigraphy study

    Directory of Open Access Journals (Sweden)

    Hsiao-Yean Chiu

    2013-09-01

    Conclusion: Poor sleep efficiency and longer sleep duration are common symptoms in acute TBI patients. Both head injury severity and age predicted the trajectories of daytime and 24-hour sleep duration during the acute phase of TBI, whereas gender predicted the trajectories of 24-hour sleep duration in the mild TBI subgroup.

  17. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    von Stackelberg, Arend; Locatelli, Franco; Zugmaier, Gerhard; Handgretinger, Rupert; Trippett, Tanya M; Rizzari, Carmelo; Bader, Peter; O'Brien, Maureen M; Brethon, Benoît; Bhojwani, Deepa; Schlegel, Paul Gerhardt; Borkhardt, Arndt; Rheingold, Susan R; Cooper, Todd Michael; Zwaan, Christian M; Barnette, Phillip; Messina, Chiara; Michel, Gérard; DuBois, Steven G; Hu, Kuolung; Zhu, Min; Whitlock, James A; Gore, Lia

    2016-12-20

    Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m 2 /d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m 2 /d for the first 7 days, followed by 15 µg/m 2 /d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.

  18. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

    DEFF Research Database (Denmark)

    Saber, Anne T.; Jacobsen, Nicklas R.; Jackson, Petra

    2014-01-01

    Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction...... epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk...

  19. Mimicry of the immunodominant conformation-dependent antigenic site of hepatitis A virus by motifs selected from synthetic peptide libraries.

    Science.gov (United States)

    Mattioli, S; Imberti, L; Stellini, R; Primi, D

    1995-09-01

    Hepatitis A virus (HAV) is a positive-strand RNA virus with a genome length of approximately 7,480 nucleotides. Although HAV morphogenesis is thought to be similar to that of poliovirus, the prototype picornavirus, the complete characterization of the antigenic structure of this virus remains elusive. All the available evidences, however, support the existence, on HAV virions and empty capsids, of an immunodominant neutralization antigenic site which is conformation dependent and whose structure involves residues of both VP1 and VP3 capsid proteins. This particular feature and the difficulty of obtaining high virus yield in tissue cultures make HAV an ideal target for developing synthetic peptides that simulate the structure of its main antigenic determinant. To this end we utilized, in the present work, the divide-couple-recombine approach to generate a random library composed of millions of different hexapeptides. This vast library was screened with a well-characterized anti-HAV monoclonal antibody. By this strategy we identified a peptide that reacted specifically with monoclonal and polyclonal anti-HAV antibodies and, in mice, induced a specific anti-virus immune response. Furthermore, the peptide could also be used in an enzyme-linked immunosorbent assay for revealing a primary immunoglobulin M immune response in sera of acutely infected human patients. Interestingly, no sequence homology was found between the identified peptide and the HAV capsid proteins VP1 and VP3. Collectively, these data represent an additional important paradigm of a mimotope capable of mimicking an antigenic determinant with unknown tertiary structure.

  20. Selected acute phase CSF factors in ischemic stroke: findings and prognostic value

    Directory of Open Access Journals (Sweden)

    Intskirveli Nino

    2011-03-01

    Full Text Available Abstract Background Study aimed at investigation of pathogenic role and prognostic value of several selected cerebrospinal fluid acute phase factors that can reflect the severity of ischemic brain damage. Methods Ninety five acute ischemic stroke patients were investigated. Ischemic region visualized at the twenty fourth hour by conventional Magnetic Resonance Imaging. Stroke severity evaluated by National Institute Health Stroke Scale. One month outcome of disease was assessed by Barthel Index. Cerebrospinal fluid was taken at the sixth hour of stroke onset. CSF pro- and anti-inflammatory cytokines were studied by Enzyme Linked Immunosorbent Assay. Nitric Oxide and Lipoperoxide radical were measured by Electron Paramagnetic Resonance. CSF Nitrate levels were detected using the Griess reagent. Statistics performed by SPSS-11.0. Results At the sixth hour of stroke onset, cerebrospinal fluid cytokine levels were elevated in patients against controls. Severe stroke patients had increased interleukin-6 content compared to less severe strokes (P Conclusion According to present study the cerebrospinal fluid contents of interleukin-6 and nitrates seem to be the most reliable prognostic factors in acute phase of ischemic stroke.

  1. [Pulmonary function of children with acute leukemia in maintenance phase of chemotherapy].

    Science.gov (United States)

    de Macêdo, Thalita Medeiros Fernandes; Campos, Tania Fernandes; Mendes, Raquel Emanuele de França; França, Danielle Corrêa; Chaves, Gabriela Suéllen da Silva; de Mendonça, Karla Morganna Pereira Pinto

    2014-12-01

    The aim of this study was to assess the pulmonary function of children with acute leukemia. Cross-sectional observational analytical study that enrolled 34 children divided into groups A (17 with acute leukemia in the maintenance phase of chemotherapy) and B (17 healthy children). The groups were matched for sex, age and height. Spirometry was measured using a spirometer Microloop Viasys(®) in accordance with American Thoracic Society and European Respiratory Society guidelines. Maximal respiratory pressures were measured with an MVD300 digital manometer (Globalmed(®)). Maximal inspiratory pressures and maximal expiratory pressures were measured from residual volume and total lung capacity, respectively. Group A showed a significant decrease in maximal inspiratory pressures when compared to group B. No significant difference was found between the spirometric values of the two groups, nor was there any difference between maximal inspiratory pressure and maximal expiratory pressure values in group A compared to the lower limit values proposed as reference. Children with acute leukemia, myeloid or lymphoid, during the maintenance phase of chemotherapy exhibited unchanged spirometric variables and maximal expiratory pressure; However, there was a decrease in inspiratory muscle strength. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  2. Acute-phase responses in healthy and diseased rhesus macaques (Macaca mulatta)

    DEFF Research Database (Denmark)

    Krogh, Anne Kirstine Havnsøe; Lundsgaard, Jo F. H.; Bakker, Jaco

    2014-01-01

    Five acute-phase reactants—serum amyloid A (SAA), C-reactive protein (CRP), haptoglobin, albumin, and iron—were measured using commercially available assays in 110 healthy rhesus macaques (Macaca mulatta), and reference intervals were established for future use in health monitoring of this species....... Reference intervals established were as follows: SAA, 29.5–87.7 mg/L; CRP, 0–17.5 mg/L; haptoglobin, 354.3–2,414.7 mg/L; albumin, 36.1–53.0 g/L; and iron, 13.3–40.2 lmol/L. Furthermore, changes in the acute-phase reactants were studied in two additional groups of animals: eight rhesus macaques suffering...... from acute traumatic injuries and nine rhesus macaques experimentally infected with Mycobacterium tuberculosis reflecting a chronic active inflammation. In animals with inflammation, SAA and haptoglobin concentrations were moderately increased, while CRP increased more than 200-fold. In addition, marked...

  3. Are there differences in acute phase inflammation markers regarding the type of heart failure?

    Directory of Open Access Journals (Sweden)

    Jaime Agüero-Ramón-Llin

    2011-09-01

    Full Text Available This study aimed to determine if there are differences in inflammatory markers in the acute phase between systolic heart failure and heart failure with preserved systolic function. One hundred and thirty-one patients with acute heart failure were recruited consecutively. At admission, plasma fibrinogen, Creactive protein, sialic acid, von Willebrand factor, vascular endothelial growth factor, interleukin-6 and NTproBNP were all evaluated. If the ejection fraction was 45% or over patients were included in the HF-PSF group; the remaining patients were included in the SHF group. The HF-PSF patients were older (72±10 vs 63±12 years, P<0.001, presented a higher rate of atrial fibrillation (56.1 vs 21.3%, P<0.001, and had a lower rate of hemoglobin (12.2±2 vs 13.3±2.1 g/dL, P<0.01. No significant differences were observed in the inflammation markers analyzed among SHF and HFPSF groups. In the acute phase of heart failure there is a marked elevation of inflammatory markers but there are no differences in the inflammatory markers analyzed between the two different types of heart failure

  4. Delirium in the acute phase after stroke: comparison between methods of detection.

    Science.gov (United States)

    Infante, Maria Teresa; Pardini, Matteo; Balestrino, Maurizio; Finocchi, Cinzia; Malfatto, Laura; Bellelli, Giuseppe; Mancardi, Giovanni Luigi; Gandolfo, Carlo; Serrati, Carlo

    2017-06-01

    Delirium is an acute neuropsychiatric syndrome, very common in hospitalized people with medical and neurological conditions. The identification of delirium after stroke is not an easy task and validated psychometric instruments are needed to correctly identify it. We decided to verify if (1) formal training in DSM-V criteria is needed to correctly identify post-stroke delirium, (2) if the use of a brief psychometric instrument such as 4AT improves its identification, (3) the applicability of these scales in the stroke setting. In the first phase of this study we retrospectively studied 102 acute stroke patients in Stroke Units of San Martino Hospital (Genova, Italy) to evaluate delirium with clinical criteria, first by a neurologist without a formal training in DSM-V criteria and after training. Then, we enrolled 100 new acute stroke patients who underwent screening for delirium using 4AT scale and DSM-V criteria. In the first phase, DSM-V criteria training significantly increased the ability to capture delirium (5 vs. 15%). In the second phase, the 4AT was used for delirium screening revealing a 52% of cases of delirium, the same observed by the consensus diagnosis of two senior neurologists (that was 50%). In the second phase, the use of 4AT scale allowed to capture post-stroke delirium as well as the consensus diagnosis by two neurologists. The identification of post-stroke delirium is not an easy task and requires both formal training in DSM-V criteria as well as the application of brief scales, such as the 4AT.

  5. Acute versus chronic phase mechanisms in a rat model of CRPS.

    Science.gov (United States)

    Wei, Tzuping; Guo, Tian-Zhi; Li, Wen-Wu; Kingery, Wade S; Clark, John David

    2016-01-19

    Tibia fracture followed by cast immobilization in rats evokes nociceptive, vascular, epidermal, and bone changes resembling complex regional pain syndrome (CRPS). In most cases, CRPS has three stages. Over time, this acute picture, allodynia, warmth, and edema observed at 4 weeks, gives way to a cold, dystrophic but still painful limb. In the acute phase (at 4 weeks post fracture), cutaneous immunological and NK1-receptor signaling mechanisms underlying CRPS have been discovered; however, the mechanisms responsible for the chronic phase are still unknown. The purpose of this study is to understand the mechanisms responsible for the chronic phases of CRPS (at 16 weeks post fracture) at both the peripheral and central levels. We used rat tibial fracture/cast immobilization model of CRPS to study molecular, vascular, and nociceptive changes at 4 and 16 weeks post fracture. Immunoassays and Western blotting were carried out to monitor changes in inflammatory response and NK1-receptor signaling in the skin and spinal cord. Skin temperature and thickness were measured to elucidate vascular changes, whereas von Frey testing and unweighting were carried out to study nociceptive changes. All data were analyzed by one-way analysis of variance (ANOVA) followed by Neuman-Keuls multiple comparison test to compare among all cohorts. In the acute phase (at 4 weeks post fracture), hindpaw allodynia, unweighting, warmth, edema, and/or epidermal thickening were observed among 90 % fracture rats, though by 16 weeks (chronic phase), only the nociceptive changes persisted. The expression of the neuropeptide signaling molecule substance P (SP), NK1 receptor, inflammatory mediators TNFα, IL-1β, and IL-6 and nerve growth factor (NGF) were elevated at 4 weeks in sciatic nerve and/or skin, returning to normal levels by 16 weeks post fracture. The systemic administration of a peripherally restricted IL-1 receptor antagonist (anakinra) or of anti-NGF inhibited nociceptive behaviors at 4

  6. Risk factors for and impact of respiratory failure on mortality in the early phase of acute pancreatitis

    DEFF Research Database (Denmark)

    Dombernowsky, Tilde; Kristensen, Marlene Østermark; Rysgaard, Sisse

    2016-01-01

    : Retrospective cohort study including 359 patients admitted with acute pancreatitis. Information was gathered from electronic patient records. We defined respiratory failure based on the modified Marshall scoring system in the revised Atlanta criteria. Predictors of respiratory failure were evaluated......, or pneumonia may develop respiratory failure, suggests that acute lung injury, possibly associated with systemic inflammation, may be important.......BACKGROUND: The incidence of respiratory failure and other respiratory complications in the early phase of acute pancreatitis (AP) is not well investigated. OBJECTIVE: To evaluate the incidence and risk factors of respiratory failure, and its impact on mortality in the early phase AP. METHODS...

  7. Prostate hypofractionated radiation therapy with injection of hyaluronic acid: acute toxicities in a phase 2 study.

    Science.gov (United States)

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-03-15

    Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    International Nuclear Information System (INIS)

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-01-01

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity

  9. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); EMR3738, Université Lyon 1, Lyon (France); Decullier, Evelyne; Bin, Sylvie [Pole Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon (France); Université Lyon 1, Lyon (France); EA SIS, Université de Lyon, Lyon (France); Faix, Antoine [Department of Urology, Clinique Beausoleil, Montpellier (France); Ruffion, Alain [Université Lyon 1, Lyon (France); Department of Urology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Jalade, Patrice [Department of Medical Physics, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Fenoglietto, Pascal [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France); Udrescu, Corina; Enachescu, Ciprian [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Azria, David [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France)

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  10. Thrombus length discrepancy on dual-phase CT can predict clinical outcome in acute ischemic stroke

    International Nuclear Information System (INIS)

    Park, Mina; Kim, Kyung-eun; Lee, Seung-Koo; Shin, Na-Young; Lim, Soo Mee; Song, Dongbeom; Heo, Ji Hoe; Kim, Jin Woo; Oh, Se Won

    2016-01-01

    The thrombus length may be overestimated on early arterial computed tomography angiography (CTA) depending on the collateral status. We evaluated the value of a grading system based on the thrombus length discrepancy on dual-phase CT in outcome prediction. Forty-eight acute ischemic stroke patients with M1 occlusion were included. Dual-phase CT protocol encompassed non-contrast enhanced CT, CTA with a bolus tracking technique, and delayed contrast enhanced CT (CECT) performed 40s after contrast injection. The thrombus length discrepancy between CTA and CECT was graded by using a three-point scale: G0 = no difference; G1 = no difference in thrombus length, but in attenuation distal to thrombus; G2 = difference in thrombus length. Univariate and multivariate analyses were performed to define independent predictors of poor clinical outcome at 3 months. The thrombus discrepancy grade showed significant linear relationships with both the collateral status (P = 0.008) and the presence of antegrade flow on DSA (P = 0.010) with good interobserver agreement (κ = 0.868). In a multivariate model, the presence of thrombus length discrepancy (G2) was an independent predictor of poor clinical outcome [odds ratio = 11.474 (1.350-97.547); P =0.025]. The presence of thrombus length discrepancy on dual-phase CT may be a useful predictor of unfavourable clinical outcome in acute M1 occlusion patients. (orig.)

  11. Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

    Energy Technology Data Exchange (ETDEWEB)

    Shannahan, Jonathan H. [Curriculum in Toxicology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Alzate, Oscar [Systems Proteomics Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Winnik, Witold M.; Andrews, Debora [Proteomics Core, Research Core Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Schladweiler, Mette C. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Ghio, Andrew J. [Clinical Research Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Chapel Hill, NC 27599 (United States); Gavett, Stephen H. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Kodavanti, Urmila P., E-mail: Kodavanti.Urmila@epa.gov [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2012-04-15

    Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins involved

  12. T cell Receptor Alpha Variable 12-2 bias in the immunodominant response to Yellow fever virus

    OpenAIRE

    Bovay, Amandine; Zoete, Vincent; Dolton, Garry; Bulek, Anna M.; Cole, David K.; Rizkallah, Pierre J.; Fuller, Anna; Beck, Konrad; Michielin, Olivier; Speiser, Daniel E.; Sewell, Andrew K.; Fuertes Marraco, Silvia A.

    2018-01-01

    The repertoire of human αβ T-cell receptors (TCRs) is generated via somatic recombination of germline gene segments. Despite this enormous variation, certain epitopes can be immunodominant, associated with high frequencies of antigen-specific T cells and/or exhibit bias toward a TCR gene segment. Here, we studied the TCR repertoire of the HLA-A*0201-restricted epitope LLWNGPMAV (hereafter, A2/LLW) from Yellow Fever virus, which generates an immunodominant CD8 javax.xml.bind.JAXBElement@714aac...

  13. Type 2 diabetes mellitus with early phase acute inflammatory protein on serum protein electrophoresis

    Directory of Open Access Journals (Sweden)

    ET Tuladhar

    2012-03-01

    Full Text Available Background: The onset of Type 2 diabetes has been associated with low grade systemic inflammation. The inflammatory status has been studied by measuring acute phase reactant proteins like hsCRP, α1- antitrypsin, α1-acid glycoprotein, ceruloplasmin, fibrinogen. Most of these acute phase reactants form α1 and α2 bands on electropherogram of serum proteins. The aim of this study was to evaluate inflammatory status in controlled and uncontrolled type 2 diabetes using cellulose acetate electrophoresis and to find the impact of glycemic status as indicated by HbA1c on inflammation process. Materials and Methods: Serum protein electrophoresis was done on serum samples of 60 cases of Diabetes [controlled and uncontrolled] using cellulose acetate paper technique. The electropherogram obtained was stained with Ponseu S and then quantitated using densitometer. Glycemic status was studied by HbA1c analysis. The density of α1and α2 bands in electropherogram were correlated with HbA1c level. Result: A significant increase in the percentage of α1 and α2 band proteins (0.765 and 0.716, p<0.001 were found with the increasing level of HbA1c. With cutoff of HbA1c 7% (American Diabetic Association recommended, the α1 and α2 serum proteins concentration are significantly higher (p<0.001 in uncontrolled diabetes mellitus compared to controlled diabetes mellitus Conclusion: Cellulose acetate electrophoresis of serum proteins show early phase acute inflammatory status in uncontrolled type 2 diabetes mellitus. The process of systemic inflammation worsens with uncontrolled glycemia as indicated by HbA1c. Inflammatory status should be studied adjunct to glycemic status. DOI: http://dx.doi.org/10.3126/jpn.v2i3.6024 JPN 2012; 2(3: 211-214

  14. Flight performance of western sandpipers, Calidris mauri, remains uncompromised when mounting an acute phase immune response.

    Science.gov (United States)

    Nebel, Silke; Buehler, Deborah M; MacMillan, Alexander; Guglielmo, Christopher G

    2013-07-15

    Migratory birds have been implicated in the spread of some zoonotic diseases, but how well infected individuals can fly remains poorly understood. We used western sandpipers, Calidris mauri, to experimentally test whether flight is affected when long-distance migrants are mounting an immune response and whether migrants maintain immune defences during a flight in a wind tunnel. We measured five indicators of innate immunity in 'flown-healthy' birds (flying in a wind tunnel without mounting an immune response), 'flown-sick' birds (flying while mounting an acute phase response, which is part of induced innate immunity), and a non-flying control group ('not-flown'). Voluntary flight duration did not differ between flown-healthy and flown-sick birds, indicating that mounting an acute phase response to simulated infection did not hamper an individual's ability to fly for up to 3 h. However, in comparison to not-flown birds, bacterial killing ability of plasma was significantly reduced after flight in flown-sick birds. In flown-healthy birds, voluntary flight duration was positively correlated with bacterial killing ability and baseline haptoglobin concentration of the blood plasma measured 1-3 weeks before experimental flights, suggesting that high quality birds had strong immune systems and greater flight capacity. Our findings indicate that flight performance is not diminished by prior immune challenge, but that flight while mounting an acute phase response negatively affects other aspects of immune function. These findings have important implications for our understanding of the transmission of avian diseases, as they suggest that birds can still migrate while fighting an infection.

  15. Determinants of fatigue after first-ever ischemic stroke during acute phase.

    Directory of Open Access Journals (Sweden)

    Shan-Shan Wang

    Full Text Available Fatigue after stroke is common and has a negative impact on rehabilitation and survival. However, its pathogenesis and contributing factors remain unclear. The purpose of this study was to identify factors influencing the occurrence of fatigue after first-ever ischemic stroke in acute phase.We examined 265 consecutive patients with first-ever ischemic stroke during acute phase (within 2 weeks in two tertiary stroke care hospitals in Henan, China. We documented patients' demographic and clinical characteristics through face-to-face interviews using structured questionnaires and reviews of medical records. Post-stroke fatigue was defined as a score of ≥4 using the Fatigue Severity Scale. Multivariate logistic regression was used to examine post-stroke fatigue in relation to socio-demographic, lifestyle, clinical characteristics and family function.About 40% first-ever ischemic stroke patients experienced post-stroke fatigue in acute phase. Post-stroke fatigue was associated with lack of exercise before stroke (adjusted odds ratio 4.01, 95% CI 1.95-8.24, family dysfunction (2.63, 1.20-5.80, depression (2.39, 1.02-5.58, the presence of pre-stroke fatigue (4.89, 2.13-11.21, use of sedative medications (4.14, 1.58-10.88, coronary heart disease (3.38, 1.46-7.79 and more severe Modified Rankin Scale (2.55, 1.65-3.95.The causes of post-stroke fatigue are multifaceted. More physical exercise, improving family function, reducing depression and appropriate use of sedative medications may be helpful in preventing post-stroke fatigue.

  16. Value of dynamic susceptibility contrast perfusion MRI in the acute phase of transient global amnesia.

    Directory of Open Access Journals (Sweden)

    Alex Förster

    Full Text Available Transient global amnesia (TGA is a transitory, short-lasting neurological disorder characterized by a sudden onset of antero- and retrograde amnesia. Perfusion abnormalities in TGA have been evaluated mainly by use of positron emission tomography (PET or single-photon emission computed tomography (SPECT. In the present study we explore the value of dynamic susceptibility contrast perfusion-weighted MRI (PWI in TGA in the acute phase.From a MRI report database we identified TGA patients who underwent MRI including PWI in the acute phase and compared these to control subjects. Quantitative perfusion maps (cerebral blood flow (CBF and volume (CBV were generated and analyzed by use of Signal Processing In NMR-Software (SPIN. CBF and CBV values in subcortical brain regions were assessed by use of VOI created in FIRST, a model-based segmentation tool in the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB Software Library (FSL.Five TGA patients were included (2 men, 3 women. On PWI, no relevant perfusion alterations were found by visual inspection in TGA patients. Group comparisons for possible differences between TGA patients and control subjects showed significant lower rCBF values bilaterally in the hippocampus, in the left thalamus and globus pallidus as well as bilaterally in the putamen and the left caudate nucleus. Correspondingly, significant lower rCBV values were observed bilaterally in the hippocampus and the putamen as well as in the left caudate nucleus. Group comparisons for possible side differences in rCBF and rCBV values in TGA patients revealed a significant lower rCBV value in the left caudate nucleus.Mere visual inspection of PWI is not sufficient for the assessment of perfusion changes in TGA in the acute phase. Group comparisons with healthy control subjects might be useful to detect subtle perfusion changes on PWI in TGA patients. However, this should be confirmed in larger data sets and serial PWI

  17. Nursing diagnoses and interventions for post-acute-phase battered women.

    Science.gov (United States)

    Carlson-Catalano, J

    1998-01-01

    To identify nursing diagnoses and interventions applicable for post-acute-phase battered women. Eight battered women were interviewed twice for 2 hours. Gordon's functional health patterns provided the framework for data collection. Fifty-three nursing diagnoses and 52 nursing interventions were indicated in the data; 24 nursing diagnoses and 26 nursing interventions were present in all participants' data. With the use of comprehensive interventions, nurses can make a major contribution to society by enabling battered women to move to a more protected lifestyle.

  18. Acute phase proteins in bovine milk in an experimental model of Staphylococcus aureus subclinical mastitis

    DEFF Research Database (Denmark)

    Eckersall, P D; Young, F J; Nolan, A M

    2006-01-01

    and serum amyloid A increase in serum during mastitis. The concentrations of these proteins were determined in an experimental model using a field strain of Staphylococcus aureus to induce subclinical mastitis in dairy cows. The expression of mRNA coding for these proteins was assessed and the presence of M......The objectives were to establish the origin of 2 acute phase proteins in milk during subclinical bovine mastitis and to characterize the relationship between those proteins in milk and blood. Haptoglobin (Hp) and mammary-associated serum amyloid A (M-SAA3) appear in milk during mastitis, whereas Hp...

  19. [Antipsychotic Treatment of the Adult Patient in the Acute Phase of Schizophrenia].

    Science.gov (United States)

    Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos; García Valencia, Jenny; Jaramillo González, Luis Eduardo; de la Hoz, Ana María; Arenas, Álvaro; Tamayo Martínez, Nathalie

    2014-01-01

    To determine the efficacy and safety of different antipsychotic drugs in the management of patients diagnosed with schizophrenia in the acute phase. To formulate evidence-based recommendations on the antipsychotic (AP) drug management strategies for the treatment of the adult diagnosed with schizophrenia in the acute phase. Clinical practice guidelines were prepared, using the guidelines of the Methodology Guide of the Ministry of Health and Social Protection, in order to identify, synthesise, and evaluate the evidence and formulate recommendations as regards the management and follow-up of adult patients diagnosed with schizophrenia. The evidence of the NICE 82 guideline was adopted and updated, which answered the question on the management of the acute phase of adults with a diagnosis of schizophrenia. The evidence and its level were presented to the Guideline Development Group (GDG) in order to formulate recommendations following the methodology proposed by the GRADE approach. Clozapine, olanzapine, risperidone, ziprasidone, amisulpride, paliperidone, haloperidol, quetiapine, and aripiprazole were more effective than placebo for the majority of psychotic symptoms and the abandonment of treatment, but asenapine was not. Paliperidone, risperidone, quetiapine, clozapine, and olanzapine showed significant increases in weight compared to placebo. Haloperidol, risperidone, ziprasidone, and paliperidone had a higher risk of extrapyramidal symptoms than placebo. There was a significant risk of sedation or drowsiness with, risperidone, haloperidol, ziprasidone, quetiapine, olanzapine, and clozapine in the comparisons with placebo. Of the results of the comparisons between AP, it was shown that clozapine and paliperidone had a clinically significant effect compared to haloperidol and quetiapine, respectively. Olanzapine and risperidone had a lower risk of abandoning the treatment in general, and due to adverse reactions in two comparisons of each one, haloperidol was the

  20. Hemorrhagic intra splenic pseudocyst as a complication of chronic pancreatitis in acute phase - a case report

    International Nuclear Information System (INIS)

    Almeida, Fabiola Assuncao de; Marchiori, Edson; Mello, Walter de Assis; Nogueira, Aline Silva; Sales, Anderson Ribeiro; Martins, Renata Romano; Santos, Tereza Cristina C.R.S. dos

    1999-01-01

    The authors report a case of hemorrhagic intra splenic pseudocyst as a complication of chronic pancreatitis in acute phase. A 43-year-old woman, chronic alcoholic, who had pancreatitis 5 years ago, with symptoms of strong abdominal pain in the epigastrium, nausea and fever. Abdominal sonography showed a lesion contiguous to the spleen and computed tomography demonstrated an heterogeneous lesion of not well defined limits, in the lateral and posterior parts of the spleen. The patient was submitted to Roux-Y cystojejunostomy, he does not present any symptoms at the moment, and is undergoing clinical control. (author)

  1. Vaccinia-based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection.

    Science.gov (United States)

    Kwon, Ji-Sun; Yoon, Jungsoon; Kim, Yeon-Jung; Kang, Kyuho; Woo, Sunje; Jung, Dea-Im; Song, Man Ki; Kim, Eun-Ha; Kwon, Hyeok-Il; Choi, Young Ki; Kim, Jihye; Lee, Jeewon; Yoon, Yeup; Shin, Eui-Cheol; Youn, Jin-Won

    2014-08-01

    Growing concerns about unpredictable influenza pandemics require a broadly protective vaccine against diverse influenza strains. One of the promising approaches was a T cell-based vaccine, but the narrow breadth of T-cell immunity due to the immunodominance hierarchy established by previous influenza infection and efficacy against only mild challenge condition are important hurdles to overcome. To model T-cell immunodominance hierarchy in humans in an experimental setting, influenza-primed C57BL/6 mice were chosen and boosted with a mixture of vaccinia recombinants, individually expressing consensus sequences from avian, swine, and human isolates of influenza internal proteins. As determined by IFN-γ ELISPOT and polyfunctional cytokine secretion, the vaccinia recombinants of influenza expanded the breadth of T-cell responses to include subdominant and even minor epitopes. Vaccine groups were successfully protected against 100 LD50 challenges with PR/8/34 and highly pathogenic avian influenza H5N1, which contained the identical dominant NP366 epitope. Interestingly, in challenge with pandemic A/Cal/04/2009 containing mutations in the dominant epitope, only the group vaccinated with rVV-NP + PA showed improved protection. Taken together, a vaccinia-based influenza vaccine expressing conserved internal proteins improved the breadth of influenza-specific T-cell immunity and provided heterosubtypic protection against immunologically close as well as distant influenza strains. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Modulation of task-related cortical connectivity in the acute and subacute phase after stroke

    DEFF Research Database (Denmark)

    Larsen, Lisbeth H.; Zibrandtsen, Ivan C.; Wienecke, Troels

    2018-01-01

    The functional relevance of cortical reorganization post-stroke is still not well understood. In this study, we investigated task-specific modulation of cortical connectivity between neural oscillations in key motor regions during the early phase after stroke. EEG and EMG recordings were examined...... from 15 patients and 18 controls during a precision grip task using the affected hand. Each patient attended two sessions in the acute and subacute phase (median of 3 and 34 days) post-stroke. Dynamic causal modelling (DCM) for induced responses was used to investigate task-specific modulations...... of oscillatory couplings in a bilateral network comprising supplementary motor area (SMA), dorsal premotor cortex (PMd) and primary motor cortex (M1). Fourteen models were constructed for each subject, and the input induced by the experimental manipulation (task) was set to inferior parietal lobule (IPL...

  3. Affective symptoms and cognitive functions in the acute phase of Graves' thyrotoxicosis

    DEFF Research Database (Denmark)

    Vogel, Asmus; Elberling, Tina V; Hørding, Merete

    2007-01-01

    of cognitive deficits) had decreased significantly, with further normalisation 1-year after treatment initiation. In conclusion, patients had subjective reports of cognitive deficits in the toxic phase of Graves' thyrotoxicosis but comprehensive neuropsychological testing revealed no cognitive impairment......In the acute phase of Graves' thyrotoxicosis patients often have subjective cognitive complaints. Continuing controversy exists about the nature of these symptoms and whether they persist after treatment. This prospective study included 31 consecutively referred, newly diagnosed, and untreated....... No significant differences between the patient and the control group on neuropsychological test performances were found. Thyroid levels did not correlate with the neuropsychological test performances or psychiatric ratings. After reaching euthyroidism the level of affective symptoms (including reports...

  4. Acute Phase Proteins and Variables of Protein Metabolism in Dairy Cows during the Pre- and Postpartal Period

    Directory of Open Access Journals (Sweden)

    Cs. Tóthová

    2008-01-01

    Full Text Available The objective of the present study was to compare the concentrations of acute phase proteins and selected variables of protein metabolism in dairy cows of the Slovak Spotted breed from 4 weeks before parturition to 10 weeks after parturition. Acute phase proteins - haptoglobin (Hp and serum amyloid A (SAA - and variables of protein metabolism - total proteins, albumin, urea, creatinine, total immunoglobulins - were evaluated in blood serum. Significant differences were found in average values of the Hp and SAA concentrations in several groups during the monitored period (P P P P P P P P P < 0.001. The above mentioned results indicate that in the time around parturition there are significant changes in concentrations of acute phase proteins, as well as in the whole protein metabolism of dairy cows. These facts suggest that the postparturient period is a critical biological phase, throughout which there is the highest incidence of metabolic disorders.

  5. HIV infection and drugs of abuse: role of acute phase proteins.

    Science.gov (United States)

    Samikkannu, Thangavel; Rao, Kurapati V K; Arias, Adriana Y; Kalaichezian, Aarthi; Sagar, Vidya; Yoo, Changwon; Nair, Madhavan P N

    2013-09-17

    HIV infection and drugs of abuse such as methamphetamine (METH), cocaine, and alcohol use have been identified as risk factors for triggering inflammation. Acute phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) are the biomarkers of inflammation. Hence, the interactive effect of drugs of abuse with acute phase proteins in HIV-positive subjects was investigated. Plasma samples were utilized from 75 subjects with METH use, cocaine use, alcohol use, and HIV-positive alone and HIV-positive METH, cocaine, and alcohol users, and age-matched control subjects. The plasma CRP and SAA levels were measured by ELISA and western blot respectively and the CD4 counts were also measured. Observed results indicated that the CRP and SAA levels in HIV-positive subjects who are METH, cocaine and alcohol users were significantly higher when compared with either drugs of abuse or HIV-positive alone. The CD4 counts were also dramatically reduced in HIV-positive with drugs of abuse subjects compared with only HIV-positive subjects. These results suggest that, in HIV-positive subjects, drugs of abuse increase the levels of CRP and SAA, which may impact on the HIV infection and disease progression.

  6. Undernutrition, the Acute Phase Response to Infection, and Its Effects on Micronutrient Status Indicators12

    Science.gov (United States)

    Bresnahan, Kara A.; Tanumihardjo, Sherry A.

    2014-01-01

    Infection and undernutrition are prevalent in developing countries and demonstrate a synergistic relation. Undernutrition increases infection-related morbidity and mortality. The acute phase response (APR) is an innate, systemic inflammatory reaction to a wide array of disruptions in a host’s homeostasis, including infection. Released from immune cells in response to deleterious stimuli, proinflammatory cytokines act on distant tissues to induce behavioral (e.g., anorexia, weakness, and fatigue) and systemic effects of the APR. Cytokines act to increase energy and protein requirements to manifest fever and support hepatic acute phase protein (APP) production. Blood concentrations of glucose and lipid are augmented to provide energy to immune cells in response to cytokines. Additionally, infection decreases intestinal absorption of nutrients and can cause direct loss of micronutrients. Traditional indicators of iron, zinc, and vitamin A status are altered during the APR, leading to inaccurate estimations of deficiency in populations with a high or unknown prevalence of infection. Blood concentrations of APPs can be measured in nutrition interventions to assess the time stage and severity of infection and correct for the APR; however, standardized cutoffs for nutrition applications are needed. Protein-energy malnutrition leads to increased gut permeability to pathogens, abnormal immune cell populations, and impaired APP response. Micronutrient deficiencies cause specific immune impairments that affect both innate and adaptive responses. This review describes the antagonistic interaction between the APR and nutritional status and emphasizes the need for integrated interventions to address undernutrition and to reduce disease burden in developing countries. PMID:25398733

  7. Measurement of serum amyloid A1 (SAA1), a major isotype of acute phase SAA.

    Science.gov (United States)

    Xu, Yuanyuan; Yamada, Toshiyuki; Satoh, Takahiko; Okuda, Yasuaki

    2006-01-01

    Serum amyloid A (SAA), a plasma precursor of reactive amyloid deposits, is a multigene product. SAA1 and SAA2, with primary structures that are 93% identical (98 of 104 amino acids), behave as acute phase proteins, as demonstrated by their increasing levels in plasma. Heretofore, it has been understood that SAA1 predominates and functions as an isotype in plasma. However, accurate measurements differentiating the two isotypes have not been reported. In this study, using monoclonal antibodies specific for SAA1, we developed an enzyme-linked immunosorbent assay (ELISA) for SAA1. The levels and ratios of SAA1 in total SAA (TSAA) were investigated in healthy subjects and patients with rheumatoid arthritis (RA). The SAA1/TSAA ratio was 74 +/- 12% and 77 +/- 12% in healthy subjects and RA patients, respectively. In RA patients, the ratios were not influenced by SAA1 genotype, which has been proposed to affect plasma SAA values. The kinetics of SAA1 in inflamed patients undergoing hemodialysis was found to be parallel with total SAA and C-reactive protein. Finally, this study confirmed that SAA1 is a major isotype of acute phase SAA and may determine total SAA values. This specific assay could be used in the evaluation of SAA behavior in several clinical conditions.

  8. Is Customization in Antidepressant Prescribing Associated with Acute-Phase Treatment Adherence?

    Science.gov (United States)

    Merrick, Elizabeth L; Hodgkin, Dominic; Panas, Lee; Soumerai, Stephen B; Ritter, Grant

    2012-03-01

    OBJECTIVES: The objective was to explore whether prescribing variation is associated with duration of antidepressant use during the acute phase of treatment. Improving quality of care and increasing the extent to which treatment is patient-centered and customized are interrelated goals. Prescribing variation may be considered a marker of customization, and could be associated with better antidepressant treatment adherence. METHODS: A cross-sectional secondary data analysis examining the association between providers' antidepressant prescribing variation and patient continuity of antidepressant treatment. The data source was two states' Medicaid claims for dual-eligible Medicaid/Medicare patients. The sample included 383 patients with new episodes of antidepressant treatment, representing 70 providers with at least four patients in the sample. We tested two alternate measures of prescribing concentration: 1) share of prescriber's initial antidepressant prescribing accounted for by the two most common regimens, and 2) Herfindahl index. The HEDIS performance measure of effective acute-phase treatment (at least 84 out of 114 days with antidepressant) was the dependent variable. KEY FINDINGS: In multivariate analyses, the concentration measure based on the top two regimens was significant and inversely related to duration adequacy (p customized care.

  9. Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

    Directory of Open Access Journals (Sweden)

    Anastasia V. Ponasenko

    2017-01-01

    Full Text Available Infective endocarditis (IE is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE.

  10. Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

    Science.gov (United States)

    Rutkovskaya, Natalia V.; Kondyukova, Natalia V.; Odarenko, Yuri N.; Kazachek, Yana V.; Tsepokina, Anna V.; Barbarash, Leonid S.

    2017-01-01

    Infective endocarditis (IE) is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE. PMID:28659664

  11. Cortisol evaluation during the acute phase of traumatic brain injury-A prospective study.

    Science.gov (United States)

    Bensalah, Meriem; Donaldson, Malcolm; Aribi, Yamina; Iabassen, Malek; Cherfi, Lyes; Nebbal, Mustapha; Medjaher, Meriem; Haffaf, ElMehdi; Abdennebi, Benaissa; Guenane, Kamel; Djermane, Adel; Kemali, Zahra; OuldKablia, Samia

    2018-05-01

    Biochemical diagnosis of adrenal insufficiency (AI) is difficult in the context of traumatic brain injury (TBI). To assess the frequency and predictive factors of AI in victims of TBI from Algiers. Between November 2009 and December 2013, TBI victims had a single 8-9 am serum cortisol measurement during the acute postinjury period (0-7 days). AI was defined according to basal cortisol levels of 83, 276 and 414 nmol/L. Variables studied were TBI severity according to Glasgow coma scale, duration of intubation and coma, pupillary status, hypotension, anaemia, brain imaging findings, diabetes insipidus and medication. Insulin tolerance test was performed during the recovery phase, defining AI as peak cortisol 414 nmol/L. Hydrocortisone replacement is advised in TBI patients with morning cortisol <276 nmol/L or those <414 nmol/L with additional risk factors for AI. As acute and subsequent AI are poorly correlated, patients with moderate/severe TBI require adrenal re-evaluation during the recovery phase. © 2018 John Wiley & Sons Ltd.

  12. Differential immunodominance hierarchy of CD8+ T-cell responses in HLA-B*27

    DEFF Research Database (Denmark)

    Adland, Emily; Hill, Matilda; Lavandier, Nora

    2018-01-01

    The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05- restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We stu...

  13. Determination and application of immunodominant regions of SARS coronavirus spike and nucleocapsid proteins recognized by sera from different animal species.

    Science.gov (United States)

    Yu, Meng; Stevens, Vicky; Berry, Jody D; Crameri, Gary; McEachern, Jennifer; Tu, Changchun; Shi, Zhengli; Liang, Guodong; Weingartl, Hana; Cardosa, Jane; Eaton, Bryan T; Wang, Lin-Fa

    2008-02-29

    Knowledge of immunodominant regions in major viral antigens is important for rational design of effective vaccines and diagnostic tests. Although there have been many reports of such work done for SARS-CoV, these were mainly focused on the immune responses of humans and mice. In this study, we aim to search for and compare immunodominant regions of the spike (S) and nucleocapsid (N) proteins which are recognized by sera from different animal species, including mouse, rat, rabbit, civet, pig and horse. Twelve overlapping recombinant protein fragments were produced in Escherichia coli, six each for the S and N proteins, which covered the entire coding region of the two proteins. Using a membrane-strip based Western blot approach, the reactivity of each antigen fragment against a panel of animal sera was determined. Immunodominant regions containing linear epitopes, which reacted with sera from all the species tested, were identified for both proteins. The S3 fragment (aa 402-622) and the N4 fragment (aa 220-336) were the most immunodominant among the six S and N fragments, respectively. Antibodies raised against the S3 fragment were able to block the binding of a panel of S-specific monoclonal antibodies (mAb) to SARS-CoV in ELISA, further demonstrating the immunodominance of this region. Based on these findings, one-step competition ELISAs were established which were able to detect SARS-CoV antibodies from human and at least seven different animal species. Considering that a large number of animal species are known to be susceptible to SARS-CoV, these assays will be a useful tool to trace the origin and transmission of SARS-CoV and to minimise the risk of animal-to-human transmission.

  14. Virtual histology study of atherosclerotic plaque composition in patients with stable angina and acute phase of acute coronary syndromes without ST segment elevation

    Directory of Open Access Journals (Sweden)

    Ivanović Miloš

    2013-01-01

    Full Text Available Introduction. Rupture of vulnerable atherosclerotic plaques is the cause of most acute coronary syndromes (ACS. Postmortem studies which compared stable coronary lesions and atherosclerotic plaques in patients who have died because of ACS indicated high lipid-core content as one of the major determinants of plaque vulnerability. Objective. Our primary goal was to assess the potential relations of plaque composition determined by IVUS-VH (Intravascular Ultrasound - Virtual Histology in patients with stable angina and subjects in acute phase of ACS without ST segment elevation. Methods. The study comprised of 40 patients who underwent preintervention IVUS examination. Tissue maps were reconstructed from radio frequency data using IVUS-VH software. Results. We analyzed 53 lesions in 40 patients. Stable angina was diagnosed in 24 patients (29 lesions, while acute phase of ACS without ST elevation was diagnosed in 16 patients (24 lesions. In the patients in acute phase of ACS without ST segment elevation IVUS-VH examination showed a significantly larger area of the necrotic core at the site of minimal lumen area and a larger mean of the necrotic core volume in the entire lesion comparing to stable angina subjects (1.84±0.90 mm2 vs. 0.96±0.69 mm2; p<0.001 and 20.94±15.79 mm3 vs. 11.54±14.15 mm3; p<0.05 respectively. Conclusion. IVUS-VH detected that the necrotic core was significantly larger in atherosclerotic lesions in patients in acute phase of ACS without ST elevation comparing to the stable angina subjects and that it could be considered as a marker of plaque vulnerability.

  15. Therapeutical effect on blood-flow in three-phase scanning in primary malignant tumours and acute osteomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Kovacic, K; Kusic, Z [Clinical Hospital Sestre Milosrdnice, Zagreb (Croatia). Dept. of Oncology and Nuclear Medicine; Cepulic, M [Children` s Hospital, Zagreb (Croatia)

    1994-10-01

    In the studies where the bone scan was limited only to the late static image, the main disadvantage was its nonspecifity. With three-phase bone scan the number of false positive findings was reduced by some peculiar diseases; for instance, acute hematogenous osteomyelitis. It is well known that various diseases, such as nonunion of the fracture, some surgical interventions, avascular necrosis... can imitate acute osteomyelitis on the static image. These diseases can only be differentiated from inflammation by blood-flow. Therefore, in all patients with the diagnosis of primary bone disease tumor, inflammation, trauma, aseptic necrosis... three-phase bone scintigraphy is performed. Here, only the patients with acute osteomyelitis and primary malignant bone tumors will be presented: the basic scintigram was done before the therapy started, and the second one as a part of the follow-up - in some patients during the therapy and in some after its ending. We noticed that the most reliable part of three-phase bone scan responding to the therapy is angioscintigraphy (blood-flow) and in some cases early static (blood-pool) image. These two phases, especially the first one, are in good correlation with the clinic, in contrast to the third phase which is delayed. From the presented cases it could be concluded that in acute osteomyelitis and primary malignant tumors, blood-flow and blood-pool images are unavoidable phases of the bone scanning when we want to correctly evaluate the effects of the therapy. (author).

  16. Characterization of an immunodominant cancer-specific O-glycopeptide epitope in murine podoplanin (OTS8)

    DEFF Research Database (Denmark)

    Steentoft, Catharina; Schjoldager, Katrine T; Cló, Emiliano

    2010-01-01

    antibody 237, developed to a spontaneous murine fibrosarcoma, was shown to be directed to murine podoplanin (OTS8) with truncated Tn O-glycans. Our understanding of such cancer-specific auto-antibodies to truncated glycoforms of glycoproteins is limited. Here we have investigated immunogenicity...... of a chemoenzymatically produced Tn-glycopeptide derived from the putative murine podoplanin O-glycopeptide epitope. We found that the Tn O-glycopeptide was highly immunogenic in mice and produced a Tn-glycoform specific response with no reactivity against unglycosylated peptides or the O-glycopeptide with extended O......-glycan (STn and T glycoforms). The immunodominant epitope was strictly dependent on the peptide sequence, required Tn at a specific single Thr residue (Thr(77)), and antibodies to the epitope were not found in naive mice. We further tested a Tn O-glycopeptide library derived from human podoplanin...

  17. Multidetector row computed tomography of acute pancreatitis: Utility of single portal phase CT scan in short-term follow up

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Yongwonn [Department of Radiology, Konkuk University Medical Center, 4-12, Hwayang-dong, Gwangjin-gu, Seoul 143-729 (Korea, Republic of); Park, Hee Sun, E-mail: heesun.park@gmail.com [Department of Radiology, Konkuk University Medical Center, 4-12, Hwayang-dong, Gwangjin-gu, Seoul 143-729 (Korea, Republic of); Kim, Young Jun; Jung, Sung Il; Jeon, Hae Jeong [Department of Radiology, Konkuk University Medical Center, 4-12, Hwayang-dong, Gwangjin-gu, Seoul 143-729 (Korea, Republic of)

    2012-08-15

    Objective: The purpose of this study is to evaluate the question of whether nonenhanced CT or contrast enhanced portal phase CT can replace multiphasic pancreas protocol CT in short term monitoring in patients with acute pancreatitis. Materials and methods: This retrospective study was approved by the Institutional Review Board. From April 2006 to May 2010, a total of 52 patients having acute pancreatitis who underwent initial dual phase multidetector row CT (unenhanced, arterial, and portal phase) at admission and a short term (within 30 days) follow up dual phase CT (mean interval 10.3 days, range 3-28 days) were included. Two abdominal radiologists performed an independent review of three sets of follow up CT images (nonenhanced scan, single portal phase scan, and dual phase scan). Interpretation of each image set was done with at least 2-week interval. Radiologists evaluated severity of acute pancreatitis with regard to pancreatic inflammation, pancreatic necrosis, and extrapancreatic complication, based on the modified CT severity index. Scores of each image set were compared using a paired t-test and interobserver agreement was evaluated using intraclass correlation coefficient statistics. Results: Mean scores of sum of CT severity index on nonenhanced scan, portal phase scan, and dual phase scan were 5.7, 6.6, and 6.5 for radiologist 1, and 5.0, 5.6, and 5.8 for radiologist 2, respectively. In both radiologists, contrast enhanced scan (portal phase scan and dual phase scan) showed significantly higher severity score compared with that of unenhanced scan (P < 0.05), while portal phase and dual phase scan showed no significant difference each other. The trend was similar regarding pancreatic inflammation and extrapancreatic complications, in which contrast enhanced scans showed significantly higher score compared with those of unenhanced scan, while no significant difference was observed between portal phase scan and dual phase scan. In pancreatic necrosis

  18. Profile of Infections in Newly Diagnosed Patients with Acute Leukemia During the Induction Phase of Treatment

    International Nuclear Information System (INIS)

    Sayed, H.A.; Talaat, S.M.; El-Mahallawy, H.A.; Kaddah, A.M.; Ismael, H.T.

    2009-01-01

    Acute leukemia is the most common pediatric malignancy. Despite the significant progress in the treatment of infectious complications, infection-related morbidity and mortality continue to be of great importance. Prompt initiation of the appropriate empiric antibiotic treatment has improved infection outcome. The aim of the present study is to assess the type, frequency, and severity of infectious complications in a cohort of pediatric cancer patients treated at a single medical institution. We also aim to identify factors affecting bloodstream infections in newly diagnosed ALL and AML pediatric patients during the induction phase of treatment. Patients and Methods: This study was carried out at the Department of Pediatric Oncology, National Cancer Institute, Cairo University, during the time period from January 1st to June 30th 2007. Inclusion criteria were pediatric age group (from 0-16 years), newly diagnosed acute leukemia, positive blood culture and documented site of infection. Data were analyzed using the SPSS package version 15. A p-value £0.05 was considered significant. Results: This is a retrospective study including 100 newly diagnosed cases of acute leukemia. Fifty-four patients had ALL, and 46 patients had AML. 348 infectious episodes were recorded. Blood stream infections (BSI) occurred once or twice in 32%, 3-4 episodes in 58%, and five or more episodes in 10% of the cases. Gram-positive cocci were the most frequently observed cause of BSI, accounting for 77.9% of the total isolates followed by Gram negative organisms seen in 18.9% and mixed infections in 8%. The majority of the episodes (n= 208, 58.4%) responded to first-line empirical antibiotic therapy. Conclusion: Clinical and laboratory risk factors could be identified and can help prediction of serious BSI.

  19. Oxidative stress and acute-phase response in patients with pressure sores.

    Science.gov (United States)

    Cordeiro, Maria Bernarda Cavalcanti; Antonelli, Elida Juliana; da Cunha, Daniel Ferreira; Júnior, Alceu Afonso Jordão; Júnior, Virmondes Rodrigues; Vannucchi, Helio

    2005-09-01

    We investigated the relation between oxidative stress and the occurrence of the acute-phase response with serum ascorbic acid and alpha-tocopherol levels in patients with pressure sores. The following groups of patients were studied: 1) those who had patients with pressure sores, 2) those who had pneumonia, and 3) those who did not develop pressure sores or any type of infection (control). Concentrations of total proteins, albumin, creatinine, iron, ferritin, transferrin, C-reactive protein, alpha1-acid glycoprotein, total iron-binding capacity, ascorbic acid, alpha-tocopherol, and malondialdehyde were measured during the first days of hospitalization. Albumin concentrations were significantly lower (P pressure sores compared with controls. Concentrations of ascorbic acid and alpha-tocopherol were significantly decreased (P pressure sores or infection, whereas malondialdehyde concentrations were significantly increased (P pressure sores and 10 of 12 patients (83.33%) with pneumonia presented serum ascorbic acid concentrations below the reference value (34 to 91 micromol/L). Concentrations of ascorbic acid and alpha-tocopherol versus malondialdehyde were significantly correlated in the three patient groups (r = -0.44, P pressure sores and acute infection present a systemic inflammatory response accompanied by an increase in lipid peroxidation that is associated with decreased serum ascorbic acid and alpha-tocopherol levels, suggesting that these patients may be at risk for important nutritional deficiencies.

  20. Transient dysautonomia in an acute phase of encephalopathy with biphasic seizures and late reduced diffusion.

    Science.gov (United States)

    Ichimiya, Yuko; Kaku, Noriyuki; Sakai, Yasunari; Yamashita, Fumiya; Matsuoka, Wakato; Muraoka, Mamoru; Akamine, Satoshi; Mizuguchi, Soichi; Torio, Michiko; Motomura, Yoshitomo; Hirata, Yuichiro; Ishizaki, Yoshito; Sanefuji, Masafumi; Torisu, Hiroyuki; Takada, Hidetoshi; Maehara, Yoshihiko; Ohga, Shouichi

    2017-08-01

    Paroxysmal sympathetic hyperactivity (PSH) is a dysautonomic condition that is associated with various types of acquired brain injuries. Traumatic brain lesions have been documented as the leading cause of PSH. However, detailed clinical features of pediatric PSH caused by intrinsic brain lesions remain to be elusive. We present a 3-year-old boy, who had been diagnosed as having cerebral palsy, developmental delay and epilepsy after perinatal hypoxia-induced brain injury. He developed status epilepticus with fever on the third day of respiratory infection. Whereas the seizure was terminated by systemic infusion of midazolam, consciousness remained disturbed for the next 48h. Serial magnetic resonance imaging studies revealed that acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) evolved on 3days after the seizure. Therapeutic hypothermia was immediately introduced, however, the brain lesion extended to the whole subcortical white matters on day 8. The intermittent bilateral dilation of pupils with increased blood pressure and tachycardia were observed until day 12. Real-time monitoring of electroencephalograms ruled out the recurrent attacks of seizures. The abnormal signs of autonomic nervous system gradually ceased and never relapsed after recovery from the hypothermia. PSH or a transient condition of dysautonomia may emerge and persist during the acute phase of AESD. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  1. Changes in plasma homocyst(e)ine in the acute phase after stroke.

    Science.gov (United States)

    Howard, Virginia J; Sides, Elizabeth G; Newman, George C; Cohen, Stanley N; Howard, George; Malinow, M Rene; Toole, James F

    2002-02-01

    Elevated plasma homocyst(e)ine [H(e)] concentration has been associated with an increased risk of stroke. Although the literature suggests that H(e) increases from the acute to the convalescent phase after a stroke, it is not known whether H(e) changes within the acute period. A prospective, multicenter study was conducted to examine changes in H(e) during the 2 weeks after an incident stroke. Blood samples were collected at days 1, 3, 5, 7, and between 10 and 14 days after the stroke. Seventy-six participants (51 men) were enrolled from 9 sites from February 1997 through June 1998. Mean age was 65.6 years, and subjects had at least two H(e) measurements. The estimated mean H(e) level at baseline was 11.3+/-0.5 micromol/L, which increased consistently to a mean of 12.0+/-0.05, 12.4+/-0.5, 13.3+/-0.5, and 13.7+/-0.7 micromol/L at days 3, 5, 7, and 10 to 14, respectively. The magnitude of the change in H(e) was not affected by age, sex, smoking status, alcohol use, history of hypertension or diabetes, or Rankin Scale Score. ; These data suggest that the clinical interpretation of H(e) after stroke and the eligibility for clinical trials assessing treatment for elevated H(e) levels require an adjustment in time since stroke to properly interpret the observed H(e) levels.

  2. Global aphasia as a predictor of mortality in the acute phase of a first stroke

    Directory of Open Access Journals (Sweden)

    F F Oliveira

    2011-01-01

    Full Text Available OBJECTIVE: To establish whether vascular aphasic syndromes can predict stroke outcomes. METHOD: Thirty-seven adults were evaluated for speech and language within 72 hours after a single first-ever ischemic brain lesion, in blind association to CT and/or MR. RESULTS: Speech or language disabilities were found in seven (87.5% of the eight deceased patients and twenty-six (89.7% of the twenty-nine survivors. Global aphasia was identified in eleven patients, all with left hemisphere lesions (nine mute; five deceased, consisting on a risk factor for death in the acute stroke phase (ρ=0.022. Age (z=1.65; ρ>0.09, thrombolysis (ρ=0.591, infarct size (ρ=0.076 and side (ρ=0.649 did not significantly influence survival. Absence of aphasia did not predict a better evolution, regardless of the affected hemisphere. Prevalence of cardiovascular risk factors was similar for all patient groups. CONCLUSION: Global aphasia in acute stroke can adversely affect prognosis, translated into impairment of dominant perisylvian vascular territories, with mutism as an important semiological element.

  3. Body composition and phase angle in Russian children in remission from acute lymphoblastic leukemia

    Science.gov (United States)

    Tseytlin, G. Ja; Khomyakova, I. A.; Nikolaev, D. V.; Konovalova, M. V.; Vashura, A. Yu; Tretyak, A. V.; Godina, E. Z.; Rudnev, S. G.

    2010-04-01

    Elevated degree of body fatness and changes in other body composition parameters are known to be common effects of treatment for acute lymphoblastic leukemia (ALL) in children. In order to study peculiarities of somatic growth and development in ALL survivors, we describe the results of BIA body composition analysis of 112 boys and 108 girls aged 5-18 years in remission from ALL (remission time range 1-13 years) compared to data from the same number of age- and sex-matched healthy controls (n=220). Detrimental effect on height in ALL boys was observed, whereas girls experienced additional weight gain compared to healthy subjects. In ALL patients, resistance, body fat, and percent body fat were significantly increased. The reactance, phase angle, absolute and relative values of skeletal muscle and body cell mass were significantly decreased. Principal component analysis revealed an early prevalence of adiposity traits in the somatic growth and development of ALL girls compared to healthy controls.

  4. Use of escitalopram to prevent depression and cognitive impairments in the acute phase of stroke

    Directory of Open Access Journals (Sweden)

    Dina Rustemovna Khasanova

    2013-01-01

    Full Text Available The purpose of the study was to comparatively analyze the rate of post-stroke depression and cognitive impairments in escitalopram (cipralex-treated and untreated (control patients. Emotional and affective cognitive symptoms, neurological deficit, and day-to-day activity were evaluated over time 1, 3, and 6 months after treatment. The results of the study indicated that escitalopram used to prevent depression in the acute phase of stroke provided a good effect. This drug caused a prompter recovery of cognitive impairments and reduced the pace of development of neurodegenerative disorders underlying the post-stroke 2D (depression and dementia syndrome. The study group was recorded to have more favorable functional outcomes of stroke and patient mobility indicators associated with lower disability rates.

  5. Pituitary dysfunction in traumatic brain injury: Is evaluation in the acute phase worthwhile?

    Directory of Open Access Journals (Sweden)

    Pradip P Dalwadi

    2017-01-01

    Full Text Available Introduction: Traumatic brain injury (TBI is an under-recognized cause of hypopituitarism. According to recent data, it could be more frequent than previously known. However, there is a scarcity of data in Indian population. Aims: The main aim of the study was to determine the prevalence of pituitary hormone deficiencies in the acute phase of TBI. The secondary objectives were to correlate the severity of trauma with basal hormone levels and to determine whether initial hormone deficiencies predict mortality. Subjects and Methods: Forty-nine TBI patients (41 men and 8 women were included in this study. Pituitary functions were evaluated within 24 h of admission. Results: Gonadotropin deficiency was found in 65.3% patient while 46.9% had low insulin-like growth factor-1, 12.24% had cortisol level <7 mcg/dl. Cortisol and prolactin level were positively correlated with the severity of TBI suggestive of stress response. Free triiodothyronine (fT3 and free thyroxine were significantly lower in patients with increasing severity of tuberculosis. Logistic regression analysis revealed that mortality after TBI was unrelated to the basal pituitary hormone levels except low T3 level, which was found to be positively related to mortality. Conclusions: Pituitary dysfunction is common after TBI and the most commonly affected axes are growth hormone and gonadotropin axis. Low fT3 correlates best with mortality. During the acute phase of TBI, at least an assessment of cortisol is vital as undetected cortisol deficiency can be life-threatening

  6. Selective coronarography and ventriculography with Iopamidol in the acute phase of myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Ricci Maccarini, P; Benenati, P M; Bellanti, G; Piscitelli, G

    1988-01-01

    The new techniques for an early treatement of acute myocardial infarction (AMI), such as thrombolysis and percutaneous transluminal angioplasty, often necessitate rapid and accurate radiological evaluation of coronaric lesions and left ventricular function. The aim of the present study was to evaluate both safety and tolerability of selective coronarography (SC) and left ventriculography (LVG), with iopamidol 370 mg I/ml as a contrast medium, in the acute phase of AMI. Thirty-nine patients aged 26-29 years, were examined: 18 group A, within 4 days (mean 2.6+-0.8 SD) and 21, group B, within 5-15 days after AMI (mean 8.8+-3 SD). Contrast media (cm) dosage varied from 150 to 300 ml (2.43-5.5 ml/bw). During the procedure, ECG was continuosly recorded; left ventricular pressure was registered immediately and 30 minutes after cm administration. During the following 9 days ECG tracings and plasmatic cytolysisenzymes were monitored. During the examination no patient complained of any symptoms. After LVG slight elevations in end diastolic pressure were detected in all patients (mean increase 4.7 mmHg), which were not relevant from a clinical point of view. In 11/39 cases ventricular tachycardia was observed, which spontaneously ceased. During SC no change in ECG tracings was registered except in one patient, group A, in whom complete transitory heart block was detected. After SC no alteration in instrumental and biochemical parameters was registered except in one patient, group B, in whom a reinfarction due to right coronaric artery occlusion was observed. In conclusion, these results suggest that both SC and LVG with iopamidol are safe techniques also in the early phase of myocardial infarction. 24 refs.

  7. EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery.

    Science.gov (United States)

    Zhang, Shao-jie; Ke, Zheng; Li, Le; Yip, Shea-ping; Tong, Kai-yu

    2013-04-01

    Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague-Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely correlated with the neural

  8. EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery

    International Nuclear Information System (INIS)

    Zhang, Shao-jie; Ke, Zheng; Tong, Kai-yu; Li, Le; Yip, Shea-ping

    2013-01-01

    Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague–Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p < 0.05) and De Ryck's test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely

  9. Differential Effects of Acute Stress on Anticipatory and Consummatory Phases of Reward Processing

    Science.gov (United States)

    Kumar, Poornima; Berghorst, Lisa H.; Nickerson, Lisa D.; Dutra, Sunny J.; Goer, Franziska; Greve, Douglas; Pizzagalli, Diego A.

    2014-01-01

    Anhedonia is one of the core symptoms of depression and has been linked to blunted responses to rewarding stimuli in striatal regions. Stress, a key vulnerability factor for depression, has been shown to induce anhedonic behavior, including reduced reward responsiveness in both animals and humans, but the brain processes associated with these effects remain largely unknown in humans. Emerging evidence suggests that stress has dissociable effects on distinct components of reward processing, as it has been found to potentiate motivation/‘wanting’ during the anticipatory phase but reduce reward responsiveness/‘liking’ during the consummatory phase. To examine the impact of stress on reward processing, we used a monetary incentive delay (MID) task and an acute stress manipulation (negative performance feedback) in conjunction with functional magnetic resonance imaging (fMRI). Fifteen healthy participants performed the MID task under no-stress and stress conditions. We hypothesized that stress would have dissociable effects on the anticipatory and consummatory phases in reward-related brain regions. Specifically, we expected reduced striatal responsiveness during reward consumption (mirroring patterns previously observed in clinical depression) and increased striatal activation during reward anticipation consistent with non-human findings. Supporting our hypotheses, significant Phase (Anticipation/Consumption) x Stress (Stress/No-stress) interactions emerged in the putamen, nucleus accumbens, caudate and amygdala. Post-hoc tests revealed that stress increased striatal and amygdalar activation during anticipation but decreased striatal activation during consumption. Importantly, stress-induced striatal blunting was similar to the profile observed in clinical depression under baseline (no-stress) conditions in prior studies. Given that stress is a pivotal vulnerability factor for depression, these results offer insight to better understand the etiology of this

  10. Acute low-level alcohol consumption reduces phase locking of event-related oscillations in rodents.

    Science.gov (United States)

    Amodeo, Leslie R; Wills, Derek N; Ehlers, Cindy L

    2017-07-14

    Event-related oscillations (EROs) are rhythmic changes that are evoked by a sensory and/or cognitive stimulus that can influence the dynamics of the EEG. EROs are defined by the decomposition of the EEG signal into magnitude (energy) and phase information and can be elicited in both humans and animals. EROs have been linked to several relevant genes associated with ethanol dependence phenotypes in humans and are altered in selectively bred alcohol-preferring rats. However, pharmacological studies are only beginning to emerge investigating the impact low intoxicating doses of ethanol can have on event-related neural oscillations. The main goal of this study was to investigate the effects of low levels of voluntary consumption of ethanol, in rats, on phase locking of EROs in order to give further insight into the acute intoxicating effects of ethanol on the brain. To this end, we allow rats to self-administer unsweetened 20% ethanol over 15 intermittent sessions. This method results in a stable low-dose consumption of ethanol. Using an auditory event-related potential "oddball" paradigm, we investigated the effects of alcohol on the phase variability of EROs from electrodes implanted into the frontal cortex, dorsal hippocampus, and amygdala. We found that intermittent ethanol self-administration was sufficient to produce a significant reduction in overall intraregional synchrony across all targeted regions. These data suggest that phase locking of EROs within brain regions known to be impacted by alcohol may represent a sensitive biomarker of low levels of alcohol intoxication. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice

    DEFF Research Database (Denmark)

    Poulsen, Sarah Søs; Knudsen, Kristina Bram; Jackson, Petra

    2017-01-01

    of acute phase proteins to the blood. We identified physicochemical determinants of MWCNT-induced systemic acute phase response by analyzing effects of pulmonary exposure to 14 commercial, well-characterized MWCNTs in female C57BLI6J mice pulmonary exposed to 0, 6, 18 or 54 lag MWCNT/mouse. Plasma levels...... of acute phase response proteins serum amyloid A1/2 (SAA1/2) and SAA3 were determined on day 1, 28 or 92. Expression levels of hepatic Saal and pulmonary Saa3 mRNA levels were assessed to determine the origin of the acute phase response proteins. Pulmonary Saa3 mRNA expression levels were greater...... limited changes were observed on day 28 and 92. SAA1/2 and SAA3 protein levels did not correlate and only SAA3 protein levels correlated with neutrophil influx. The multiple regression analyses revealed a protective effect of MWCNT length on SAA1/2 protein level on day 1, such that a longer length...

  12. CD26: A Prognostic Marker of Acute Lymphoblastic Leukemia in Children in the Post Remission Induction Phase.

    Science.gov (United States)

    Mehde, Atheer Awad; Yusof, Faridah; Adel Mehdi, Wesen; Zainulabdeen, Jwan Abdulmohsin

    2015-01-01

    ALL is an irredeemable disease due to the resistance to treatment. There are several influences which are involved in such resistance to chemotherapy, including oxidative stress as a result of the generation of reactive oxygen species (ROS) and presence of hypodiploid cells. Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase-4, is a 110 kDa, multifunctional, membrane-bound glycoprotein. The aim of this study was to evaluate the clinical significance of serum CD26 in patients with acute lymphoblastic leukaemia patients in the post remission induction phase, as well as the relationship between CD26 activity and the oxidative stress status. CD26, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), in addition to activity of related enzymes myeloperoxidase, glutathione- s-transferase and xanthine oxidase, were analysed in sixty children with acute lymphoblastic leukaemia in the post remission induction phase. The study showed significant elevation in CD26, TOS and OSI levels in patients with acute lymphoblastic leukaemia in the post remission induction phase in comparison to healthy control samples. In contrast, myeloperoxidase, glutathione-s-transferase and xanthine oxidase activities were decreased significantly. A significant correlation between CD26 concentration and some oxidative stress parameters was evident in ALL patients. Serum levels of CD26 appear to be useful as a new biomarker of oxidative stress in children with acute lymphoblastic leukaemia in the post remission induction phase, and levels of antioxidants must be regularly estimated during the treatment of children with ALL.

  13. Serum protein capillary electrophoresis and measurement of acute phase proteins in a captive cheetah (Acinonyx jubatus) population.

    Science.gov (United States)

    Depauw, Sarah; Delanghe, Joris; Whitehouse-Tedd, Katherine; Kjelgaard-Hansen, Mads; Christensen, Michelle; Hesta, Myriam; Tugirimana, Pierrot; Budd, Jane; Dermauw, Veronique; Janssens, Geert P J

    2014-09-01

    Renal and gastrointestinal pathologies are widespread in the captive cheetah (Acinonyx jubatus) population but are often diagnosed at a late stage, because diagnostic tools are limited to the evaluation of clinical signs or general blood examination. Presently, no data are available on serum proteins and acute-phase proteins in cheetahs during health or disease, although they might be important to improve health monitoring. This study aimed to quantify serum proteins by capillary electrophoresis in 80 serum samples from captive cheetahs, categorized according to health status and disease type. Moreover, serum amyloid A concentrations were measured via a turbidimetric immunoassay validated in domestic cats, whereas haptoglobin and C-reactive protein were determined by non-species-specific functional tests. Cheetahs classified as healthy had serum protein and acute phase protein concentrations within reference ranges for healthy domestic cats. In contrast, unhealthy cheetahs had higher (P cheetahs suffering from chronic kidney disease were significantly greater compared to the reportedly healthy cheetahs. Our study indicates that serum proteins in the cheetah can be analyzed by routine capillary electrophoresis, whereas acute-phase proteins can be measured using available immunoassays or non-species-specific techniques, which are also likely to be applicable in other exotic felids. Moreover, results suggest that serum amyloid A and haptoglobin are important acute-phase proteins in the diseased cheetah and highlight the need to evaluate their role as early-onset markers for disease.

  14. Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function

    NARCIS (Netherlands)

    Sander, L.E.; Sackett, S.D.; Dierssen, U.; Beraza, N.; Linke, R.; Müller, M.R.; Blander, J.M.; Tacke, F.; Trautwein, C.

    2010-01-01

    Acute-phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and antiinflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined.

  15. Hepatic acute phase proteins control innate immune responses during infection by promoting myeloid derived suppressor cell function

    NARCIS (Netherlands)

    Sander, Leif E.; Dutton Sackett, Sara; Dierssen, Uta; Beraza, Naiara; Linke, Reinhold P.; Muller, Michael; Magarian Blander, Julie; Tacke, Frank; Trautwein, Christian

    2010-01-01

    Acute phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and anti-inflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined.

  16. Editorial: dose-dependent ZnO particle-induced acute phase response in humans warrants re-evaluation of occupational exposure limits for metal oxides

    DEFF Research Database (Denmark)

    Vogel, Ulla Birgitte; Cassee, Flemming R.

    2018-01-01

    in autonomic imbalance and particle-induced pulmonary inflammation and acute phase response.The acute phase response is the systemic response to acute and chronic inflammatory states caused by for example bacterial infection, virus infection, trauma and infarction. It is characterized by differential...... studies and SAA has been causally related to the formation of plaques in the aorta in animal studies.In a recent paper in Particle and Fibre Toxicology, Christian Monse et al. provide evidence that inhalation of ZnO nanoparticles induces dose-dependent acute phase response in humans at dose levels well...

  17. STAT3 Activation in Skeletal Muscle Links Muscle Wasting and the Acute Phase Response in Cancer Cachexia

    Science.gov (United States)

    Kunzevitzky, Noelia; Guttridge, Denis C.; Khuri, Sawsan; Koniaris, Leonidas G.; Zimmers, Teresa A.

    2011-01-01

    Background Cachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6), and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA) are synthesized by hepatocytes in response to IL-6 as part of the innate immune response. To gain insight into the relationships among these observations, we studied mice with moderate and severe Colon-26 (C26)-carcinoma cachexia. Methodology/Principal Findings Moderate and severe C26 cachexia was associated with high serum IL-6 and IL-6 family cytokines and highly similar patterns of skeletal muscle gene expression. The top canonical pathways up-regulated in both were the complement/coagulation cascade, proteasome, MAPK signaling, and the IL-6 and STAT3 pathways. Cachexia was associated with increased muscle pY705-STAT3 and increased STAT3 localization in myonuclei. STAT3 target genes, including SOCS3 mRNA and acute phase response proteins, were highly induced in cachectic muscle. IL-6 treatment and STAT3 activation both also induced fibrinogen in cultured C2C12 myotubes. Quantitation of muscle versus liver fibrinogen and SAA protein levels indicates that muscle contributes a large fraction of serum acute phase proteins in cancer. Conclusions/Significance These results suggest that the STAT3 transcriptome is a major mechanism for wasting in cancer. Through IL-6/STAT3 activation, skeletal muscle is induced to synthesize acute phase proteins, thus establishing a molecular link between the observations of high IL-6, increased acute phase response proteins and muscle wasting in cancer. These results suggest a mechanism by which STAT3 might causally influence muscle wasting by altering the profile of genes expressed and translated in muscle such

  18. Involvement of activated leukocytes in the regulation of plasma levels of acute phase proteins in microgravity simulation experiments

    Science.gov (United States)

    Larina, Olga; Bekker, Anna; Turin-Kuzmin, Alexey

    2016-07-01

    Earth-based studies of microgravity effects showed the induction of the mechanisms of acute phase reaction (APR). APR comprises the transition of stress-sensitive protein kinases of macrophages and other responsive cells into the active state and the phosphorylation of transcription factors which in turn stimulate the production of acute-phase reaction cytokines. Leukocyte activation is accompanied by the acceleration of the formation of oxygen radicals which can serve a functional indice of leukocyte cell state. The series of events at acute phase response result in selective changes in the synthesis of a number of secretory blood proteins (acute phase proteins, APPs) in liver cells thus contributing the recovery of homeostasis state in the organism. Earlier experiment with head-down tilt showed the increase in plasma concentrations of two cytokine mediators of acute phase response, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) being the outcome of the activation of producer cells, foremost, leukocytes. In experiment with 4-day dry immersion chemiluminescent (ChL) reply of the whole blood samples to a test stimulus were studied along with the measurements of plasma levels of APPs, namely, alpha1-antitrypsin (alpha1-AT), alpha1-acid glycoprotein (alpha1-AGP), alpha2-macroglobulin (alpha2-M), ceruloplasmin (Cer), haptoglobin (Hp), C3-complement component (C3), C-reactive protein (CRP). Eight individuals aged 21.2 ± 3.2 years were the test subjects in the investigation. Protein studies showed a noticeable increase in the mean plasma levels of all APPs measured in experiment thus producing the evidence of the activation of acute phase response mechanisms while individual patterns revealed variability during the immersion period. The overall trends were similar to these in the previous immersion series. The augment in the strength of signal in stimulated light emission tests was higher after 1- and 2-day of immersion exposure than before the

  19. Acute phase protein concentrations in serum and milk from healthy cows, cows with clinical mastitis and cows with extramammary inflammatory conditions

    NARCIS (Netherlands)

    Nielsen, B.H.; Jacobsen, S.; Andersen, P.H.; Niewold, T.A.; Heegaard, P.M.H.

    2004-01-01

    The concentrations of the two acute phase proteins, serum amyloid A and haptoglobin, in serum and milk were compared in 10 cows with clinical mastitis, 11 cows with extramammary inflammatory conditions and 10 clinically healthy control cows. The concentrations of both acute phase proteins were

  20. Fasa Registry on Acute Myocardial Infarction (FaRMI: Feasibility Study and Pilot Phase Results.

    Directory of Open Access Journals (Sweden)

    Ehsan Bahramali

    Full Text Available Myocardial infarction (MI is the leading cause of death in Iran. Every attempt to improve treatment patterns and patient outcomes needs a surveillance system to both consider the efficacy and safety measures. Fasa Registry on Myocardial Infarction (FaRMI is the first population-based registry for acute MI in Iran targeted to provide meticulous description of patients' characteristics, to explore the management patterns of these patients, to discover the degree of adherence to the practice guidelines, and to investigate the determinants of poor in-hospital and later outcomes.A diagnosis of acute MI (type I, II and III was made upon the accepted criteria by the attending cardiologists and types IV and V MI were excluded. Two registrar nurses gathered data on demographics, place of residence and ethnicity, past medical history, risk factors, and the clinical course. Management patterns in the pre-hospital setting, during the hospital stay and at the discharge time were recorded. Routine laboratory results and cardiac biomarkers on three consecutive days were registered.pilot phase included the first 95 patients, 63.5% of whom were men and 31.5% were women. With a mean age of 62.89±13.75 years among participants, the rate of premature MI was 31.8%. ST segment elevation MI accounted for 68.2% cases and inferior wall was the most prevalent region involved followed by anterior and posterior walls.Obtained data on the characteristics of patients suffering an MI event revealed the major determinants of delay in initiation of therapies and contributors of poor outcome. Completeness of data was guaranteed upon involvement of multiple checkpoints and data quality was secured by means of automatic validation processes in addition to weekly physicians' roundups.Execution of FaRMI in the form presented is feasible and it will build up a comprehensive population-based registry for MI in the region.

  1. Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants.

    Directory of Open Access Journals (Sweden)

    Leena B Mithal

    Full Text Available Early onset sepsis (EOS is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection.In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7-32.2 were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12; presumed sepsis (PS, n = 30; and no sepsis (controls, n = 30. Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™. In addition, placental histopathologic data were linked to biomarker results.cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP, serum amyloid A (SAA, haptoglobin (Hp, serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01. SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01 and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants.This study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and identification of infants with EOS.

  2. The role of the acute phase protein PTX3 in the ventilator-induced lung injury

    Directory of Open Access Journals (Sweden)

    JM Real

    2008-06-01

    Full Text Available The pentraxin 3 (PTX3 is an acute phase proinflammatory protein produced by fibroblasts and alveolar epithelial cells. We have previously demonstrated that PTX3 is a key modulator of inflammation. Mechanical ventilation (MV is a life saving therapeutic approach for patients with acute lung injury that, nevertheless could lead to an inflammatory response and tissue injury (ventilator-induced lung injury: VILI, representing a major cause of iatrogenic lung damage in intensive units. Our objective was to investigate the role of PTX3 in VILI. PTX3 transgenic, knockout and Wt control mice (n = 12/group were ventilated (45ml·kg–1 until respiratory system Elastance increased 50% (Ers150%, an indicator of VILI. Histological analysis demonstrated that using a Ers150% was appropriate for our analysis since identical degrees of inflammation were observed in Tg, KO and Wt mice as assessed by leukocyte infiltration, oedema, alveolar collapse and number of breaks in alveolar septa. However, Tg mice reached Ers150% faster than Wt controls (p = 0.0225. We also showed that the lack of PTX3 does not abolish the occurrence of VILI in KOs. Gene expression profile of PTX3, IL-1beta, IL-6, KC, IFNgamma, TGFbeta and PCIII were investigated by QPCR. MV drastically up modulated PTX3 as well as IL-1beta, IL-6, IFNgamma and KC. Alternatively, mice were ventilated for 20, 40 and 60 min. The faster kinetics of Tg mice to reach Ers150% was accompanied by an earlier augmentation of IL-1b and PTX3 expression. The kinetics of local PTX3 expression in the lungs of ventilated mice strongly suggests the involvement of this pentraxin in the pathogenesis of VILI.

  3. Measurement of renal blood flow by phase-contrast magnetic resonance imaging during septic acute kidney injury: a pilot investigation.

    Science.gov (United States)

    Prowle, John R; Molan, Maurice P; Hornsey, Emma; Bellomo, Rinaldo

    2012-06-01

    In septic patients, decreased renal perfusion is considered to play a major role in the pathogenesis of acute kidney injury. However, the accurate measurement of renal blood flow in such patients is problematic and invasive. We sought to overcome such obstacles by measuring renal blood flow in septic patients with acute kidney injury using cine phase-contrast magnetic resonance imaging. Pilot observational study. University-affiliated general adult intensive care unit. Ten adult patients with established septic acute kidney injury and 11 normal volunteers. Cine phase-contrast magnetic resonance imaging measurement of renal blood flow and cardiac output. The median age of the study patients was 62.5 yrs and eight were male. At the time of magnetic resonance imaging, eight patients were mechanically ventilated, nine were on continuous hemofiltration, and five required vasopressors. Cine phase-contrast magnetic resonance imaging examinations were carried out without complication. Median renal blood flow was 482 mL/min (range 335-1137) in septic acute kidney injury and 1260 mL/min (range 791-1750) in healthy controls (p = .003). Renal blood flow indexed to body surface area was 244 mL/min/m2 (range 165-662) in septic acute kidney injury and 525 mL/min/m2 (range 438-869) in controls (p = .004). In patients with septic acute kidney injury, median cardiac index was 3.5 L/min/m2 (range 1.6-8.7), and median renal fraction of cardiac output was only 7.1% (range 4.4-10.8). There was no rank correlation between renal blood flow index and creatinine clearance in patients with septic acute kidney injury (r = .26, p = .45). Cine phase-contrast magnetic resonance imaging can be used to noninvasively and safely assess renal perfusion during critical illness in man. Near-simultaneous accurate measurement of cardiac output enables organ blood flow to be assessed in the context of the global circulation. Renal blood flow seems consistently reduced as a fraction of cardiac output in

  4. Acute morbidity reduction using 3DCRT for prostate carcinoma; a randomised phase III study

    International Nuclear Information System (INIS)

    Koper, P.; Putten, W. van; Stroom, J.; Korevaar, G.; Heijmen, B.; Wijnmaalen, A.; Jansen, P.; Hanssens, P.; Griep, C.; Krol, A.; Samson, M.; Levendag, P.

    1997-01-01

    Purpose: A randomised phase III toxicity study (conventional vs conformal radiotherapy) was performed for prostatic carcinoma to study the effects on the (acute) morbidity of intestinal/rectosigmoid and bladder. The observed toxicity was compared with Dose Volume Histograms to reveal possible volume (reduction) effects. Methods: In the phase III study 266 T1-4 N0M0 prostate cancer patients were entered. Patients were randomised for conventional and conformal radiotherapy (total dose 66 Gy, minimum PTV dose 95% ICRU and a CTV-PTV margin of 10 mm in both study arms). The GTV was limited to the prostate only in T1 tumors. In all other patients the GTV was defined to be prostate and seminal vesicles for the complete treatment course. The CTV-PTV margin (10mm) was created by a automated program to ensure the minimum prescribed margin. The rectosigmoid was defined to be the rectum including the sigmoid within the Treatment Volume (ICRU). Acute toxicity was evaluated using the EORTC/RTOG morbidity score and weekly quality of life questionnaires. The radiation technique comparison was done by Dose volume Histogram analysis using the Area Under The Curve (AUC) for different dose levels. In this preliminary DVH analysis we present the data for the first 100 patients. Results: Patient and tumor characteristics were evenly distributed between both study groups. The maximum toxicity is reached at 75% of the tumordose (TD) (rectal grade I 59% grade II 26%, bladder grade I 48%, grade II 16% and grade III 1% [catheter for urinary retention]). Comparing both study arms there seems to be a reduction in intestinal morbidity (grade II and higher resp. 32% vs 19% p=0.02). Further analysis revealed a marked reduction in medication for anal symptoms; this accounts for a large part of the significant difference in intestinal toxicity (grade II conventional vs conformal rectosigmoid 18% vs 14% and anal 16% vs 8%). For bladder morbidity no difference for mobidity higher than grade I is

  5. Carrier protein influences immunodominance of a known epitope: implication in peptide vaccine design.

    Science.gov (United States)

    Ghosh, Moumita; Solanki, Ashish K; Roy, Koushik; Dhoke, Reema R; Ashish; Roy, Syamal

    2013-09-23

    We investigated how the processing of a given antigen by antigen presenting cells (APC) is dictated by the conformation of the antigen and how this governs the immunodominance hierarchy. To address the question, a known immunodominant sequence of bacteriophage lambda repressor N-terminal sequence 12-26 [λR(12-26)] was engineered at the N and C termini of a heterologous leishmanial protein, Kinetoplastid membrane protein-11 (KMP-11); the resulting proteins were defined as N-KMP-11 and C-KMP-11 respectively. The presence of λR(12-26) in N-KMP-11 and C-KMP-11 was established by western blot analysis with antibody to λR(12-26) peptide. N-KMP-11 but not C-KMP-11 could stimulate the anti λR(12-26) T-cell clonal population very efficiently in the presence of APCs. Priming of BALB/c mice with N-KMP-11 or C-KMP-11 generated similar levels of anti-KMP-11 IgG, but anti-λR(12-26) specific IgG was observed only upon priming with N-KMP-11. Interestingly, uptake of both N-KMP-11 and C-KMP-11 by APCs was similar but catabolism of N-KMP-11 but not C-KMP-11 was biphasic and fast at the initial time point. Kratky plots of small angle X-ray scattering showed that while N-KMP-11 adopts flexible Gaussian type of topology, C-KMP-11 prefers Globular nature. To show that KMP-11 is not unique as a carrier protein, an epitope (SPITBTNLBTMBK) of Plasmodium yoelii (PY) apical membrane protein 1[AMA-1 (136-148)], is placed at the C and N terminals of a dominant T-cell epitope of ovalbumin protein OVA(323-339) and the resulting peptides are defined as PY-OVA and OVA-PY respectively. Interestingly, only OVA-PY could stimulate anti-OVA T-cells and produce IgG response upon priming of BALB/c mice with it. Thus for rational design of peptide vaccine it is important to place the dominant epitope appropriately in the context of the carrier protein. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Comparison of parasite loads in serum and blood samples from patients in acute and chronic phases of Chagas disease.

    Science.gov (United States)

    Hernández, Carolina; Teherán, Aníbal; Flórez, Carolina; Ramírez, Juan David

    2018-04-17

    Molecular methods have been developed for the detection and quantification of Trypanosoma cruzi DNA in blood samples from patients with Chagas disease. However, aspects of sample processing necessary for quantitative real-time PCR (qPCR), such as the addition of guanidine hydrochloride to whole blood samples, may limit timely access to molecular diagnosis. We analysed 169 samples from serum and guanidine-EDTA blood (GEB) obtained from patients in acute and chronic phases of Chagas disease. We applied qPCR targeted to the satellite DNA region. Finally, we compared the parasite loads and cycle of threshold values of the qPCR. The results confirmed the usefulness of serum samples for the detection and quantification of parasite DNA in patients with Chagas disease, especially in the acute phase. However, the parasite loads detected in serum samples from patients in the chronic phase were lower than those detected in GEB samples. The epidemiological implications of the findings are herein discussed.

  7. A robust quantitative solid phase immunoassay for the acute phase protein C-reactive protein (CRP) based on cytidine 5 '-diphosphocholine coupled dendrimers

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Pedersen, H. G.; Jensen, A. L.

    2009-01-01

    C-reactive protein (CRP) is an important acute phase protein, being used as a sensitive indicator of inflammation and infection and is also associated with the risk of cardiovascular problems. The present paper describes a robust and sensitive ELISA for CRP, based on the affinity of CRP for phosp......C-reactive protein (CRP) is an important acute phase protein, being used as a sensitive indicator of inflammation and infection and is also associated with the risk of cardiovascular problems. The present paper describes a robust and sensitive ELISA for CRP, based on the affinity of CRP...... was applied to determination of pig and human CRP using commercially available antibodies against human CRP. The assay was shown to be more sensitive than previously published immunoassays employing albumin-coupled cytidine diphosphocholine. The coating was stable for at least 30 days at room temperature...

  8. Evaluation of Respiratory Muscle Strength in the Acute Phase of Stroke: The Role of Aging and Anthropometric Variables.

    Science.gov (United States)

    Luvizutto, Gustavo José; Dos Santos, Maria Regina Lopes; Sartor, Lorena Cristina Alvarez; da Silva Rodrigues, Josiela Cristina; da Costa, Rafael Dalle Molle; Braga, Gabriel Pereira; de Oliveira Antunes, Letícia Cláudia; Souza, Juli Thomaz; de Carvalho Nunes, Hélio Rubens; Bazan, Silméia Garcia Zanati; Bazan, Rodrigo

    2017-10-01

    During hospitalization, stroke patients are bedridden due to neurologic impairment, leading to loss of muscle mass, weakness, and functional limitation. There have been few studies examining respiratory muscle strength (RMS) in the acute phase of stroke. This study aimed to evaluate the RMS of patients with acute stroke compared with predicted values and to relate this to anthropometric variables, risk factors, and neurologic severity. This is a cross-sectional study in the acute phase of stroke. After admission, RMS was evaluated by maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP); anthropometric data were collected; and neurologic severity was evaluated by the National Institutes of Health Stroke Scale. The analysis of MIP and MEP with predicted values was performed by chi-square test, and the relationship between anthropometric variables, risk factors, and neurologic severity was determined through multiple linear regression followed by residue analysis by the Shapiro-Wilk test; P < .05 was considered statistically significant. In the 32 patients studied, MIP and MEP were reduced when compared with the predicted values. MIP declined significantly by 4.39 points for each 1 kg/m 2 increase in body mass index (BMI), and MEP declined significantly by an average of 3.89 points for each 1 kg/m 2 increase in BMI. There was no statistically significant relationship between MIP or MEP and risk factors, and between MIP or MIP and neurologic severity in acute phase of stroke. There is a reduction of RMS in the acute phase of stroke, and RMS was lower in individuals with increased age and BMI. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  9. Effects of balneotherapy on the reactants of acute inflammation phase in Ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Stamenković Bojana

    2009-01-01

    Full Text Available Introduction. Ankylosing spondylitis (AS is a chronic inflammatory disease that affects sacroiliac joints, spinal column and peripheral joints. Beside medication therapy, physical and balneotherapy play an important role in its complex treatment. Objective. The aim of the research was to establish serum concentrations of C-reactive protein (CRP, α 1-acid glycoprotein (α 1-AGP, ceruloplasmine (CP and erythrocyte sedimentation rate (SE before and after the balneotherapy in ankylosing spondylitis. Methods. The research included 50 AS patients according to the revised New York criteria, of mean age 43 years, who were treated for 14 days on the average at the Clinic for Rheumatology of the Institute 'Niška Banja'. All the patients received medications and balneotherapy (radioactive oligomineral baths, peloid, massage, kinesitherapy; the serum concentrations of CRP, α1-AGP, CP and SE were measured before and after balneotherapy. Serum proteins were determined using original Nor Partigen plates Boehringer. Erythrocyte sedimentation rate was measured by Westergreen method. Balneotherapy was applied individually, intensively or mildly, depending on the AS stage and activity phase. Results. After dosed balneotherapy, a significant decrease in the concentrations of CP (p<0.05, α1-AGP (p<0.01 and CRP (p<0.05 was registered in the serums of AS patients. ESR was not significantly reduced. Conclusion. The research proved that α 1-acid glycoprotein, ceruloplasmine and C-reactive protein represent more sensitive inflammation markers as compared to erythrocyte sedimentation rate. The identification of acute phase reactants is important in the evaluation of dosed balneotherapy efficiency in the treatment of ankylosing spondylitis.

  10. [Examination of acute phase proteins concentrations in children with allergic rhinitis].

    Science.gov (United States)

    Steiner, Iwona; Sobieska, Magdalena; Pucher, Beata; Grzegorowski, Michał; Samborski, Włodzimierz

    2006-01-01

    Allergic rhinitis is an inflammatory disorder of upper respiratory tract (about 15 per cent of the population in industrialized countries suffer from this condition), characterized by frequent sneezing and a runny or stuffy nose sometimes accompanied by watery eyes. As the most common allergic condition, allergic rhinitis affects people of all ages. Boys are twice as likely to get allergic rhinitis than girls. The median age of onset of the condition is 10 years old, meaning that equal numbers of children develop the condition before and after age 10. Symptoms usually appear in childhood first and then lessen by the age of 30 or 40. Seasonal allergic rhinitis usually results from tree, grass or weed pollen. With this type of rhinitis, symptoms will decrease with the arrival of cold weather. Perennial allergic rhinitis can cause year-round symptoms. This allergic reaction is the result of indoor irritants such as feathers, mold spores, animal dander (hair and skin shed by pets) or dust mites. It is often aggravated by a food allergy, the most common being an allergy to milk. Acute phase proteins (APP) belong to the most ancient part of the unspecific immunity and contribute markedly to the keeping of homeostasis. As much as 30 various proteins are for the moment regarded as APP. Being multifunctional regulators and effectors APP stay in multiple relations to practically all types of cells and molecules. Among APP following functional groups may be described: transport proteins (transferrin, ceruloplasmin and haptoglobin), clotting factors (fibrinogen), antiproteases (alpha1-antitrypsin, alpha1-antichymotrypsin, alpha2-macroglobulin), complement components (C3, C4) and several proteins of hardly known function, like C-reactive protein (CRP), serum amyloid A, acid alpha1-glycoprotein (AGP) and others. From a group of 32 children, aged from 5 to 14 years, with symptoms of seasonal allergic rhinitis, and from a control group of 10 healthy children sex and age matched

  11. Emergence of the acute-phase protein hemopexin in jawed vertebrates.

    Science.gov (United States)

    Dooley, Helen; Buckingham, E Bryan; Criscitiello, Michael F; Flajnik, Martin F

    2010-01-01

    When released from damaged erythrocytes free heme not only provides a source of iron for invading bacteria but also highly toxic due to its ability to catalyze free radical formation. Hemopexin (Hx) binds free heme with very high-affinity and thus protects against heme toxicity, sequesters heme from pathogens, and helps conserve valuable iron. Hx is also an acute-phase serum protein (APP), whose expression is induced by inflammation. To date Hx has been identified as far back in phylogeny as bony fish where it is called warm-temperature acclimation-related 65 kDa protein (WAP65), as serum protein levels are increased at elevated environmental temperatures as well as by infection. During analysis of nurse shark (Ginglymostoma cirratum) plasma we isolated a Ni(2+)-binding serum glycoprotein and characterized it as the APP Hx. We subsequently cloned Hx from nurse shark and another cartilaginous fish species, the little skate Leucoraja erinacea. Functional analysis showed shark Hx, like that of mammals, binds heme but is found at unusually high levels in normal shark serum. As an Hx orthologue could not be found in the genomes of jawless vertebrates or lower deuterostomes it appears to have arisen just prior to the emergence of jawed vertebrates, coincident with the second round of genome-wide duplication and the appearance of tetrameric hemoglobin (Hb). Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Controversial results of therapy with mesenchymal stem cells in the acute phase of canine distemper disease.

    Science.gov (United States)

    Pinheiro, A O; Cardoso, M T; Vidane, A S; Casals, J B; Passarelli, D; Alencar, A L F; Sousa, R L M; Fantinato-Neto, P; Oliveira, V C; Lara, V M; Ambrósio, C E

    2016-05-23

    Distemper disease is an infectious disease reported in several species of domestic and wild carnivores. The high mortality rate of animals infected with canine distemper virus (CDV) treated with currently available therapies has driven the study of new efficacious treatments. Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic option for many degenerative, hereditary, and inflammatory diseases. Therefore, the aim of this study was to characterize stem cells derived from the canine fetal olfactory epithelium and to assess the systemic response of animals infected with CDV to symptomatic therapy and treatment with MSCs. Eight domestic mongrel dogs (N = 8) were divided into two groups: support group (SG) (N = 5) and support group + cell therapy (SGCT) (N = 3), which were monitored over 15 days. Blood samples were collected on days 0, 6, 9, 12, and 15 to assess blood count and serum biochemistry (urea, creatinine, alanine transferase, alkaline phosphatase, gamma-glutamyl transferase, total protein, albumin, and globulin), and urine samples were obtained on days 0 and 15 for urinary evaluation (urine I). The results showed a high mortality rate (SG = 4 and SGCT = 2), providing inadequate data on the clinical course of CDV infection. MSC therapy resulted in no significant improvement when administered during the acute phase of canine distemper disease, and a prevalence of animals with high mortality rate was found in both groups due to the severity of symptoms.

  13. Acute phase proteins: Biomarkers of infection and inflammation in veterinary medicine.

    Science.gov (United States)

    Eckersall, P D; Bell, R

    2010-07-01

    Acute phase proteins (APPs) have been used as biomarkers of inflammation, infection and trauma for decades in human medicine but have been relatively under-utilised in the context of veterinary medicine. However, significant progress has been made in the detection, measurement and application of APPs as biomarkers in both companion and farm animal medicine over recent years. In the dog, C-reactive protein, haptoglobin and serum amyloid A have been identified as significant diagnostic 'markers' of steroid-responsive meningitis-arteritis, while in cats and cattle haptoglobin and alpha(1) acid glycoprotein and haptoglobin and serum amyloid A have proved valuable biomarkers of disease, respectively. In dairy cattle, haptoglobin and a mammary-associated serum amyloid A3 isoform, produced by the inflamed mammary gland during episodes of mastitis, have great potential as biomarkers of this economically important disease. Understanding the use of APP as biomarkers of inflammatory conditions of domestic animals has expanded significantly over recent years, and, with the insights provided by ongoing research, it is likely that these compounds will be increasingly used in the future in the diagnosis and prognosis of both companion and farm animal disease. Copyright 2010 Elsevier Ltd. All rights reserved.

  14. Evaluation of the effects of honey on acute-phase deep burn wounds.

    Science.gov (United States)

    Nakajima, Yukari; Mukai, Kanae; Nasruddin; Komatsu, Emi; Iuchi, Terumi; Kitayama, Yukie; Sugama, Junko; Nakatani, Toshio

    2013-01-01

    This study aimed to clarify the effects of honey on acute-phase deep burn wounds. Two deep burn wounds were created on mice which were divided into four groups: no treatment, silver sulfadiazine, manuka honey, and Japanese acacia honey. Wound sizes were calculated as expanded wound areas and sampled 30 minutes and 1-4 days after wounding for histological observation. The wound sections were subjected to hematoxylin and eosin and immunohistological staining to detect necrotic cells, apoptotic cells, neutrophils, and macrophages. The no treatment group formed a scar. The redness around the wound edges in the silver sulfadiazine group was the most intense. All groups exhibited increased wound areas after wounding. The proportions of necrotic cells and the numbers of neutrophils in the manuka and acacia honey groups were lower than those in the no treatment and silver sulfadiazine groups until day 3; however, there were no significant differences between all groups on day 4. These results show that honey treatment on deep burn wounds cannot prevent wound progression. Moreover, comparing our observations with those of Jackson, there are some differences between humans and animals in this regard, and the zone of hyperemia and its surrounding area fall into necrosis, which contributes to burn wound progression.

  15. Evaluation of the Effects of Honey on Acute-Phase Deep Burn Wounds

    Directory of Open Access Journals (Sweden)

    Yukari Nakajima

    2013-01-01

    Full Text Available This study aimed to clarify the effects of honey on acute-phase deep burn wounds. Two deep burn wounds were created on mice which were divided into four groups: no treatment, silver sulfadiazine, manuka honey, and Japanese acacia honey. Wound sizes were calculated as expanded wound areas and sampled 30 minutes and 1–4 days after wounding for histological observation. The wound sections were subjected to hematoxylin and eosin and immunohistological staining to detect necrotic cells, apoptotic cells, neutrophils, and macrophages. The no treatment group formed a scar. The redness around the wound edges in the silver sulfadiazine group was the most intense. All groups exhibited increased wound areas after wounding. The proportions of necrotic cells and the numbers of neutrophils in the manuka and acacia honey groups were lower than those in the no treatment and silver sulfadiazine groups until day 3; however, there were no significant differences between all groups on day 4. These results show that honey treatment on deep burn wounds cannot prevent wound progression. Moreover, comparing our observations with those of Jackson, there are some differences between humans and animals in this regard, and the zone of hyperemia and its surrounding area fall into necrosis, which contributes to burn wound progression.

  16. Presentation of an immunodominant immediate-early CD8+ T cell epitope resists human cytomegalovirus immunoevasion.

    Directory of Open Access Journals (Sweden)

    Stefanie Ameres

    Full Text Available Control of human cytomegalovirus (HCMV depends on CD8+ T cell responses that are shaped by an individual's repertoire of MHC molecules. MHC class I presentation is modulated by a set of HCMV-encoded proteins. Here we show that HCMV immunoevasins differentially impair T cell recognition of epitopes from the same viral antigen, immediate-early 1 (IE-1, that are presented by different MHC class I allotypes. In the presence of immunoevasins, HLA-A- and HLA-B-restricted T cell clones were ineffective, but HLA-C*0702-restricted T cell clones recognized and killed infected cells. Resistance of HLA-C*0702 to viral immunoevasins US2 and US11 was mediated by the alpha3 domain and C-terminal region of the HLA heavy chain. In healthy donors, HLA-C*0702-restricted T cells dominated the T cell response to IE-1. The same HLA-C allotype specifically protected infected cells from attack by NK cells that expressed a corresponding HLA-C-specific KIR. Thus, allotype-specific viral immunoevasion allows HCMV to escape control by NK cells and HLA-A- and HLA-B-restricted T cells, while the virus becomes selectively vulnerable to an immunodominant population of HLA-C-restricted T cells. Our work identifies a T cell population that may be of particular efficiency in HCMV-specific immunotherapy.

  17. Characterization of an Immunodominant Epitope in the Endodomain of the Coronavirus Membrane Protein

    Directory of Open Access Journals (Sweden)

    Hui Dong

    2016-12-01

    Full Text Available The coronavirus membrane (M protein acts as a dominant immunogen and is a major player in virus assembly. In this study, we prepared two monoclonal antibodies (mAbs; 1C3 and 4C7 directed against the transmissible gastroenteritis virus (TGEV M protein. The 1C3 and 4C7 mAbs both reacted with the native TGEV M protein in western blotting and immunofluorescence (IFA assays. Two linear epitopes, 243YSTEART249 (1C3 and 243YSTEARTDNLSEQEKLLHMV262 (4C7, were identified in the endodomain of the TGEV M protein. The 1C3 mAb can be used for the detection of the TGEV M protein in different assays. An IFA method for the detection of TGEV M protein was optimized using mAb 1C3. Furthermore, the ability of the epitope identified in this study to stimulate antibody production was also evaluated. An immunodominant epitope in the TGEV membrane protein endodomain was identified. The results of this study have implications for further research on TGEV replication.

  18. Acute phase and transport protein synthesis in simulated infection in undernourished men using uniformly labelled Spirulina Platensis

    International Nuclear Information System (INIS)

    Reeds, P.J.; Opekun, A.; Jahoor, F.; Wong, W.W.; Klein, P.D.

    1994-01-01

    Although it has been known for many years that injury and infection lead to body nitrogen loss, the reason has remained obscure. In this paper, we develop the argument that the processes that are activated during infection demand the provision of specific amino acids which have to be supplied from body protein. In particular, we show that the positive acute phase proteins are very rich in the aromatic amino acids and the exaggerated use of these amino acids (phenylalanine, tryptophan and tyrosine) in acute phase protein synthesis lead to an endogenous ''amino acid imbalance'' which restricts the use of other amino acids for tissue protein synthesis. Minimally invasive protocols, involving the administration of 15 N and 13 C-labelled amino acids for studying whole body nitrogen turnover, amino acid oxidation and plasma protein synthesis are described. (author). 22 refs, 3 tabs

  19. Cytokine and acute phase protein gene expression in liver biopsies from dairy cows with a lipopolysaccharide - induced mastitis

    DEFF Research Database (Denmark)

    Vels, J; Røntved, Christine M.; Bjerring, Martin

    2009-01-01

    A minimally invasive liver biopsy technique was tested for its applicability to study the hepatic acute phase response (APR) in dairy cows with Escherichia coli lipopolysaccharide (LPS)-induced mastitis. The hepatic mRNA expression profiles of the inflammatory cytokines, tumor necrosis factor (TNF......, a minimally invasive liver biopsy technique can be used for studying the hepatic APR in diseased cattle. Lipopolysaccharide-induced mastitis resulted in a time-dependent production of inflammatory cytokines and SAA and Hp in the liver of dairy cows.......- ), IL-1β, IL-6, and IL-10, and the acute phase proteins serum amyloid A isoform 3 (SAA3), haptoglobin (Hp), and 1-acid glycoprotein (AGP) were determined by real-time reverse transcription-PCR. Fourteen primiparous cows in mid lactation were challenged with 200 µg of LPS (n = 8) or NaCl solution (n = 6...

  20. Serum protein capillary electrophoresis and measurement of acute phase proteins in a captive cheetah (Acinonyx jubatus) population

    DEFF Research Database (Denmark)

    Depauw, Sarah; Delanghe, Joris; Whitehouse-Tedd, Katherine

    2014-01-01

    Renal and gastrointestinal pathologies are widespread in the captive cheetah (Acinonyx jubatus) population but are often diagnosed at a late stage, because diagnostic tools are limited to the evaluation of clinical signs or general blood examination. Presently, no data are available on serum...... proteins and acute-phase proteins in cheetahs during health or disease, although they might be important to improve health monitoring. This study aimed to quantify serum proteins by capillary electrophoresis in 80 serum samples from captive cheetahs, categorized according to health status and disease type....... Moreover, serum amyloid A concentrations were measured via a turbidimetric immunoassay validated in domestic cats, whereas haptoglobin and C-reactive protein were determined by non-species-specific functional tests. Cheetahs classified as healthy had serum protein and acute phase protein concentrations...

  1. Association of psychopathology with quality of life in acute phase of schizophrenia; an experience from east India

    Directory of Open Access Journals (Sweden)

    Suravi Patra

    2012-01-01

    Full Text Available Objective: To find the association of patient characteristic and psychopathology with quality of life in acute phase of schizophrenia. Materials and Methods: Socio-demographic variables of patient, psychopathology and quality of life were assessed. Spearman′s Correlation coefficients were measured using SPSS version 15.0. Results: Quality of life of the patients varied in different domains. Male gender, unmarried status and higher educational status predicted a poorer quality of life. The domains of physical and psychological well-being of WHO-QOL were correlated with PANSS general and total scores whereas environmental and social health showed no correlation with PANSS scores. Conclusion: Domains of subjective quality of life in acute phase of schizophrenia are associated variedly with socio-demographic variables and symptomatology.

  2. Anti-inflammatory effect of diclofenac diethylammonium gel on acute phase of ligature induced periodontitis in rats

    OpenAIRE

    Botelho, Marco A.; Paixão, Mônica S.; Rachid, Ítalo; Bannet, Leonard Edward; Patrus, Ana Helena; Mattos, Thiago Borges; Queiroz, Dinalva; Ruela, Ronaldo; Costa, Jose M. C; Quintans Júnior, Lucindo José

    2010-01-01

    This study aimed to evaluate the effect of a diclofenac diethylammonium gel 10 mg/g (DD) on acute phase of ligature induced periodontitis model in rats. Experimental Periodontitis Disease (EPD) was induced in 30 Wistar rats subjected to ligature placement on left molars. Animals were treated with (DD), immediately after (EPD) induction. Saline-based gel (SG) was utilized as negative control and DD gel 10 mg/g was the tested substance. Animals were randomly assigned into the groups. The period...

  3. Impact of Diet Supplemented by Coconut Milk on Corticosterone and Acute Phase Protein Level under High Stocking Density

    Directory of Open Access Journals (Sweden)

    Majid SHAKERI

    2016-05-01

    Full Text Available The purpose of this study was to investigate effects of coconut milk supplementation on corticosterone and acute phase protein level under high stocking density. A total 300 Cobb 500 male chicks were placed in cages and stocked as 10 birds/cage (normal stocking density and 15 birds/cage (high stocking density. The treatments were as (i control diet and stocked at 10 and 15 birds/cage (ii control diet + 3% coconut milk from 1-42 day and stocked at 10 and 15 birds/cage (iii control diet + 5% coconut milk from 1-42 day and stocked at 10 and 15 birds/cage. On day 42, 20 birds per treatment were slaughtered to collect blood samples. The results showed higher level of corticosterone and acute phase protein level in control diet compare to other supplemented diets with coconut milk. In conclusion, coconut milk decreased the level of corticosterone and acute phase protein when chicks were subjected to high stocking density.

  4. Acute Phase Proteins and their Relation to Energy Metabolites in Dairy Cows during the Pre- and Postpartal Period

    Directory of Open Access Journals (Sweden)

    Gabriel Kováč

    2009-01-01

    Full Text Available The objective of this study was to evaluate the concentrations of selected acute phase proteins – haptoglobin (Hp and serum amyloid A (SAA, and selected variables of energy metabolism in blood serum of dairy cows during different stages of the pre- and postpartal period. The analyses were performed in dairy cows of the Slovak spotted breed and its crossbreeds (n = 57. The cows were divided into 9 groups according to the evaluated part of reproduction cycle – from 4 weeks before parturition to 10 weeks after parturition. Significant differences were found in mean Hp and SAA concentrations during the monitored period (P P P P P P P < 0.001. Moreover, significant correlations were found between Hp and non-esterified fatty acids, Hp and β-hydroxybutyrate, as well as between SAA and non-esterified fatty acids. Our results indicate that the acute phase response occurs in cows around parturition, and suggest that there are relationships between mediators of immune response and several indices of energy metabolism. Our results also suggest that in cows with higher concentrations of non-esterified fatty acids, indicating a certain degree of lipid mobilisation, higher values of acute phase proteins may be found.

  5. Nomothetic and idiographic symptom change trajectories in acute-phase cognitive therapy for recurrent depression.

    Science.gov (United States)

    Vittengl, Jeffrey R; Clark, Lee Anna; Thase, Michael E; Jarrett, Robin B

    2013-08-01

    We tested nomothetic and idiographic convergence and change in 3 symptom measures during acute-phase cognitive therapy (CT) for depression and compared outcomes among patients showing different change patterns. Outpatients (N = 362; 69% women; 85% White; age M = 43 years) with recurrent major depressive disorder according to criteria in the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000) completed the Hamilton Rating Scale for Depression (Hamilton, 1960), Beck Depression Inventory (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961), and Inventory for Depressive Symptomatology-Self-Report (Rush, Gullion, Basco, Jarrett, & Trivedi, 1996) on 14 occasions as well as pre/post-CT measures of social-interpersonal functioning and negative cognitive content. The 3 symptom measures marked the same severity and change constructs, and we offer improved formulas for intermeasure score conversions via their common factor. Pre/post-CT symptom reductions were large (ds = 1.71-1.92), and nomothetic symptom curves were log-linear (larger improvements earlier and smaller improvements later in CT). Nonetheless, only 30% of individual patients showed clear log-linear changes, whereas other patients showed linear (e.g., steady decreases; 20%), 1-step (e.g., a quick drop; 16%), and unclassified (34%) patterns. Log-linear, linear, and 1-step patients were generally similar to one another and superior to unclassified patients post-CT in symptom levels, response and stable remission rates, social-interpersonal functioning, and cognitive content (median d = 0.69). Reaching a low-symptom "destination" at the end of CT via any coherent "path" is more important in the short term than which path patients take. We discuss implications for theories of change, clinical monitoring of individuals' progress in CT, and the need to investigate long-term outcomes of patients with differing patterns of symptom change. PsycINFO Database Record

  6. [Types of Care for Adult Patients Diagnosed With Acute and Maintenance Phase Schizophrenia].

    Science.gov (United States)

    Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos; Oviedo Lugo, Gabriel Fernando; de la Hoz Bradford, Ana María; Castro Díaz, Sergio Mario; García Valencia, Jenny; Jaramillo González, Luis Eduardo; Ávila-Guerra, Mauricio

    2014-01-01

    To assist the clinician in making decisions about the types of care available for adults with schizophrenia. To determine which are the modalities of treatment associated with better outcomes in adults with schizophrenia. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. Patients who were in Assertive community treatment had a lower risk of new hospitalizations. For the intensive case management, the results favored this intervention in the outcomes: medium term readmissions, social functioning and satisfaction with services. The crisis resolution teams was associated with better outcomes on outcomes of readmissions, social functioning and service satisfaction in comparison with standard care. The use of different modalities of care leads to the need of a comprehensive approach to patients to reduce the overall disability associated with the disease. Evidence shows overall benefit for most outcomes studied without encountering hazards for health of patients. This evaluation is recommended to use the professional ways of providing health services that are community-based and have a multidisciplinary group. It is not recommended the modality "day hospital" during the acute phase of schizophrenia in adults. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  7. Comparison of the outcome of burn patients using acute-phase plasma base deficit.

    Science.gov (United States)

    Salehi, S H; As'adi, K; Mousavi, J

    2011-12-31

    Background. In recent years, plasma base deficit has been used as a marker to determine the status of tissue perfusion in trauma patients and also to predict the outcome of these patients. This study was performed to investigate the effect of plasma base deficit in predicting burn patient outcome. Methods. This prospective cohort study was performed from October 2009 to October 2010 in the acute phase of burn patients who were admitted within 6 h post-injury to Motahari Burn Hospital in Iran. The patients were divided into two groups based on the plasma base deficit in the first 24 h post-injury: group A, in which the mean plasma base deficit was less than or equal to -6 (more negative), and group B, in which the mean plasma base deficit greater than -6. Statistical analysis was performed using SPSS v.16 software. Results. Thirty-eight patients were enrolled in each group. The mean plasma base deficit in group A (-7.76 ± 2.18 mmol) was significantly less than that in group B (-1.19 ± 2.82) mmol (p 0.05) and despite removal of interfering factors, there were significant differences between the systemic inflammatory response syndrome and the multiple organ dysfunction syndrome score and the percentage of sepsis between the two groups (p 0.05). Conclusion. The plasma base deficit can be used as a valuable marker in the resuscitation of burn patients, along with clinical criteria. Physiological indicators (burn percentage, age, and mucosal burns) are not sufficient to predict mortality and morbidity in burn patients, and it is necessary to investigate the role of biochemical markers such as base deficit in determining the final outcome of burn patients.

  8. Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice.

    Directory of Open Access Journals (Sweden)

    Sarah S Poulsen

    Full Text Available Pulmonary exposure to multi-walled carbon nanotubes (MWCNTs has been linked to an increased risk of developing cardiovascular disease in addition to the well-documented physicochemical-dependent adverse lung effects. A proposed mechanism is through a strong and sustained pulmonary secretion of acute phase proteins to the blood. We identified physicochemical determinants of MWCNT-induced systemic acute phase response by analyzing effects of pulmonary exposure to 14 commercial, well-characterized MWCNTs in female C57BL/6J mice pulmonary exposed to 0, 6, 18 or 54 μg MWCNT/mouse. Plasma levels of acute phase response proteins serum amyloid A1/2 (SAA1/2 and SAA3 were determined on day 1, 28 or 92. Expression levels of hepatic Saa1 and pulmonary Saa3 mRNA levels were assessed to determine the origin of the acute phase response proteins. Pulmonary Saa3 mRNA expression levels were greater and lasted longer than hepatic Saa1 mRNA expression. Plasma SAA1/2 and SAA3 protein levels were related to time and physicochemical properties using adjusted, multiple regression analyses. SAA3 and SAA1/2 plasma protein levels were increased after exposure to almost all of the MWCNTs on day 1, whereas limited changes were observed on day 28 and 92. SAA1/2 and SAA3 protein levels did not correlate and only SAA3 protein levels correlated with neutrophil influx. The multiple regression analyses revealed a protective effect of MWCNT length on SAA1/2 protein level on day 1, such that a longer length resulted in lowered SAA1/2 plasma levels. Increased SAA3 protein levels were positively related to dose and content of Mn, Mg and Co on day 1, whereas oxidation and diameter of the MWCNTs were protective on day 28 and 92, respectively. The results of this study reveal very differently controlled pulmonary and hepatic acute phase responses after MWCNT exposure. As the responses were influenced by the physicochemical properties of the MWCNTs, this study provides the first step

  9. Modulation of the acute phase response following a lipopolysaccharide challenge in pigs supplemented with an all-natural saccharomyces cerevisiae fermentation product

    Science.gov (United States)

    This study was designed to determine if feeding a Saccharamyces cerevisiae fermentation product to weaned pigs would reduce the stress and acute phase responses (APR) following an acute lipopolysaccharide (LPS) challenge. Pigs (n = 20; 6.4 ± 0.2 kg BW) were obtained and transported to an environment...

  10. Diverse heterologous primary infections radically alter immunodominance hierarchies and clinical outcomes following H7N9 influenza challenge in mice.

    Directory of Open Access Journals (Sweden)

    Susu Duan

    2015-02-01

    Full Text Available The recent emergence of a novel H7N9 influenza A virus (IAV causing severe human infections in China raises concerns about a possible pandemic. The lack of pre-existing neutralizing antibodies in the broader population highlights the potential protective role of IAV-specific CD8(+ cytotoxic T lymphocyte (CTL memory specific for epitopes conserved between H7N9 and previously encountered IAVs. In the present study, the heterosubtypic immunity generated by prior H9N2 or H1N1 infections significantly, but variably, reduced morbidity and mortality, pulmonary virus load and time to clearance in mice challenged with the H7N9 virus. In all cases, the recall of established CTL memory was characterized by earlier, greater airway infiltration of effectors targeting the conserved or cross-reactive H7N9 IAV peptides; though, depending on the priming IAV, each case was accompanied by distinct CTL epitope immunodominance hierarchies for the prominent K(bPB(1703, D(bPA(224, and D(bNP(366 epitopes. While the presence of conserved, variable, or cross-reactive epitopes between the priming H9N2 and H1N1 and the challenge H7N9 IAVs clearly influenced any change in the immunodominance hierarchy, the changing patterns were not tied solely to epitope conservation. Furthermore, the total size of the IAV-specific memory CTL pool after priming was a better predictor of favorable outcomes than the extent of epitope conservation or secondary CTL expansion. Modifying the size of the memory CTL pool significantly altered its subsequent protective efficacy on disease severity or virus clearance, confirming the important role of heterologous priming. These findings establish that both the protective efficacy of heterosubtypic immunity and CTL immunodominance hierarchies are reflective of the immunological history of the host, a finding that has implications for understanding human CTL responses and the rational design of CTL-mediated vaccines.

  11. Serum levels of chicken mannan-binding lectin (MBL) during virus infections; indication that chicken MBL is an acute phase reactant

    DEFF Research Database (Denmark)

    Nielsen, O.L.; Jensenius, J. C.; Jørgensen, Poul Henrik

    1999-01-01

    Mannan-binding lectin (MBL) is a serum collectin which is believed to be an opsonin of the innate immune defence against various microorganisms. MBL is a minor acute phase reactant in man. We investigated the concentration of serum MBL in chickens infected with infectious bronchitis virus (IBV...... levels returned to normal values 6-10 days after infection. The results indicated that MBL is a minor acute phase reactant in chickens....

  12. Can cerebral blood flow measurement predict clinical outcome in the acute phase in patients with artherosclerotic occlusive carotid artery disease?

    International Nuclear Information System (INIS)

    Hokari, Masaaki; Yasuda, Hiroshi; Iwasaki, Motoyuki; Iwasaki, Yoshinobu; Abe, Satoru; Saito, Hisatoshi; Kuroda, Satoshi; Nakayama, Naoki

    2010-01-01

    It has been thought that the clinical course of patients with acute carotid occlusive disease depends on their collateral cerebral blood flow (CBF) and duration of ischemia. However, there have been few clinical reports to prove this hypothesis. Therefore, we performed CBF study in patients with artherosclerotic carotid occlusive disease in the very acute phase, and precisely assessed the prognosis of those patients under intensive medical therapy. This prospective study included a total of 44 patients (72±13 years) who were admitted to our hospital between April, 2007 and December, 2008. To evaluate their initial CBF, single photon emission computed tomography (SPECT) studies were performed within 6 hours after the onset. All patients included in this study were medically treated and were periodically followed up by neurological and radiological examination. Moreover, in patients with reduced CBF (ipsilateral CBF/contralateral CBF x 100: %CBF <80%), dobutamine-induce hyperdynamic therapy was performed. Multivariate analysis was performed to detect significant predictors for the occurrence of further cerebral infarction. Multivariate analysis showed that the occurrence of further infarction was associated with older age and smaller %CBF. Of 44 patients, 21 experienced further cerebral infarction within 10 days after onset. Fourteen out of 15 patients with %CBF <60% developed cerebral infarction. This study showed that the prognosis of the patients with artherosclerotic carotid occlusive disease in the acute phase is associated with their initial residual CBFs. It may be difficult to stop the developed cerebral infarction in those patients with %CBF <60% despite intensive medical therapy. (author)

  13. Perceptions of Hematopoietic Stem Cell Transplantation and Coping Predict Emotional Distress During the Acute Phase After Transplantation.

    Science.gov (United States)

    Baliousis, Michael; Rennoldson, Michael; Dawson, David L; Mills, Jayne; das Nair, Roshan

    2017-01-01

    To test whether a widely used model of adjustment to illness, the self-regulatory model, explains the patterns of distress during acute hematopoietic stem cell transplantation (HSCT). According to the model, perceptions of HSCT, coping, and coping appraisals are associated with distress.
. Longitudinal, correlational.
. The Centre for Clinical Haematology at Nottingham City Hospital and the Department of Haematology at Royal Hallamshire Hospital in Sheffield, both in the United Kingdom.
. 45 patients receiving mostly autologous transplantations for a hematologic malignancy.
. Patients were assessed at baseline, on transplantation day, and two and four weeks after transplantation using three questionnaires. Psychological distress, including depression, anxiety, stress, and overall distress (DASS-21); use of different coping styles (Brief COPE); and perceptions of HSCT and coping appraisals (Brief IPQ).
. As suggested by the self-regulatory model, greater distress was associated with negative perceptions of HSCT, controlling for the effects of confounding variables. Mixed support was found for the model's predictions about the impact of coping styles on distress. Use of active and avoidant coping styles was associated with more distress during the acute phase after HSCT.
. Negative perceptions of HSCT and coping contribute to psychological distress during the acute phase after HSCT and suggest the basis for intervention.
. Eliciting and discussing patients' negative perceptions of HSCT beforehand and supporting helpful coping may be important ways to reduce distress during HSCT.

  14. Brain magnetic resonance imaging in acute phase of pandemic influenza A (H1N1) 2009--associated encephalopathy in children.

    Science.gov (United States)

    Ishida, Yu; Kawashima, Hisashi; Morichi, Shinichiro; Yamanaka, Gaku; Okumura, Akihisa; Nakagawa, Satoshi; Morishima, Tsuneo

    2015-02-01

    Pandemic influenza A (H1N1) 2009 has been shown to be associated more with neurological complications than the seasonal influenza virus. In this study, we focused on the clinical usefulness of magnetic resonance imaging (MRI) in the acute phase of influenza A (H1N1) 2009-associated encephalopathy. A questionnaire was distributed to pediatric and general hospitals in Japan that treat children with encephalopathy. We conducted a questionnaire-based study involving the collection of information regarding 207 patients with encephalopathy. Brain MRI was performed in 97 of these 207 patients in the age group of 9 months to 15 years (mean, 7.5 years) within 48 hours after the development of encephalopathy symptoms. Sixty-six patients (68%) showed normal imaging. Diffuse brain edema was visible in five patients and an abnormal signal in the deep gray matter in two patients which is consistent with acute necrotizing encephalopathy. Abnormal signals of the splenial lesion, subcortical white matter (bright tree appearance), and cortical area were observed in 15, 1, and 8 patients, respectively. From our findings based on the questionnaire results, we suggest that MRI is useful for determining fatal cases of pandemic influenza A (H1N1) 2009 infection when performed in the acute phase. However, MRI is not useful in predicting the development of sequelae. Georg Thieme Verlag KG Stuttgart · New York.

  15. Transcriptional profiling of Actinobacillus pleuropneumoniae during the acute phase of a natural infection in pigs

    Directory of Open Access Journals (Sweden)

    Harel Josée

    2010-02-01

    Full Text Available Abstract Background Actinobacillus pleuropneumoniae is the etiological agent of porcine pleuropneumonia, a respiratory disease which causes great economic losses worldwide. Many virulence factors are involved in the pathogenesis, namely capsular polysaccharides, RTX toxins, LPS and many iron acquisition systems. In order to identify genes that are expressed in vivo during a natural infection, we undertook transcript profiling experiments with an A. pleuropneumoniae DNA microarray, after recovery of bacterial mRNAs from serotype 5b-infected porcine lungs. AppChip2 contains 2033 PCR amplicons based on the genomic sequence of App serotype 5b strain L20, representing more than 95% of ORFs greater than 160 bp in length. Results Transcriptional profiling of A. pleuropneumoniae recovered from the lung of a pig suffering from a natural infection or following growth of the bacterial isolate in BHI medium was performed. An RNA extraction protocol combining beadbeating and hot-acid-phenol was developed in order to maximize bacterial mRNA yields and quality following total RNA extraction from lung lesions. Nearly all A. pleuropneumoniae transcripts could be detected on our microarrays, and 150 genes were deemed differentially expressed in vivo during the acute phase of the infection. Our results indicate that, for example, gene apxIVA from an operon coding for RTX toxin ApxIV is highly up-regulated in vivo, and that two genes from the operon coding for type IV fimbriae (APL_0878 and APL_0879 were also up-regulated. These transcriptional profiling data, combined with previous comparative genomic hybridizations performed by our group, revealed that 66 out of the 72 up-regulated genes are conserved amongst all serotypes and that 3 of them code for products that are predicted outer membrane proteins (genes irp and APL_0959, predicted to code for a TonB-dependent receptor and a filamentous hemagglutinin/adhesin respectively or lipoproteins (gene APL_0920. Only 4

  16. Early coordinated rehabilitation in acute phase after hip fracture - a model for increased patient participation.

    Science.gov (United States)

    Asplin, Gillian; Carlsson, Gunnel; Zidén, Lena; Kjellby-Wendt, Gunilla

    2017-10-17

    Studies have shown that patients with hip fracture treated in a Comprehensive Geriatric Care (CGC) unit report better results in comparison to orthopaedic care. Furthermore, involving patients in their healthcare by encouraging patient participation can result in better quality of care and improved outcomes. To our knowledge no study has been performed comparing rehabilitation programmes within a CGC unit during the acute phase after hip fracture with focus on improving patients' perceived participation and subsequent effect on patients' function. A prospective, controlled, intervention performed in a CGC unit and compared with standard care. A total of 126 patients with hip fracture were recruited who were prior to fracture; community dwelling, mobile indoors and independent in personal care. Intervention Group (IG): 63 patients, mean age 82.0 years and Control Group (CG): 63 patients mean age 80.5 years. coordinated rehabilitation programme with early onset of patient participation and intensified occupational therapy and physiotherapy after hip fracture surgery. The primary outcome measure was self-reported patient participation at discharge. Secondary outcome measures were: TLS-BasicADL; Bergs Balance Scale (BBS); Falls Efficacy Scale FES(S); Short Physical Performance Battery (SPPB) and Timed Up and Go (TUG) at discharge and 1 month and ADL staircase for instrumental ADL at 1 month. At discharge a statistically significant greater number of patients in the IG reported higher levels of participation (p < 0.05) and independence in lower body hygiene (p < 0.05) and dressing (p < 0.001). There were however no statistically significant differences at discharge and 1 month between groups in functional balance and confidence, performance measures or risk for falls. This model of OT and PT coordinated inpatient rehabilitation had a positive effect on patients' perceived participation in their rehabilitation and ADL at discharge but did not appear to

  17. Elevation of intact and proteolytic fragments of acute phase proteins constitutes the earliest systemic antiviral response in HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Holger B Kramer

    2010-05-01

    Full Text Available The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, beta-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA occurred as early as 5-7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha-1-antitrypsin (AAT, termed virus inhibitory peptide (VIRIP, was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.

  18. Acute social stress before the planning phase improves memory performance in a complex real life-related prospective memory task.

    Science.gov (United States)

    Glienke, Katharina; Piefke, Martina

    2016-09-01

    Successful execution of intentions, but also the failure to recall are common phenomena in everyday life. The planning, retention, and realization of intentions are often framed as the scientific concept of prospective memory. The current study aimed to examine the influence of acute stress on key dimensions of complex "real life" prospective memory. To this end, we applied a prospective memory task that involved the planning, retention, and performance of intentions during a fictional holiday week. Forty healthy males participated in the study. Half of the subjects were stressed with the Socially Evaluated Cold Pressor Test (SECPT) before the planning of intentions, and the other half of the participants underwent a control procedure at the same time. Salivary cortisol was used to measure the effectiveness of the SECPT stress induction. Stressed participants did not differ from controls in planning accuracy. However, when we compared stressed participants with controls during prospective memory retrieval, we found statistically significant differences in PM across the performance phase. Participants treated with the SECPT procedure before the planning phase showed improved prospective memory retrieval over time, while performance of controls declined. Particularly, there was a significant difference between the stress and control group for the last two days of the holiday week. Interestingly, control participants showed significantly better performance for early than later learned items, which could be an indicator of a primacy effect. This differential effect of stress on performance was also found in time- and event-dependent prospective memory. Our results demonstrate for the first time, that acute stress induced before the planning phase may improve prospective memory over the time course of the performance phase in time- and event-dependent prospective memory. Our data thus indicate that prospective memory can be enhanced by acute stress. Copyright © 2016

  19. Dual-phase CT for the assessment of acute vascular injuries in high-energy blunt trauma: the imaging findings and management implications.

    Science.gov (United States)

    Iacobellis, Francesca; Ierardi, Anna M; Mazzei, Maria A; Magenta Biasina, Alberto; Carrafiello, Gianpaolo; Nicola, Refky; Scaglione, Mariano

    2016-01-01

    Acute vascular injuries are the second most common cause of fatalities in patients with multiple traumatic injuries; thus, prompt identification and management is essential for patient survival. Over the past few years, multidetector CT (MDCT) using dual-phase scanning protocol has become the imaging modality of choice in high-energy deceleration traumas. The objective of this article was to review the role of dual-phase MDCT in the identification and management of acute vascular injuries, particularly in the chest and abdomen following multiple traumatic injuries. In addition, this article will provide examples of MDCT features of acute vascular injuries with correlative surgical and interventional findings.

  20. Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study

    Directory of Open Access Journals (Sweden)

    Erick Huarcaya

    2011-06-01

    Full Text Available Human Bartonellosis has an acute phase characterized by fever and hemolytic anemia, and a chronic phase with bacillary angiomatosis-like lesions. This cross-sectional pilot study evaluated the immunology patterns using pre- and post-treatment samples in patients with Human Bartonellosis. Patients between five and 60 years of age, from endemic areas in Peru, in the acute or chronic phases were included. In patients in the acute phase of Bartonellosis a state of immune peripheral tolerance should be established for persistence of the infection. Our findings were that elevation of the anti-inflammatory cytokine IL-10 and numeric abnormalities of CD4+ and CD8+ T-Lymphocyte counts correlated significantly with an unfavorable immune state. During the chronic phase, the elevated levels of IFN-γ and IL-4 observed in our series correlated with previous findings of endothelial invasion of B. henselae in animal models.

  1. Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study.

    Science.gov (United States)

    Huarcaya, Erick; Best, Ivan; Rodriguez-Tafur, Juan; Maguiña, Ciro; Solórzano, Nelson; Menacho, Julio; Lopez De Guimaraes, Douglas; Chauca, Jose; Ventosilla, Palmira

    2011-01-01

    Human Bartonellosis has an acute phase characterized by fever and hemolytic anemia, and a chronic phase with bacillary angiomatosis-like lesions. This cross-sectional pilot study evaluated the immunology patterns using pre- and post-treatment samples in patients with Human Bartonellosis. Patients between five and 60 years of age, from endemic areas in Peru, in the acute or chronic phases were included. In patients in the acute phase of Bartonellosis a state of immune peripheral tolerance should be established for persistence of the infection. Our findings were that elevation of the anti-inflammatory cytokine IL-10 and numeric abnormalities of CD4(+) and CD8(+) T-Lymphocyte counts correlated significantly with an unfavorable immune state. During the chronic phase, the elevated levels of IFN-γ and IL-4 observed in our series correlated with previous findings of endothelial invasion of B. henselae in animal models.

  2. The MASP family of Trypanosoma cruzi: changes in gene expression and antigenic profile during the acute phase of experimental infection.

    Directory of Open Access Journals (Sweden)

    Sara Lopes dos Santos

    acute phase of Chagas disease.

  3. Evaluation of the prevalence of stress and its phases in acute myocardial infarction in patients active in the labor market

    Directory of Open Access Journals (Sweden)

    Luciane Boreki Lucinda

    2015-02-01

    Full Text Available Introduction: Acute myocardial infarction is a social health problem of epidemiological relevance, with high levels of morbidity and mortality. Stress is one of the modifiable risk factors that triggers acute myocardial infarction. Stress is a result of a set of physiological reactions, which when exaggerated in intensity or duration can lead to imbalances in one's organism, resulting in vulnerability to diseases. Objective: To identify the presence of stress and its phases in hospitalized and active labor market patients with unstable myocardial infarction and observe its correlation with the life of this population with stress. Methods: The methodology used was a quantitative, descriptive and transversal research approach conducted with a total of 43 patients, who were still active in the labor market, presenting or not morbidities. Data collection occurred on the fourth day of their hospitalization and patients responded to Lipp's Stress Symptom Inventory for adults. Results: Thirty-one patients (72.1% presented stress and twelve (27.8% did not. In patients with stress, the identified phases were: alert - one patient (3.2%; resistance -twenty-two patients (71.0%; quasi-exhaustion - six patients (19.4% and exhaustion - two patients (6.5%. All women researched presented stress. Conclusion: The results suggest a high level of stress, especially in the resistance phase, in the male infarcted population, hospitalized and active in the labor market.

  4. Proinflammatory and anti-inflammatory cytokines present in the acute phase of experimental colitis treated with Saccharomyces boulardii.

    Science.gov (United States)

    Grijó, Nathália Nahas; Borra, Ricardo Carneiro; Sdepanian, Vera Lucia

    2010-09-01

    To study the proinflammatory and anti-inflammatory cytokines present in the acute phase of trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis treated with Saccharomyces boulardii. Thirty male Wistar rats were divided into three groups: (1) treated group--received Saccharomyces boulardii for 14 days; (2) non-treated group--received sodium chloride solution for 14 days; (3) control group. Colitis was induced on the seventh day of the study in the treated and the non-treated groups using TNBS (10 mg) dissolved in 50% ethanol. Quantification of cytokines, including interleukin (IL)-1beta (IL-1beta), IL-6, transforming growth factor-beta (TGF-beta), IL-10 and tumor necrosis factor-alpha (TNF-alpha), in the serum and colonic tissue collected on day 14 were carried out using an enzyme-linked immunosorbent assay (ELISA). The mean concentrations of TGF-beta in both the serum and the colonic tissue of the treated group were statistically higher than that of the control group. The mean concentration of TGF-beta in the colonic tissue of the non-treated group was also statistically higher than the control group. The group treated with Saccharomyces boulardii showed increased amounts of TGF-beta, an anti-inflammatory cytokine, during the acute phase of colitis. There were no differences in the amount of TNF-alpha, IL-1beta, IL-6, and IL-10 between the treated and the non-treated or the control groups during the acute phase of experimental colitis induced by TNBS.

  5. Acute phase proteins in dogs naturally infected with the Giant Kidney Worm (Dioctophyme renale)

    DEFF Research Database (Denmark)

    Schmidt, Elizabeth M. S.; Kjelgaard-Hansen, Mads; Thomas, Funmilola

    2016-01-01

    of nephrectomy on circulating concentrations of select acute phase proteins (APP) such as serum amyloid A (SAA), C-reactive protein (CRP), and haptoglobin(HP). Methods: Nephrectomy was performed in infected dogs and the worms were collected for identification. Blood samples were taken 24 hours before surgery...... the 12 dogs evaluated in this study. Dogs showed significantly increased HP concentrations(P SAA concentrations before surgery, and cortisol concentrations were significantly higher at admission when compared to recovery. No significant correlations were found between the number...

  6. A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia

    DEFF Research Database (Denmark)

    Garzon, Ramiro; Savona, Michael; Baz, Rachid

    2017-01-01

    of selinexor in patients with advanced hematological malignancies. Ninety-five patients with relapsed or refractory acute myeloid leukemia (AML) were enrolled between January 2013 and June 2014 to receive 4, 8, or 10 doses of selinexor in a 21- or 28-day cycle. The most frequently reported adverse events (AEs...

  7. Value of the Doppler index of myocardial performance in the early phase of acute myocardial infarction

    DEFF Research Database (Denmark)

    Poulsen, S H; Jensen, S E; Tei, C

    2000-01-01

    Prospective assessment of a nongeometric Doppler-derived index of combined systolic and diastolic myocardial performance was performed in 64 patients with acute myocardial infarction (MI) within 1 hour after their arrival to the hospital and in 39 age-matched healthy subjects. The index is defined...

  8. Acute Heart Failure Clinical Drug Development : From Planning to Proof of Activity to Phase III

    NARCIS (Netherlands)

    Cotter, Gad; Voors, Adriaan A.; Weatherley, Beth Davison; Pang, Peter S.; Teerlink, John R.; Filippatos, Gerasimos; Ponikowski, Piotr; Milo-Cotter, Olga; Dittrich, Howard; Teichman, Sam L.; Adams, Kirkwood F.; Gheorghiade, Mihai; Metra, Marco

    2010-01-01

    Over the last decades, attempts to develop new therapies for acute heart failure (AHF) have largely failed. Limitations in understanding the pathophysiology of AHF, its natural history, the effects of current therapies, the properties of new agents, and, importantly, study designs and execution have

  9. Age- and Sex-Associated Effects on Acute-Phase Proteins in Göttingen Minipigs

    DEFF Research Database (Denmark)

    Christoffersen, Berit Ø; Jensen, Søren J.; Ludvigsen, Trine P

    2015-01-01

    , 16, 24 and 40-48 wk) of male and female Göttingen minipigs. In addition, minipigs were tested under 2 housing conditions, after acute LPS challenge, and after diet-induced obesity with and without mild diabetes. Changing the pigs to a new environment induced significant increases in CRP, PMAP...

  10. Schematic X-ray diagnostic examination for the acute phase after a blunt thoraco-abdominal injury

    International Nuclear Information System (INIS)

    Kingma, L.M.

    1981-01-01

    The radiodiagnostic examination in the acute phase after a blunt thoracoabdominal injury can be made more reliable by repeating the examination after half an hour. The classical radiodiagnostic examination of the thorax and the abdomen is completed by a detail view of the upper abdomen. This X-ray plays a decisive part in the diagnosis of lesions of the liver, the spleen and both hemi-diafragms. The intravenous urogram is not only important because of the information gained about the condition of the urinary tract, but is also of great value to the management of shock and to regulate the infusion of fluids in the acute phase. One of the most important conclusions from this investigation is that the exclusion of pathology in trauma-patients is just as important as the demonstration of it. By ignoring the indications for urography and the significance of possible haematuria unnecessary loss of time can be avoided. The statistical relevance of the observations is shown in many examples, with the exception of the time-limits imposed in the selection of the patients. It could not be proved that the X-ray scheme is only of more value in the early post traumatic period. There was no correlation found between the passage of time since trauma and the significance of the results of the radiodiagnostic examination. Finally, advice is given about a scheme for the radiodiagnostic examination of patients with a blunt thoraco-abdominal injury, based upon the observations and conclusions in this dissertation. (Auth.)

  11. Expression of complement and pentraxin proteins in acute phase response elicited by tumor photodynamic therapy: the engagement of adrenal hormones.

    Science.gov (United States)

    Merchant, Soroush; Huang, Naiyan; Korbelik, Mladen

    2010-12-01

    Treatment of solid tumors by photodynamic therapy (PDT) was recently shown to trigger a strong acute phase response. Using the mouse Lewis lung carcinoma (LLC) model, the present study examined complement and pentraxin proteins as PDT-induced acute phase reactants. The results show a distinct pattern of changes in the expression of genes encoding these proteins in the tumor, as well as host liver and spleen, following PDT mediated by photosensitizer Photofrin™. These changes were influenced by glucocorticoid hormones, as evidenced by transcriptional activation of glucocorticoid receptor and the upregulation of gene encoding this receptor. The expression of gene for glucocorticoid-induced zipper (GILZ) protein, whose activity is particularly susceptible to glucocorticoid regulation, was also changed in PDT-treated tumors. A direct demonstration that tumor PDT induces glucocorticoid hormone upregulation is provided by documenting elevated levels of serum corticosterone in mice bearing PDT-treated LLC tumors. Tumor response to PDT was negatively affected by blocking glucocorticoid receptor activity, which suggests that glucocorticoid hormones have a positive impact on the therapeutic outcome with this therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Increased levels of proteins of the acute inflammatory phase in the peritoneal fluid of women with advanced stages of endometriosis.

    Science.gov (United States)

    Polak, Grzegorz; Barczyński, Bartłomiej; Bednarek, Wiesława; Kwaśniewski, Wojciech; Wertell, Iwona; Derewianka-Polak, Magdalena; Makara-Studzińska, Marta; Kotarski, Jan

    2015-06-01

    Most investigators agree that endometriosis is associated with a state of subclinical, non-infectious peritoneal inflammation. The objective of the study was to assess concentrations of two markers of the acute inflammatory phase proteins, haptoglobin and ceruloplasmin, in peritoneal fluid of endometriotic women. 229 women who underwent diagnostic or therapeutic laparoscopy were included in the study Minimal, mild, moderate and severe endometriosis according to ASRM was confirmed in 119 women (study groups), whereas 110 patients suffered from simple serous or dermoid ovarian cysts (reference groups). Haptoglobin and ceruloplasmin concentrations in the peritoneal fluid samples aspirated during laparoscopy were measured using commercially available radial immunodiffusion kits. The concentration of haptoglobin in the peritoneal fluid of women with endometriosis was significantly higher as compared to patients with serous and dermoid ovarian cysts. Significantly higher haptoglobin level was observed in patients with severe and moderate endometriosis as compared to women from both reference groups. No significant difference in the peritoneal fluid ceruloplasmin levels was found between patients with endometriosis and women from reference groups. However, it was noted that ceruloplasmin levels are higher in the subgroup of patients with severe endometriosis as compared to both reference groups and women with mild disease. Our results support the hypothesis that endometriosis is associated with subclinical inflammation within the peritoneal cavity It may be speculated that pro-inflammatory stimuli strong enough to cause an increase in acute inflammatory phase proteins peritoneal fluid concentrations are observed only in the advanced stages of the disease.

  13. Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice

    DEFF Research Database (Denmark)

    Poulsen, Sarah Søs; Knudsen, Kristina Bram; Jackson, Petra

    2017-01-01

    of acute phase response proteins serum amyloid A1/2 (SAA1/2) and SAA3 were determined on day 1, 28 or 92. Expression levels of hepatic Saal and pulmonary Saa3 mRNA levels were assessed to determine the origin of the acute phase response proteins. Pulmonary Saa3 mRNA expression levels were greater...... and lasted longer than hepatic Saal mRNA expression. Plasma SAA1/2 and SAA3 protein levels were related to time and physicochemical properties using adjusted, multiple regression analyses. SAA3 and SAA1/2 plasma protein levels were increased after exposure to almost all of the MWCNTs on day 1, whereas...... limited changes were observed on day 28 and 92. SAA1/2 and SAA3 protein levels did not correlate and only SAA3 protein levels correlated with neutrophil influx. The multiple regression analyses revealed a protective effect of MWCNT length on SAA1/2 protein level on day 1, such that a longer length...

  14. Intensity Modulated Radiotherapy (IMRT) in locally advanced thyroid cancer: Acute toxicity results of a phase I study

    International Nuclear Information System (INIS)

    Urbano, Teresa Guerrero; Clark, Catharine H.; Hansen, Vibeke N.; Adams, Elizabeth J.; Miles, Elizabeth A.; Mc Nair, Helen; Bidmead, A. Margaret; Warrington, Jim; Dearnaley, David P.; Harmer, Clive; Harrington, Kevin J.; Nutting, Christopher M.

    2007-01-01

    Background and purpose: This phase 1 study was designed to determine the toxicity of accelerated fractionation IMRT in locally advanced thyroid cancer. Methods: Patients with high risk locally advanced thyroid cancer who required post-operative EBRT were recruited. A single-phase inverse-planned-simultaneous-boost was delivered by IMRT: 58.8 Gy/28F (daily) to the primary tumour and involved nodes and 50 Gy/28F to the elective nodes. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) was collected. Results: Thirteen patients were treated (7 medullary thyroid, 2 Hurthle cell and 4 well differentiated thyroid cancer). G3 and G2 radiation dermatitis rates were 38.5% and 31%; G3 and G2 mucositis rates 8% and 53% and G3 and G2 pain 23% and 54%. Thirty-one percentage required enteral feeding. G3 and G2 xerostomia rates were 0% and 31%. Recovery was seen, with 62% patients having dysphagia G ≤ 1 2 months after IMRT. Thirty percent of patients developed L'Hermitte's syndrome. No grade 4 toxicity was observed. No dose limiting toxicity was found. Conclusions: Accelerated fractionation IMRT in this group of patients is feasible and safe. The acute toxicity appeared acceptable and early indicators of late toxicity moderate and similar to what would be expected with conventional RT. Longer follow up is required to quantify late side effects

  15. Glutamate excitoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

    Science.gov (United States)

    Campos, Francisco; Pérez-Mato, María; Agulla, Jesús; Blanco, Miguel; Barral, David; Almeida, Angeles; Brea, David; Waeber, Christian; Castillo, José; Ramos-Cabrer, Pedro

    2012-01-01

    Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

  16. Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Michael Huber

    2006-11-01

    Full Text Available BACKGROUND: To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus. METHODS AND FINDINGS: Sera from two groups of patients-25 with acute HIV-1 infection and 31 with chronic infection-were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies. CONCLUSIONS: Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.

  17. Gene expression profiling of porcine skeletal muscle in the early recovery phase following acute physical activity

    DEFF Research Database (Denmark)

    Hansen, Jeanette; Conley, Lene; Hedegaard, Jakob

    2012-01-01

    Acute physical activity elicits changes in gene expression in skeletal muscles to promote metabolic changes and to repair exercise-induced muscle injuries. In the present time-course study, pigs were submitted to an acute bout of treadmill running until near exhaustion to determine the impact...... associated with proteolytic events, such as the muscle-specific E3 ubiquitin ligase atrogin-1, were significantly upregulated, suggesting that protein breakdown, prevention of protein aggregation and stabilization of unfolded proteins are important processes for restoration of cellular homeostasis. We also...... detected an upregulation of genes that are associated with muscle cell proliferation and differentiation, including MUSTN1, ASB5 and CSRP3, possibly reflecting activation, differentiation and fusion of satellite cells to facilitate repair of muscle damage. In addition, exercise increased expression...

  18. Treatment for Sulfur Mustard Lung Injuries; New Therapeutic Approaches from Acute to Chronic Phase

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    Zohreh Poursaleh

    2012-09-01

    Full Text Available Objective: Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980-1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries.Method:This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment.Results:Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion:Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  19. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

    Directory of Open Access Journals (Sweden)

    Poursaleh Zohreh

    2012-09-01

    Full Text Available Abstract Objective Sulfur mustard (SM is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988. It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments.

  20. Infection pattern of neutropenic patients in post-chemotherapy phase of acute leukemia treatment

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    Ahmad Ahmadzadeh

    2013-12-01

    Full Text Available Neutropenia following chemotherapy regimens in leukemia patients is of major concern since it makes these patients vulnerable to infections. If we can identify which germs are causing these infections, they can be annihilated or, at least, the most appropriate antibiotic therapy can be started immediately, even before we have the results of the culture. This retrospective multi-center study took place in 2012 and included patients with acute leukemia who had already undergone chemotherapy and who had been febrile for at least 16 hours. In order to assess the type of infection, different environments were chosen and the results were compared by t-test and x2 tests. This study took place in four hospitals in Tehran and Ahwaz, Iran. The study population was made up of 89 patients: 37 with acute lymphoblastic leukemia and 52 with acute myeloid leukemia. The results revealed that blood was the most common site of infection. From all our positive cultures, it was seen that 85.4% of them had gram-negative bacteria with a dominance of E. coli of 25.8% over the other colonies. Also, antibiograms revealed the sensitivity of almost all the gram-negatives to amino glycosides. In contrast with most of the literature, in our patients, gram-negatives are the most common cause of infection and, therefore, administering amino glycosides would be the safest antibiotic therapy to prescribe before culture results are available.

  1. Fine-mapping of immunodominant linear B-cell epitopes of the Staphylococcus aureus SEB antigen using short overlapping peptides.

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    Zhuo Zhao

    Full Text Available Staphylococcal enterotoxin B (SEB is one of the most potent Staphylococcus aureus exotoxins (SEs. Due to its conserved sequence and stable structure, SEB might be a good candidate antigen for MRSA vaccines. Although cellular immune responses to SEB are well-characterized, much less is known regarding SEB-specific humoral immune responses, particularly regarding detailed epitope mapping. In this study, we utilized a recombinant nontoxic mutant of SEB (rSEB and an AlPO4 adjuvant to immunize BALB/c mice and confirmed that rSEB can induce a high antibody level and effective immune protection against MRSA infection. Next, the antisera of immunized mice were collected, and linear B cell epitopes within SEB were finely mapped using a series of overlapping synthetic peptides. Three immunodominant B cell epitopes of SEB were screened by ELISA, including a novel epitope, SEB205-222, and two known epitopes, SEB97-114 and SEB247-261. Using truncated peptides, an ELISA was performed with peptide-KLH antisera, and the core sequence of the three immunodominant B cell epitopes were verified as SEB97-112, SEB207-222, and SEB247-257. In vitro, all of the immunodominant epitope-specific antisera (anti-SEB97-112, anti-SEB207-222 and anti-SEB247-257 were observed to inhibit SEB-induced T cell mitogenesis and cytokine production from splenic lymphocytes of BALB/c mice. The homology analysis indicated that SEB97-112 and SEB207-222 were well-conserved among different Staphylococcus aureus strains. The 3D crystal structure of SEB indicated that SEB97-112 was in the loop region inside SEB, whereas SEB207-222 and SEB247-257 were in the β-slice region outside SEB. In summary, the fine-mapping of linear B-cell epitopes of the SEB antigen in this study will be useful to understand anti-SEB immunity against MRSA infection further and will be helpful to optimize MRSA vaccine designs that are based on the SEB antigen.

  2. Absolute coronary blood flow measurement and microvascular resistance in ST-elevation myocardial infarction in the acute and subacute phase

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    Wijnbergen, Inge; Veer, Marcel van ' t [Department of Cardiology, Catharina Hospital, Eindhoven (Netherlands); Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven (Netherlands); Lammers, Jeroen; Ubachs, Joey [Department of Cardiology, Catharina Hospital, Eindhoven (Netherlands); Pijls, Nico H.J., E-mail: nico.pijls@cze.nl [Department of Cardiology, Catharina Hospital, Eindhoven (Netherlands); Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven (Netherlands)

    2016-03-15

    Background/Purpose: In a number of patients with acute myocardial infarction (AMI), myocardial hypoperfusion, known as the no-reflow phenomenon, persists after primary percutaneous intervention (PPCI). The aim of this study was to evaluate the feasibility and safety of a new quantitative method of measuring absolute blood flow and resistance within the perfusion bed of an infarct-related artery. Furthermore, we sought to study no-reflow by correlating these measurements to the index of microvascular resistance (IMR) and the area at risk (AR) as determined by cardiac magnetic resonance imaging (CMR). Methods: Measurements of absolute flow and myocardial resistance were performed in 20 patients with ST-segment elevation myocardial infarction (STEMI), first immediately following PPCI and then again after 3–5 days. These measurements used the technique of thermodilution during a continuous infusion of saline. Flow was expressed in ml/min per gram of tissue within the area at risk. Results: The average time needed for measurement of absolute flow, resistance and IMR was 20 min, and all measurements could be performed without complication. A higher flow supplying the AR correlated with a lower IMR in the acute phase. Absolute flow increased from 3.14 to 3.68 ml/min/g (p = 0.25) and absolute resistance decreased from 1317 to 1099 dyne.sec.cm-5/g (p = 0.40) between the first day and fifth day after STEMI. Conclusions: Measurement of absolute flow and microvascular resistance is safe and feasible in STEMI patients and may allow for a better understanding of microvascular (dys)function in the early phase of AMI. - Highlights: • We measured absolute coronary blood flow and microvascular resistance in STEMI patients in the acute phase and in the subacute phase, using the technique of thermodilution with low grade intracoronary continuous infusion of saline. • These measurements are safe and feasible during PPCI in STEMI patients. • In STEMI patients, absolute flow

  3. Effects of Partial and Acute Total Sleep Deprivation on Performance across Cognitive Domains, Individuals and Circadian Phase

    Science.gov (United States)

    Lo, June C.; Groeger, John A.; Santhi, Nayantara; Arbon, Emma L.; Lazar, Alpar S.; Hasan, Sibah; von Schantz, Malcolm; Archer, Simon N.; Dijk, Derk-Jan

    2012-01-01

    Background Cognitive performance deteriorates during extended wakefulness and circadian phase misalignment, and some individuals are more affected than others. Whether performance is affected similarly across cognitive domains, or whether cognitive processes involving Executive Functions are more sensitive to sleep and circadian misalignment than Alertness and Sustained Attention, is a matter of debate. Methodology/Principal Findings We conducted a 2 × 12-day laboratory protocol to characterize the interaction of repeated partial and acute total sleep deprivation and circadian phase on performance across seven cognitive domains in 36 individuals (18 males; mean ± SD of age = 27.6±4.0 years). The sample was stratified for the rs57875989 polymorphism in PER3, which confers cognitive susceptibility to total sleep deprivation. We observed a deterioration of performance during both repeated partial and acute total sleep deprivation. Furthermore, prior partial sleep deprivation led to poorer cognitive performance in a subsequent total sleep deprivation period, but its effect was modulated by circadian phase such that it was virtually absent in the evening wake maintenance zone, and most prominent during early morning hours. A significant effect of PER3 genotype was observed for Subjective Alertness during partial sleep deprivation and on n-back tasks with a high executive load when assessed in the morning hours during total sleep deprivation after partial sleep loss. Overall, however, Subjective Alertness and Sustained Attention were more affected by both partial and total sleep deprivation than other cognitive domains and tasks including n-back tasks of Working Memory, even when implemented with a high executive load. Conclusions/Significance Sleep loss has a primary effect on Sleepiness and Sustained Attention with much smaller effects on challenging Working Memory tasks. These findings have implications for understanding how sleep debt and circadian rhythmicity

  4. Synthesis and structural insight into ESX-1 Substrate Protein C, an immunodominant Mycobacterium tuberculosis-secreted antigen.

    Science.gov (United States)

    Son, Soo Jung; Harris, Paul W R; Squire, Chris J; Baker, Edward N; Brimble, Margaret A

    2016-05-01

    Tuberculosis, the second leading cause of death from a single infectious agent, is recognized as a major threat to human health due to a lack of practicable vaccines against the disease and the widespread occurrence of drug resistance. With a pressing need for a novel protein target as a platform for new vaccine development, ESX-1 Substrate Protein C (EspC) was recently identified as a novel Mycobacterium tuberculosis-secreted antigen that is as immunodominant as the two specific immunodiagnostic T-cell antigens, CFP-10 and ESAT-6. Here, we present the first chemical total synthesis, folding conditions, and circular dichroism data of EspC. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 267-274, 2016. © 2016 Wiley Periodicals, Inc.

  5. Immunisation With Immunodominant Linear B Cell Epitopes Vaccine of Manganese Transport Protein C Confers Protection against Staphylococcus aureus Infection.

    Directory of Open Access Journals (Sweden)

    Hui-Jie Yang

    Full Text Available Vaccination strategies for Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA infections have attracted much research attention. Recent efforts have been made to select manganese transport protein C, or manganese binding surface lipoprotein C (MntC, which is a metal ion associated with pathogen nutrition uptake, as potential candidates for an S. aureus vaccine. Although protective humoral immune responses to MntC are well-characterised, much less is known about detailed MntC-specific B cell epitope mapping and particularly epitope vaccines, which are less-time consuming and more convenient. In this study, we generated a recombinant protein rMntC which induced strong antibody response when used for immunisation with CFA/IFA adjuvant. On the basis of the results, linear B cell epitopes within MntC were finely mapped using a series of overlapping synthetic peptides. Further studies indicate that MntC113-136, MntC209-232, and MntC263-286 might be the original linear B-cell immune dominant epitope of MntC, furthermore, three-dimensional (3-d crystal structure results indicate that the three immunodominant epitopes were displayed on the surface of the MntC antigen. On the basis of immunodominant MntC113-136, MntC209-232, and MntC263-286 peptides, the epitope vaccine for S. aureus induces a high antibody level which is biased to TH2 and provides effective immune protection and strong opsonophagocytic killing activity in vitro against MRSA infection. In summary, the study provides strong proof of the optimisation of MRSA B cell epitope vaccine designs and their use, which was based on the MntC antigen in the development of an MRSA vaccine.

  6. The acute phase response of haptoglobin and serum amyloid A (SAA) in cattle undergoing experimental infection with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Godson, D.L.; Toussaint, M.J.M.

    2000-01-01

    respiratory syncytial virus (BRSV), analysing the induction of the two most dominant bovine acute phase proteins haptoglobin and serum amyloid A (SAA). Strong and reproducible acute phase responses were detected for both proteins, peaking at around 7-8 days after inoculation of BRSV, while no response...... was seen in mock-inoculated control animals. The serum concentrations reached for SAA and haptoglobin during the BRSV-induced acute phase response were generally the same or higher than previously reported for bacterial infections in calves. The magnitude and the duration of the haptoglobin response...... was found to correlate well with the severity of clinical signs (fever) and with the extent of lung consolidation while SAA responded most rapidly to infection....

  7. Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study

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    Felix Kaspar

    2016-01-01

    Full Text Available Objective. This study compared acute and late effect of single-bout endurance training (ET and high-intensity interval training (HIIT on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. Design. Cohort study with repeated-measures design. Methods. Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL, IL-1β, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1, insulin growth factor 1 (IGF-1, and C-reactive protein (CRP. Statistical analysis was with Wilcoxon signed-rank tests. Results. ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (−20%; p=0.047 and a decrease of MCP-1 (−17.9%; p=0.03. Conclusion. This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis.

  8. Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study

    Science.gov (United States)

    Kaspar, Felix; Jelinek, Herbert F.; Perkins, Steven; Al-Aubaidy, Hayder A.; deJong, Bev; Butkowski, Eugene

    2016-01-01

    Objective. This study compared acute and late effect of single-bout endurance training (ET) and high-intensity interval training (HIIT) on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. Design. Cohort study with repeated-measures design. Methods. Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL), IL-1β, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1), insulin growth factor 1 (IGF-1), and C-reactive protein (CRP). Statistical analysis was with Wilcoxon signed-rank tests. Results. ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (−20%; p = 0.047) and a decrease of MCP-1 (−17.9%; p = 0.03). Conclusion. This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis. PMID:27212809

  9. Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study.

    Science.gov (United States)

    Kaspar, Felix; Jelinek, Herbert F; Perkins, Steven; Al-Aubaidy, Hayder A; deJong, Bev; Butkowski, Eugene

    2016-01-01

    This study compared acute and late effect of single-bout endurance training (ET) and high-intensity interval training (HIIT) on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. Cohort study with repeated-measures design. Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL), IL-1β, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1), insulin growth factor 1 (IGF-1), and C-reactive protein (CRP). Statistical analysis was with Wilcoxon signed-rank tests. ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (-20%; p = 0.047) and a decrease of MCP-1 (-17.9%; p = 0.03). This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis.

  10. Longitudinal social-interpersonal functioning among higher-risk responders to acute-phase cognitive therapy for recurrent major depressive disorder.

    Science.gov (United States)

    Vittengl, Jeffrey R; Clark, Lee Anna; Thase, Michael E; Jarrett, Robin B

    2016-07-15

    Social-interpersonal dysfunction increases disability in major depressive disorder (MDD). Here we clarified the durability of improvements in social-interpersonal functioning made during acute-phase cognitive therapy (CT), whether continuation CT (C-CT) or fluoxetine (FLX) further improved functioning, and relations of functioning with depressive symptoms and relapse/recurrence. Adult outpatients (N=241) with recurrent MDD who responded to acute-phase CT with higher risk of relapse (due to unstable or partial remission) were randomized to 8 months of C-CT, FLX, or pill placebo plus clinical management (PBO) and followed 24 additional months. We analyzed repeated measures of patients' social adjustment, interpersonal problems, dyadic adjustment, depressive symptoms, and major depressive relapse/recurrence. Large improvements in social-interpersonal functioning occurring during acute-phase CT (median d=1.4) were maintained, with many patients (median=66%) scoring in normal ranges for 32 months. Social-interpersonal functioning did not differ significantly among C-CT, FLX, and PBO arms. Beyond concurrently measured residual symptoms, deterioration in social-interpersonal functioning preceded and predicted upticks in depressive symptoms and major depressive relapse/recurrence. Results may not generalize to other patient populations, treatment protocols, or measures of social-interpersonal functioning. Mechanisms of risk connecting poorer social-interpersonal functioning with depression were not studied. Average improvements in social-interpersonal functioning among higher-risk responders to acute phase CT are durable for 32 months. After acute-phase CT, C-CT or FLX may not further improve social-interpersonal functioning. Among acute-phase CT responders, deteriorating social-interpersonal functioning provides a clear, measurable signal of risk for impending major depressive relapse/recurrence and opportunity for preemptive intervention. Copyright © 2016 Elsevier B

  11. Acute tubular necrosis (ATN) presenting with an unusually prolonged period of marked polyuria heralded by an abrupt oliguric phase.

    Science.gov (United States)

    Ramoutar, Virin; Landa, Cristian; James, Leighton R

    2014-08-22

    A 50-year-old African-American man presented with acute tubular necrosis (ATN) secondary to hypotension from non-typhoid Salmonella gastroenteritis and bacteraemia. The oliguric phase lasted only 24 h followed by prolonged polyuria for 20 days, with urine output in excess of 16 L/day at maximum. As indexed in PubMed this is only the second published case of this nature since 1974, in which an abrupt oliguric phase of 24 h or less heralded prolonged polyuria in ATN. The diagnosis is challenging as fractional excretion of sodium early in the clinical course and rapid normalisation of serum creatinine with intravenous fluids (IVF) may point towards prerenal azotaemia resulting in a premature discharge from hospital. Patients with an abrupt oliguric phase may suffer a secondary renal insult from the profound fluid loss that is to follow and may need inpatient monitoring with supplemental IVF to prevent deleterious outcomes. 2014 BMJ Publishing Group Ltd.

  12. Liver genomic responses to ciguatoxin: evidence for activation of phase I and phase II detoxification pathways following an acute hypothermic response in mice.

    Science.gov (United States)

    Morey, Jeanine S; Ryan, James C; Bottein Dechraoui, Marie-Yasmine; Rezvani, Amir H; Levin, Edward D; Gordon, Christopher J; Ramsdell, John S; Van Dolah, Frances M

    2008-06-01

    Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (p or = 1.5 and p < or = 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4 degrees C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene expression in pathways involving eicosanoid biosynthesis and cholesterol homeostasis was also noted. Cytochrome P450s (Cyps) were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial downregulation at 1 h but were quickly and strongly upregulated at 4 and 24 h post-exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice.

  13. Acute phase protein concentrations in serum and milk from healthy cows, cows with clinical mastitis and cows with extramammary inflammatory conditions

    DEFF Research Database (Denmark)

    Nielsen, B.H.; Jacobsen, S.; Andersen, P.H.

    2004-01-01

    The concentrations of the two acute phase proteins, serum amyloid A and haptoglobin, in serum and milk were compared in 10 cows with clinical mastitis, 11 cows with extramammary inflammatory conditions and 10 clinically healthy control cows. The concentrations of both acute phase proteins were...... higher in the serum and milk of the cows with mastitis than in the cows in the other two groups. Four of the cows with extramammary inflammatory conditions had serum amyloid A concentrations in serum above 100 mug/ml, but negligible concentrations in milk, indicating that a pathogen must be present...

  14. Focused and divided attention abilities in the acute phase of recovery from moderate to severe traumatic brain injury.

    Science.gov (United States)

    Robertson, Kayela; Schmitter-Edgecombe, Maureen

    2017-01-01

    Impairments in attention following traumatic brain injury (TBI) can significantly impact recovery and rehabilitation effectiveness. This study investigated the multi-faceted construct of selective attention following TBI, highlighting the differences on visual nonsearch (focused attention) and search (divided attention) tasks. Participants were 30 individuals with moderate to severe TBI who were tested acutely (i.e. following emergence from PTA) and 30 age- and education-matched controls. Participants were presented with visual displays that contained either two or eight items. In the focused attention, nonsearch condition, the location of the target (if present) was cued with a peripheral arrow prior to presentation of the visual displays. In the divided attention, search condition, no spatial cue was provided prior to presentation of the visual displays. The results revealed intact focused, nonsearch, attention abilities in the acute phase of TBI recovery. In contrast, when no spatial cue was provided (divided attention condition), participants with TBI demonstrated slower visual search compared to the control group. The results of this study suggest that capitalizing on intact focused attention abilities by allocating attention during cognitively demanding tasks may help to reduce mental workload and improve rehabilitation effectiveness.

  15. Spouses' conceptions of the pre-hospital phase when their partners suffered an acute myocardial infarction--a qualitative analysis.

    Science.gov (United States)

    Johansson, Ingela; Swahn, Eva; Strömberg, Anna

    2008-09-01

    Delay from onset of acute myocardial infarction symptoms to the delivery of medical care is a major determinant of prognosis. Although studies have explored patient reasons for delay, there are only limited data concerning experiences of the spouse. Was to describe spouses' conceptions of the pre-hospital phase when their partners suffered an acute myocardial infarction. A phenomenographic approach was applied. Fifteen spouses were interviewed rational, and consulting others. The category respecting independence contained: accepting the need for control, marital roles and experiences, restraining emotions, and seeking agreement. Our findings suggest that spouses have a strong influence on the course of events. When accepting the partner's need for control through following earlier marital roles and experiences, restraining own emotions and seeking agreement, this seemed to contribute to delay. However, when the spouse was resourceful by sharing the experience, having knowledge, understanding the severity, being rational and consulting others when needed, this seemed to have a positive influence on the pre-hospital time.

  16. Ultrasound of the coracoclavicular ligaments in the acute phase of an acromioclavicular disjunction: Comparison of radiographic, ultrasound and MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Faruch Bilfeld, Marie; Lapegue, Franck; Chiavassa Gandois, Helene; Bayol, Marie Aurelie; Sans, Nicolas [CHU Toulouse-Purpan, Service de Radiologie, Toulouse Cedex 9 (France); Bonnevialle, Nicolas [CHU Toulouse-Purpan, Service d' Orthopedie, Toulouse Cedex 9 (France)

    2017-02-15

    Acromioclavicular joint injuries are typically diagnosed by clinical and radiographic assessment with the Rockwood classification, which is crucial for treatment planning. The purpose of this study was to describe how the ultrasound findings of acromioclavicular joint injury compare with radiography and MRI findings. Forty-seven patients with suspected unilateral acromioclavicular joint injury after acute trauma were enrolled in this prospective study. All patients underwent digital radiography, ultrasound and 3T MRI. A modified Rockwood classification was used to evaluate the coracoclavicular ligaments. The classifications of acromioclavicular joint injuries diagnosed with radiography, ultrasound and MRI were compared. MRI was used as the gold standard. The agreement between the ultrasound and MRI findings was very good, with a correlation coefficient of 0.83 (95 % CI: 0.72-0.90; p < 0.0001). Ultrasound detected coracoclavicular ligament injuries with a sensitivity of 88.9 %, specificity of 90.0 %, positive predictive value of 92.3 % and negative predictive value of 85.7 %. The agreement between the ultrasound and radiography findings was poor, with a correlation coefficient of 0.69 (95 % CI: 0.51-0.82; p < 0.0001). Ultrasound is an effective examination for the diagnostic work-up of lesions of the coracoclavicular ligaments in the acute phase of an acromioclavicular injury. (orig.)

  17. Acute-Phase Blood Pressure Levels Correlate With a High Risk of Recurrent Strokes in Young-Onset Ischemic Stroke.

    Science.gov (United States)

    Mustanoja, Satu; Putaala, Jukka; Gordin, Daniel; Tulkki, Lauri; Aarnio, Karoliina; Pirinen, Jani; Surakka, Ida; Sinisalo, Juha; Lehto, Mika; Tatlisumak, Turgut

    2016-06-01

    High blood pressure (BP) in acute stroke has been associated with a poor outcome; however, this has not been evaluated in young adults. The relationship between BP and long-term outcome was assessed in 1004 consecutive young, first-ever ischemic stroke patients aged 15 to 49 years enrolled in the Helsinki Young Stroke Registry. BP parameters included systolic (SBP) and diastolic BP, pulse pressure, and mean arterial pressure at admission and 24 hours. The primary outcome measure was recurrent stroke in the long-term follow-up. Adjusted for demographics and preexisting comorbidities, Cox regression models were used to assess independent BP parameters associated with outcome. Of our patients (63% male), 393 patients (39%) had prestroke hypertension and 358 (36%) used antihypertensive treatment. The median follow-up period was 8.9 years (interquartile range 5.7-13.2). Patients with a recurrent stroke (n=142, 14%) had significantly higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure (Pstroke. Patients with SBP ≥160 mm Hg compared with those with SBP strokes (hazard ratio 3.3 [95% confidence interval, 2.05-4.55]; Pstroke, while the 24-hour BP levels were not. In young ischemic stroke patients, high acute phase BP levels are independently associated with a high risk of recurrent strokes. © 2016 American Heart Association, Inc.

  18. Critical Analysis of the Efficacy of Meditation Therapies for Acute and Subacute Phase Treatment of Depressive Disorders: A Systematic Review

    Science.gov (United States)

    Jain, Felipe A.; Walsh, Roger N.; Eisendrath, Stuart J.; Christensen, Scott; Cahn, B. Rael

    2014-01-01

    Background Recently, the application of meditative practices to the treatment of depressive disorders has met with increasing clinical and scientific interest, due to a lower side-effect burden, potential reduction of polypharmacy, as well as theoretical considerations that such interventions may target some of the cognitive roots of depression. We aimed to determine the state of the evidence supporting this application. Methods Randomized, controlled trials of techniques meeting the Agency for Healthcare Research and Quality (AHRQ) definition of meditation, for participants suffering from clinically diagnosed depressive disorders, not currently in remission, were selected. Meditation therapies were separated into praxis (i.e. how they were applied) components, and trial outcomes were reviewed. Results Eighteen studies meeting inclusionary criteria were identified, encompassing seven distinct techniques and 1173 patients, with Mindfulness-Based Cognitive Therapy comprising the largest proportion. Studies including patients suffering from acute major depressive episodes (N = 10 studies), and those with residual subacute clinical symptoms despite initial treatment (N = 8), demonstrated moderate to large reductions in depression symptoms within group, and relative to control groups. There was significant heterogeneity of techniques and trial designs. Conclusions A substantial body of evidence indicates that meditation therapies may have salutary effects on patients suffering from clinical depressive disorders during the acute and subacute phases of treatment. Due to methodological deficiences and trial heterogeneity, large-scale, randomized controlled trials with well-described comparator interventions and measures of expectation are needed to clarify the role of meditation in the depression treatment armamentarium. PMID:25591492

  19. Ultrasound of the coracoclavicular ligaments in the acute phase of an acromioclavicular disjunction: Comparison of radiographic, ultrasound and MRI findings

    International Nuclear Information System (INIS)

    Faruch Bilfeld, Marie; Lapegue, Franck; Chiavassa Gandois, Helene; Bayol, Marie Aurelie; Sans, Nicolas; Bonnevialle, Nicolas

    2017-01-01

    Acromioclavicular joint injuries are typically diagnosed by clinical and radiographic assessment with the Rockwood classification, which is crucial for treatment planning. The purpose of this study was to describe how the ultrasound findings of acromioclavicular joint injury compare with radiography and MRI findings. Forty-seven patients with suspected unilateral acromioclavicular joint injury after acute trauma were enrolled in this prospective study. All patients underwent digital radiography, ultrasound and 3T MRI. A modified Rockwood classification was used to evaluate the coracoclavicular ligaments. The classifications of acromioclavicular joint injuries diagnosed with radiography, ultrasound and MRI were compared. MRI was used as the gold standard. The agreement between the ultrasound and MRI findings was very good, with a correlation coefficient of 0.83 (95 % CI: 0.72-0.90; p < 0.0001). Ultrasound detected coracoclavicular ligament injuries with a sensitivity of 88.9 %, specificity of 90.0 %, positive predictive value of 92.3 % and negative predictive value of 85.7 %. The agreement between the ultrasound and radiography findings was poor, with a correlation coefficient of 0.69 (95 % CI: 0.51-0.82; p < 0.0001). Ultrasound is an effective examination for the diagnostic work-up of lesions of the coracoclavicular ligaments in the acute phase of an acromioclavicular injury. (orig.)

  20. Cardiac index after acute ST-segment elevation myocardial infarction measured with phase-contrast cardiac magnetic resonance imaging

    International Nuclear Information System (INIS)

    Klug, Gert; Reinstadler, Sebastian Johannes; Feistritzer, Hans-Josef; Schwaiger, Johannes P.; Reindl, Martin; Mair, Johannes; Mueller, Silvana; Franz, Wolfgang-Michael; Metzler, Bernhard; Kremser, Christian; Mayr, Agnes

    2016-01-01

    Phase-contrast CMR (PC-CMR) might provide a fast and robust non-invasive determination of left ventricular function in patients after ST-segment elevation myocardial infarction (STEMI). Cine sequences in the left-ventricular (LV) short-axis and free-breathing, retrospectively gated PC-CMR were performed in 90 patients with first acute STEMI and 15 healthy volunteers. Inter- and intra-observer agreement was determined. The correlations of clinical variables age, gender, ejection fraction, NT pro-brain natriuretic peptide [NT-proBNP] with cardiac index (CI) were calculated. For CI, there was a strong agreement of cine CMR with PC-CMR in healthy volunteers (r: 0.82, mean difference: -0.14 l/min/m 2 , error ± 23 %). Agreement was lower in STEMI patients (r: 0.61, mean difference: -0.17 l/min/m 2 , error ± 32 %). In STEMI patients, CI measured with PC-CMR showed lower intra-observer (1 % vs. 9 %) and similar inter-observer variability (9 % vs. 12 %) compared to cine CMR. CI was significantly correlated with age, ejection fraction and NT-proBNP values in STEMI patients. The agreement of PC-CMR and cine CMR for the determination of CI is lower in STEMI patients than in healthy volunteers. After acute STEMI, CI measured with PC-CMR decreases with age, LV ejection fraction and higher NT-proBNP. (orig.)

  1. Investigation of the solubility and the potentials for purification of serum amyloid A (SAA) from equine acute phase serum

    DEFF Research Database (Denmark)

    Christensen, Michelle Brønniche; Sørensen, Jens Christian; Jacobsen, Stine

    2013-01-01

    BACKGROUND: Serum amyloid A (SAA) is useful as a diagnostic marker of systemic inflammation in horses, but only heterologous assays based on non-equine calibration and standardization are available for measurements of equine SAA. More accurate measurements could be obtained using purified species......-specific SAA in native conformation for assay calibration and standardization. Further knowledge about the biochemical properties of SAA would facilitate a future production of native species-specific calibration material Therefore, the aim of the study was an investigation of the solubility and potentials...... for purification of equine SAA based on biochemical properties.Freeze dried equine acute phase serum was dissolved in 70% 2-propanol, 8 M urea, and milli-Q water, respectively. Supercritical fluid extraction (SFE), size-exclusive chromatography (FPLC-SEC), and preparative isoelectric focusing (IEF) were performed...

  2. Early Diagnosis of Congenital Trypanosoma cruzi Infection, Using Shed Acute Phase Antigen, in Ushuaia, Tierra del Fuego, Argentina

    Science.gov (United States)

    Mallimaci, María Cristina; Sosa-Estani, Sergio; Russomando, Graciela; Sanchez, Zunilda; Sijvarger, Carina; Alvarez, Isabel Marcela; Barrionuevo, Lola; Lopez, Carlos; Segura, Elsa Leonor

    2010-01-01

    Chagas' disease, or American trypanosomiasis, is caused by the protozoan parasite Trypanasoma cruzi. It is estimated that 15,000 new cases of congenital T. cruzi transmission occur in the Americas each year. The aim of this study was to estimate the rate of congenital T. cruzi infection in infants born to infected women living in Ushuaia, Argentina, as well to assess a serologic test using Shed Acute Phase Antigen (SAPA) for a timely diagnosis of congenital infection. The rate of congenital infection among children in the study was 4.4% (3/68). Our results show that for infants younger than 30 days of age, matched blood samples from mother and infant were capable of identifying congenital transmission of infection using an enzyme-linked immunosorbent assay with SAPA. For infants older than 3 months, congenital infection could be ruled out using the same procedure. PMID:20064996

  3. Plastic Change along the Intact Crossed Pathway in Acute Phase of Cerebral Ischemia Revealed by Optical Intrinsic Signal Imaging

    Directory of Open Access Journals (Sweden)

    Xiaoli Guo

    2016-01-01

    Full Text Available The intact crossed pathway via which the contralesional hemisphere responds to the ipsilesional somatosensory input has shown to be affected by unilateral stroke. The aim of this study was to investigate the plasticity of the intact crossed pathway in response to different intensities of stimulation in a rodent photothrombotic stroke model. Using optical intrinsic signal imaging, an overall increase of the contralesional cortical response was observed in the acute phase (≤48 hours after stroke. In particular, the contralesional hyperactivation is more prominent under weak stimulations, while a strong stimulation would even elicit a depressed response. The results suggest a distinct stimulation-response pattern along the intact crossed pathway after stroke. We speculate that the contralesional hyperactivation under weak stimulations was due to the reorganization for compensatory response to the weak ipsilateral somatosensory input.

  4. Association between feline immunodeficiency virus (FIV) plasma viral RNA load, concentration of acute phase proteins and disease severity.

    Science.gov (United States)

    Kann, Rebecca K C; Seddon, Jennifer M; Kyaw-Tanner, Myat T; Henning, Joerg; Meers, Joanne

    2014-08-01

    Veterinarians have few tools to predict the rate of disease progression in FIV-infected cats. In contrast, in HIV infection, plasma viral RNA load and acute phase protein concentrations are commonly used as predictors of disease progression. This study evaluated these predictors in cats naturally infected with FIV. In older cats (>5 years), log10 FIV RNA load was higher in the terminal stages of disease compared to the asymptomatic stage. There was a significant association between log10 FIV RNA load and both log10 serum amyloid A concentration and age in unwell FIV-infected cats. This study suggests that viral RNA load and serum amyloid A warrant further investigation as predictors of disease status and prognosis in FIV-infected cats. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. The Utility of Acute-Phase Proteins in the Assessment of Treatment Response in Dogs With Bacterial Pneumonia

    DEFF Research Database (Denmark)

    Viitanen, S. J.; Lappalainen, A. K.; Christensen, M. B.

    2017-01-01

    Background: Acute-phase proteins (APPs) are sensitive markers of inflammation, and serum C-reactive protein (CRP) recently has been shown to be a useful diagnostic marker in dogs with bacterial pneumonia (BP). In humans with community-acquired pneumonia, APPs also have great utility as follow......-up markers aiding in the assessment of treatment response. Objectives: The aim of our study was to investigate the applicability of APPs as markers of treatment response in dogs with BP. Animals: Nineteen dogs diagnosed with BP and 64 healthy dogs. Methods: The study was conducted as a prospective...... longitudinal observational study. Serum CRP, serum amyloid A (SAA), and haptoglobin concentrations were followed during a natural course of BP. Normalization of serum CRP was used to guide the duration of antibiotic treatment (treatment was stopped 5–7 days after CRP normalized) in 8 of 17 dogs surviving...

  6. Role of lysosomal enzymes released by alveolar macrophages in the pathogenesis of the acute phase of hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    J. L. Pérez-Arellano

    1995-01-01

    Full Text Available Hydrolytic enzymes are the major constituents of alveolar macrophages (AM and have been shown to be involved in many aspects of the inflammatory pulmonary response. The aim of this study was to evaluate the role of lysosomal enzymes in the acute phase of hypersensitivity pneumonitis (HPs. An experimental study on AM lysosomal enzymes of an HP-guinea-pig model was performed. The results obtained both in vivo and in vitro suggest that intracellular enzymatic activity decrease is, at least partly, due to release of lysosomal enzymes into the medium. A positive but slight correlation was found between extracellular lysosomal activity and four parameters of lung lesion (lung index, bronchoalveolar fluid total (BALF protein concentration, BALF LDH and BALF alkaline phosphatase activities. All the above findings suggest that the AM release of lysosomal enzymes during HP is a factor involved, although possibly not the only one, in the pulmonary lesions appearing in this disease.

  7. Physiologic and systemic acute phase inflammatory responses in young horses repeatedly infected with cyathostomins and Strongylus vulgaris.

    Science.gov (United States)

    Andersen, U V; Reinemeyer, C R; Toft, N; Olsen, S N; Jacobsen, S; Nielsen, M K

    2014-03-17

    Migrating Strongylus vulgaris and encysted cyathostomin larvae cause a localized inflammatory response in horses. It is unknown whether these larvae elicit a systemic acute phase response (APR), evidenced by changes in serum amyloid A (SAA), haptoglobin (Hp), iron (Fe), albumin, or albumin/globulin (A/G) ratio. In this study, 28 horses were randomly allocated to receive either pyrantel tartrate or a pelleted placebo formulation in their daily feed. Concurrent with treatment, all the horses were administered 5000 pyrantel-susceptible cyathostomin infective larvae once daily, 5 days a week, for 24 weeks. Beginning in the fifth week, the horses also received 25 S. vulgaris larvae once weekly for the remainder of the study. At regular biweekly intervals, fecal samples were collected for quantitative egg counts, and whole blood and serum samples were collected for measurement of packed cell volume, total protein, albumin, globulin, A/G ratio, SAA, Hp, and Fe. On days 161-164, all the horses were euthanatized and necropsied. Samples were collected for enumeration of total luminal worm burdens, encysted cyathostomin larval populations, and migrating S. vulgaris larvae. Concentrations of Hp, Fe, and A/G ratio were associated significantly with strongyle burdens. Only treated male horses had significant increases in serum albumin. Larval S. vulgaris did not associate with Fe, whereas Fe was associated negatively with both total cyathostomin burdens and encysted L4s. The A/G ratios differed significantly between the two treatment groups. Significant differences between groups and individual time points were also observed for Hp and Fe, whereas SAA concentrations remained low throughout the study. In general, this study illustrated that experimental inoculations with S. vulgaris and cyathostomins may be associated with changes in Hp, Fe, and serum proteins, but not with SAA. Overall, these changes suggest that mixed strongyle infections elicit a mild acute phase reaction

  8. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    Science.gov (United States)

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (Ppreeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. © 2015 American Heart Association, Inc.

  9. The diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in Urinary Tract Infection (UTI) in camels.

    Science.gov (United States)

    El-Deeb, Wael M; Buczinski, Sébastien

    2015-01-01

    The present study aimed to investigate the diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in urinary tract infection (UTI) in camels. We describe the clinical, bacteriological and biochemical findings in 89 camels. Blood and urine samples from diseased (n = 74) and control camels (n = 15) were submitted to laboratory investigations. The urine analysis revealed high number of RBCS and pus cells. The concentrations of serum and erythrocytic malondialdehyde (sMDA & eMDA), Haptoglobin (Hp), serum amyloid A (SAA), Ceruloplasmin (Cp), fibrinogen (Fb), albumin, globulin and interleukin 6 (IL-6) were higher in diseased camels when compared to healthy ones. Catalase, super oxide dismutase and glutathione levels were lower in diseased camels when compared with control group. Forty one of 74 camels with UTI were successfully treated. The levels of malondialdehyde, catalase, super oxide dismutase, glutathione, Hp, SAA, Fb, total protein, globulin and IL-6 were associated with the odds of treatment failure. The MDA showed a great sensitivity (Se) and specificity (Sp) in predicting treatment failure (Se 85%/Sp 100%) as well as the SAA (Se 92%/Sp 87%) and globulin levels (Se 85%/Sp 100%) when using the cutoffs that maximizes the sum of Se + Sp. Multivariate logistic regression analysis revealed that two models had a high accuracy to predict failure with the first model including sex, sMDA and Hp as covariates (area under the receiver operating characteristic curve (AUC) = 0.92) and a second model using sex, SAA and Hp (AUC = 0.89). Conclusively, the oxidative stress biomarkers and acute phase proteins could be used as diagnostic and prognostic biomarkers in camel UTI management. Efforts should be forced to investigate such biomarkers in other species with UTI.

  10. Characterization of the local immune response to cyst antigens during the acute and elimination phases of primary murine giardiasis.

    Science.gov (United States)

    Abdul-Wahid, Aws; Faubert, Gaétan

    2008-05-01

    During the course of a giardial infection, the host's immune system is presented with a variety of Giardia antigens as trophozoites differentiate, through encysting cells, to form the infective cysts. Previous studies examining the host's immune response during giardial infections have focused on trophozoite-derived antigens (Ags). In this study, we were interested to determine if the host's immune system reacts to cyst Ags during the acute and elimination phases, when there is cyst shedding. For this purpose, we used antigenic extracts from trophozoites (Troph), encysting cells (ENC), and purified giardial cyst walls (PCW), as well as purified recombinant cyst wall protein 2 (rCWP2). Comparative analysis of the parasite extracts using SDS-PAGE analysis and surface-enhanced laser desorption/ionization time of flight mass spectrometry resulted in the detection of 175 protein entities, of which 26 were Troph-specific proteins, 17 ENC-specific proteins, and 31 were PCW-specific proteins. On the other hand, we detected 34 proteins shared between Troph and ENC, 19 proteins that were shared between ENC and PCW, and 29 proteins that were common to Troph and PCW. Finally, we detected 19 proteins that were shared by all three extract samples. BALB/c mice were infected with 10(5)Giardia muris cysts and sacrificed either at the acute or elimination phases of infection (days 12 and 40, respectively), and lymphocytes were isolated from the Peyer's patches (PP). Using flow cytometry, we detected significant increases in the number of PP-derived CD4(+) and CD19(+), but not CD8(+) lymphocytes. Quantification of the number of mucosal IL-4 and IFN-gamma secreting T-lymphocytes by enzyme-linked immunosorbent spot assay showed that these cells reacted by secreting similar levels of IL-4 and IFN-gamma, regardless of the Ag or the phase of infection. Analysis of intestinal humoral immune responses by ELISA resulted in the detection of Ag-specific IgA and IgG intestinal antibodies

  11. Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs.

    Science.gov (United States)

    Kamat, Pranitha; Vandenberghe, Stijn; Christen, Stephan; Bongoni, Anjan K; Meier, Bernhard; Rieben, Robert; Khattab, Ahmed A

    2016-01-01

    Calcium and iron overload participate in the mechanisms of ischemia/reperfusion (I/R) injury during myocardial infarction (MI). Calcium overload induces cardiomyocyte death by hypercontraction, while iron catalyses generation of reactive oxygen species (ROS). We therefore hypothesized that dexrazoxane, an intracellular metal chelator, would attenuate I/R injury. MI was induced in pigs by occlusion of the left anterior descending artery for 1 hour followed by 2 hours reperfusion. Thirty minutes before reperfusion either 5 mg/ml dexrazoxane (n = 5) or saline (n = 5) was infused intravenously. Myocardial necrosis as percentage of the area at ischemic risk was found to be similar in both groups (77.2 ± 18% for dexrazoxane and 76.4 ± 14% for saline group) as determined by triphenyl tetrazolium chloride staining of the ischemic myocardium. Also, serum levels of troponin-I were similar in both groups. A conductance catheter was used to measure left ventricular pressure and volume at all times. Markers for tissue damage due to ROS (HNE), endothelial cell activation (CD31) and inflammation (IgG, C3b/c, C5b9, MCP-1) were assessed on tissue and/or in serum. No significant differences were observed between the groups for the parameters analyzed. To conclude, in this clinically relevant model of early reperfusion after acute myocardial ischemia, dexrazoxane lacked attenuating effects on I/R injury as shown by the measured parameters.

  12. Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs.

    Directory of Open Access Journals (Sweden)

    Pranitha Kamat

    Full Text Available Calcium and iron overload participate in the mechanisms of ischemia/reperfusion (I/R injury during myocardial infarction (MI. Calcium overload induces cardiomyocyte death by hypercontraction, while iron catalyses generation of reactive oxygen species (ROS. We therefore hypothesized that dexrazoxane, an intracellular metal chelator, would attenuate I/R injury. MI was induced in pigs by occlusion of the left anterior descending artery for 1 hour followed by 2 hours reperfusion. Thirty minutes before reperfusion either 5 mg/ml dexrazoxane (n = 5 or saline (n = 5 was infused intravenously. Myocardial necrosis as percentage of the area at ischemic risk was found to be similar in both groups (77.2 ± 18% for dexrazoxane and 76.4 ± 14% for saline group as determined by triphenyl tetrazolium chloride staining of the ischemic myocardium. Also, serum levels of troponin-I were similar in both groups. A conductance catheter was used to measure left ventricular pressure and volume at all times. Markers for tissue damage due to ROS (HNE, endothelial cell activation (CD31 and inflammation (IgG, C3b/c, C5b9, MCP-1 were assessed on tissue and/or in serum. No significant differences were observed between the groups for the parameters analyzed. To conclude, in this clinically relevant model of early reperfusion after acute myocardial ischemia, dexrazoxane lacked attenuating effects on I/R injury as shown by the measured parameters.

  13. A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome.

    Science.gov (United States)

    Kirschbaum, Mark; Gojo, Ivana; Goldberg, Stuart L; Bredeson, Christopher; Kujawski, Lisa A; Yang, Allen; Marks, Peter; Frankel, Paul; Sun, Xing; Tosolini, Alessandra; Eid, Joseph E; Lubiniecki, Gregory M; Issa, Jean-Pierre

    2014-10-01

    Patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) may respond to treatment with epigenetic-modifying agents. Histone deacetylase inhibitors may synergize with hypomethylating agents. This phase 1 dose-escalation study was designed to determine the maximum tolerated dose, recommended phase 2 dose, safety and tolerability of vorinostat plus decitabine in patients with relapsed/refractory AML, newly-diagnosed AML, or intermediate- to high-grade MDS. Thirty-four patients received concurrent therapy with decitabine plus vorinostat and 37 received sequential therapy with decitabine followed by vorinostat. Twenty-nine patients had relapsed/refractory AML, 31 had untreated AML and 11 had MDS. The target maximum administered dose (MAD) of decitabine 20 mg/m(2) daily for 5 d plus vorinostat 400 mg/d for 14 d was achieved for concurrent and sequential schedules, with one dose-limiting toxicity (Grade 3 QTc prolongation) reported in the sequential arm. Common toxicities were haematological and gastrointestinal. Responses were observed more frequently at the MAD on the concurrent schedule compared with the sequential schedule in untreated AML (46% vs. 14%), relapsed/refractory AML (15% vs. 0%) and MDS (60% vs. 0%). Decitabine plus vorinostat given concurrently or sequentially appears to be safe and well-tolerated. Concurrent therapy shows promising clinical activity in AML or MDS, warranting further investigation. © 2014 John Wiley & Sons Ltd.

  14. ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4) is a new acute-phase protein isolated from cattle during experimental infection

    DEFF Research Database (Denmark)

    Pineiro, M.; Andres, M.; Iturralde, M.

    2004-01-01

    We have isolated from calf serum a protein with an apparent M, of 120,000. The protein was detected by using antibodies against major acute-phase protein in pigs with acute inflammation. The amino acid sequence of an internal fragment revealed that this protein is the bovine counterpart of ITIH4......, and Peptostreptococcus indolicus to induce an acute-phase reaction. All animals developed moderate to severe clinical mastitis and exhibited remarkable increases in ITIH4 concentration in serum (from 3 to 12 times the initial values, peaking at 48 to 72 h after infection) that correlated with the severity of the disease....... Animals with experimental infections with bovine respiratory syncytial virus (BRSV) also showed increases in ITIH4 concentration (from two- to fivefold), which peaked at around 7 to 8 days after inoculation. Generally, no response was seen after a second infection of the same animals with the virus...

  15. Expression of acute phase proteins and inflammatory cytokines in mouse mammary gland following Staphylococcus aureus challenge and in response to milk accumulation

    DEFF Research Database (Denmark)

    Nazemi, Sasan; Aalbæk, Bent; Kjelgaard-Hansen, Mads

    2014-01-01

    We used a mouse model of pathogenic (Staphylococcus aureus) and non-pathogenic (teat sealing) mammary inflammation to investigate mRNA expression of several inflammatory cytokines and acute phase proteins (APP) in mammary tissue and liver, and the appearance of some of these factors in plasma and...

  16. Pathophysiological aspects of the acute phase response and the anaemia of chronic disease : with a focus on iron metabolism: With a focus on iron metabolism

    NARCIS (Netherlands)

    R.A. Feelders (Richard)

    1999-01-01

    textabstractThe acute phase response refers to a coordinated series of reactions in response to a variety of stimuli and involves all major body systems. This generalized host response is characterized by fever, changes in local vascular permeability, modulation of hepatic protein synthesis

  17. DNA strand breaks, acute phase response and inflammation following pulmonary exposure by instillation to the diesel exhaust particle NIST1650b in mice

    DEFF Research Database (Denmark)

    Kyjovska, Zdenka O.; Jacobsen, Nicklas R.; Saber, Anne T.

    2015-01-01

    by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary acute phase response was analysed by Saa3 mRNA levels by real-time quantitative polymerase chain reaction. Instillation of DEP induced a strong neutrophil influx 1 and 3 days, but not 28 days post-exposure. Saa3 m...

  18. Effect of BSA Antigen Sensitization during the Acute Phase of Influenza A Viral Infection on CD11c+ Pulmonary Antigen Presenting Cells

    Directory of Open Access Journals (Sweden)

    Fumitaka Sato

    2009-01-01

    Conclusions: BSA antigen sensitization during the acute phase of influenza A viral infection enhanced IL-10 production from naive CD4+ T cell interaction with CD11c+ pulmonary APCs. The IL-10 secretion evoked Th2 responses in the lungs with downregulation of Th1 responses and was important for the eosinophil recruitment into the lungs after BSA antigen challenge.

  19. ROLE OF THE MATERNAL ACUTE PHASE RESPONSE AND TUMOR NECROSIS FACTOR ALPHA IN THE DEVELOPMENTAL TOXICITY OF LIPOPOLYSACCHARIDE IN THE CD-1 MOUSE

    Science.gov (United States)

    ABSTRACT The acute phase response (APR) functions to reset metabolic homeostasis following infectious, toxic or traumatic insult. TNF- , a putative mediator of the APR, has been associated with fetal death in rodents and preterm labor and delivery in humans. We hypothesized...

  20. Evidence that estrogen receptors play a limited role in mediating enhanced recovery of bile flow in female rats in the acute phase of liver ischemia reperfusion injury

    NARCIS (Netherlands)

    de Vries, Heleen A. H.; Ponds, Fraukje A. M.; Nieuwenhuijs, Vincent B.; Morphett, Arthur; Padbury, Robert T. A.; Barritt, Greg J.

    2013-01-01

    Introduction. Female patients exhibit better survival and less hepatic damage from ischemia reperfusion (IR) injury following surgery. However, the effects of sex and estrogens on liver function in the acute phase of IR are not well understood. Objective. The aim was to investigate this question.

  1. Quantifying factors determining the rate of CTL escape and reversion during acute and chronic phases of HIV infection

    Energy Technology Data Exchange (ETDEWEB)

    Ganusov, Vitaly V [Los Alamos National Laboratory; Korber, Bette M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory

    2009-01-01

    Human immunodeficiency virus (HIV) often evades cytotoxic T cell (CTL) responses by generating variants that are not recognized by CTLs. However, the importance and quantitative details of CTL escape in humans are poorly understood. In part, this is because most studies looking at escape of HIV from CTL responses are cross-sectional and are limited to early or chronic phases of the infection. We use a novel technique of single genome amplification (SGA) to identify longitudinal changes in the transmitted/founder virus from the establishment of infection to the viral set point at 1 year after the infection. We find that HIV escapes from virus-specific CTL responses as early as 30-50 days since the infection, and the rates of viral escapes during acute phase of the infection are much higher than was estimated in previous studies. However, even though with time virus acquires additional escape mutations, these late mutations accumulate at a slower rate. A poor correlation between the rate of CTL escape in a particular epitope and the magnitude of the epitope-specific CTL response suggests that the lower rate of late escapes is unlikely due to a low efficacy of the HIV-specific CTL responses in the chronic phase of the infection. Instead, our results suggest that late and slow escapes are likely to arise because of high fitness cost to the viral replication associated with such CTL escapes. Targeting epitopes in which virus escapes slowly or does not escape at all by CTL responses may, therefore, be a promising direction for the development of T cell based HIV vaccines.

  2. Unreliability of three commercial Coxiella burnetii phase II IgM ELISA kits for the seroscreening of acute Q fever in human cases.

    Science.gov (United States)

    Stephen, Selvaraj; Ambroise, Stanley; Pradeep, Jothimani; Gunasekaran, Dhandapany; Sangeetha, Balakrishnan; Sarangapani, Kengamuthu

    2017-09-01

    Seroprevalence of Q fever (QF) caused by Coxiella burnetii has been reported from different parts of India. Usually serological/molecular tests are employed for detection of infection. The present study was undertaken to verify the validity of three different QF phase II IgM ELISA kits for acute QF diagnosis by comparing with the gold standard indirect fluorescent antibody assay (IFA). Fifty eight serum samples collected from 42 patients (26 patients provided acute sample only and 16 both acute and convalescent samples) which were examined by all three commercial kits, were cross-checked with QF Phase II IgM IFA for confirmation. Eleven patients were positive for C. burnetii antibodies by IFA in acute and/or convalescent serum samples. Taking IFA as a reference, percentages of sensitivity, specificity, positive predictive value and negative predictive value for Virion-Serion/Vircell/NovaTec were 36.36, 61.29, 25.00, 73.08; 81.82, 35.48, 31.03, 84.62 and 100, 25.81, 32.35, 100 per cent, respectively. The three different ELISA kits exhibited poor agreement amongst them and unacceptable level of false positivity. IFA remains to be the only option for diagnosing acute QF. Discrepancy between the clinical findings and IFA/ELISA results needs confirmation by C. burnetii DNA detection in real-time polymerase chain reaction.

  3. [Effects of balneotherapy on the reactants of acute inflammation phase in ankylosing spondylitis].

    Science.gov (United States)

    2009-01-01

    Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects sacroiliac joints, spinal column and peripheral joints. Beside medication therapy, physical and balneotherapy play an important role in its complex treatment. The aim of the research was to establish serum concentrations of C-reactive protein (CRP), alpha 1-acid glycoprotein (alpha 1-AGP), ceruloplasmine (CP) and erythrocyte sedimentation rate (SE) before and after the balneotherapy in ankylosing spondylitis. The research included 50 AS patients according to the revised New York criteria, of mean age 43 years, who were treated for 14 days on the average at the Clinic for Rheumatology of the Institute "Niska Banja". All the patients received medications and balneotherapy (radioactive oligomineral baths, peloid, massage, kinesitherapy); the serum concentrations of CRP, al-AGP, CP and SE were measured before and after balneotherapy. Serum proteins were determined using original Nor Partigen plates Boehringer. Erythrocyte sedimentation rate was measured by Westergreen method. Balneotherapy was applied individually, intensively or mildly, depending on the AS stage and activity phase. After dosed balneotherapy, a significant decrease in the concentrations of CP (p balneotherapy efficiency in the treatment of ankylosing spondylitis.

  4. A PAF receptor antagonist inhibits acute airway inflammation and late-phase responses but not chronic airway inflammation and hyperresponsiveness in a primate model of asthma

    Directory of Open Access Journals (Sweden)

    R. H. Gundel

    1992-01-01

    Full Text Available We have examined the effects of a PAF receptor antagonist, WEB 2170, on several indices of acute and chronic airway inflammation and associated changes in lung function in a primate model of allergic asthma. A single oral administration WEB 2170 provided dose related inhibition of the release of leukotriene C4 (LTC4 and prostaglandin D2 (PGD2 recovered and quantified in bronchoalveolar lavage (BAL fluid obtained during the acute phase response to inhaled antigen. In addition, oral WEB 2170 treatment in dual responder primates blocked the acute influx of neutrophils into the airways as well as the associated late-phase airway obstruction occurring 6 h after antigen inhalation. In contrast, a multiple dosing regime with WEB 2170 (once a day for 7 consecutive days failed to reduce the chronic airway inflammation (eosinophilic and associated airway hyperresponsiveness to inhaled methacholine that is characteristic of dual responder monkeys. Thus, we conclude that the generation of PAF following antigen inhalation contributes to the development of lipid mediators, acute airway inflammation and associated late-phase airway obstruction in dual responder primates; however, PAF does not play a significant role in the maintenance of chronic airway inflammation and associated airway hyperresponsiveness in this primate model.

  5. Effects of glucocorticoid combined with antibiotics on serum infection indexes, acute phase proteins and stress hormones in patients with severe pneumonia

    Directory of Open Access Journals (Sweden)

    Yang Yu

    2017-10-01

    Full Text Available Objective: To study the effects of glucocorticoid combined with antibiotics on serum infection indexes, acute phase proteins and stress hormones in patients with severe pneumonia. Methods: a total of 80 patients with severe pneumonia who were hospitalized between August 2014 and January 2017 were retrospectively analyzed and divided into the routine treatment group (n=46 who received conventional antibiotic therapy and the combined treatment group (n=34 who received glucocorticoid combined with antibiotic therapy, and the differences in infection indexes, acute proteins and stress hormones were compared between the two groups of patients before and after treatment. Results: The differences in serum levels of infection indexes, acute phase proteins and stress hormones were not statistically significant between the two groups before treatment. After 1 week of treatment, serum infection indexes CRP and PCT levels of observation group were lower than those of control group; serum acute phase proteins α1-AT, α1-AG and CER levels were lower than those of control group; serum stress hormones Cor, AngⅠ and AngⅡ levels were lower than those of control group. Conclusion: Glucocorticoid combined with antibiotics can effectively inhibit systemic infection and stress and optimize the illness in patients with severe pneumonia.

  6. Gender differences in quality of life and functional disability for depression outpatients with or without residual symptoms after acute phase treatment in China.

    Science.gov (United States)

    Zhao, Na; Wang, Xiaohong; Wu, Wenyuan; Hu, Yongdong; Niu, Yajuan; Wang, Xueyi; Gao, Chengge; Zhang, Ning; Fang, Yiru; Huang, Jizhong; Liu, Tiebang; Jia, Fujun; Zhu, Xuequan; Hu, Jian; Wang, Gang

    2017-09-01

    Depression is associated with substantial personal suffering and reduced quality of life and functioning. The aim of this study was to investigate gender differences on quality of life and functional impairment of outpatients with depression after acute phase treatment. 1503 depression outpatients were recruited from eleven hospitals in China. Subjects were evaluated with sociodemographic characteristics, history and self-report instruments, related to severity of symptoms, function and quality of life. All data were analyzed to determine the gender differences. Men had a younger age at onset and the first onset age, higher education compared to women in total patients and with or without residual symptoms group. Using regression analysis, it was found that gender was significantly statistically related to severity scores of SDS and had no correlation with Q-LES-Q-SF total scores. In the residual symptoms group, greater functional impairment was noted by men in the area of work and social life. Significant gender differences of mood, work and sexual life in quality of life were observed. This is a cross-sectional study of depressed outpatients and duration of acute phase treatment may not an adequate time to measure changes. Depression appears to affect men more seriously than women after acute phase treatment. Men had a younger age at onset and the first onset age, higher education, more functional impairment and lower satisfaction of quality of life in mood, work and sexual life. Gender differences affect acute treatment, remission and recovery. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer

    International Nuclear Information System (INIS)

    Hille, Andrea; Schmidberger, Heinz; Hermann, Robert M.; Christiansen, Hans; Saile, Bernhard; Pradier, Olivier; Hess, Clemens F.

    2005-01-01

    Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo and the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding

  8. Excavating the surface-associated and secretory proteome of Mycobacterium leprae for identifying vaccines and diagnostic markers relevant immunodominant epitopes.

    Science.gov (United States)

    Rana, Aarti; Thakur, Shweta; Bhardwaj, Nupur; Kumar, Devender; Akhter, Yusuf

    2016-12-01

    For centuries, Mycobacterium leprae, etiological agent of leprosy, has been afflicting mankind regardless of extensive use of live-attenuated vaccines and antibiotics. Surface-associated and secretory proteins (SASPs) are attractive targets against bacteria. We have integrated biological knowledge with computational approaches and present a proteome-wide identification of SASPs. We also performed computational assignment of immunodominant epitopes as coordinates of prospective antigenic candidates in most important class of SASPs, the outer membrane proteins (OMPs). Exploiting the known protein sequence and structural characteristics shared by the SASPs from bacteria, 17 lipoproteins, 11 secretory and 19 novel OMPs (including 4 essential proteins) were identified in M. leprae As OMPs represent the most exposed antigens on the cell surface, their immunoinformatics analysis showed that the identified 19 OMPs harbor T-cell MHC class I epitopes and class II epitopes against HLA-DR alleles (54), while 15 OMPs present potential T-cell class II epitopes against HLA-DQ alleles (6) and 7 OMPs possess T-cell class II epitopes against HLA-DP alleles (5) of humans. Additionally, 11 M. leprae OMPs were found to have B-cell epitopes and these may be considered as prime candidates for the development of new immunotherapeutics against M. leprae. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Conserved region at the COOH terminus of human immunodeficiency virus gp120 envelope protein contains an immunodominant epitope

    International Nuclear Information System (INIS)

    Palker, T.J.; Matthews, T.J.; Clark, M.E.

    1987-01-01

    A highly immunogenic epitope from a conserved COOH-terminal region of the human immunodeficiency virus (HIV) gp120 envelope protein has been identified with antisera from HIV-seropositive subjects and a synthetic peptide (SP-22) containing 15 amino acids from this region (Ala-Pro-Thr-Lys-Ala-Lys-Arg-Arg-Val-Val-Gln-Arg-Glu-Lys-Arg). Peptide SP-22 absorbed up to 100% of anti-gp120 antibody reactivity from select HIV + patient sera in immunoblot assays and up to 79% of serum anti-gp120 antibody reactivity in competition RIA. In RIA, 45% of HIV-seropositive subjects had antibodies that bound to peptide SP-22. Human anti-SP-22 antibodies that bound to and were eluted from an SP-22 affinity column reacted with gp120 in RIA and immunoblot assays but did not neutralize HIV or inhibit HIV-induced syncytium formation in vitro, even though these antibodies comprised 70% of all anti-gp120 antibodies in the test serum. In contrast, the remaining 30% of SP-22 nonreactive anti-gp120 antibodies did not react with gp120 in immunoblot assays but did react in RIA and neutralized HIV in vitro. Thus, ≅ 50% of HIV-seropositive patients make high titers of nonneutralizing antibodies to an immunodominant antigen on gp120 defined by SP-22. Moreover, the COOH terminus of gp120 contains the major antigen or antigens identified by human anti-gp120 antibodies in immunoblot assays

  10. Protein-energy malnutrition developing after global brain ischemia induces an atypical acute-phase response and hinders expression of GAP-43.

    Science.gov (United States)

    Smith, Shari E; Figley, Sarah A; Schreyer, David J; Paterson, Phyllis G

    2014-01-01

    Protein-energy malnutrition (PEM) is a common post-stroke problem. PEM can independently induce a systemic acute-phase response, and pre-existing malnutrition can exacerbate neuroinflammation induced by brain ischemia. In contrast, the effects of PEM developing in the post-ischemic period have not been studied. Since excessive inflammation can impede brain remodeling, we investigated the effects of post-ischemic malnutrition on neuroinflammation, the acute-phase reaction, and neuroplasticity-related proteins. Male, Sprague-Dawley rats were exposed to global forebrain ischemia using the 2-vessel occlusion model or sham surgery. The sham rats were assigned to control diet (18% protein) on day 3 after surgery, whereas the rats exposed to global ischemia were assigned to either control diet or a low protein (PEM, 2% protein) diet. Post-ischemic PEM decreased growth associated protein-43, synaptophysin and synaptosomal-associated protein-25 immunofluorescence within the hippocampal CA3 mossy fiber terminals on day 21, whereas the glial response in the hippocampal CA1 and CA3 subregions was unaltered by PEM. No systemic acute-phase reaction attributable to global ischemia was detected in control diet-fed rats, as reflected by serum concentrations of alpha-2-macroglobulin, alpha-1-acid glycoprotein, haptoglobin, and albumin. Acute exposure to the PEM regimen after global brain ischemia caused an atypical acute-phase response. PEM decreased the serum concentrations of albumin and haptoglobin on day 5, with the decreases sustained to day 21. Serum alpha-2-macroglobulin concentrations were significantly higher in malnourished rats on day 21. This provides the first direct evidence that PEM developing after brain ischemia exerts wide-ranging effects on mechanisms important to stroke recovery.

  11. A prospective phase II trial of EGCG in treatment of acute radiation-induced esophagitis for stage III lung cancer

    International Nuclear Information System (INIS)

    Zhao, Hanxi; Xie, Peng; Li, Xiaolin; Zhu, Wanqi; Sun, Xindong; Sun, Xiaorong; Chen, Xiaoting; Xing, Ligang; Yu, Jinming

    2015-01-01

    Background: Acute radiation-induced esophagitis (ARIE) is one of main toxicities complicated by thoracic radiotherapy, influencing patients’ quality of life and radiotherapy proceeding seriously. It is difficult to be cured rapidly so far. Our phase I trial preliminarily showed that EGCG may be a promising strategy in the treatment of ARIE. Materials and methods: We prospectively enrolled patients with stage III lung cancer from the Shandong Tumor Hospital & Institute in China from January 2013 to September 2014. All patients received concurrent or sequential chemo-radiotherapy, or radiotherapy only. EGCG was administrated once ARIE appeared. EGCG was given with the concentration of 440 μmol/L during radiotherapy and additionally two weeks after radiotherapy. RTOG score, dysphagia and pain related to esophagitis were recorded every week. Results: Thirty-seven patients with stage IIIA and IIIB lung cancer were enrolled in this trial. In comparison to the original, the RTOG score in the 1st, 2nd, 3rd, 4th, 5th week after EGCG prescription and the 1st, 2nd week after radiotherapy decreased significantly (P = 0.002, 0.000, 0.000, 0.001, 0.102, 0.000, 0.000, respectively). The pain score of each week was significantly lower than the baseline (P = 0.000, 0.000, 0.000, 0.000, 0.006, 0.000, 0.000, respectively). Conclusion: This trial confirmed that the oral administration of EGCG is an effective and safe method to deal with ARIE. A phase III randomized controlled trial is expected to further corroborate the consequence of EGCG in ARIE treatment

  12. Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan.

    Science.gov (United States)

    Koh, Katsuyoshi; Ogawa, Chitose; Okamoto, Yasuhiro; Kudo, Kazuko; Inagaki, Jiro; Morimoto, Tsuyoshi; Mizukami, Hideya; Ecstein-Fraisse, Evelyne; Kikuta, Atsushi

    2016-08-01

    A phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), efficacy and pharmacogenetic characteristics of clofarabine in seven Japanese pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Patients in Cohort 1 received clofarabine 30 mg/m(2)/day for 5 days, followed by 52 mg/m(2)/day for 5 days in subsequent cycles. Cohort 2 patients were consistently treated with 52 mg/m(2)/day for 5 days. No more than six cycles were performed. Every patient had at least one ≥Grade 3 adverse event (AE). AEs (≥Grade 3) related to clofarabine were anaemia, neutropenia, febrile neutropenia, thrombocytopenia, alanine aminotransferase increased, aspartate aminotransferase increased, haemoglobin decreased, and platelet (PLT) count decreased. C max and AUC of clofarabine increased in a dose-dependent fashion, but its elimination half-life (T 1/2) did not appear to be dependent on dose or duration of treatment. Clofarabine at 52 mg/m(2)/day shows similarly tolerable safety and PK profiles compared to those in previous studies. No complete remission (CR), CR without PLT recovery, or partial remission was observed. Since clofarabine is already used as a key drug for relapsed/refractory ALL patients in many countries, the efficacy of clofarabine in Japanese pediatric patients should be evaluated in larger study including more patients, such as by post-marketing surveillance.

  13. Acute phase response in lactating dairy cows during hyperinsulinemic hypoglycaemic and hyperinsulinemic euglycaemic clamps and after intramammary LPS challenge.

    Science.gov (United States)

    De Matteis, L; Bertoni, G; Lombardelli, R; Wellnitz, O; Van Dorland, H A; Vernay, M C M B; Bruckmaier, R M; Trevisi, E

    2017-06-01

    The link between energy availability, turnover of energy substrates and the onset of inflammation in dairy cows is complex and poorly investigated. To clarify this, plasma inflammatory variables were measured in mid-lactating dairy cows allocated to three groups: hyperinsulinemic hypoglycaemic clamp, induced by insulin infusion (HypoG, n = 5); hyperinsulinemic euglycaemic clamp, induced by insulin and glucose infusion (EuG; n = 6); control, receiving a saline solution infusion (NaCl; n = 6). At 48 h after the start of i.v. infusions, two udder quarters per cow were challenged with 200 μg of E. coli lipopolysaccharide (LPS). Individual blood samples were taken before clamps, before LPS challenge (i.e. 48 h after clamps) and 6.5 h after. At 48 h, positive acute phase proteins (posAPP) did not differ among groups, whereas albumin and cholesterol (index of lipoproteins), negative APP (negAPP), were lower (p insulin at the tissue-level makes dairy cows more susceptible to inflammatory events. In contrast, HypoG seems to attenuate the inflammatory response. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  14. The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

    Directory of Open Access Journals (Sweden)

    Paulina Dumnicka

    2017-02-01

    Full Text Available Acute pancreatitis (AP is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1 we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2 we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients.

  15. Clinical factors associated with success of proportional assist ventilation in the acute phase of critical illness: pilot study.

    Science.gov (United States)

    Delgado, M; Zavala, E; Tomás, R; Fernandez, R

    2014-03-01

    Proportional assist ventilation plus (PAV+) applies pressure depending on the patient's inspiratory effort, automatically adjusting flow and volume assist to changes in respiratory mechanics. We aimed to assess the clinical factors associated with the success of PAV+ as first-line support in the acute phase of critical illness. A prospective cohort study was carried out. Mechanically ventilated patients>24h were switched from assist-control ventilation to PAV+ as soon as they regained spontaneous breathing activity. PAV+ was set to deliver the highest assistance. We compared patients in whom PAV+ succeeded versus those in whom it failed. PAV+ succeeded in 12 (63%) patients, but failed in 7 (37%) due to tachypnea (n=4), hypercapnia (n=2), and metabolic acidosis (n=1), but without statistical significance. Both groups had similar clinical parameters. On the day of inclusion, total work of breathing per breath was lower in the successful PAV+ group (WOBTOT: 0.95 [0.8-1.35] vs. 1.6 [1.4-1.8] J/L; Psuccess was WOBTOTfactors associated with failure, though statistical significance was not reached. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  16. Protein-energy malnutrition induces an aberrant acute-phase response and modifies the circadian rhythm of core temperature.

    Science.gov (United States)

    Smith, Shari E; Ramos, Rafaela Andrade; Refinetti, Roberto; Farthing, Jonathan P; Paterson, Phyllis G

    2013-08-01

    Protein-energy malnutrition (PEM), present in 12%-19% of stroke patients upon hospital admission, appears to be a detrimental comorbidity factor that impairs functional outcome, but the mechanisms are not fully elucidated. Because ischemic brain injury is highly temperature-sensitive, the objectives of this study were to investigate whether PEM causes sustained changes in temperature that are associated with an inflammatory response. Activity levels were recorded as a possible explanation for the immediate elevation in temperature upon introduction to a low protein diet. Male, Sprague-Dawley rats (7 weeks old) were fed a control diet (18% protein) or a low protein diet (PEM, 2% protein) for either 7 or 28 days. Continuous core temperature recordings from bioelectrical sensor transmitters demonstrated a rapid increase in temperature amplitude, sustained over 28 days, in response to a low protein diet. Daily mean temperature rose transiently by day 2 (p = 0.01), falling to normal by day 4 (p = 0.08), after which mean temperature continually declined as malnutrition progressed. There were no alterations in activity mean (p = 0.3) or amplitude (p = 0.2) that were associated with the early rise in mean temperature. Increased serum alpha-2-macroglobulin (p protein diet had no effect on the signaling pathway of the pro-inflammatory transcription factor, NFκB, in the hippocampus. In conclusion, PEM induces an aberrant and sustained acute-phase response coupled with long-lasting effects on body temperature.

  17. Inhibition of Acute Phase Inflammation by Laminaria japonica through Regulation of iNOS-NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Seong Kyu Park

    2013-01-01

    Full Text Available Laminaria japonica has been frequently used as food supplements in many of the Asian countries and as a drug in traditional oriental medicine. This research investigated the effects of Laminaria japonica extract (LJE on acute phase inflammation in a carrageenan-induced paw edema model, as assessed by histomorphometric and immunohistochemical analyses. The effect of LJE was also evaluated in Raw264.7 cells stimulated with lipopolysaccharide (LPS in the aspect of the inhibition of nitric oxide (NO, prostaglandin E2 (PGE2, and proinflammatory cytokines production. NO, PGE2, tumor necrosis factor (TNF-α, interleukin-1β, and interleukin-6 contents were assayed by ELISA, and inducible NO synthase (iNOS and cyclooxygenase (COX-2 expressions were determined by western blot analyses. In rats, LJE treatment inhibited carrageenan-induced paw edema formation and infiltration of inflammatory cells in H&E staining. LJE treatment prevented the ability of LPS to increase the levels of iNOS and COX-2 protein in a concentration-dependent manner. Consistently, LJE suppressed the production of TNF-α, interleukin-1β, and interleukin-6. Treatment of the cells with LJE caused inhibition of inhibitor of κBα phosphorylation induced by LPS, suggesting LJE repression of nuclear factor-κB activity by LPS. In conclusion, this study shown here may be of help to understand the action mechanism of LJE and the anti-inflammatory use of L. japonica.

  18. Overestimation of Albumin Measured by Bromocresol Green vs Bromocresol Purple Method: Influence of Acute-Phase Globulins.

    Science.gov (United States)

    Garcia Moreira, Vanessa; Beridze Vaktangova, Nana; Martinez Gago, Maria Dolores; Laborda Gonzalez, Belen; Garcia Alonso, Sara; Fernandez Rodriguez, Eloy

    2018-05-22

    Usually serum albumin is measured with dye-binding assay as bromocresol green (BCG) and bromocresol purple (BCP) methods. The aim of this paper was to examine the differences in albumin measurements between the Advia2400 BCG method (AlbBCG), Dimension RxL BCP (AlbBCP) and capillary zone electrophoresis (CZE). Albumin concentrations from 165 serum samples were analysed using AlbBCG, AlbBCP and CZE. CZE was employed to estimate different serum protein fractions. Influence of globulins on albumin concentration discrepancies between methods was estimated as well as the impact of the albumin method on aCa concentrations. Medcalc was employed for statistical analysis, setting a value of P albumin concentrations. AlbBCG were positively biased versus CZE (3.54 g/L). There was good agreement between CZE and ALbBCP (Albumin results from the BCP and BCG methods may result in unacceptable differences and clinical confusion, especially at lower albumin concentrations. Serum acute phase proteins contribute to overestimating the albumin concentration using AlbBCG.

  19. Inotuzumab ozogamicin in adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia: a phase 1/2 study.

    Science.gov (United States)

    DeAngelo, Daniel J; Stock, Wendy; Stein, Anthony S; Shustov, Andrei; Liedtke, Michaela; Schiffer, Charles A; Vandendries, Erik; Liau, Katherine; Ananthakrishnan, Revathi; Boni, Joseph; Laird, A Douglas; Fostvedt, Luke; Kantarjian, Hagop M; Advani, Anjali S

    2017-06-27

    This study evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of inotuzumab ozogamicin (InO) for CD22-positive relapsed/refractory acute lymphoblastic leukemia. In phase 1, patients received InO 1.2 (n = 3), 1.6 (n = 12), or 1.8 (n = 9) mg/m 2 per cycle on days 1, 8, and 15 over a 28-day cycle (≤6 cycles). The recommended phase 2 dose (RP2D) was confirmed (expansion cohort; n = 13); safety and activity of InO were assessed in patients receiving the RP2D in phase 2 (n = 35) and in all treated patients (n = 72). The RP2D was 1.8 mg/m 2 per cycle (0.8 mg/m 2 on day 1; 0.5 mg/m 2 on days 8 and 15), with reduction to 1.6 mg/m 2 per cycle after complete remission (CR) or CR with incomplete marrow recovery (CRi). Treatment-related toxicities were primarily cytopenias. Four patients experienced treatment-related venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS; 1 fatal). Two VOD/SOS events occurred during treatment without intervening transplant; of 24 patients proceeding to poststudy transplant, 2 experienced VOD/SOS after transplant. Forty-nine (68%) patients had CR/CRi, with 41 (84%) achieving minimal residual disease (MRD) negativity. Median progression-free survival was 3.9 (95% confidence interval, 2.9-5.4) months; median overall survival was 7.4 (5.7-9.2) months for all treated patients, with median 23.7 (range, 6.8-29.8) months of follow-up for all treated patients alive at data cutoff. Achievement of MRD negativity was associated with higher InO exposure. InO was well tolerated and demonstrated high single-agent activity and MRD-negativity rates. This trial was registered at www.clinicaltrials.gov as #NCT01363297.

  20. Volumetric Integral Phase-shift Spectroscopy for Noninvasive Detection of Hemispheric Bioimpedance Asymmetry in Acute Brain Pathology

    Science.gov (United States)

    2018-05-10

    Stroke; Stroke, Acute; Ischemic Stroke; Hemorrhage; Clot (Blood); Brain; Subarachnoid Hemorrhage; Cerebral Infarction; Cerebral Hemorrhage; Cerebral Stroke; Intracerebral Hemorrhage; Intracerebral Injury

  1. Meat juice: An alternative matrix for assessing animal health by measuring acute phase proteins. Correlations of pig-MAP and haptoglobin concentrations in pig meat juice and plasma.

    Science.gov (United States)

    Piñeiro, M; Gymnich, S; Knura, S; Piñeiro, C; Petersen, B

    2009-10-01

    Quantification of acute phase proteins (APPs) in blood can be used for monitoring animal health and welfare on farms, and could be also of interest for the detection of diseased animals during the meat inspection process. However serum or plasma is not always available for end-point analysis at slaughter. Meat juice might provide an adequate, alternative matrix that can be easily obtained for post-mortem analysis at abattoirs. The concentrations of pig Major Acute phase Protein (pig-MAP) and haptoglobin, two of the main APPs in pigs, were determined in approximately 300 paired samples of plasma and meat juice from the diaphragm (pars costalis), obtained after freezing and thawing the muscle. APPs concentrations in meat juice were closely correlated to those in plasma (r=0.695 for haptoglobin, r=0.858 for pig-MAP, panimal health in pig production, with implications for food safety and meat quality.

  2. Pulmonary response to surface‐coated nanotitanium dioxide particles includes induction of acute phase response genes, inflammatory cascades, and changes in microRNAs: A toxicogenomic study

    DEFF Research Database (Denmark)

    Halappanavar, Sabina; Jackson, Petra; Williams, Andrew

    2011-01-01

    with acute phase, inflammation and immune response 5 days post exposure with concomitant changes in several miRNAs. The role of these miRNAs in pulmonary response to inhaled particles is unknown and warrants further research. Environ. Mol. Mutagen., 2011. © 2011 Wiley‐Liss, Inc....... in increased levels of mRNA for acute phase markers serum amyloid A‐1 (Saa1) and serum amyloid A‐3 (Saa3), several C‐X‐C and C‐C motif chemokines, and cytokine tumor necrosis factor genes. Protein analysis of Saa1 and 3 showed selective upregulation of Saa3 in lung tissues. Sixteen miRNAs were induced by more...... than 1.2‐fold (adjusted P‐value changes in the expression of genes associated...

  3. Potential of acute phase proteins as predictor of postpartum uterine infections during transition period and its regulatory mechanism in dairy cattle

    Directory of Open Access Journals (Sweden)

    A. Manimaran

    2016-01-01

    Full Text Available Among the various systemic reactions against infection or injury, the acute phase response is the cascade of reaction and mostly coordinated by cytokines-mediated acute phase proteins (APPs production. Since APPs are sensitive innate immune molecules, they are useful for early detection of inflammation in bovines and believed to be better discriminators than routine hematological parameters. Therefore, the possibility of using APPs as a diagnostic and prognostic marker of inflammation in major bovine health disorders including postpartum uterine infection has been explored by many workers. In this review, we discussed specifically importance of postpartum uterine infection, the role of energy balance in uterine infections and potential of APPs as a predictor of postpartum uterine infections during the transition period and its regulatory mechanism in dairy cattle.

  4. Pig major acute-phase protein and haptoglobin serum concentrations correlate with PCV2 viremia and the clinical course of postweaning multisystemic wasting syndrome

    DEFF Research Database (Denmark)

    Grau-Roma, Llorenc; Heegaard, Peter M. H.; Hjulsager, Charlotte Kristiane

    2009-01-01

    -PMWS affected pigs. In addition, evidence of infection with other pathogens and its relation with variations in APP's concentrations was also assessed. Fourteen independent batches of 100 to 154 pigs were monitored from birth to PMWS outbreak occurrence in 11 PMWS affected farms. Pigs displaying PMWS-like signs......The aim of the present longitudinal study was to assess the evolution of two acute phase proteins (APPs), pig-major acute phase protein (pig-MAP) and haptoglobin (HPT), in serum from pigs that developed postweaning multisystemic wasting syndrome (PMWS) in comparison to healthy and wasted non...... and age-matched healthy controls were euthanized during the clinical outbreak. PMWS was diagnosed according to internationally accepted creteria and pigs were classified as: i)PMWS cases, ii) wasted non-PMWS cases and iii) healthy pigs. At the moment of PMWS occurrence, pig-MAP and HPT concentration...

  5. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2–4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    International Nuclear Information System (INIS)

    Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; Ende, Piet van den; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.

    2012-01-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2–4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2–4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2–4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  6. Mass-spectrometric identification of T-kininogen I/thiostatin as an acute-phase inflammatory protein suppressed by curcumin and capsaicin.

    Science.gov (United States)

    Joe, Bina; Nagaraju, Anitha; Gowda, Lalitha R; Basrur, Venkatesha; Lokesh, Belur R

    2014-01-01

    Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I.

  7. Mass-spectrometric identification of T-kininogen I/thiostatin as an acute-phase inflammatory protein suppressed by curcumin and capsaicin.

    Directory of Open Access Journals (Sweden)

    Bina Joe

    Full Text Available Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I.

  8. A Phase 2 Trial of Once-Weekly Hypofractionated Breast Irradiation: First Report of Acute Toxicity, Feasibility, and Patient Satisfaction

    Energy Technology Data Exchange (ETDEWEB)

    Dragun, Anthony E., E-mail: aedrag01@louisville.edu [Department of Radiation Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Quillo, Amy R. [Department of Surgical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Riley, Elizabeth C. [Department of Medical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Roberts, Teresa L.; Hunter, Allison M. [Department of Radiation Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Rai, Shesh N. [Department of Biostatistics and Epidemiology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Callender, Glenda G. [Department of Surgical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Jain, Dharamvir [Department of Medical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); McMasters, Kelly M. [Department of Surgical Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States); Spanos, William J. [Department of Radiation Oncology, University of Louisville School of Medicine, James Graham Brown Cancer Center, Louisville, Kentucky (United States)

    2013-03-01

    Purpose: To report on early results of a single-institution phase 2 trial of a 5-fraction, once-weekly radiation therapy regimen for patients undergoing breast-conserving surgery (BCS). Methods and Materials: Patients who underwent BCS for American Joint Committee on Cancer stage 0, I, or II breast cancer with negative surgical margins were eligible to receive whole breast radiation therapy to a dose of 30 Gy in 5 weekly fractions of 6 Gy with or without an additional boost. Elective nodal irradiation was not permitted. There were no restrictions on breast size or the use of cytotoxic chemotherapy for otherwise eligible patients. Patients were assessed at baseline, treatment completion, and at first posttreatment follow-up to assess acute toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and quality of life (European Organization for Research and Treatment of Cancer QLQ-BR23). Results: Between January and September 2011, 42 eligible patients underwent weekly hypofractionated breast irradiation immediately following BCS (69.0%) or at the conclusion of cytotoxic chemotherapy (31.0%). The rates of grade ≥2 radiation-induced dermatitis, pain, fatigue, and breast edema were 19.0%, 11.9%, 9.5%, and 2.4%, respectively. Only 1 grade 3 toxicity—pain requiring a course of narcotic analgesics—was observed. One patient developed a superficial cellulitis (grade 2), which resolved with the use of oral antibiotics. Patient-reported moderate-to-major breast symptoms (pain, swelling, and skin problems), all decreased from baseline through 1 month, whereas breast sensitivity remained stable over the study period. Conclusions: The tolerance of weekly hypofractionated breast irradiation compares well with recent reports of daily hypofractionated whole-breast irradiation schedules. The regimen appears feasible and cost-effective. Additional follow-up with continued accrual is needed to assess late toxicity, cosmesis, and disease-specific outcomes.

  9. A Phase 2 Trial of Once-Weekly Hypofractionated Breast Irradiation: First Report of Acute Toxicity, Feasibility, and Patient Satisfaction

    International Nuclear Information System (INIS)

    Dragun, Anthony E.; Quillo, Amy R.; Riley, Elizabeth C.; Roberts, Teresa L.; Hunter, Allison M.; Rai, Shesh N.; Callender, Glenda G.; Jain, Dharamvir; McMasters, Kelly M.; Spanos, William J.

    2013-01-01

    Purpose: To report on early results of a single-institution phase 2 trial of a 5-fraction, once-weekly radiation therapy regimen for patients undergoing breast-conserving surgery (BCS). Methods and Materials: Patients who underwent BCS for American Joint Committee on Cancer stage 0, I, or II breast cancer with negative surgical margins were eligible to receive whole breast radiation therapy to a dose of 30 Gy in 5 weekly fractions of 6 Gy with or without an additional boost. Elective nodal irradiation was not permitted. There were no restrictions on breast size or the use of cytotoxic chemotherapy for otherwise eligible patients. Patients were assessed at baseline, treatment completion, and at first posttreatment follow-up to assess acute toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and quality of life (European Organization for Research and Treatment of Cancer QLQ-BR23). Results: Between January and September 2011, 42 eligible patients underwent weekly hypofractionated breast irradiation immediately following BCS (69.0%) or at the conclusion of cytotoxic chemotherapy (31.0%). The rates of grade ≥2 radiation-induced dermatitis, pain, fatigue, and breast edema were 19.0%, 11.9%, 9.5%, and 2.4%, respectively. Only 1 grade 3 toxicity—pain requiring a course of narcotic analgesics—was observed. One patient developed a superficial cellulitis (grade 2), which resolved with the use of oral antibiotics. Patient-reported moderate-to-major breast symptoms (pain, swelling, and skin problems), all decreased from baseline through 1 month, whereas breast sensitivity remained stable over the study period. Conclusions: The tolerance of weekly hypofractionated breast irradiation compares well with recent reports of daily hypofractionated whole-breast irradiation schedules. The regimen appears feasible and cost-effective. Additional follow-up with continued accrual is needed to assess late toxicity, cosmesis, and disease-specific outcomes

  10. Evaluation of Sialic Acid and Acute Phase Proteins (Haptoglobin and Serum Amyloid A in Clinical and Subclinical Bovine Mastitis

    Directory of Open Access Journals (Sweden)

    S. Nazifi*, M. Haghkhah1, Z. Asadi, M. Ansari-Lari2, M. R. Tabandeh3, Z. Esmailnezhad and M. Aghamiri

    2011-01-01

    Full Text Available The present study was conducted to evaluate the concentrations of sialic acids (total, lipid bound and protein bound and their correlation with acute phase proteins (haptoglobin and serum amyloid A in clinical and subclinical mastitis of cattle. Thirty subclinical mastitic cows with positive California mastitis test (CMT test and no clinical signs of mastitis, 10 clinical mastitic cows and 10 healthy cows with negative CMT test and normal somatic cell count were selected. Milk and blood samples were collected after confirmation of clinical and subclinical mastitis by somatic cell count and bacterial identification. Serum haptoglobin (Hp, serum amyloid A (SAA, total sialic acid (TSA, lipid bound sialic acid (LBSA and protein bound sialic acid (PBSA were measured by validated standard methods. Haptoglobin and SAA increased significantly in both types of mastitis compared with control group (P<0.001. However, the ratio of HP/SAA was significantly different from the control group only in clinical mastitis. The results showed that TSA and LBSA were significantly different in control group compared with clinical and subclinical mastitis (P<0.001. Protein bound sialic acid did not change in subclinical mastitis in comparison with control group (P=0.86. There was positive correlation between LBSA and PBSA in clinical mastitis (r=0.72, P=0.02 whereas significant negative correlation was observed between LBSA and PBSA in subclinical mastitis (r=-0.62, P<0.001. Results also showed no correlation between Hp and SAA with each other or with any other parameters in study groups.

  11. The rat acute-phase protein {alpha}{sub 2}-macroglobulin plays a central role in amifostine-mediated radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Mirjana, Mihailovic; Goran, Poznanovic; Nevena, Grdovic; Melita, Vidakovic; Svetlana, Dinic; Ilijana, Grigorov; Desanka, Bogojevic, E-mail: mista@ibiss.bg.ac.r [Department of Molecular Biology, Institute for Biological Research ' Sinisa Stankovic' , University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade (Serbia)

    2010-09-15

    Previously we reported that elevated circulating concentrations of the acute-phase (AP) protein {alpha}{sub 2}-macroglobulin ({alpha}{sub 2}M), either as typically occurring in pregnant female rats or after administration to male rats, provides radioprotection, displayed as 100% survival of experimental animals exposed to total-body irradiation with 6.7 Gy (LD{sub 50/30}) x-rays, that is as effective as that afforded by the synthetic radioprotector amifostine. The finding that amifostine administration induces a 45-fold increase in {alpha}{sub 2}M in the circulation led us to hypothesise that {alpha}{sub 2}M assumes an essential role in both natural and amifostine-mediated radioprotection in the rat. In the present work we examined the activation of cytoprotective mechanisms in rat hepatocytes after the exogenous administration of {alpha}{sub 2}M and amifostine. Our results showed that the IL6/JAK/STAT3 hepatoprotective signal pathway, described in a variety of liver-injury models, upregulated the {alpha}{sub 2}M gene in amifostine-pretreated animals. In both {alpha}{sub 2}M- and amifostine-pretreated rats we observed the activation of the Akt signalling pathways that mediate cellular survival. At the cellular level this was reflected as a significant reduction of irradiation-induced DNA damage that allowed for the rapid and complete restoration of liver mass and ultimately at the level of the whole organism the complete restoration of body weight. We conclude that the selective upregulation of {alpha}{sub 2}M plays a central role in amifostine-provided radioprotection.

  12. Usefulness of acute phase proteins in differentiating between feline infectious peritonitis and other diseases in cats with body cavity effusions.

    Science.gov (United States)

    Hazuchova, Katarina; Held, Susanne; Neiger, Reto

    2017-08-01

    Objectives The aim of this study was to evaluate the measurement of acute phase proteins (APPs) as a diagnostic tool to differentiate between feline infectious peritonitis (FIP) and other diseases in cats with body cavity effusions. Methods Cats with pleural, abdominal or pericardial effusion were prospectively enrolled. Cats were classified as having or not having FIP based on immunohistochemistry (if available) or a sophisticated statistical method using machine learning methodology with concepts from game theory. Cats without FIP were further subdivided into three subgroups: cardiac disease, neoplasia and other diseases. Serum amyloid A (SAA), haptoglobin (Hp) and α 1 -acid glycoprotein (AGP) were measured in serum and effusion, using assays previously validated in cats. Results Serum and effusion samples were available for the measurement of APPs from 88 and 67 cats, respectively. Concentrations of the APPs in serum and effusion were significantly different in cats with and without FIP ( P <0.001 for all three APPs). The best APP to distinguish between cats with and without FIP was AGP in the effusion; a cut-off value of 1550 µg/ml had a sensitivity and specificity of 93% each for diagnosing FIP. Conclusions and relevance AGP, particularly if measured in effusion, was found to be useful in differentiating between FIP and other diseases, while SAA and Hp were not. The concentration of all three APPs in some diseases (eg, septic processes, disseminated neoplasia) was as high as in cats with FIP; therefore, none of these can be recommended as a single diagnostic test for FIP.

  13. Bolus and continuous infusion mitoxantrone in newly diagnosed adult acute lymphoblastic leukemia: results of two consecutive phase II clinical studies.

    Science.gov (United States)

    Koc, Y; Akpek, G; Kansu, E; Kars, A; Tekuzman, G; Baltali, E; Güler, N; Barista, I; Güllü, I; Ozisik, Y; Firat, D

    1998-01-01

    Two consecutive phase II clinical studies were designed to evaluate the efficacy and safety of bolus and continuous infusion (CI) mitoxantrone (MTZ) in 39 patients with newly diagnosed acute lymphocytic leukemia (ALL). MTZ was used as part of the classical ALL induction regimen. Twenty patients were treated with bolus MTZ (10 mg/m2 for 3 days) combined with vincristine and prednisone. The same regimen was given to a second set of 19 patients, except that MTZ was administered as a 24-hr CI. Both groups received bimonthly intensifications with vincristine and prednisone for 3 years, along with oral maintenance therapy. Patients in the CI-MTZ study arm received additional MTZ on the first day of intensification cycles. Seventeen patients (85%) in the bolus arm and 15 patients (79%) in the CI arm achieved complete remission (CR). Median disease-free survivals (DFS) in the bolus and CI groups were 11 and 15 months after median follow-ups of 16 (3.5-96) and 13 (2.3-32) months, respectively. At 2.5 years, DFS rates were 29.4% and 34.4% in the bolus and CI groups (p > 0.05). There were no significant differences between two groups in rates of early death, degree of organ toxicity, or duration of neutropenia and thrombocytopenia. Significant cardiac toxicity was not observed in either group. Bolus or CI administration of MTZ was equally effective and was well tolerated. Neither the mode of administration nor increasing the dose intensity of MTZ by incorporating intensification cycles reduced relapse rates. Development of new antileukemia agents and novel treatment approaches are still needed to improve the high relapse rates in adult ALL once a complete response is achieved.

  14. Comprehensive mapping of common immunodominant epitopes in the West Nile virus nonstructural protein 1 recognized by avian antibody responses.

    Directory of Open Access Journals (Sweden)

    Encheng Sun

    Full Text Available West Nile virus (WNV is a mosquito-borne flavivirus that primarily infects birds but occasionally infects humans and horses. Certain species of birds, including crows, house sparrows, geese, blue jays and ravens, are considered highly susceptible hosts to WNV. The nonstructural protein 1 (NS1 of WNV can elicit protective immune responses, including NS1-reactive antibodies, during infection of animals. The antigenicity of NS1 suggests that NS1-reactive antibodies could provide a basis for serological diagnostic reagents. To further define serological reagents for diagnostic use, the antigenic sites in NS1 that are targeted by host immune responses need to be identified and the potential diagnostic value of individual antigenic sites also needs to be defined. The present study describes comprehensive mapping of common immunodominant linear B-cell epitopes in the WNV NS1 using avian WNV NS1 antisera. We screened antisera from chickens, ducks and geese immunized with purified NS1 for reactivity against 35 partially overlapping peptides covering the entire WNV NS1. This study identified twelve, nine and six peptide epitopes recognized by chicken, duck and goose antibody responses, respectively. Three epitopes (NS1-3, 14 and 24 were recognized by antibodies elicited by immunization in all three avian species tested. We also found that NS1-3 and 24 were WNV-specific epitopes, whereas the NS1-14 epitope was conserved among the Japanese encephalitis virus (JEV serocomplex viruses based on the reactivity of avian WNV NS1 antisera against polypeptides derived from the NS1 sequences of viruses of the JEV serocomplex. Further analysis showed that the three common polypeptide epitopes were not recognized by antibodies in Avian Influenza Virus (AIV, Newcastle Disease Virus (NDV, Duck Plague Virus (DPV and Goose Parvovirus (GPV antisera. The knowledge and reagents generated in this study have potential applications in differential diagnostic approaches and

  15. Use of an immunodominant p17 antigenic fraction of Neospora caninum in detection of antibody response in cattle

    Directory of Open Access Journals (Sweden)

    Gema Álvarez García

    2006-08-01

    Full Text Available A Neospora caninum 17 kDa protein fraction (p17 has been described as an immunodominant antigen (IDA under reducing and non-reducing conditions. The aim of the present study was to investigate the diagnostic utility of p17 in cattle. In order to achieve this, p17 was purified by electroelution from whole N. caninum tachyzoite soluble extract and a p17-based Western blot (WB-p17 was developed. The p17 recognition was measured by densitometry and expressed as OD values to check the validity of the WB-p17. A total of 131 sera including sequential samples from naturally- and experimentally-infected calves and breeding cattle were analysed by WB-p17 and compared with IFAT using whole formalin-fixed tachyzoites as a reference test. The results obtained highlight the feasibility of using the N. caninum p17 in a diagnostic test in cattle. Firstly, the assay based on the p-17 antigen discriminated between known positive and negative sera from different cattle populations, breeding cattle and calves. Secondly, the p17 antigen detected fluctuations in the antibody levels and seroconversion in naturally- and experimentally-infected cattle. Significant differences in p-17 antigen recognition were observed between naturally infected aborting and non-aborting cattle, as well as significant antibody fluctuations over time in experimentally infected cattle, which varied between groups. Furthermore, the results obtained with WB-p17 are in accordance with the results obtained with the IFAT, as high agreement values were obtained when all bovine subpopulations were included (kappa = 0.86.

  16. Spinal neuropeptide expression and neuropathic behavior in the acute and chronic phases after spinal cord injury: Effects of progesterone administration.

    Science.gov (United States)

    Coronel, María F; Villar, Marcelo J; Brumovsky, Pablo R; González, Susana L

    2017-02-01

    Patients with spinal cord injury (SCI) develop chronic pain that severely compromises their quality of life. We have previously reported that progesterone (PG), a neuroprotective steroid, could offer a promising therapeutic strategy for neuropathic pain. In the present study, we explored temporal changes in the expression of the neuropeptides galanin and tyrosine (NPY) and their receptors (GalR1 and GalR2; Y1R and Y2R, respectively) in the injured spinal cord and evaluated the impact of PG administration on both neuropeptide systems and neuropathic behavior. Male rats were subjected to spinal cord hemisection at T13 level, received daily subcutaneous injections of PG or vehicle, and were evaluated for signs of mechanical and thermal allodynia. Real time PCR was used to determine relative mRNA levels of neuropeptides and receptors, both in the acute (1day) and chronic (28days) phases after injury. A significant increase in Y1R and Y2R expression, as well as a significant downregulation in GalR2 mRNA levels, was observed 1day after SCI. Interestingly, PG early treatment prevented Y1R upregulation and resulted in lower NPY, Y2R and GalR1 mRNA levels. In the chronic phase, injured rats showed well-established mechanical and cold allodynia and significant increases in galanin, NPY, GalR1 and Y1R mRNAs, while maintaining reduced GalR2 expression. Animals receiving PG treatment showed basal expression levels of galanin, NPY, GalR1 and Y1R, and reduced Y2R mRNA levels. Also, and in line with previously published observations, PG-treated animals did not develop mechanical allodynia and showed reduced sensitivity to cold stimulation. Altogether, we show that SCI leads to considerable changes in the spinal expression of galanin, NPY and their associated receptors, and that early and sustained PG administration prevents them. Moreover, our data suggest the participation of galaninergic and NPYergic systems in the plastic changes associated with SCI-induced neuropathic pain

  17. Screening and identification of T helper 1 and linear immunodominant antibody-binding epitopes in the spike 2 domain and the nucleocapsid protein of feline infectious peritonitis virus.

    Science.gov (United States)

    Satoh, Ryoichi; Furukawa, Tomoko; Kotake, Masako; Takano, Tomomi; Motokawa, Kenji; Gemma, Tsuyoshi; Watanabe, Rie; Arai, Setsuo; Hohdatsu, Tsutomu

    2011-02-17

    The antibody-dependent enhancement (ADE) of feline infectious peritonitis virus (FIPV) infection has been recognized in experimentally infected cats, and cellular immunity is considered to play an important role in preventing the onset of feline infectious peritonitis (FIP). In the present study, we synthesized eighty-one kinds of peptides derived from the spike (S)2 domain of type I FIPV KU-2 strain, the S2 domain of type II FIPV 79-1146 strain, and the nucleocapcid (N) protein of FIPV KU-2 strain. To detect the T helper (Th)1 epitope, peripheral blood mononuclear cells (PBMCs) obtained from FIPV-infected cats were cultured with each peptide, and Th1-type immune responses were measured using feline interferon (fIFN)-γ production as an index. To detect the linear immunodominant antibody-binding epitope, we investigated the reactivity of plasma collected from FIPV-infected cats against each peptide by ELISA. Four and 2 peptides containing Th1 epitopes were identified in the heptad repeat (HR)1 and inter-helical (IH) regions of the S2 domain of type I FIPV, respectively, and these were located on the N-terminal side of the regions. In the S2 domain of type II FIPV, 2, 3, and 2 peptides containing Th1 epitopes were identified in the HR1, IH, and HR2 regions, respectively, and these were mainly located on the C-terminal side of the regions. In the S2 domain of type I FIPV, 3 and 7 peptides containing linear immunodominant antibody-binding epitopes were identified in the IH and HR2 regions, respectively. In the S2 domain of type II FIPV, 4 peptides containing linear immunodominant antibody-binding epitopes were identified in the HR2 region. The Th1 epitopes in the S2 domain of type I and II FIPV were located in different regions, but the linear immunodominant antibody-binding epitopes were mostly located in the HR2 region. Eight peptides containing Th1 epitopes were identified in N protein, and 3 peptides derived from residues 81 to 100 and 137 to 164 showed strong

  18. Screening and identification of T helper 1 and linear immunodominant antibody-binding epitopes in spike 1 domain and membrane protein of feline infectious peritonitis virus.

    Science.gov (United States)

    Takano, Tomomi; Morioka, Hiroyuki; Gomi, Kohji; Tomizawa, Keisuke; Doki, Tomoyoshi; Hohdatsu, Tsutomu

    2014-04-01

    Feline infectious peritonitis virus (FIP virus: FIPV) causes a fatal disease in wild and domestic cats. The development of an FIP-preventive vaccine requires an antigen that does not induce antibody-dependent enhancement, and T helper (Th)1 activity plays an important role in protect against FIPV infection. In the present study, we identified synthetic peptides including Th1 and a linear immunodominant antibody-binding epitope in the S1 domain and M protein of FIPV. We also identified peptides that strongly induce Th1 activity from those derived from the structural proteins (S, M, and N proteins) of FIPV based on this and previous studies (Satoh et al. [19]). No Th1 epitope-containing peptide was identified in the peptides derived from the S1 domain of type I FIPV. In contrast, 7 Th1 epitope-containing peptides were identified in the S1 domain of type II FIPV, and no linear immunodominant antibody-binding epitope was contained in any of these peptides. Eleven Th1 epitope-containing peptides common to each serotype were identified in the M protein-derived peptides, and 2 peptides (M-11 and M-12) contained the linear immunodominant antibody-binding epitope. Of the peptides derived from the S, M, and N proteins of FIPV, those that induced significantly stronger Th1 activity than that of the FIPV antigen were rescreened, and 4 peptides were identified. When 3 of these peptides (M-9, I-S2-15, and II-S1-24) were selected and administered with CpG-ODNs to SPF cats, M-9 and II-S1-24 induced Th1 activity. Our results may provide important information for the development of a peptide-based vaccine against FIPV infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Platelet degranulation and monocyte-platelet complex formation are increased in the acute and convalescent phases after ischaemic stroke or transient ischaemic attack.

    LENUS (Irish Health Repository)

    McCabe, Dominick J H

    2004-06-01

    Flow cytometric studies suggest that platelets are activated in ischaemic stroke or transient ischaemic attack (TIA). However, few studies have measured circulating leucocyte-platelet complexes in this patient population. Whole blood flow cytometry was used to quantify the expression of CD62P-, CD63-, and PAC1-binding, and the percentages of leucocyte-platelet complexes in acute (1-27 d, n = 79) and convalescent (79-725 d, n = 70) ischaemic cerebrovascular disease (CVD) patients compared with controls without CVD (n = 27). We performed a full blood count, and measured plasma levels of soluble P-selectin, soluble E-selectin, and von Willebrand factor antigen (VWF:Ag) as additional markers of platelet and\\/or endothelial cell activation. The median percentage CD62P expression and the median percentage monocyte-platelet complexes were higher in both acute and convalescent CVD patients than controls (P <\\/= 0.02). The mean white cell count and mean VWF:Ag levels were significantly elevated in the acute and convalescent phases after ischaemic stroke or TIA (P <\\/= 0.02). Otherwise, there was no significant increase in any other marker of platelet or endothelial activation in CVD patients. There was a positive correlation between the percentage expression of CD62P and the percentages of both neutrophil-platelet and monocyte-platelet complexes in the acute phase, and the percentages of all leucocyte-platelet complexes in the convalescent phase after ischaemic CVD. This study provides evidence for ongoing excessive platelet and\\/or endothelial activation in ischaemic CVD patients despite treatment with antithrombotic therapy.

  20. Monozygotic twin pairs discordant for Hashimoto's thyroiditis share a high proportion of thyroid peroxidase autoantibodies to the immunodominant region A. Further evidence for genetic transmission of epitopic "fingerprints"

    DEFF Research Database (Denmark)

    Brix, Thomas Heiberg; Hegedüs, Laszlo; Gardas, Andrzej

    2011-01-01

    Thyroid peroxidase antibodies (TPOAbs) in patients with Hashimoto's thyroiditis (HT) predominantly react with two immunodominant regions (IDR-A, IDR-B). Theoretically, as shown for the level of TPOAbs, the autoantibody epitopic recognition of the IDRs could be under genetic control. To examine this......, we compared the distribution of TPOAb epitopic fingerprints between healthy monozygotic (MZ) co-twins and siblings to patients with clinically overt HT with a control group of euthyroid subjects, matched for sex and age, but without autoimmune thyroid disease (AITD) among their first-degree relatives...

  1. IGHV1-69-Encoded Antibodies Expressed in Chronic Lymphocytic Leukemia React with Malondialdehyde-Acetaldehyde Adduct, an Immunodominant Oxidation-Specific Epitope

    DEFF Research Database (Denmark)

    Que, Xuchu; Widhopf Ii, George F; Amir, Shahzada

    2013-01-01

    The immunoglobulins expressed by chronic lymphocytic leukemia (CLL) B cells are highly restricted, suggesting they are selected for binding either self or foreign antigen. Of the immunoglobulin heavy-chain variable (IGHV) genes expressed in CLL, IGHV1-69 is the most common, and often is expressed...... are products of enhanced lipid peroxidation and a major target of innate natural antibodies. Specifically, CLL69C bound immunodominant OSE adducts termed MAA (malondialdehyde-acetaldehyde-adducts), which are found on apoptotic cells, inflammatory tissues, and atherosclerotic lesions. It also reacted...

  2. Clinical Trial of AC105 (Mg/PEG) for Treatment of Acute Spinal Cord Injury (SCI). Phase 2

    Science.gov (United States)

    2013-10-01

    glycol with a molecular weight of 3350 Daltons ( PEG 3350 ), is manufactured by Dow Chemical Company and complies with NF, FCC and EurPh requirements...Mg/ PEG ) for Treatment of Acute Spinal Cord Injury (SCI) PRINCIPAL INVESTIGATOR: Andrew Blight, PhD RECIPIENT: Acorda Therapeutics...of AC105 (Mg/ PEG ) for Treatment of Acute Spinal Cord Injury (SCI) 5b. GRANT NUMBER W81XWH-12-2 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

  3. Medical relief activities conducted by Nippon Medical School in the acute phase of the Great East Japan Earthquake 2011.

    Science.gov (United States)

    Fuse, Akira; Shuto, Yuki; Ando, Fumihiko; Shibata, Masafumi; Watanabe, Akihiro; Onda, Hidetaka; Masuno, Tomohiko; Yokota, Hiroyuki

    2011-01-01

    At 14:46 on March 11, 2011, the Great East Japan Earthquake and tsunami occurred off the coast of Honshu, Japan. In the acute phase of this catastrophe, one of our teams was deployed as a Tokyo Disaster Medical Assistance Team (DMAT) to Kudan Kaikan in Tokyo, where the ceiling of a large hall had partially collapsed as the result of the earthquake, to conduct triage at the scene: 6 casualties were assigned to the red category (immediate), which included 1 case of cardiopulmonary arrest and 1 of flail chest; 8 casualties in the yellow category (delayed); and 22 casualties in the green category (minor). One severely injured person was transported to our hospital. Separately, our medical team was deployed to Miyagi 2 hours after the earthquake in our multipurpose medical vehicle as part of Japan DMAT (J-DMAT). We were the first DMAT from the metropolitan area to arrive, but we were unable to start medical relief activities because the information infrastructure had been destroyed and no specific information had yet reached the local headquarters. Early next morning, J-DMAT decided to support Sendai Medical Center and search and rescue efforts in the affected area and to establish a staging care unit at Camp Kasuminome of the Japan Self-Defense Force. Our team joined others to establish the staging care unit. Because information was still confused until day 3 of the disaster and we could not adequately grasp onsite medical needs, our J-DMAT decided to provide onsite support at Ishinomaki Red Cross Hospital, a disaster base hospital, and relay information about its needs to the local J-DMAT headquarters. Although our medical relief teams were deployed as quickly as possible, we could not begin medical relief activities immediately owing to the severely damaged information infrastructure. Only satellite mobile phones could be operated, and information on the number of casualties and the severity of shortages of lifeline services could be obtained only through a "go and

  4. Effects of combined liver and udder biopsying on the acute phase response of dairy cows with experimentally induced E. coli mastitis

    DEFF Research Database (Denmark)

    Khatun, Momena; Sørensen, Peter; Ingvartsen, Klaus Lønne

    2013-01-01

    A minimally invasive biopsy technique was evaluated for udder tissue collection in dairy cows with Escherichia coli mastitis. Meanwhile, the effect of taking repeated liver and udder biopsies on the systemic and local acute phase response (APR) of the dairy cows was investigated during the disease...... the systemic and local APR in dairy cows during E. coli mastitis, if the timing of biopsying and other types of sampling is planned accordingly....... The cows were divided into a biopsy group (B) (n = 16) and a no-biopsy group (NB) (n = 16) and were sampled in the acute disease stage and in the recovery stage. The cows’ pre-disease period served as a control period for establishing baseline values for the investigated parameters. A total of 32 Holstein...

  5. Analysis of the acute phase responses of Serum Amyloid A, Haptoglobin and Type 1 Interferon in cattle experimentally infected with foot-and-mouth disease virus serotype O

    DEFF Research Database (Denmark)

    Stenfeldt, Carolina; Heegaard, Peter M. H.; Stockmarr, Anders

    2011-01-01

    A series of challenge experiments were performed in order to investigate the acute phase responses to foot-and-mouth disease virus (FMDV) infection in cattle and possible implications for the development of persistently infected "carriers". The host response to infection was investigated through...... periods exceeding 28 days in order to determine the carrier-status of individual animals. The systemic host response to FMDV in infected animals was evaluated in comparison to similar measurements in sera from 6 mock-inoculated control animals.There was a significant increase in serum concentrations....... There was a statistically significant difference in the HP response between carriers and non-carriers with a lower response in the animals that subsequently developed into FMDV carriers. It was concluded that the induction of SAA, HP and type 1 IFN in serum can be used as markers of acute infection by FMDV in cattle....

  6. Identification of Immunodominant Responses to the Plasmodium falciparum Antigens PfUIS3, PfLSA1 and PfLSAP2 in Multiple Strains of Mice.

    Directory of Open Access Journals (Sweden)

    Rhea J Longley

    Full Text Available Malaria, caused by the Plasmodium parasite, remains a serious global public health concern. A vaccine could have a substantial impact on eliminating this disease, alongside other preventative measures. We recently described the development of three novel, viral vectored vaccines expressing either of the antigens PfUIS3, PfLSA1 and PfLSAP2. Each vaccination regimen provided high levels of protection against chimeric parasite challenge in a mouse model, largely dependent on CD8+ T cells. In this study we aimed to further characterize the induced cellular immune response to these vaccines. We utilized both the IFNγ enzyme-linked immunosorbent spot assay and intracellular cytokine staining to achieve this aim. We identified immunodominant peptide responses for CD4+ and CD8+ T cells for each of the antigens in BALB/c, C57BL/6 and HLA-A2 transgenic mice, creating a useful tool for researchers for subsequent study of these antigens. We also compared these immunodominant peptides with those generated from epitope prediction software, and found that only a small proportion of the large number of epitopes predicted by the software were identifiable experimentally. Furthermore, we characterized the polyfunctionality of the induced CD8+ T cell responses. These findings contribute to our understanding of the immunological mechanisms underlying these protective vaccines, and provide a useful basis for the assessment of these and related vaccines as clinical constructs.

  7. X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide

    International Nuclear Information System (INIS)

    Feng, Youjun; Qi, Jianxun; Zhang, Huimin; Wang, Jinzi; Liu, Jinhua; Jiang, Fan; Gao, Feng

    2005-01-01

    X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide. Simian immunodeficiency virus (SIV) in the rhesus macaque is regarded as a classic animal model, playing a crucial role in HIV vaccine strategies and therapeutics by characterizing various cytotoxic T-lymphocyte (CTL) responses in macaque monkeys. However, the availability of well documented structural reports focusing on rhesus macaque major histocompatibility complex class I (MHC I) molecules remains extremely limited. Here, a complex of the rhesus macaque MHC I molecule (Mamu-A*02) with human β 2 m and an immunodominant SIV-Gag nonapeptide, GESNLKSLY (GY9), has been crystallized. The crystal diffracts X-rays to 2.7 Å resolution and belongs to space group C2, with unit-cell parameters a = 124.11, b = 110.45, c = 100.06 Å, and contains two molecules in the asymmetric unit. The availability of the structure, which is being solved by molecular replacement, will provide new insights into rhesus macaque MHC I (Mamu-A*02) presenting pathogenic SIV peptides

  8. X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Youjun [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate School, Chinese Academy of Sciences, Beijing (China); Qi, Jianxun [Graduate School, Chinese Academy of Sciences, Beijing (China); Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Zhang, Huimin; Wang, Jinzi [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Liu, Jinhua [College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China); Jiang, Fan [Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Gao, Feng, E-mail: gaofeng@im.ac.cn [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China)

    2006-01-01

    X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide. Simian immunodeficiency virus (SIV) in the rhesus macaque is regarded as a classic animal model, playing a crucial role in HIV vaccine strategies and therapeutics by characterizing various cytotoxic T-lymphocyte (CTL) responses in macaque monkeys. However, the availability of well documented structural reports focusing on rhesus macaque major histocompatibility complex class I (MHC I) molecules remains extremely limited. Here, a complex of the rhesus macaque MHC I molecule (Mamu-A*02) with human β{sub 2}m and an immunodominant SIV-Gag nonapeptide, GESNLKSLY (GY9), has been crystallized. The crystal diffracts X-rays to 2.7 Å resolution and belongs to space group C2, with unit-cell parameters a = 124.11, b = 110.45, c = 100.06 Å, and contains two molecules in the asymmetric unit. The availability of the structure, which is being solved by molecular replacement, will provide new insights into rhesus macaque MHC I (Mamu-A*02) presenting pathogenic SIV peptides.

  9. Protracted Administration of L-Asparaginase in Maintenance Phase Is the Risk Factor for Hyperglycemia in Older Patients with Pediatric Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Yoshida, Hideki; Imamura, Toshihiko; Saito, Akiko M.; Takahashi, Yoshihiro; Suenobu, So-ichi; Hasegawa, Daiichiro; Deguchi, Takao; Hashii, Yoshiko; Kawasaki, Hirohide; Endo, Mikiya; Hori, Hiroki; Suzuki, Nobuhiro; Kosaka, Yoshiyuki; Kato, Koji; Yumura-Yagi, Keiko; Hara, Junichi; Oda, Megumi; Sato, Atsushi; Horibe, Keizo

    2015-01-01

    Although L-asparaginase related hyperglycemia is well known adverse event, it is not studied whether the profile of this adverse event is affected by intensification of L-asparaginase administration. Here, we analyzed the profile of L-asparaginase related hyperglycemia in a 1,176 patients with pediatric acute lymphoblastic leukemia treated according to the Japan Association of Childhood Leukemia Study ALL-02 protocol using protracted L-asparaginase administration in maintenance phase. We determined that a total of 75 L-asparaginase related hyperglycemia events occurred in 69 patients. Although 17 events (17/1176, 1.4%) developed in induction phase, which was lower incidence than those (10–15%) in previous reports, 45 events developed during the maintenance phase with protracted L-asparaginase administration. Multivariate analysis showed that older age at onset (≥10 years) was a sole independent risk factor for L-asparaginase-related hyperglycemia (Phyperglycemia. These findings suggest that protracted administration of L-asparaginase is the risk factor for hyperglycemia when treating adolescent and young adult acute lymphoblastic leukemia patients. PMID:26317422

  10. The Effectiveness Test of Oil Phase Ointment Containing Snakehead Fish (Channa striata Extract on Open Stage II Acute Wounded Wistar Strain Male Rats

    Directory of Open Access Journals (Sweden)

    Fransisca Daisa

    2017-08-01

    Full Text Available The snakehead (Channa striata contained fatty acids omega-3 and omega-6 are useful as nutrients in accelerating the wound healing process. This study aims to determine the effectiveness of the oil phase extract ointment snakehead in the healing of acute wounds open stage II. Testing the effectiveness of wound healing using 6 groups: normal, gel bioplacenton (positive control, ointment base (negative control, ointments snakehead extract oil phase concentration of 10; 20 and 40% of the 4 rats with acute wounds open stage II and observation until day 16 injury. The area of the wound was measured with the image J program Macbiophotonic, calculated% healing power, and AUC values. A statistical test to the total AUC values per rat with SPSS for Windows 22.0 program using One Way ANOVA and Post-hoc LSD test. The results showed a significant difference in the negative group with ointment concentration of 20% (p <0.05. The treatment group phase ointment fish oil extract is effective for wound healing is best to have a concentration of 20% for percentage of wound healing power of 97.157% and the average AUC value of 865.683% of the day.

  11. Endogenous acute phase serum amyloid A lacks pro-inflammatory activity, contrasting the two recombinant variants that activate human neutrophils through different receptors

    Directory of Open Access Journals (Sweden)

    Karin eChristenson

    2013-04-01

    Full Text Available Most notable among the acute phase proteins is serum amyloid A (SAA, levels of which can increase 1000-fold during infections, aseptic inflammation, and/or trauma. Chronically elevated SAA levels are associated with a wide variety of pathological conditions, including obesity and rheumatic diseases. Using a recombinant hybrid of the two human SAA isoforms (SAA1 and 2 that does not exist in vivo, numerous in vitro studies have given rise to the notion that acute phase SAA is a pro-inflammatory molecule with cytokine-like properties. It is however unclear whether endogenous acute phase SAA per se mediates pro-inflammatory effects. We tested this in samples from patients with inflammatory arthritis and in a transgenic mouse model that expresses human SAA1. Endogenous human SAA did not drive production of pro-inflammatory IL-8/KC in either of these settings. Human neutrophils derived from arthritis patients displayed no signs of activation, despite being exposed to severely elevated SAA levels in circulation, and SAA-rich sera also failed to activate cells in vitro. In contrast, two recombinant SAA variants (the hybrid SAA and SAA1 both activated human neutrophils, inducing L-selectin shedding, production of reactive oxygen species, and production of IL-8. The hybrid SAA was approximately 100-fold more potent than recombinant SAA1. Recombinant hybrid SAA and SAA1 activated neutrophils through different receptors, with recombinant SAA1 being a ligand for formyl peptide receptor 2 (FPR2. We conclude that even though recombinant SAAs can be valuable tools for studying neutrophil activation, they do not reflect the nature of the endogenous protein.

  12. Feeding common carp Cyprinus carpio with b-glucan supplemented \\ud diet stimulates C-reactive protein and complement immune acute\\ud phase responses following PAMPs injection

    OpenAIRE

    Pionnier, Nicolas; Falco, Alberto; Miest, Joanna J.; Shrive, Annette K.; Hoole, Dave

    2014-01-01

    The effect of β-glucan as a feed additive on the serum and gene profile of C-reactive protein (CRP) and complement acute phase responses was ascertained in common carp Cyprinus carpio. In addition effects of subsequent intraperitoneal injections of pathogen-associated molecular patterns (PAMPs), i.e. LPS or poly(I:C), to mimic bacterial or viral infection respectively, were studied. Carp were first orally fed with β-glucan (MacroGard®) with a daily β-glucan intake of 6 mg per kg body weight o...

  13. Comparison of efficacy of continuous epidural block and pulsed radiofrequency to the dorsal root ganglion for management of pain persisting beyond the acute phase of herpes zoster.

    Directory of Open Access Journals (Sweden)

    Eung Don Kim

    Full Text Available There is little evidence regarding the effectiveness of intervention methods in the treatment of zoster-related pain (ZAP after the acute phase of zoster. Generally, if ZAP remains after more than 180 days from its onset, the likelihood of pain reduction is very low; this condition is considered as a "well established" post-herpetic neuralgia (PHN. Although the clinical efficacy of intrathecal steroid injection and spinal cord stimulation (SCS for ZAP management has been reported, these interventions are not widely used due to inherent disadvantages. Continuous epidural block is widely used in clinical practice, and the effectiveness of pulsed radiofrequency (PRF to the dorsal root ganglion (DRG in the treatment of ZAP already has been reported.The purpose of this study was to compare the clinical efficacy of continuous epidural block and DRG PRF beyond acute phase of zoster, bur before PHN was well established (from 30 days to180 days after zoster onset.Retrospective comparative study.A total of 42 medical records were analyzed. Patients were divided into two groups according to the type of procedure utilized: continuous epidural block (continuous epidural group and DRG PRF (PRF group. The clinical efficacy of the procedure was evaluated using a numeric rating scale (NRS and the medication dose before and 1 to 6 months after the procedure.There was a significant decrease in the NRS value with time in both groups. However, this decrease was more significant in the PRF group than in the continuous epidural group. The medication doses decreased significantly in the PRF group over time, but not in the continuous epidural group. The rate of clinically meaningful PHN (NRS≥3 was also lower in the PRF group than in the continuous epidural group.This study revealed that DRG PRF was more effective than a continuous epidural block in treating ZAP after the acute phase of zoster. A neuromodulation method such as DRG PRF may be a useful option for

  14. Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

    DEFF Research Database (Denmark)

    Bengtson, Stefan; Knudsen, Kristina Bram; Kyjovska, Zdenka O.

    2017-01-01

    assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only......We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we...

  15. Episodes of Guillain-Barré syndrome associated with the acute phase of HIV-1 infection and with recurrence of viremia

    Directory of Open Access Journals (Sweden)

    Castro Gleusa de

    2006-01-01

    Full Text Available We report a severe case of Guillain-Barré syndrome (GBS characterized by flaccid areflexive tetraplegia and signs of autonomic instability related to acute HIV-1 infection, and the occurrence of relapse episodes coinciding with the detection of HIV-1 RNA in blood during the phase of irregular treatment with antiretroviral agents. The patient has been asymptomatic for 3 years and has an HIV-1 load below the limit of detection. The recurrence of GBS in this case may be related to alterations of the immunologic response caused by disequilibrium in the host-HIV relationship due to the increase in HIV-1 viremia.

  16. An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237 in acute myelogenous leukemia and myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Stuart L. Goldberg

    2014-01-01

    Full Text Available Alisertib (MLN8237 is an investigational, oral, selective, Aurora A kinase (AAK inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML or high-grade myelodysplastic syndrome received alisertib 50 mg BID for 7 days in 21-day cycles. Responses in 6/35 AML patients (17% response rate with an additional 49% stable disease, 34% transfusion independence included 1 complete response lasting >1 year. No responses were observed in MDS patients. Adverse events >30% included diarrhea, fatigue, nausea, febrile neutropenia, and stomatitis. Results suggest modest activity in AML, supporting further research to better understand how AAK inhibition may induce leukemic cell senescence.

  17. Level of the proteins of the acute phase as criterions of the antibacterial therapy effectiveness in the E.coli associated experimental peritonitis

    Directory of Open Access Journals (Sweden)

    V. V. Minukhin

    2013-08-01

    Full Text Available Introduction. Peritonitis is accompanied by increase of acute-phase proteins levels. C – reactive protein (CRP is acutephase protein which is produced in human organism in response to tissue injury, infection or inflammation. CRP is produced in small quantities (<1mg/l under normal conditions. Measurement of CRP levels in serum is used for setting of the diagnosis and diseases monitoring as well as efficacy of their treatment. Seromucoid (orosomucoid, alpha-1 acid glucoprotein is one of acutephase proteins. Levels of serum orosomucoid are elevated since onset of the inflammatory process due to microbial contamination develops in peritonitis. Levels of alpha – 1 acid glucoprotein is elevated during acute phase of inflammation. Alpha – 1 acid glucoprotein is one of main acutephase proteins. Aim of the study. To determinate levels of seromucoid and CRP in serum of experimental animals and to evaluate the duration of the inflammatory process and the efficacy of antimicrobial therapy in mice with experimentally induced peritonitis. Material and methods of study. Levels of CRP were determined with the use of a half – quantitative immunoturbidimetric method. Levels of seromucoids were determined by means of the immunoturbidimetric method. Levels of CRP and seromucoid were determined in serum obtained from mice in which experimental peritonitis were induced by Escherichia coli. Mice were divided into 6 groups depending on methods of treatment: the 1st group: Amikacin; the 2nd group: gatifloxacin; the 3rd group: Amikacin combined with Gatiflocsacin; the 4th group: Amikacin combined with Bacteriophagum Coli-Proteicum; the 5th group: Gatiflocsacin combined with Bacteriophagum Coli-Proteicum; the 6th group: Amikacin combined with Gatiflocsacin and Bacteriophagum Coli-Proteicum; Studies were conducted on the 3rd and the 5th day after the start of antimicrobial therapy. Results of study. Studies showed that the positive CRP test and the

  18. Myocardial enhancement pattern in patients with acute myocardial infarction on two-phase contrast-enhanced Ecg-gated multidetector-row computed tomography

    International Nuclear Information System (INIS)

    Ko, S.M.; Seo, J.B.; Hong, M.K.; Do, K.H.; Lee, S.H.; Lee, J.S.; Song, J.W.; Park, S.J.; Park, S.W.; Lim, T.H.

    2006-01-01

    Aim: To evaluate the myocardial enhancement pattern of the left ventricle on two-phase contrast-enhanced electrocardiogram (ECG)-gated multidetector computed tomography (MDCT) images in patients with acute myocardial infarction (AMI). METHODS: Two-phase contrast-enhanced ECG-gated MDCT examinations were performed in 16 patients with AMI. The presence, location and pattern of myocardial enhancement were evaluated. MDCT findings were compared with the catheter angiographic results. RESULTS: Subendocardial (n=9) or transmural (n=6) area of early perfusion defects of the myocardium was detected in 15 of 16 patients (94%) on early-phase CT images. Variable delayed myocardial enhancement patterns on late-phase CT images were observed in 12 patients (75%): (1) subendocardial residual perfusion defect and subepicardial late enhancement (n=6); (2) transmural late enhancement (n=1); (3) isolated subendocardial late enhancement (n=1); and (4) isolated subendocardial residual perfusion defect (n=2). On catheter angiography, 14 of 15 corresponding coronary arteries showed significant stenosis. CONCLUSION: Variable abnormal myocardial enhancement pattern was seen on two-phase, contrast-enhanced ECG-gated MDCT in patients with AMI. Assessment of myocardial attenuation on CT angiography gives additional information of the location and extent of infarction

  19. Acute versus subacute angiography in patients with non-ST-elevation myocardial infarction - the NONSTEMI trial phase I

    DEFF Research Database (Denmark)

    Stengaard, Carsten; Sørensen, Jacob T; Rasmussen, Martin B

    2016-01-01

    randomized to subacute CAG it was two days. Time from randomization to initial revascularization was 1.3 h versus 2.4 days, and the median hospital stay was 4.0 days versus 4.5 days. Among patients randomized to subacute CAG, 17% crossed over to acute CAG and 5% developed STEMI before catheterization...

  20. Ultrasound of the coracoclavicular ligaments in the acute phase of an acromioclavicular disjonction: Comparison of radiographic, ultrasound and MRI findings.

    Science.gov (United States)

    Faruch Bilfeld, Marie; Lapègue, Franck; Chiavassa Gandois, Hélène; Bayol, Marie Aurélie; Bonnevialle, Nicolas; Sans, Nicolas

    2017-02-01

    Acromioclavicular joint injuries are typically diagnosed by clinical and radiographic assessment with the Rockwood classification, which is crucial for treatment planning. The purpose of this study was to describe how the ultrasound findings of acromioclavicular joint injury compare with radiography and MRI findings. Forty-seven patients with suspected unilateral acromioclavicular joint injury after acute trauma were enrolled in this prospective study. All patients underwent digital radiography, ultrasound and 3T MRI. A modified Rockwood classification was used to evaluate the coracoclavicular ligaments. The classifications of acromioclavicular joint injuries diagnosed with radiography, ultrasound and MRI were compared. MRI was used as the gold standard. The agreement between the ultrasound and MRI findings was very good, with a correlation coefficient of 0.83 (95 % CI: 0.72-0.90; p acromioclavicular injury. • Ultrasound is appropriate for acute acromioclavicular trauma due to its accessibility. • Ultrasound contributes to the diagnostic work-up of acute lesions of the coracoclavicular ligaments. • Ultrasound is appropriate in patients likely to benefit from surgical treatment. • Ultrasound could be a supplement to standard radiography in acute acromioclavicular trauma.

  1. Multi-modal magnetic resonance imaging in the acute and sub-acute phase of mild traumatic brain injury: can we see the difference?

    Science.gov (United States)

    Toth, Arnold; Kovacs, Noemi; Perlaki, Gabor; Orsi, Gergely; Aradi, Mihaly; Komaromy, Hedvig; Ezer, Erzsebet; Bukovics, Peter; Farkas, Orsolya; Janszky, Jozsef; Doczi, Tamas; Buki, Andras; Schwarcz, Attila

    2013-01-01

    Advanced magnetic resonance imaging (MRI) methods were shown to be able to detect the subtle structural consequences of mild traumatic brain injury (mTBI). The objective of this study was to investigate the acute structural alterations and recovery after mTBI, using diffusion tensor imaging (DTI) to reveal axonal pathology, volumetric analysis, and susceptibility weighted imaging (SWI) to detect microhemorrhage. Fourteen patients with mTBI who had computed tomography with negative results underwent MRI within 3 days and 1 month after injury. High resolution T1-weighted imaging, DTI, and SWI, were performed at both time points. A control group of 14 matched volunteers were also examined following the same imaging protocol and time interval. Tract-Based Spatial Statistics (TBSS) were performed on DTI data to reveal group differences. T1-weighted images were fed into Freesurfer volumetric analysis. TBSS showed fractional anisotropy (FA) to be significantly (corrected ptime points when performing MRI studies on patients with mTBI.

  2. A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.

    Science.gov (United States)

    Vormoor, B; Veal, G J; Griffin, M J; Boddy, A V; Irving, J; Minto, L; Case, M; Banerji, U; Swales, K E; Tall, J R; Moore, A S; Toguchi, M; Acton, G; Dyer, K; Schwab, C; Harrison, C J; Grainger, J D; Lancaster, D; Kearns, P; Hargrave, D; Vormoor, J

    2017-06-01

    Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies. © 2016 Wiley Periodicals, Inc.

  3. Pre-fracture nutritional status is predictive of functional status at discharge during the acute phase with hip fracture patients: A multicenter prospective cohort study.

    Science.gov (United States)

    Inoue, Tatsuro; Misu, Syogo; Tanaka, Toshiaki; Sakamoto, Hiroki; Iwata, Kentaro; Chuman, Yuki; Ono, Rei

    2017-10-01

    Malnutrition is common in patients with hip fractures, and elderly patients with hip fractures lose functional independence and often fail to recover previous functional status. The aim of this study was to determine whether pre-fracture nutritional status predicts functional status of patients with hip fracture at discharge from acute hospitals. In the present multicenter prospective cohort study, pre-fracture nutritional status was assessed using the Mini Nutritional Assessment Short-Form (MNA-SF). At discharge from acute hospitals, functional status was evaluated using a functional independent measurement instrument (FIM). Subsequently, multiple regression analyses were performed using FIM as the dependent variable and MNA-SF as the independent variable. Among the 204 patients analyzed in the present study, the mean length of hospital stay was 26.2 ± 12.6 days, and according to MNA-SF assessments, 51 (25.0%) patients were malnourished, 98 (48.0%) were at risk of malnutrition, and 55 (27.0%) were well-nourished before fracture. At discharge, FIM scores were higher in patients who were well-nourished than in those who were malnourished or were at risk of malnutrition (p fracture nutritional status was a significant independent predictor for functional status at discharge during the acute phase, warranting early assessment of nutritional status and early intervention for successful postoperative rehabilitation. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  4. Detection of single-phase CTA occult vessel occlusions in acute ischemic stroke using CT perfusion-based wavelet-transformed angiography

    Energy Technology Data Exchange (ETDEWEB)

    Kunz, Wolfgang G.; Sommer, Wieland H.; Meinel, Felix G.; Ertl-Wagner, Birgit; Thierfelder, Kolja M. [Ludwig-Maximilian-University Hospital Munich, Institute for Clinical Radiology, Munich (Germany); Havla, Lukas; Dietrich, Olaf [Ludwig-Maximilian-University Hospital Munich, Josef Lissner Laboratory for Biomedical Imaging of the Institute for Clinical Radiology, Munich (Germany); Dorn, Franziska [Ludwig-Maximilian-University Hospital Munich, Department of Neuroradiology, Munich (Germany); Buchholz, Grete [Ludwig-Maximilian-University Hospital Munich, Department of Neurology, Munich (Germany)

    2017-06-15

    To determine the detection rate of intracranial vessel occlusions using CT perfusion-based wavelet-transformed angiography (waveletCTA) in acute ischemic stroke patients, in whom single-phase CTA (spCTA) failed to detect an occlusion. Subjects were selected from a cohort of 791 consecutive patients who underwent multiparametric CT including whole-brain CT perfusion. Inclusion criteria were (1) significant cerebral blood flow (CBF) deficit, (2) no evidence of vessel occlusion on spCTA and (3) follow-up-confirmed acute ischemic infarction. waveletCTA was independently analysed by two readers regarding presence and location of vessel occlusions. Logistic regression analysis was performed to identify predictors of waveletCTA-detected occlusions. Fifty-nine patients fulfilled the inclusion criteria. Overall, an occlusion was identified using waveletCTA in 31 (52.5 %) patients with negative spCTA. Out of 47 patients with middle cerebral artery infarction, 27 occlusions (57.4 %) were detected by waveletCTA, mainly located in the M2 (15) and M3 segments (8). The presence of waveletCTA-detected occlusions was associated with larger CBF deficit volumes (odds ratio (OR) = 1.335, p = 0.010) and shorter times from symptom onset (OR = 0.306, p = 0.041). waveletCTA is able to detect spCTA occult vessel occlusions in about half of acute ischemic stroke patients and may potentially identify more patients eligible for endovascular therapy. (orig.)

  5. Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia.

    Science.gov (United States)

    Roboz, Gail J; Montesinos, Pau; Selleslag, Dominik; Wei, Andrew; Jang, Jun-Ho; Falantes, Jose; Voso, Maria T; Sayar, Hamid; Porkka, Kimmo; Marlton, Paula; Almeida, Antonio; Mohan, Sanjay; Ravandi, Farhad; Garcia-Manero, Guillermo; Skikne, Barry; Kantarjian, Hagop

    2016-02-01

    Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML.

  6. Accelerated Partial Breast Irradiation With IMRT: New Technical Approach and Interim Analysis of Acute Toxicity in a Phase III Randomized Clinical Trial

    International Nuclear Information System (INIS)

    Livi, Lorenzo; Buonamici, Fabrizio Banci; Simontacchi, Gabriele; Scotti, Vieri; Fambrini, Massimiliano; Compagnucci, Antonella; Paiar, Fabiola; Scoccianti, Silvia; Pallotta, Stefania; Detti, Beatrice; Agresti, Benedetta; Talamonti, Cinzia; Mangoni, Monica; Bianchi, Simonetta; Cataliotti, Luigi; Marrazzo, Livia; Bucciolini, Marta; Biti, Giampaolo

    2010-01-01

    Purpose: To evaluate with a randomized clinical trial the possibility of treating the index quadrant with external intensity-modulated radiotherapy (IMRT) in a selected group of patients with early-stage breast cancer and to analyze the acute toxicity. Methods and Materials: From September 2005, a randomized Phase III clinical trial has been conducted to compare conventional (tangential field) fractionated whole breast treatment (Arm A) with accelerated partial breast irradiation plus intensity-modulated radiotherapy (Arm B). For intensity-modulated radiotherapy, the clinical target volume was drawn with a uniform 1-cm margin around the surgical clips in three dimensions. The ipsilateral and contralateral breast, ipsilateral and contralateral lung, heart, and spinal cord were contoured as organs at risk. All the regions of interest were contoured according to the International Commission on Radiation Units and Measurements reports 50 and 62 recommendations. Results: In September 2008, 259 patients were randomized and treated. The mean clinical target volume in Arm B was 44 cm 3 and the mean planning target volume was 123 cm 3 . The mean value of the ratio between the planning target volume and the ipsilateral breast volume was 21%. The rate of Grade 1 and Grade 2 acute skin toxicity was 22% and 19% in Arm A (Radiation Therapy Oncology Group scale), respectively. The tolerance in Arm B was excellent with only 5% Grade 1 and 0.8% Grade 2 acute skin toxicity. The planning constraints were fully satisfied in most patients. In a very few cases, this was not possible because of very unfavorable anatomy. Quality assurance procedures were performed according to our internal quality assurance protocol, with excellent results. Conclusion: In the present preliminary analysis, we have demonstrated that accelerated partial breast irradiation is feasible, with very low acute toxicity.

  7. Emergence of CD4+ and CD8+ Polyfunctional T Cell Responses Against Immunodominant Lytic and Latent EBV Antigens in Children With Primary EBV Infection

    Directory of Open Access Journals (Sweden)

    Janice K. P. Lam

    2018-03-01

    Full Text Available Long term carriers were shown to generate robust polyfunctional T cell (PFC responses against lytic and latent antigens of Epstein-Barr virus (EBV. However, the time of emergence of PFC responses against EBV antigens, pattern of immunodominance and difference between CD4+ and CD8+ T cell responses during various stages of EBV infection are not clearly understood. A longitudinal study was performed to assess the development of antigen-specific PFC responses in children diagnosed to have primary symptomatic (infectious mononucleosis [IM] and asymptomatic (AS EBV infection. Evaluation of IFN-γ secreting CD8+ T cell responses upon stimulation by HLA class I-specific peptides of EBV lytic and latent proteins by ELISPOT assay followed by assessment of CD4+ and CD8+ PFC responses upon stimulation by a panel of overlapping EBV peptides for co-expression of IFN-γ, TNF-α, IL-2, perforin and CD107a by flow cytometry were performed. Cytotoxicity of T cells against autologous lymphoblastoid cell lines (LCLs as well as EBV loads in PBMC and plasma were also determined. Both IM and AS patients had elevated PBMC and plasma viral loads which declined steadily during a 12-month period from the time of diagnosis whilst decrease in the magnitude of CD8+ T cell responses toward EBV lytic peptides in contrast to increase toward latent peptides was shown with no significant difference between those of IM and AS patients. Both lytic and latent antigen-specific CD4+ and CD8+ T cells demonstrated polyfunctionality (defined as greater or equal to three functions concurrent with enhanced cytotoxicity against autologous LCLs and steady decrease in plasma and PBMC viral loads over time. Immunodominant peptides derived from BZLF1, BRLF1, BMLF1 and EBNA3A-C proteins induced the highest proportion of CD8+ as well as CD4+ PFC responses. Diverse functional subtypes of both CD4+ and CD8+ PFCs were shown to emerge at 6–12 months. In conclusion, EBV antigen-specific CD4+ and CD

  8. Immunodominant IgM and IgG Epitopes Recognized by Antibodies Induced in Enterovirus A71-Associated Hand, Foot and Mouth Disease Patients.

    Directory of Open Access Journals (Sweden)

    Kam Leng Aw-Yong

    Full Text Available Enterovirus A71 (EV-A71 is one of the main causative agents of hand, foot and mouth disease (HFMD. Unlike other enteroviruses that cause HFMD, EV-A71 is more frequently associated with severe neurological complications and fatality. To date, no effective licensed antivirals are available to combat EV-A71 infection. Little is known about the immunogenicity of viral non-structural proteins in humans. Previous studies have mainly focused on characterization of epitopes of EV-A71 structural proteins by using immunized animal antisera. In this study, we have characterized human antibody responses against the structural and non-structural proteins of EV-A71. Each viral protein was cloned and expressed in either bacterial or mammalian systems, and tested with antisera by western blot. Results revealed that all structural proteins (VP1-4, and non-structural proteins 2A, 3C and 3D were targets of EV-A71 IgM, whereas EV-A71 IgG recognized all the structural and non-structural proteins. Sixty three synthetic peptides predicted to be immunogenic in silico were synthesized and used for the characterization of EV-A71 linear B-cell epitopes. In total, we identified 22 IgM and four IgG dominant epitopes. Synthetic peptide PEP27, corresponding to residues 142-156 of VP1, was identified as the EV-A71 IgM-specific immunodominant epitope. PEP23, mapped to VP1 41-55, was recognized as the EV-A71 IgG cross-reactive immunodominant epitope. The structural protein VP1 is the major immunodominant site targeted by anti-EV-A71 IgM and IgG antibodies, but epitopes against non-structural proteins were also detected. These data provide new understanding of the immune response to EV-A71 infection, which benefits the development of diagnostic tools, potential therapeutics and subunit vaccine candidates.

  9. An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase.

    Science.gov (United States)

    Olmo, Francisco; Urbanová, Kristína; Rosales, Maria Jose; Martín-Escolano, Ruben; Sánchez-Moreno, Manuel; Marín, Clotilde

    2015-12-01

    In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz), two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by (1)H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD) inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent.

  10. The diagnostic value of Tc-99m PYP, Tl-201 dual isotope SPECT to predict the viability of damaged myocardium in the acute phase of myocardial infarction

    International Nuclear Information System (INIS)

    Matsuo, Hitoshi; Watanabe, Sachiro; Arai, Masazumi

    1991-01-01

    To assess the diagnostic value of Tc-99m pyrophosphate (PYP), Tl-201 dual isotope SPECT for the evaluation of myocardial viability, segmental comparison between dual isotope SPECT and exercise, delayed, and reinjected Tl study were performed with 18 acute myocardial infarction (AMI) patients. Among 72 damaged myocardial segments, 48 segments (67%) were judged as viable by chronic phase Tl studies. The segments with severely reduced Tl uptake by dual SPECT showed significantly lower prevalence of viable myocardium than the segments with reduced and normal Tl uptake (p<0.001). The segments with PYP accumulation localized to the subendocardium represented the favorable outcome compared with the transmural accumulation (p<0.001). And overlap segments show better prognosis than the segments without overlap (p<0.05). Most importantly, we can get better predictive accuracy of myocardial scar by dual isotope SPECT than the judgement by Tl or PYP SPECT alone (83.3% vs 77.8%, 68.1%). Thus, we conclude that Tc-99m PYP, Tl-201 dual isotope SPECT is useful to assess the severity of myocardial damage in the acute phase of myocardial infarction. (author)

  11. Indices of anti-dengue immunoglobulin G subclasses in adult Mexican patients with febrile and hemorrhagic dengue in the acute phase.

    Science.gov (United States)

    Posadas-Mondragón, Araceli; Aguilar-Faisal, José Leopoldo; Chávez-Negrete, Adolfo; Guillén-Salomón, Edith; Alcántara-Farfán, Verónica; Luna-Rojas, Lucero; Ávila-Trejo, Amanda Marineth; Del Carmen Pacheco-Yépez, Judith

    2017-10-01

    Heterologous secondary infections are at increased risk of developing dengue hemorrhagic fever (DHF) because of antibody-dependent enhancement (ADE). IgG subclasses can fix and activate complement and bind to Fcɣ receptors. These factors may also play an important role in the development of ADE and thus in the pathogenesis of DHF. The aim of this study was to analyze the indices of anti-dengue IgG subclasses in adult patients with febrile and hemorrhagic dengue in the acute phase. In 2013, 129 patients with dengue fever (DF) and 57 with DHF in Veracruz, Mexico were recruited for this study and anti-dengue IgM and IgG determined by capture ELISA. Anti-dengue IgG subclasses were detected by indirect ELISA. Anti-dengue IgG2 and IgG3 subclasses were detected in patients with dengue. IgG1 increased significantly in the sera of patients with both primary and secondary infections and DHF, but was higher in patients with secondary infections. The IgG4 subclass index was significantly higher in the sera of patients with DHF than in that of those with DF, who were in the early and late acute phase of both primary and secondary infection. In conclusion, indices of subclasses IgG1 and IgG4 were higher in patients with DHF. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  12. Level of response and safety of pharmacological monotherapy in the treatment of acute bipolar I disorder phases: a systematic review and meta-analysis

    Science.gov (United States)

    Tamayo, Jorge M.; Zarate, Carlos A.; Vieta, Eduard; Vázquez, Gustavo; Tohen, Mauricio

    2010-01-01

    In recent years, combinations of pharmacological treatments have become common for the treatment of bipolar disorder type I (BP I); however, this practice is usually not evidence-based and rarely considers monotherapy drug regimen (MDR) as an option in the treatment of acute phases of BP I. Therefore, we evaluated comparative data of commonly prescribed MDRs for both manic and depressive phases of BP I. Medline, PsycINFO, EMBASE, the Cochrane Library, the ClinicalStudyResults.org and other data sources were searched from 1949 to March 2009 for placebo and active controlled randomized clinical trials (RCTs). Risk ratios (RRs) for response, remission, and discontinuation rates due to adverse events (AEs), lack of efficacy, or discontinuation due to any cause, and the number needed to treat or harm (NNT or NNH) were calculated for each medication individually and for all evaluable trials combined. The authors included 31 RCTs in the analyses comparing a MDR with placebo or with active treatment for acute mania, and 9 RCTs comparing a MDR with placebo or with active treatment for bipolar depression. According to the collected evidence, most of the MDRs when compared to placebo showed significant response and remission rates in acute mania. In the case of bipolar depression only quetiapine and, to a lesser extent, olanzapine showed efficacy as MDR. Overall, MDRs were well tolerated with low discontinuation rates due to any cause or AE, although AE profiles differed among treatments. We concluded that most MDRs were efficacious and safe in the treatment of manic episodes, but very few MDRs have demonstrated being efficacious for bipolar depressive episodes. PMID:20128953

  13. Comparative Analysis of the Solid Phases of Bronchoalveolar Lavage and Oral Fluid in Children with Acute Necrotizing Pneumonia

    Directory of Open Access Journals (Sweden)

    V.N. Grona

    2014-05-01

    Full Text Available The growing number of acute lung abscesses, and pleural empyema, high invalidization and mortality determine the necessity for search of new methods of its diagnosis and treatment. The aim of this research was to study the morphological characteristics of in bronchoalveolar lavage and oral fluid facies in children with acute destructive pneumonias and to find out correlations between them. We examined 24 patients of department of purulent surgery in age from 1 to 14 years. Collection of mixed unstimulated oral fluid was carried out by spitting into special tubes, bronchoalveolar lavage was obtained by bronchoscopy. There has been revealed a correlation between morphological pattern of bronchoalveolar lavage and oral fluid in children depending on the pathological condition of the body.

  14. A phase III double-blind randomised study of rectal sucralfate suspension in the prevention of acute radiation proctitis

    International Nuclear Information System (INIS)

    O'Brien, Peter C.; Franklin, C. Ian; Dear, Keith B.G.; Hamilton, Christopher C.; Poulsen, Michael; Joseph, David J.; Spry, Nigel; Denham, James W.

    1997-01-01

    Background and purpose: A limited number of studies have suggested that oral sucralfate reduces the acute and late gastro-intestinal side-effects of pelvic radiotherapy and sucralfate enemas ameliorate symptoms of chronic proctitis. Sucralfate may act via local bFGF at the mucosal level in promoting angiogenesis and reducing epithelial associated microvascular injury. This multi-institutional study was designed to test the hypothesis that sucralfate given as an enema would have a significant protective effect against acute radiation induced rectal injury by direct application to the mucosa. Materials and methods: Eighty-six patients having radiotherapy for localised carcinoma of the prostate were randomised in a double-blind placebo-controlled study to receive either 15 ml of placebo suspension or 3 g of sucralfate in 15 ml suspension, given as a once daily enema during and for 2 weeks following radiotherapy. Assessment was based on the EORTC/RTOG acute toxicity criteria and a patient self-assessment diary. Results: There was no significant difference between placebo and sucralfate for peak incidences of EORTC/RTOG proctitis. For the placebo and sucralfate arms 95 and 88% (difference 7 ± 11%) suffered some degree of proctitis, with 71 and 61% (difference 10 ± 19%) reaching grade 2, respectively. The median period to onset of grade 2 proctitis was 33.5 and 36 days, with the median duration being 9.5 and 15 days, respectively, again these difference being non-significant. Thirty-five and 37% of patients rated the effect of radiotherapy on bowel habit as 'a lot' with a moderate or severe effect on normal daily living in 52 and 49%, respectively. Conclusion: This study suggests that sucralfate given as a once daily enema does not substantially reduce the incidence of symptoms associated with acute radiation proctitis and its routine clinical use cannot be recommended. This cohort of patients will be followed to determine if any difference develops in relation to late

  15. Detection and localization of acute upper and lower gastrointestinal (GI) bleeding with arterial phase multi-detector row helical CT

    Energy Technology Data Exchange (ETDEWEB)

    Jaeckle, T.; Stuber, G.; Hoffmann, M.H.K.; Jeltsch, M.; Schmitz, B.L.; Aschoff, A.J. [University Hospital of Ulm, Diagnostic and Interventional Radiology, Ulm (Germany)

    2008-07-15

    The purpose of this study was to evaluate the accuracy of multi-detector row helical CT (MDCT) for detection and localization of acute upper and lower gastrointestinal (GI) hemorrhage or intraperitoneal bleeding. Thirty-six consecutive patients with clinical signs of acute bleeding underwent biphasic (16- or 40-channel) MDCT. MDCT findings were correlated with endoscopy, angiography or surgery. Among the 36 patients evaluated, 26 were examined for GI bleeding and 10 for intraperitoneal hemorrhage. Confirmed sites of GI bleeding were the stomach (n = 5), duodenum (n = 5), small bowel (n = 6), large bowel (n = 8) and rectum (n = 2). The correct site of bleeding was identifiable on MDCT in 24/26 patients with GI bleeding. In 20 of these 24 patients, active CM extravasation was apparent during the exam. Among the ten patients with intraperitoneal hemorrhage, MDCT correctly identified the bleeding source in nine patients. Our findings suggest that fast and accurate localization of acute gastrointestinal and intraperitoneal bleeding is achievable on MDCT. (orig.)

  16. Detection and localization of acute upper and lower gastrointestinal (GI) bleeding with arterial phase multi-detector row helical CT

    International Nuclear Information System (INIS)

    Jaeckle, T.; Stuber, G.; Hoffmann, M.H.K.; Jeltsch, M.; Schmitz, B.L.; Aschoff, A.J.

    2008-01-01

    The purpose of this study was to evaluate the accuracy of multi-detector row helical CT (MDCT) for detection and localization of acute upper and lower gastrointestinal (GI) hemorrhage or intraperitoneal bleeding. Thirty-six consecutive patients with clinical signs of acute bleeding underwent biphasic (16- or 40-channel) MDCT. MDCT findings were correlated with endoscopy, angiography or surgery. Among the 36 patients evaluated, 26 were examined for GI bleeding and 10 for intraperitoneal hemorrhage. Confirmed sites of GI bleeding were the stomach (n = 5), duodenum (n = 5), small bowel (n = 6), large bowel (n = 8) and rectum (n = 2). The correct site of bleeding was identifiable on MDCT in 24/26 patients with GI bleeding. In 20 of these 24 patients, active CM extravasation was apparent during the exam. Among the ten patients with intraperitoneal hemorrhage, MDCT correctly identified the bleeding source in nine patients. Our findings suggest that fast and accurate localization of acute gastrointestinal and intraperitoneal bleeding is achievable on MDCT. (orig.)

  17. The Immunodominance Change and Protection of CD4+ T-Cell Responses Elicited by an Envelope Protein Domain III-Based Tetravalent Dengue Vaccine in Mice.

    Directory of Open Access Journals (Sweden)

    Hsin-Wei Chen

    Full Text Available Dengue is the leading cause of mosquito-borne viral infections and no vaccine is available now. Envelope protein domain III (ED3 is the major target for the binding of dengue virus neutralizing antibodies; however, the ED3-specifc T-cell response is less well understood. To investigate the T-cell responses to four serotypes of dengue virus (DENV-1 to 4, we immunized mice using either a tetravalent ED3-based DNA or protein vaccine, or combined both as a DNA prime-protein boost strategy (prime-boost. A significant serotype-dependent IFN-γ or IL-4 response was observed in mice immunized with either the DNA or protein vaccine. The IFN-γ response was dominant to DENV-1 to 3, whereas the IL-4 response was dominant to DENV-4. Although the similar IgG titers for the four serotypes were observed in mice immunized with the tetravalent vaccines, the neutralizing antibody titers varied and followed the order of 2 = 3>1>4. Interestingly, the lower IFN-γ response to DENV-4 is attributable to the immunodominance change between two CD4+ T-cell epitopes; one T-cell epitope located at E349-363 of DENV-1 to 3 was more immunogenic than the DENV-4 epitope E313-327. Despite DENV-4 specific IFN-γ responses were suppressed by immunodominance change, either DENV-4-specific IFN-γ or neutralizing antibody responses were still recalled after DENV-4 challenge and contributed to virus clearance. Immunization with the prime-boost elicited both IFN-γ and neutralizing antibody responses and provided better protection than either DNA or protein immunization. Our findings shed light on how ED3-based tetravalent dengue vaccines sharpen host CD4 T-cell responses and contribute to protection against dengue virus.

  18. Immunomodulatory effects of high-protein diet with resveratrol supplementation on radiation-induced acute-phase inflammation in rats.

    Science.gov (United States)

    Kim, Kyoung-Ok; Park, HyunJin; Chun, Mison; Kim, Hyun-Sook

    2014-09-01

    We hypothesized that a high-protein diet and/or resveratrol supplementation will improve acute inflammatory responses in rats after receiving experimental abdominal radiation treatment (ART). Based on our previous study, the period of 10 days after ART was used as an acute inflammation model. Rats were exposed to a radiation dose of 17.5 Gy and were supplied with a control (C), 30% high-protein diet (HP), resveratrol supplementation (RES), or HP with RES diet ([HP+RES]). At day 10 after ART, we measured profiles of lipids, proteins, and immune cells in blood. The levels of clusters of differentiating 4(+) (CD4(+)) cells and regulatory T cells, serum proinflammatory cytokines, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine were also measured. ART caused significant disturbances of lipid profiles by increasing triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and decreasing high-density lipoprotein cholesterol. The proinflammatroy cytokine levels were also increased by ART. All the experimental diets (HP, RES, and [HP+RES]) significantly decreased levels of TG, monocytes, proinflammatory cytokines, and 8-OHdG, whereas the platelet counts were increased. In addition, the HP and [HP+RES] diets decreased the concentrations of plasma LDL-C and total cholesterol. Also, the HP and RES diets decreased regulatory T cells compared with those of the control diet in ART group. Further, the HP diet led to a significant recovery of white blood cell counts, as well as increased percentages of lymphocyte and decreased percentages of neutrophils. In summary, RES appeared to be significantly effective in minimizing radiation-induced damage to lipid metabolism and immune responses. Our study also demonstrated the importance of dietary protein intake in recovering from acute inflammation by radiation.

  19. Sequential Oral Hydroxyurea and Intravenous Cytosine Arabinoside in Refractory Childhood Acute Leukemia: A Pediatric Oncology Group Phase I Study

    OpenAIRE

    Dubowy, Ronald; Graham, Michael; Hakami, Nasrollah; Kletzel, Morris; Mahoney, Donald; Newman, Edward; Ravindranath, Yaddanapudi; Camitta, Bruce

    2008-01-01

    At concentrations >0.1 mM, Hydroxyurea (HU) enhances the accumulation of cytosine arabinoside (ara-C) in leukemia cells in vitro. This study of children with refractory acute leukemia was designed to take advantage of this biochemical modulation. A fixed dose of HU and an escalating dose of ara-C were used. Oral HU, 1200 mg/m2 was followed 2 hours later by ara-C, 250-3100 mg/m2 intravenously in 15 minutes. The combination was given on days 1,2,3 and 8,9,10. Thirty-three children (26 ALL, 7 AN...

  20. Enhanced presurgical pain temporal summation response predicts post-thoracotomy pain intensity during the acute postoperative phase.

    Science.gov (United States)

    Weissman-Fogel, Irit; Granovsky, Yelena; Crispel, Yonathan; Ben-Nun, Alon; Best, Lael Anson; Yarnitsky, David; Granot, Michal

    2009-06-01

    Recent evidence points to an association between experimental pain measures obtained preoperatively and acute postoperative pain (POP). We hypothesized that pain temporal summation (TS) might be an additional predictor for POP insofar as it represents the neuroplastic changes that occur in the central nervous system following surgery. Therefore, a wide range of psychophysical tests (TS to heat and mechanical repetitive stimuli, pain threshold, and suprathreshold pain estimation) and personality tests (pain catastrophizing and anxiety levels) were administered prior to thoracotomy in 84 patients. POP ratings were evaluated on the 2nd and 5th days after surgery at rest (spontaneous pain) and in response to activity (provoked pain). Linear regression models revealed that among all assessed variables, enhanced TS and higher pain scores for mechanical stimulation were significantly associated with greater provoked POP intensity (overall r2 = 0.225, P = .008). Patients who did not demonstrate TS to both modalities reported lower scores of provoked POP as compared with patients who demonstrated TS in response to at least 1 modality (F = 4.59 P = .013). Despite the moderate association between pain catastrophizing and rest POP, none of the variables predicted the spontaneous POP intensity. These findings suggest that individual susceptibility toward a greater summation response may characterize patients who are potentially vulnerable to augmented POP. This study proposed the role of pain temporal summation assessed preoperatively as a significant psychophysical predictor for acute postoperative pain intensity. The individual profile of enhanced pain summation is associated with the greater likelihood of higher postoperative pain scores.

  1. The acute phase protein ceruloplasmin as a non-invasive marker of pseudopregnancy, pregnancy, and pregnancy loss in the giant panda.

    Directory of Open Access Journals (Sweden)

    Erin L Willis

    Full Text Available After ovulation, non-pregnant female giant pandas experience pseudopregnancy. During pseudopregnancy, non-pregnant females exhibit physiological and behavioral changes similar to pregnancy. Monitoring hormonal patterns that are usually different in pregnant mammals are not effective at determining pregnancy status in many animals that undergo pseudopregnancy, including the giant panda. Therefore, a physiological test to distinguish between pregnancy and pseudopregnancy in pandas has eluded scientists for decades. We examined other potential markers of pregnancy and found that activity of the acute phase protein ceruloplasmin increases in urine of giant pandas in response to pregnancy. Results indicate that in term pregnancies, levels of active urinary ceruloplasmin were elevated the first week of pregnancy and remain elevated until 20-24 days prior to parturition, while no increase was observed during the luteal phase in known pseudopregnancies. Active ceruloplasmin also increased during ultrasound-confirmed lost pregnancies; however, the pattern was different compared to term pregnancies, particularly during the late luteal phase. In four out of the five additional reproductive cycles included in the current study where females were bred but no birth occurred, active ceruloplasmin in urine increased during the luteal phase. Similar to the known lost pregnancies, the temporal pattern of change in urinary ceruloplasmin during the luteal phase deviated from the term pregnancies suggesting that these cycles may have also been lost pregnancies. Among giant pandas in captivity, it has been presumed that there is a high rate of pregnancy loss and our results are the first to provide evidence supporting this notion.

  2. Photopenia of the femoral head on 3 phase bone scan using Tc-99m MDP with acute irritable hip in the preschool children: comparison with MR findings

    International Nuclear Information System (INIS)

    Ryu, Young Hoon; Lee, Jong Doo; Yoon, Choon Sik; Suh, Jin Suck; Jeon, Tae Joo

    1998-01-01

    The child with acute irritable hip is always a diagnostic challenge. Photopenia of femur head is described in Legg-Calve-Perthes disease (LCP). However, it can be seen in cases of septic arthritis (SA) with interruption of vascular supply. Despites being uncommon, recognition of SA as a cause of photopenia is important and requires urgent referral to decompression and drainage. This study was to evaluate causes and scintigraphic features of photopenia of femur head in patients with acute irritable hip and to correlate them with MR findings. 15 patients with acute irritable hip showed photopenia of femur head on bone scan were included. Mean age was 5.3 yrs ( 9 months to 8 yrs). There were 9 patients with LCP and 3 with septic arthritis combined with osteomyelitis. All parents underwent 3 phase bone scan and hip MRI within 2 days interval. Patterns of photopenia of femur head was divided into partial, complete and extending to the metaphysis. All patients with LCP showed partial photopenia confined to femur epiphysis. Whereas, 1 with septic arthritis demonstrated complete photopenia of femur head and in 2 with septic arthritis and 3 with septic arthritis combined with osteomyelitis revealed complete photopenia of femur head extending to the metaphyseal area. In cases with septic arthritis, increased uptake affecting both sides of hip joint except for photopenic area is also noted. On MRI, all patients with LCP showed abnormalities confined to the epiphysis. In cases with septic arthritis, abnormalities are not confined to the epiphysis and marrow edema and joint effusion were also noted. In evaluating photopenia of the femur head, it would be helpful to distinguish between the photopenia localized to the femoral epiphysis as seen in cases of LCP and complete photopenia of femur head with extension to the metaphysis as seen in cases of septic arthritis. Recognition of complete with extension to the metaphysis help guide urgent proper management of septic arthritis

  3. Photopenia of the femoral head on 3 phase bone scan using Tc-99m MDP with acute irritable hip in the preschool children: comparison with MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Young Hoon; Lee, Jong Doo; Yoon, Choon Sik; Suh, Jin Suck; Jeon, Tae Joo [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    1998-07-01

    The child with acute irritable hip is always a diagnostic challenge. Photopenia of femur head is described in Legg-Calve-Perthes disease (LCP). However, it can be seen in cases of septic arthritis (SA) with interruption of vascular supply. Despites being uncommon, recognition of SA as a cause of photopenia is important and requires urgent referral to decompression and drainage. This study was to evaluate causes and scintigraphic features of photopenia of femur head in patients with acute irritable hip and to correlate them with MR findings. 15 patients with acute irritable hip showed photopenia of femur head on bone scan were included. Mean age was 5.3 yrs ( 9 months to 8 yrs). There were 9 patients with LCP and 3 with septic arthritis combined with osteomyelitis. All parents underwent 3 phase bone scan and hip MRI within 2 days interval. Patterns of photopenia of femur head was divided into partial, complete and extending to the metaphysis. All patients with LCP showed partial photopenia confined to femur epiphysis. Whereas, 1 with septic arthritis demonstrated complete photopenia of femur head and in 2 with septic arthritis and 3 with septic arthritis combined with osteomyelitis revealed complete photopenia of femur head extending to the metaphyseal area. In cases with septic arthritis, increased uptake affecting both sides of hip joint except for photopenic area is also noted. On MRI, all patients with LCP showed abnormalities confined to the epiphysis. In cases with septic arthritis, abnormalities are not confined to the epiphysis and marrow edema and joint effusion were also noted. In evaluating photopenia of the femur head, it would be helpful to distinguish between the photopenia localized to the femoral epiphysis as seen in cases of LCP and complete photopenia of femur head with extension to the metaphysis as seen in cases of septic arthritis. Recognition of complete with extension to the metaphysis help guide urgent proper management of septic arthritis.

  4. Acute effects of static and dynamic stretching on jump performance after 15 min of reconditioning shooting phase in basketball players.

    Science.gov (United States)

    Annino, Giuseppe; Ruscello, Bruno; Lebone, Pietro; Palazzo, Francesco; Lombardo, Mauro; Padua, Elvira; Verdecchia, Luca; Tancredi, Virginia; Iellamo, Ferdinando

    2017-04-01

    The aim of this study was to assess the effects of static (SS) and dynamic stretching (DS) on vertical jump performance executed before, immediately after and at the end of the shooting phase (i.e., 15 min later), as to simulate the actual conditions preceding a match, in professional basketball players. Ten elite basketball players (age: 29±6.73 years, height: 194.67±7.75 cm, weight: 91±8.17 kg and BMI 23.8±7.91 kg.m-2) participated to the study. SS and DS protocols were administered during the first training session of the week, 48 hours after the championship match. Stretching protocols consisted in ~7 minutes of general warm-up phase followed by ~8 minutes of SS and DS, performed with a cross-over design., and ~15 minutes of a specific warm-up shooting phase (SP). Vertical jump tests consisted in counter movement jump (CMJ) and CMJ with arm swings (CMJas) and were performed immediately after the end of each stretching phase (preS, postS, postSP). A significant decrease (P=0.05; η2partial=0.29) in jumping tests height occurred in CMJas, when performed after the SS (i.e., PostS). However, no significant differences in jumping performances, occurred after the general warm phase and the specific warm-up shooting phase, between the two stretching protocols. These results would indicate that, overall, stretching routines either dynamic or static, performed before a basketball match are transient and affect only marginally leg muscles performance. Stretching routines, particularly the dynamic ones, may be useful to maintain muscle performance before a competition, provided that this latter begins shortly after.

  5. Effect of different antimicrobial treatments on serum acute phase responses and leukocyte counts in pigs after a primary and a secondary challenge infection with Actinobacillus pleuropneumoniae

    DEFF Research Database (Denmark)

    Sjölund, M; Fossum, C; Martin de la Fuente, AJM

    2011-01-01

    -free pigs were allocated to five groups of six. After acclimatisation, four groups were inoculated with A pleuropneumoniae serotype 2. At the onset of clinical signs, three of the groups of pigs were treated with enrofloxacin, tetracycline or penicillin. A fourth group served as the inoculated control......-binding lectin-A response was less evident in the pigs. Acute phase responses resembling those of the first inoculation were observed in the pigs that had not previously been inoculated and in the pigs treated with enrofloxacin. Acute phase responses were not recorded in the other three groups, where the pigs...

  6. Intensive care unit nurses' perceptions of patient participation in the acute phase of chronic obstructive pulmonary disease exacerbation: an interview study.

    Science.gov (United States)

    Kvangarsnes, Marit; Torheim, Henny; Hole, Torstein; Öhlund, Lennart S

    2013-02-01

    To report a study conducted to explore intensive care unit nurses' perceptions of patient participation in the acute phase of chronic obstructive pulmonary disease exacerbation. An acute exacerbation is a life-threatening situation, which patients often consider to be extremely frightening. Healthcare personnel exercise considerable power in this situation, which challenges general professional notions of patient participation. Critical discourse analysis. In the autumn of 2009, three focus group interviews with experienced intensive care nurses were conducted at two hospitals in western Norway. Two groups had six participants each, and one group had five (N = 17). The transcribed interviews were analysed by means of critical discourse analysis. The intensive care nurses said that an exacerbation is often an extreme situation in which healthcare personnel are exercising a high degree of control and power over patients. Patient participation during exacerbation often takes the form of non-involvement. The participating nurses attached great importance to taking a sensitive approach when meeting patients. The nurses experienced challenging ethical dilemmas. This study shows that patient participation should not be understood in universal terms, but rather in relation to a specific setting and the interactions that occur in this setting. Healthcare personnel must develop skill, understanding, and competence to meet these challenging ethical dilemmas. A collaborative inter-professional approach between physicians and nurses is needed to meet the patients' demand for involvement. © 2012 Blackwell Publishing Ltd.

  7. Occupational exposure levels of bioaerosol components are associated with serum levels of the acute phase protein Serum Amyloid A in greenhouse workers

    DEFF Research Database (Denmark)

    Madsen, Anne Mette; Thilsing, Trine; Bælum, Jesper

    2016-01-01

    to elevated levels of bioaerosols. The objective of this study is to assess whether greenhouse workers personal exposure to bioaerosol components was associated with serum levels of the acute phase proteins Serum Amyloid A (SAA) and C-reactive protein (CRP). METHODS: SAA and CRP levels were determined......-glucan. RESULTS: Serum levels of SAA and CRP were not significantly different in greenhouse workers and a reference group, or on the two work days. In a mixed model, SAA levels were positively associated with endotoxin exposure levels (p = 0.0007). Results for fungi were not clear. CRP levels were positively...... associated with endotoxin exposures (p = 0.022). Furthermore, when workers were categorized into three groups based on SAA and CRP serum levels endotoxin exposure was highest in the group with the highest SAA levels and in the group with middle and highest CRP levels. SAA and CRP levels were elevated...

  8. Are Improvements in Cognitive Content and Depressive Symptoms Correlates or Mediators during Acute-Phase Cognitive Therapy for Recurrent Major Depressive Disorder?

    Science.gov (United States)

    Vittengl, Jeffrey R; Clark, Lee Anna; Thase, Michael E; Jarrett, Robin B

    2014-01-09

    The cognitive model of depression posits that cognitive therapy's (CT) effect on depressive symptoms is mediated by changes in cognitive content (e.g., automatic negative thoughts dysfunctional attitudes, failure attributions). We tested improvement and normalization of cognitive content among outpatients ( N = 523) with recurrent major depressive disorder treated with acute-phase CT (Jarrett & Thase, 2010; Jarrett et al., 2013). We also tested whether improvement in cognitive content accounted for subsequent changes in depressive symptoms and vice versa. Five measures of content improved substantively from pre- to post-CT (median d = 0.96), and the proportions of patients scoring in "healthy" ranges increased (median 45% to 82%). Evidence for cognitive mediation of symptom reduction was limited (median r = .06), as was evidence for symptom mediation of cognitive content improvement (median r = .07). We discuss measurement and design issues relevant to detection of mediators and consider alternative theories of change.

  9. Extensive changes in innate immune gene expression in obese Göttingen minipigs do not lead to changes in concentrations of circulating cytokines and acute phase proteins

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard; Skovgaard, Kerstin; Moesgaard, S. G.

    2014-01-01

    not been studied in Göttingen minipigs. Therefore, we studied the expression of innate immune genes in liver and adipose tissues as well as serum concentrations of cytokines and acute phase proteins in obese vs. lean Göttingen minipigs. In the liver, of 35 investigated genes, the expression of nine...... was significantly different in obese pigs (three up-regulated, six down-regulated). Of 33 genes in adipose tissues, obesity was associated with changed expression of 12 genes in the visceral adipose tissue (VAT) (three up-regulated), 11 in the abdominal retroperitoneal adipose tissue (RPAT) (seven of these up......-regulated) and eight in the subcutaneous adipose tissue (SAT) from the neck (five of which were up-regulated). Obesity-associated expression changes were observed for three genes in all adipose tissues, namely chemokine (C-C motif) ligand 3-like 1 (up-regulated), CD200 molecule (down-regulated) and interleukin 1...

  10. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    DEFF Research Database (Denmark)

    Poulsen, Sarah S.; Saber, Anne T.; Mortensen, Alicja

    2015-01-01

    has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18,54 or 162 mu...... levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater...... response following CNTLarge exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk...

  11. Pulsing blue light through closed eyelids: effects on acute melatonin suppression and phase shifting of dim light melatonin onset.

    Science.gov (United States)

    Figueiro, Mariana G; Plitnick, Barbara; Rea, Mark S

    2014-01-01

    Circadian rhythm disturbances parallel the increased prevalence of sleep disorders in older adults. Light therapies that specifically target regulation of the circadian system in principle could be used to treat sleep disorders in this population. Current recommendations for light treatment require the patients to sit in front of a bright light box for at least 1 hour daily, perhaps limiting their willingness to comply. Light applied through closed eyelids during sleep might not only be efficacious for changing circadian phase but also lead to better compliance because patients would receive light treatment while sleeping. Reported here are the results of two studies investigating the impact of a train of 480 nm (blue) light pulses presented to the retina through closed eyelids on melatonin suppression (laboratory study) and on delaying circadian phase (field study). Both studies employed a sleep mask that provided narrowband blue light pulses of 2-second duration every 30 seconds from arrays of light-emitting diodes. The results of the laboratory study demonstrated that the blue light pulses significantly suppressed melatonin by an amount similar to that previously shown in the same protocol at half the frequency (ie, one 2-second pulse every minute for 1 hour). The results of the field study demonstrated that blue light pulses given early in the sleep episode significantly delayed circadian phase in older adults; these results are the first to demonstrate the efficacy and practicality of light treatment by a sleep mask aimed at adjusting circadian phase in a home setting.

  12. Phase II multicenter randomized study of amifostine for prevention of acute radiation rectal toxicity: Topical intrarectal versus subcutaneous application

    International Nuclear Information System (INIS)

    Kouloulias, Vassilis E.; Kouvaris, John R.; Pissakas, George; Mallas, Elias; Antypas, Christos; Kokakis, John D.; Matsopoulos, George; Michopoulos, Spyros; Mystakidou, Kyriaki; Vlahos, Lambros J.

    2005-01-01

    Purpose: To investigate the cytoprotective effect of subcutaneous vs. intrarectal administration of amifostine against acute radiation toxicity. Methods and materials: Patients were randomized to receive amifostine either intrarectally (Group A, n = 27) or a 500-mg flat dose subcutaneously (Group B, n = 26) before irradiation. Therapy was delivered using a four-field technique with three-dimensional conformal planning. In Group A, 1,500 mg of amifostine was administered intrarectally as an aqueous solution in 40 mL of enema. Two different toxicity scales were used: the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group (RTOG) rectal and urologic toxicity criteria and the Subjective-RectoSigmoid scale based on the endoscopic terminology of the World Organization for Digestive Endoscopy. Objective measurements with rectosigmoidoscopy were performed at baseline and 1-2 days after radiotherapy completion. The area under the curve for the time course of mucositis (RTOG criteria) during irradiation represented the mucositis index. Results: Intrarectal amifostine was feasible and well tolerated without any systemic or local side effects. According to the RTOG toxicity scale, Group A had superior results with a significantly lower incidence of Grades I-II rectal radiation morbidity (11% vs. 42%, p 0.04) but inferior results concerning urinary toxicity (48% vs. 15%, p 0.03). The mean rectal mucositis index and Subjective-RectoSigmoid score were significantly lower in Group A (0.44 vs. 2.45 [p = 0.015] and 3.9 vs. 6.0 [p = 0.01], respectively), and the mean urinary mucositis index was lower in Group B (2.39 vs. 0.34, p < 0.028). Conclusions: Intrarectal administration of amifostine (1,500 mg) seemed to have a cytoprotective efficacy in acute radiation rectal mucositis but was inferior to subcutaneous administration in terms of urinary toxicity. Additional randomized studies are needed for definitive decisions concerning the

  13. An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase

    Directory of Open Access Journals (Sweden)

    Francisco Olmo

    2015-12-01

    Full Text Available In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz, two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by 1H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent.

  14. Quantitative relationships between thallium-201 estimated myocardial infarct size and left ventricular function in the acute or convalescent phase of the first attack of myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Kataoka, Hajime (Kagoshima Univ. (Japan). Faculty of Medicine); Ueda, Keiji; Sakai, Makoto (and others)

    1983-07-01

    Correlations between left ventricular (LV) function and infarct size estimated by computer-assisted thallium (Tl)-201 scintigraphy were studied in 16 patients in the acute or convalescent phase of the first attack of transmural myocardial infarction (MI). Tl-201 estimation of the infarct size was done using a ''corrected'' circumferential profile method, by which the total defect score could be obtained. The LV function was evaluated by radionuclide angiography, echocardiography and cardiac catheterization study. The following results were obtained: 1) A close inverse relationship was found between the defect score and the ejection fraction (r = -0.649, p < 0.01). 2) The linear correlation coefficient was 0.540 (p < 0.05) between the defect score and the pulmonary arterial end-diastolic pressure and -0.616 (p < 0.02) between the defect score and the stroke volume index. There was no significant correlation between the defect score and the cardiac index. 3) There was a linear correlation between the defect score and the LV end-diastolic dimension (r = -0.852, p < 0.001). However, there was no relation between the defect score and the left atrial dimension. When the LV indices were compared between the small (S) and the large (L) defect score group, the L defect group had faster heart rate, larger LV chamber size and the smaller stroke volume index than the S defect group. However, there was no significant difference in the cardiac index between these 2 groups. These results suggest that the LV dilatation in acute or convalescent phase of the first attack of transmural MI is an ominous sign because it was usually accompanied by large infarct size. The present study also indicates that LV dilatation accompanying a large infarct does not satisfactorily compensate for LV dysfunction by Frank-Starling mechanism.

  15. Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men.

    Science.gov (United States)

    Jeukendrup, A E; Vet-Joop, K; Sturk, A; Stegen, J H; Senden, J; Saris, W H; Wagenmakers, A J

    2000-01-01

    The aim of the present study was to establish whether gastro-intestinal (GI) complaints observed during and after ultra-endurance exercise are related to gut ischaemia-associated leakage of endotoxins [lipopolysaccharide (LPS)] into the circulation and associated cytokine production. Therefore we collected blood samples from 29 athletes before, immediately after, and 1, 2 and 16 h after a long-distance triathlon for measurement of LPS, tumour necrosis factor-alpha and interleukin-6 (IL-6). As the cytokine response would trigger an acute-phase response, characteristic variables of these responses were also measured, along with creatine kinase (CK) to obtain an indicator of muscle damage. There was a high incidence (93% of all participants) of GI symptoms; 45% reported severe complaints and 7% of the participants abandoned the race because of severe GI distress. Mild endotoxaemia (5-15 pg/ml) was evident in 68% of the athletes immediately after the race, as also indicated by a reduction in IgG anti-LPS levels. In addition, we observed production of IL-6 (27-fold increase immediately after the race), leading to an acute-phase response (20-fold increase in C-reactive protein and 12% decrease in pre-albumin 16 h after the race). The extent of endotoxaemia was not correlated with the GI complaints or the IL-6 response, but did show a correlation with the elevation in C-reactive protein (r(s) 0.389; P=0.037). Creatine kinase levels were increased significantly immediately post-race, and increased further in the follow-up period. Creatine kinase levels did not correlate with those of either IL-6 or C-reactive protein. It is therefore concluded that LPS does enter the circulation after ultra-endurance exercise and may, together with muscle damage, be responsible for the increased cytokine response and hence GI complaints in these athletes.

  16. Pulsing blue light through closed eyelids: effects on acute melatonin suppression and phase shifting of dim light melatonin onset

    Directory of Open Access Journals (Sweden)

    Figueiro MG

    2014-12-01

    Full Text Available Mariana G Figueiro, Barbara Plitnick, Mark S Rea Lighting Research Center, Rensselaer Polytechnic Institute, Troy, NY, USA Abstract: Circadian rhythm disturbances parallel the increased prevalence of sleep disorders in older adults. Light therapies that specifically target regulation of the circadian system in principle could be used to treat sleep disorders in this population. Current recommendations for light treatment require the patients to sit in front of a bright light box for at least 1 hour daily, perhaps limiting their willingness to comply. Light applied through closed eyelids during sleep might not only be efficacious for changing circadian phase but also lead to better compliance because patients would receive light treatment while sleeping. Reported here are the results of two studies investigating the impact of a train of 480 nm (blue light pulses presented to the retina through closed eyelids on melatonin suppression (laboratory study and on delaying circadian phase (field study. Both studies employed a sleep mask that provided narrowband blue light pulses of 2-second duration every 30 seconds from arrays of light-emitting diodes. The results of the laboratory study demonstrated that the blue light pulses significantly suppressed melatonin by an amount similar to that previously shown in the same protocol at half the frequency (ie, one 2-second pulse every minute for 1 hour. The results of the field study demonstrated that blue light pulses given early in the sleep episode significantly delayed circadian phase in older adults; these results are the first to demonstrate the efficacy and practicality of light treatment by a sleep mask aimed at adjusting circadian phase in a home setting. Keywords: circadian phase, dim light melatonin onset, light through closed eyelids, blue light, sleep

  17. A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Morris Peter E

    2012-02-01

    Full Text Available Abstract Background The tissue factor (TF-dependent extrinsic pathway has been suggested to be a central mechanism by which the coagulation cascade is locally activated in the lungs of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS and thus represents an attractive target for therapeutic intervention. This study was designed to determine the pharmacokinetic and safety profiles of ALT-836, an anti-TF antibody, in patients with ALI/ARDS. Methods This was a prospective, randomized, placebo-controlled, dose-escalation Phase I clinical trial in adult patients who had suspected or proven infection, were receiving mechanical ventilation and had ALI/ARDS (PaO2/FiO2 ≤ 300 mm. Eighteen patients (6 per cohort were randomized in a 5:1 ratio to receive ALT-836 or placebo, and were treated within 48 hours after meeting screening criteria. Cohorts of patients were administered a single intravenously dose of 0.06, 0.08 or 0.1 mg/kg ALT-836 or placebo. Blood samples were taken for pharmacokinetic and immunogenicity measurements. Safety was assessed by adverse events, vital signs, ECGs, laboratory, coagulation and pulmonary function parameters. Results Pharmacokinetic analysis showed a dose dependent exposure to ALT-836 across the infusion range of 0.06 to 0.1 mg/kg. No anti-ALT-836 antibody response was observed in the study population during the trial. No major bleeding episodes were reported in the ALT-836 treated patients. The most frequent adverse events were anemia, observed in both placebo and ALT-836 treated patients, and ALT-836 dose dependent, self-resolved hematuria, which suggested 0.08 mg/kg as an acceptable dose level of ALT-836 in this patient population. Conclusions Overall, this study showed that ALT-836 could be safely administered to patients with sepsis-induced ALI/ARDS. Trial registration ClinicalTrials.gov: NCT01438853

  18. S-phase cell distribution in the small intestine irradiated at different times of the day. I. Acute irradiation injury

    Energy Technology Data Exchange (ETDEWEB)

    Becciolini, A; Balzi, M; Cremonini, D; Fabbrica, D [Florence Univ. (Italy). Ist. di Radiologia

    1983-01-01

    The S-phase cell distribution has been analysed to evaluate the behaviour of proliferative cells in the intestinal epithelium after irradiation at different times of the day. A marked reduction of S cell frequency was observed at early intervals after abdominal irradiation; this reduction was particularly evident in the lower half of the crypts. At subsequent intervals a progressive extension of the proliferative compartment, with labelled cells also at the top of the crypt, was present. The irradiated groups generally showed a homogeneous behaviour even if a more marked reduction in S-phase cells was observed in group C. The invertase activity, a brush border enzyme synthetized during the differentiation process, presented a different behaviour at the early intervals in the irradiated groups. When the extension of the proliferative compartment occurred the invertase activity reached values close to zero. The modifications in brush border enzymes and in S-phase cell distribution, at early killing times, led to the hypothesis of an early differentiation.

  19. Does highly symptomatic class membership in the acute phase predict highly symptomatic classification in victims 6 months after traumatic exposure?

    Science.gov (United States)

    Hansen, Maj; Hyland, Philip; Armour, Cherie

    2016-05-01

    Recently studies have indicated the existence of both posttraumatic stress disorder (PTSD) and acute stress disorder (ASD) subtypes but no studies have investigated their mutual association. Although ASD may not be a precursor of PTSD per se, there are potential benefits associated with early identification of victims at risk of developing PTSD subtypes. The present study investigates ASD and PTSD subtypes using latent class analysis (LCA) following bank robbery (N=371). Moreover, we assessed if highly symptomatic ASD and selected risk factors increased the probability of highly symptomatic PTSD. The results of LCA revealed a three class solution for ASD and a two class solution for PTSD. Negative cognitions about self (OR=1.08), neuroticism (OR=1.09) and membership of the 'High symptomatic ASD' class (OR=20.41) significantly increased the probability of 'symptomatic PTSD' class membership. Future studies are needed to investigate the existence of ASD and PTSD subtypes and their mutual relationship. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Difference in the Clinical Characteristics of Ventricular Fibrillation Occurrence in the Early Phase of an Acute Myocardial Infarction Between Patients With and Without J Waves.

    Science.gov (United States)

    Naruse, Yoshihisa; Nogami, Akihiko; Harimura, Yoshie; Ishibashi, Mayu; Noguchi, Yuichi; Sekiguchi, Yukio; Sato, Akira; Aonuma, Kazutaka

    2015-08-01

    We recently showed that the presence of J waves increases the risk of ventricular fibrillation (VF) occurrence in the early phase of an acute myocardial infarction (AMI). This study aimed to evaluate the clinical characteristics of VF occurrences in the early phase of an AMI between patients with and without J waves. This retrospective, observational study included 281 consecutive patients with an AMI (69 ± 12 years; 207 men) in whom 12-lead ECGs before AMI onset could be evaluated. The patients were classified based on a VF occurrence J waves. J waves were electrocardiographically defined as an elevation of the terminal portion of the QRS complex of >0.1 mV from baseline in at least 2 contiguous inferior or lateral leads. VF occurred in 24 patients, and J waves were present in 37. VF occurrence was more prevalent in the patients with than without J waves (27% vs. 6%; P J waves, peak creatine kinase level (P J waves, there was no significant difference in these variables. There was no association between the location of J waves and the infarct area. In patients with AMI, those with J waves were more likely to develop VF and less likely to have high-risk clinical characteristics than those without J waves. © 2015 Wiley Periodicals, Inc.

  1. Three-phase bone scintigraphy with Tc-99m MDP in the diagnosis and management of acute osteoarticular infections in children

    International Nuclear Information System (INIS)

    Coll C, Claudia; Cifras V, Jose Luis; Massardo V, Teresa; Moya S, Hernan

    2002-01-01

    One of the most important causes of residual damage in skeleton is incompletely treated osteoarticular infections (OAI). Goal: to assess the value of emergency three-phase bone scan (3FBS) in the evaluation of OAI. Methods: Thirty-eight children were studied with 54 3FBS. Results: Global analysis: 76% of the cases were principally articular; staphylococcus germs and hip's affection were the common. Nine patients with preoperative scan were positive with 16 foci, 86% confirmed by surgery cultivate. Seven children had negative 3FBS without posterior clinical symptomatology; in 5 of them it was demonstrated soft tissue involvement with normal osteoblastic phase. In 14/17 cases evaluated after surgical intervention, there was a relation between the scan and the clinical course. In two of those cases, in the 3FBS a new location was found. Conclusion: 3FBS is a helpful tool in the diagnosis and assessment of acute OAI in pediatric population. A positive 3FBS is highly accurate for OAI and a negative one rules it out securely (au)

  2. A phase 1/2 study of rigosertib in patients with myelodysplastic syndromes (MDS) and MDS progressed to acute myeloid leukemia.

    Science.gov (United States)

    Navada, Shyamala C; Fruchtman, Steven M; Odchimar-Reissig, Rosalie; Demakos, Erin P; Petrone, Michael E; Zbyszewski, Patrick S; Holland, James F; Silverman, Lewis R

    2018-01-01

    This Phase 1/2, dose-escalating study of rigosertib enrolled 22 patients with higher-risk myelodysplastic syndromes (MDS) (n=9) and acute myeloid leukemia (AML; n=13) who had relapsed or were refractory to standard therapy and for whom no second-line therapies were approved. Patients received 3- to 7-day continuous intravenous infusions of rigosertib, an inhibitor of Ras-effector pathways that interacts with the Ras-binding domains, common to several signaling proteins including Raf and PI3 kinase. Rigosertib was administered at doses of 650-1700mg/m 2 /day in 14-day cycles. Initial dose escalation followed a Fibonacci scheme, followed by recommended phase 2 dose confirmation in an expanded cohort. Rigosertib was well tolerated for up to 23 cycles, with no treatment-related deaths and 18% of patients with related serious adverse events (AEs). Common AEs were fatigue, diarrhea, pyrexia, dyspnea, insomnia, and anemia. Rigosertib exhibited biologic activity, with reduction or stabilization of bone marrow blasts and improved peripheral blood counts in a subset of patients. Ten of 19 evaluable patients (53%) demonstrated bone marrow/peripheral blood responses (n=4 MDS, n=1 AML) or stable disease (n=3 MDS, n=2 AML). Median survival was 15.7 and 2.0 months for responders and non-responders, respectively. Additional studies of rigosertib are ongoing in higher-risk MDS (NCT00854646). Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia.

    Science.gov (United States)

    Karp, Judith E; Vener, Tatiana I; Raponi, Mitch; Ritchie, Ellen K; Smith, B Douglas; Gore, Steven D; Morris, Lawrence E; Feldman, Eric J; Greer, Jacqueline M; Malek, Sami; Carraway, Hetty E; Ironside, Valerie; Galkin, Steven; Levis, Mark J; McDevitt, Michael A; Roboz, Gail R; Gocke, Christopher D; Derecho, Carlo; Palma, John; Wang, Yixin; Kaufmann, Scott H; Wright, John J; Garret-Mayer, Elizabeth

    2012-01-05

    Tipifarnib (T) exhibits modest activity in elderly adults with newly diagnosed acute myelogenous leukemia (AML). Based on preclinical synergy, a phase 1 trial of T plus etoposide (E) yielded 25% complete remission (CR). We selected 2 comparable dose levels for a randomized phase 2 trial in 84 adults (age range, 70-90 years; median, 76 years) who were not candidates for conventional chemotherapy. Arm A (T 600 mg twice a day × 14 days, E 100 mg days 1-3 and 8-10) and arm B (T 400 mg twice a day × 14 days, E 200 mg days 1-3 and 8-10) yielded similar CR, but arm B had greater toxicity. Total CR was 25%, day 30 death rate 7%. A 2-gene signature of high RASGRP1 and low aprataxin (APTX) expression previously predicted for T response. Assays using blasts from a subset of 40 patients treated with T plus E on this study showed that AMLs with a RASGRP1/APTX ratio of more than 5.2 had a 78% CR rate and negative predictive value 87%. This ratio did not correlate with outcome in 41 patients treated with conventional chemotherapies. The next T-based clinical trials will test the ability of the 2-gene signature to enrich for T responders prospectively. This study is registered at www.clinicaltrials.gov as #NCT00602771.

  4. Translational Phase I Trial of Vorinostat (Suberoylanilide Hydroxamic Acid) Combined with Cytarabine and Etoposide in Patients with Relapsed, Refractory, or High-Risk Acute Myeloid Leukemia

    Science.gov (United States)

    Gojo, Ivana; Tan, Ming; Fang, Hong-Bin; Sadowska, Mariola; Lapidus, Rena; Baer, Maria R.; Carrier, France; Beumer, Jan H.; Anyang, Bean N.; Srivastava, Rakesh K.; Espinoza-Delgado, Igor; Ross, Douglas D.

    2015-01-01

    Purpose To determine the maximum-tolerated dose (MTD) of the histone deacetylase inhibitor vorinostat combined with fixed doses of cytarabine (ara-C or cytosine arabinoside) and etoposide in patients with poor-risk or advanced acute leukemia, to obtain preliminary efficacy data, describe pharmacokinetics, and in vivo pharmacodynamic effects of vorinostat in leukemia blasts. Experimental Design In this open-label phase I study, vorinostat was given orally on days one to seven at three escalating dose levels: 200 mg twice a day, 200 mg three times a day, and 300 mg twice a day. On days 11 to 14, etoposide (100 mg/m2) and cytarabine (1 or 2 g/m2 twice a day if ≥65 or vorinostat 200 mg twice a day. Of 21 patients enrolled, seven attained a complete remission (CR) or CR with incomplete platelet recovery, including six of 13 patients treated at the MTD. The median remission duration was seven months. No differences in percentage S-phase cells or multidrug resistance transporter (MDR1 or BCRP) expression or function were observed in vivo in leukemia blasts upon vorinostat treatment. Conclusions Vorinostat 200 mg twice a day can be given safely for seven days before treatment with cytarabine and etoposide. The relatively high CR rate seen at the MTD in this poor-risk group of patients with AML warrants further studies to confirm these findings. PMID:23403629

  5. Malondialdehyde in early phase of acute pancreatitis Malondialdehído en la fase inicial de la pancreatitis aguda

    Directory of Open Access Journals (Sweden)

    Vicent Hernández

    2011-11-01

    Full Text Available Aims: to assess oxidative stress in acute pancreatitis, its evolution over time and its relationship with the severity of the disease. Methods: during a two-year period, patients with acute pancreatitis with less than 24 hours of pain were evaluated. Serum was obtained the first, second and fourth day from admittance, if complications were detected, and after recovery. Malondialdehyde was determined by high performance liquid chromatography. Twenty healthy volunteers constituted the control group. Malondialdehyde between groups was compared with Mann-Whitney and Kruskal-Wallis tests; malondialdehyde evolution was studied with Wilcoxon test. Results: one hundred and sixty-nine patients were included (91 women, median age 67 years, range 20-95; 33 suffered a severe episode. Malondialdehyde decreased from first to fourth day (0.600 vs. 0.451 vs. 0.343 μM, respectively, p 0.05. In severe attacks malondialdehyde was higher than in control group at day 2 (severe: 0.514; mild: 0.440; control: 0.347 μM, p Objetivos: valorar el estrés oxidativo en la pancreatitis aguda, su evolución a lo largo del tiempo y su relación con la gravedad de la enfermedad. Métodos: durante un periodo de dos años, se estudiaron los pacientes ingresados por pancreatitis aguda con dolor abdominal de menos de 24 horas de evolución. Se obtuvo suero de los pacientes el primer, segundo y cuarto día de ingreso, en el momento en que se detectaban complicaciones y tras la recuperación. La concentración de malondialdehído fue determinada utilizando cromatografía líquida de alta resolución. Veinte voluntarios sanos conformaron el grupo control. La concentración de malondialdehído entre los diferentes grupos se comparó utilizando el test de Mann-Whitney y el test de Kruskal-Wallis; la evolución de malondialdehído se valoró mediante el test de Wilcoxon. Resultados: se incluyeron 169 pacientes (91 mujeres, edad mediana 67 años, rango 20-95; 33 sufrieron un episodio

  6. The correlation between dysphagia and involvement of the ambiguous nucleus on MRI in acute-phase lateral medullary syndrome

    International Nuclear Information System (INIS)

    Kurono, Hiroko; Uesaka, Yoshikazu; Kunimoto, Masanari; Imafuku, Ichirou

    2006-01-01

    In this study, the clinical features and MRI findings of 21 patients admitted for acute lateral medullary syndrome, including 10 patients with dysphagia, were examined. According to Cytoarchitecture of the Human Brain Stem (Olszewski, J and Baxter, D), MRI-identified lesions were classified into four groups based on their location (upper, middle-upper, middle-lower, and lower parts of the medulla oblongata). We also examined whether each lesion involved the ambiguous nucleus (AN). We then studied the correlation between dysphagia and involvement of the AN. Ten patients had dysphagia, which improved very quickly in all but one. In the horizontal plane, lesions of all patients with dysphagia exhibited AN involvement, suggesting that dysphagia is strongly correlated with AN involvement. Among the 8 patients with lesions in the upper part of the medulla oblongata, the lesions of 7 patients included the AN, and 6 of those 7 patients had dysphagia. Among the 5 patients with lesions in the middle-upper part of the medulla oblongata, the lesions of two contained the AN, and one of those two patients had dysphagia. Among the 6 patients with lesions in the middle-lower part of the medulla oblongata, all lesions contained the AN, but only 3 of the patients exhibited dysphagia. In both patients who had lesions in the lower part of the medulla oblongata, the lesions did not include the AN and neither patient had dysphagia. Patients who had lesions involving the AN in the rostral part of the medulla oblongata were more likely to have dysphagia than the other patients. On the other hand, half of the patients with lesions involving the AN in the middle-lower part of the medulla oblongata did not have dysphagia. This might suggest that the caudal part of the AN has little involvement in the mechanisms of dysphagia. (author)

  7. A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics.

    Science.gov (United States)

    Jones, L A T; Lammertse, D P; Charlifue, S B; Kirshblum, S C; Apple, D F; Ragnarsson, K T; Poonian, D; Betz, R R; Knoller, N; Heary, R F; Choudhri, T F; Jenkins, A L; Falci, S P; Snyder, D A

    2010-11-01

    Post hoc analysis from a randomized controlled cellular therapy trial in acute, complete spinal cord injury (SCI). Description and quantitative review of study logistics, referral patterns, current practice patterns and subject demographics. Subjects were recruited to one of six international study centers. Data are presented from 1816 patients pre-screened, 75 participants screened and 50 randomized. Of the 1816 patients pre-screened, 53.7% did not meet initial study criteria, primarily due to an injury outside the time window (14 days) or failure to meet neurological criteria (complete SCI between C5 motor/C4 sensory and T11). MRIs were obtained on 339 patients; 51.0% were ineligible based on imaging criteria. Of the 75 participants enrolled, 25 failed screening (SF), leaving 50 randomized. The primary reason for SF was based on the neurological exam (51.9%), followed by failure to meet MRI criteria (22.2%). Of the 50 randomized subjects, there were no significant differences in demographics in the active versus control arms. In those participants for whom data was available, 93.8% (45 of 48) of randomized participants received steroids before study entry, whereas 94.0% (47 of 50) had spine surgery before study enrollment. The 'funnel effect' (large numbers of potentially eligible participants with a small number enrolled) impacts all trials, but was particularly challenging in this trial due to eligibility criteria and logistics. Data collected may provide information on current practice patterns and the issues encountered and addressed may facilitate design of future trials.

  8. The steroidogenic response and corpus luteum expression of the steroidogenic acute regulatory protein after human chorionic gonadotropin administration at different times in the human luteal phase.

    Science.gov (United States)

    Kohen, Paulina; Castro, Olga; Palomino, Alberto; Muñoz, Alex; Christenson, Lane K; Sierralta, Walter; Carvallo, Pilar; Strauss, Jerome F; Devoto, Luigi

    2003-07-01

    This study was designed 1) to assess corpus luteum (CL) steroidogenesis in response to exogenous human chorionic gonadotropin (hCG) at different times during the luteal phase, 2) to examine the effect of hCG on steroidogenic acute regulatory protein (StAR) expression within the CL, 3) to correlate StAR expression and luteal steroidogenic responses to hCG, and 4) to determine whether endogenous LH regulates ovarian steroidogenesis in the early luteal phase. Blood was collected before and after hCG treatment for steroid and hCGbeta determinations. CL were obtained at the time of surgery to assess StAR gene and protein expression. During the early luteal phase various women received the GnRH antagonist for 24-48 h; some of them also received hCG 24 h after the GnRH antagonist. A slight steroidogenic response to hCG was observed in early luteal phase; 17alpha-hydroxyprogesterone, but not progesterone (P4), levels were significantly increased 8 h post-hCG, indicating a differential response by the granulosa and theca-lutein cells. The 1.6- and 4.4-kb StAR transcripts and the 37-kDa preprotein and 30-kDa mature StAR protein did not change post-hCG administration in early luteal phase CL. In contrast, the StAR 4.4- and 1.6-kb transcripts diminished significantly (P < 0.05) after the antagonist treatment. Immunohistochemical staining for StAR protein was weak, particularly in granulosa-lutein cells. Treatment with hCG restored StAR mRNA and protein and plasma P4 levels within 24 h in antagonist-treated women. hCG stimulated the highest plasma concentrations of P4 and estradiol in the midluteal phase, indicating its greatest steroidogenic capacity. Midluteal tissue StAR gene and protein expression increased by 1.6- and 1.4-fold after 24 h of hCG treatment, respectively. Administration of hCG resulted in the greatest increment in plasma P4 (4-fold) and 17alpha-hydroxyprogesterone (3-fold) levels over baseline in the late luteal phase. This was associated with an increase in

  9. A prospective phase I/II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix - acute toxicity and biomarker response analysis

    International Nuclear Information System (INIS)

    Chan, P.; Doll, C.; Oza, A.; Pintilie, M.; Levin, W.; Manchul, L.; Fyles, A.; Milosevic, M.

    2003-01-01

    To evaluate the toxicity and biomarker response of celecoxib (C) as a biologic modifier in combination with definitive chemoradiotherapy (CRT) in women with cervix cancer. Fifteen cervix patients were entered into the first phase of this prospective study between March 2001 and January 2002. FIGO stages included IB(2), IIB(8), IIIB(4), and IVA(1), and median age was 51 years (range 26-62). Celecoxib 400mg orally was given b.i.d. 2 weeks prior to, and during the CRT. Toxicity assessments were performed weekly up to 12 weeks following treatment prior to further accrual using the NCIC-CTC. Hypoxia (HP5) and interstitial fluid pressure (IFP) assays were performed at day 0 and 14. Eleven patients completed the prescribed therapy. Only 2 of 4 patients discontinued C due to GI toxicity. In total there were 6 (40%) with grade 3/4 acute toxicity. Four were related to GI, one to skin reaction while the other was haematological. Although it was difficult to distinguish CRT toxicity from C, the proportion of patients with severe acute toxicity was similar to what we previously reported with CRT alone (8/24 (33%), Rodrigues, IJROBP 2001:Vol 51:(3): (Supp 1): 334). GI toxicity was more common in this study whereas haematologic effects were more frequent in the previous study. Evaluating the most recent measurable data set, 6 of 16 patients showed a decrease in HP5, (3.8 - 89.7%) while 10 of 14 patients had a reduction in IFP, (1.3 - 16.2mmHg). Two grade 4 late GI toxicity developed. Celecoxib is tolerated by patients receiving CRT for cervix cancer. Response of microenvironmental biomarkers to C was seen in the majority, suggesting a role as early markers of treatment outcome. Further follow-up is needed to assess the risk of late toxicity. The trial has been re-opened with C reduced to 300 mg b.i.d

  10. C-reactive protein and serum amyloid A as early-phase and prognostic indicators of acute radiation exposure in nonhuman primate total-body irradiation model

    Energy Technology Data Exchange (ETDEWEB)

    Ossetrova, N.I., E-mail: ossetrova@afrri.usuhs.mil [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bldg. 42, Bethesda, MD 20889-5603 (United States); Sandgren, D.J.; Blakely, W.F. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bldg. 42, Bethesda, MD 20889-5603 (United States)

    2011-09-15

    Terrorist radiological attacks or nuclear accidents could expose large numbers of people to ionizing radiation. In mass-casualty radiological incidents early medical-management requires triage tools for first-responders to quantitatively identify individuals exposed to life-threatening radiation doses and for early initiation (i.e., within one day after radiation exposure) of cytokine therapy for treatment of bone marrow acute radiation syndrome. Herein, we present results from 30 rhesus macaques total-body irradiated (TBI) to a broad dose range of 1-8.5 Gy with {sup 60}Co {gamma}-rays (0.55 Gy min{sup -1}) and demonstrate dose- and time-dependent changes in blood of C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) measured by enzyme linked immunosorbent assay (ELISA). CRP and SAA dose-response results are consistent with {approx}1 Gy and {approx}0.2 Gy thresholds for photon-exposure at 24 h after TBI, respectively. Highly significant elevations of CRP and SAA (p = 0.00017 and p = 0.0024, respectively) were found in animal plasma at 6 h after all TBI doses suggesting their potential use as early-phase biodosimeters. Results also show that the dynamics and content of CRP and SAA levels reflect the course and severity of the acute radiation sickness (ARS) and may function as prognostic indicators of ARS outcome. These results demonstrate proof-of-concept that these radiation-responsive proteins show promise as a complementary approach to conventional biodosimetry for early assessment of radiation exposures and may also contribute as diagnostic indices in the medical management of radiation accidents.

  11. Viral CTL escape mutants are generated in lymph nodes and subsequently become fixed in plasma and rectal mucosa during acute SIV infection of macaques.

    Directory of Open Access Journals (Sweden)

    Thomas H Vanderford

    2011-05-01

    Full Text Available SIV(mac239 infection of rhesus macaques (RMs results in AIDS despite the generation of a strong antiviral cytotoxic T lymphocyte (CTL response, possibly due to the emergence of viral escape mutants that prevent recognition of infected cells by CTLs. To determine the anatomic origin of these SIV mutants, we longitudinally assessed the presence of CTL escape variants in two MamuA*01-restricted immunodominant epitopes (Tat-SL8 and Gag-CM9 in the plasma, PBMCs, lymph nodes (LN, and rectal biopsies (RB of fifteen SIV(mac239-infected RMs. As expected, Gag-CM9 did not exhibit signs of escape before day 84 post infection. In contrast, Tat-SL8 escape mutants were apparent in all tissues by day 14 post infection. Interestingly LNs and plasma exhibited the highest level of escape at day 14 and day 28 post infection, respectively, with the rate of escape in the RB remaining lower throughout the acute infection. The possibility that CTL escape occurs in LNs before RBs is confirmed by the observation that the specific mutants found at high frequency in LNs at day 14 post infection became dominant at day 28 post infection in plasma, PBMC, and RB. Finally, the frequency of escape mutants in plasma at day 28 post infection correlated strongly with the level Tat-SL8-specific CD8 T cells in the LN and PBMC at day 14 post infection. These results indicate that LNs represent the primary source of CTL escape mutants during the acute phase of SIV(mac239 infection, suggesting that LNs are the main anatomic sites of virus replication and/or the tissues in which CTL pressure is most effective in selecting SIV escape variants.

  12. Leukocytosis in acute stroke

    DEFF Research Database (Denmark)

    Kammersgaard, L P; Jørgensen, H S; Nakayama, H

    1999-01-01

    Leukocytosis is a common finding in the acute phase of stroke. A detrimental effect of leukocytosis on stroke outcome has been suggested, and trials aiming at reducing the leukocyte response in acute stroke are currently being conducted. However, the influence of leukocytosis on stroke outcome has...

  13. Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Poulsen, Sarah S., E-mail: spo@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Saber, Anne T., E-mail: ats@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Mortensen, Alicja, E-mail: almo@food.dtu.dk [National Food Institute, Technical University of Denmark, Søborg (Denmark); Szarek, Józef, E-mail: szarek@uwm.edu.pl [Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn (Poland); Wu, Dongmei, E-mail: dongmei.wu@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Williams, Andrew, E-mail: andrew.williams@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Andersen, Ole, E-mail: oa@ruc.dk [Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Jacobsen, Nicklas R., E-mail: nrj@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Yauk, Carole L., E-mail: carole.yauk@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Wallin, Håkan, E-mail: hwa@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Public Health, University of Copenhagen, DK-1014 Copenhagen K (Denmark); Halappanavar, Sabina, E-mail: sabina.halappanavar@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Vogel, Ulla, E-mail: ubv@nrcwe.dk [National Research Centre for the Working Environment, DK-2100 Copenhagen (Denmark); Department of Micro- and Nanotechnology, Technical University of Denmark, DK-2800 Kgs. Lyngby (Denmark)

    2015-03-15

    Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of small, entangled (CNT{sub Small}, 0.8 ± 0.1 μm long) or large, thick MWCNTs (CNT{sub Large}, 4 ± 0.4 μm long). Liver tissues and plasma were harvested 1, 3 and 28 days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater response following CNT{sub Large} exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk of cardiovascular disease. - Highlights: • Systemic and hepatic alterations were evaluated in female mice following MWCNT instillation. • Despite being physicochemically

  14. Inhibition of post-traumatic septic proteolysis and ureagenesis and stimulation of hepatic acute-phase protein production by branched-chain amino acid TPN.

    Science.gov (United States)

    Chiarla, C; Siegel, J H; Kidd, S; Coleman, B; Mora, R; Tacchino, R; Placko, R; Gum, M; Wiles, C E; Belzberg, H

    1988-08-01

    Previous studies have shown that severe sepsis after major trauma results in the reprioritization of release of hepatic acute-phase proteins (APP). They suggest competition for leucine for nutritional utilization may be responsible. To test this hypothesis, a branched-chain enriched (46.6%) amino acid mixture (BCAA) was administered on a prospective randomized basis with standard TPN therapy to 16 septic post-trauma patients. After sepsis was diagnosed, a randomized therapy (control-TPN or BCAA-TPN) was given for 12 days, or until death occurred. Total calories and amino acid nitrogen (N) administered were not different in the two groups (t-test) and q 8 h (347 study periods) amino acid clearances, urinary urea nitrogen excretion, muscle proteolysis from 3-methyl-histidine (3-MH) excretion, and standard indices of sepsis severity and hepatic function were measured, as well as platelets (PLAT), leucocytes (WBC), albumin (ALB), and six acute-phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (A1TRIP), fibrinogen (FIBRIN), alpha-2-macroglobulin (AMACRO), ceruloplasmin (CERUL), and transferrin (TRANS). Using Scheffé analysis of all contrasts the data showed: BCAA resulted in a fall in 24-hour urea N excretion (24.0 to 20.0 gm/24 hr) and in proteolysis (138 to 126 gm/24 hr) (p less than 0.0001). Prestudy CRP levels were all elevated, but compared to control where APP reprioritization occurred, over the initial 10 days of therapy BCAA patients had a more rapid fall in CRP with a more rapid rise in FIBRIN, TRANS, CERUL, ALBUMIN, AMACRO, and A1TRIP (all p less than 0.0001) relative to CRP. Also, the sepsis-reduced clearances of glutamine and glutamate, alanine, and proline were increased (p less than 0.0001) during BCAA even though urea nitrogen production was reduced (p less than 0.0001). The increase in leucine clearance with BCAA-enriched TPN was positively correlated (r2 = 0.601; p less than 0.0001) with the increase in the sum of all APP and ALB and was

  15. Nicotine delivery efficiency of first- and second-generation e-cigarettes and its impact on relief of craving during the acute phase of use.

    Science.gov (United States)

    Rüther, Tobias; Hagedorn, Dieter; Schiela, Konstantin; Schettgen, Thomas; Osiander-Fuchs, Helga; Schober, Wolfgang

    2018-03-01

    Knowledge about the change in blood nicotine concentrations during the first five minutes (acute phase) of e-cigarette vaping is important to determine whether the used product has a dependence potential or may be an efficient nicotine replacement product. To address this issue, we monitored blood nicotine levels during the acute phase in volunteers using disposable cigalikes (CLs) and a tank model (TM) and compared them with blood nicotine levels in subjects using a tobacco cigarette (TC). In parallel, heart rate changes were continually measured and withdrawal symptoms and craving were assessed with the Questionnaire on Smoking Urges before and immediately after the vaping/smoking sessions. Additionally, at the end of each session negative health effects were rated on a visual analog scale. After five minutes of e-cigarette or TC use, the mean nicotine plasma concentrations were as follows: CLs, 5.5ng/ml; TM, 9.3ng/ml; TC, 17.1ng/ml. Nicotine levels increased significantly faster in the first 4min of consuming a TC than with the CLs and the TM. The highest rate of increase in nicotine concentration was found with the TC (6.8ng/ml) and TM (2.3ng/ml) between the 1st and 2nd minute, whereas the CLs showed comparatively small changes in the amount delivered over the five minutes. Withdrawal and craving for smoking decreased with the TM by the same amount as with the TC, even though less nicotine was delivered to the blood and considerably fewer side effects occurred. The heart rate of TM users was also markedly lower than that of the TC users. Unlike CLs, TM e-cigarettes represent an effective source of nicotine and might be used as an alternative nicotine replacement product to aid smoking cessation. However, nicotine plasma levels observed in TM users after short-time vaping have also the potential to produce and sustain nicotine addiction. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Dietary β-glucan stimulate complement and C-reactive protein acute phase responses in common carp (Cyprinus carpio) during an Aeromonas salmonicida infection.

    Science.gov (United States)

    Pionnier, Nicolas; Falco, Alberto; Miest, Joanna; Frost, Patrick; Irnazarow, Ilgiz; Shrive, Annette; Hoole, Dave

    2013-03-01

    The effect of β-glucans as feed additive on the profile of C-reactive protein (CRP) and complement acute phase responses was studied in common carp Cyprinus carpio after exposition to a bacterial infection with Aeromonas salmonicida. Carp were orally administered with β-glucan (MacroGard®) for 14 days with a daily β-glucan intake of 6 mg per kg body weight. Fish were then intraperitoneally injected with either PBS or 1 × 10⁸ bacteria per fish and sampled at time 0, 6, 12, 24, 48, 72, 96 and 120 h post-injection (p.i.) for serum and head kidney, liver and mid-gut tissues. CRP levels and complement activity were determined in the serum samples whilst the gene expression profiles of CRP and complement related genes (crp1, crp2, c1r/s, bf/c2, c3 and masp2) were analysed in the tissues by quantitative PCR. Results obtained showed that oral administration of β-glucan for 14 days significantly increased serum CRP levels up to 2 fold and serum alternative complement activity (ACP) up to 35 fold. The bacterial infection on its own (i.e. not combined with a β-glucan feeding) did have significant effects on complement response whilst CRP was not detectably induced during the carp acute phase reaction. However, the combination of the infection and the β-glucan feeding did show significant effects on both CRP and complement profiles with higher serum CRP levels and serum ACP activity in the β-glucan fed fish than in the control fed fish. In addition, a distinct organ and time dependent expression profile pattern was detected for all the selected genes: a peak of gene expression first occurred in the head kidney tissue (6 h p.i. or 12 h p.i.), then an up-regulation in the liver several hours later (24 h p.i.) and finally up- or down-regulations in the mid-gut at 24 h p.i. and 72 h p.i. In conclusion, the results of this study suggest that MacroGard® stimulated CRP and complement responses to A. salmonicida infection in common carp. Copyright © 2013 Elsevier Ltd. All

  17. Crystallization and preliminary X-ray crystallographic analysis of the rhesus macaque MHC class I molecule Mamu-B*17 complexed with an immunodominant SIVmac239 Env epitope

    International Nuclear Information System (INIS)

    Gao, Feng; Bao, Jinku

    2013-01-01

    A primitive monoclinic crystal of the rhesus macaque MHC class I molecule Mamu-B*17 complexed with an SIVmac239 Env peptide was obtained and belonged to space group P2, with unit-cell parameters a = 68.3, b = 45.0, c = 81.5 Å, β = 96.5°. The crystal diffracted to 2.55 Å resolution. Long-term nonprogression during simian immunodeficiency virus (SIV) infection has been strongly associated with the major histocompatibility complex (MHC) class I allele Mamu-B*17. Here, a complex of rhesus macaque Mamu-B*17 with rhesus macaque β 2 -microglobulin (β 2 m) and an immunodominant peptide (SIVmac239 Env241–251; LRCNDTNYSGF; Env LF11) derived from the SIV Env protein was crystallized by the hanging-drop method using PEG 3350 as a precipitating agent. The crystals belonged to the primitive monoclinic space group P2, with unit-cell parameters a = 68.3, b = 45.0, c = 81.5 Å, β = 96.5°. Assuming the presence of one molecule in the asymmetric unit, the Matthews coefficient and solvent content were calculated to be 2.96 Å 3 Da −1 and 58.5%, respectively

  18. Elimination of immunodominant epitopes from multispecific DNA-based vaccines allows induction of CD8 T cells that have a striking antiviral potential

    DEFF Research Database (Denmark)

    Riedl, Petra; Wieland, Andreas; Lamberth, Kasper

    2009-01-01

    Immunodominance limits the TCR diversity of specific antiviral CD8 T cell responses elicited by vaccination or infection. To prime multispecific T cell responses, we constructed DNA vaccines that coexpress chimeric, multidomain Ags (with CD8 T cell-defined epitopes of the hepatitis B virus (HBV...... cell immunity by multidomain Ags. The "weak" (i.e., easily suppressed) K(b)/C(93-100)-specific CD8 T cell response was efficiently elicited by a HBV core Ag-encoding vector in 1.4HBV-S(mut) tg mice (that harbor a replicating HBV genome that produces HBV surface, core, and precore Ag in the liver). K......(b)/C(93-100)-specific CD8 T cells accumulated in the liver of vaccinated 1.4HBV-S(mut) transgenic mice where they suppressed HBV replication. Subdominant epitopes in vaccines can hence prime specific CD8 T cell immunity in a tolerogenic milieu that delivers specific antiviral effects to HBV...

  19. Prediction and identification of potential immunodominant epitopes in glycoproteins B, C, E, G, and I of herpes simplex virus type 2.

    Science.gov (United States)

    Pan, Mingjie; Wang, Xingsheng; Liao, Jianmin; Yin, Dengke; Li, Suqin; Pan, Ying; Wang, Yao; Xie, Guangyan; Zhang, Shumin; Li, Yuexi

    2012-01-01

    Twenty B candidate epitopes of glycoproteins B (gB2), C (gC2), E (gE2), G (gG2), and I (gI2) of herpes simplex virus type 2 (HSV-2) were predicted using DNAstar, Biosun, and Antheprot methods combined with the polynomial method. Subsequently, the biological functions of the peptides were tested via experiments in vitro. Among the 20 epitope peptides, 17 could react with the antisera to the corresponding parent proteins in the EIA tests. In particular, five peptides, namely, gB2(466-473) (EQDRKPRN), gC2(216-223) (GRTDRPSA), gE2(483-491) (DPPERPDSP), gG2(572-579) (EPPDDDDS), and gI2(286-295) (CRRRYRRPRG) had strong reaction with the antisera. All conjugates of the five peptides with the carrier protein BSA could stimulate mice into producing antibodies. The antisera to these peptides reacted strongly with the corresponding parent glycoproteins during the Western Blot tests, and the peptides reacted strongly with the antibodies against the parent glycoproteins during the EIA tests. The antisera against the five peptides could neutralize HSV-2 infection in vitro, which has not been reported until now. These results suggest that the immunodominant epitopes screened using software algorithms may be used for virus diagnosis and vaccine design against HSV-2.

  20. Prediction and Identification of Potential Immunodominant Epitopes in Glycoproteins B, C, E, G, and I of Herpes Simplex Virus Type 2

    Directory of Open Access Journals (Sweden)

    Mingjie Pan

    2012-01-01

    Full Text Available Twenty B candidate epitopes of glycoproteins B (gB2, C (gC2, E (gE2, G (gG2, and I (gI2 of herpes simplex virus type 2 (HSV-2 were predicted using DNAstar, Biosun, and Antheprot methods combined with the polynomial method. Subsequently, the biological functions of the peptides were tested via experiments in vitro. Among the 20 epitope peptides, 17 could react with the antisera to the corresponding parent proteins in the EIA tests. In particular, five peptides, namely, gB2466–473 (EQDRKPRN, gC2216–223 (GRTDRPSA, gE2483–491 (DPPERPDSP, gG2572–579 (EPPDDDDS, and gI2286-295 (CRRRYRRPRG had strong reaction with the antisera. All conjugates of the five peptides with the carrier protein BSA could stimulate mice into producing antibodies. The antisera to these peptides reacted strongly with the corresponding parent glycoproteins during the Western Blot tests, and the peptides reacted strongly with the antibodies against the parent glycoproteins during the EIA tests. The antisera against the five peptides could neutralize HSV-2 infection in vitro, which has not been reported until now. These results suggest that the immunodominant epitopes screened using software algorithms may be used for virus diagnosis and vaccine design against HSV-2.

  1. Immune Response Induced by an Immunodominant 60 kDa Glycoprotein of the Cell Wall of Sporothrix schenckii in Two Mice Strains with Experimental Sporotrichosis

    Directory of Open Access Journals (Sweden)

    Carlos A. Alba-Fierro

    2016-01-01

    Full Text Available Cell wall (CW components of fungus Sporothrix schenckii are the major inductors antigens of immune responses. The immunodominant 60 kDa glycoprotein (gp60 has been shown to be associated with the virulence of this fungus but its role in experimental sporotrichosis is unknown. In this work, the immunological effects of CW-purified gp60 were investigated in a model of experimental subcutaneous sporotrichosis in normal and gp60-preimmunized C57BL/6 and BALB/c mice strains which were then infected with S. schenckii conidia. Results showed that both mice strains use different cytokine profiles in order to fight S. schenckii infection; C57BL/6 mice seem to use a Th17 response while BALB/c mice tend to depend on a Th1 profile. Preimmunization with gp60 showed a downregulatory effect on the immune response since cytokines levels were diminished in both strains. There were no significant differences in the magnitude of dorsoplantar inflammation between gp60-preimmunized and nonimmunized mice of both strains. However, skin lesions due to the infection in gp60-preimmunized mice were more severe in BALB/c than in C57BL/6 mice, suggesting that the antigen exerts a higher downregulatory effect on the Th1 response.

  2. Immune Response Induced by an Immunodominant 60 kDa Glycoprotein of the Cell Wall of Sporothrix schenckii in Two Mice Strains with Experimental Sporotrichosis.

    Science.gov (United States)

    Alba-Fierro, Carlos A; Pérez-Torres, Armando; Toriello, Conchita; Pulido-Camarillo, Evelyn; López-Romero, Everardo; Romo-Lozano, Yolanda; Gutiérrez-Sánchez, Gerardo; Ruiz-Baca, Estela

    2016-01-01

    Cell wall (CW) components of fungus Sporothrix schenckii are the major inductors antigens of immune responses. The immunodominant 60 kDa glycoprotein (gp60) has been shown to be associated with the virulence of this fungus but its role in experimental sporotrichosis is unknown. In this work, the immunological effects of CW-purified gp60 were investigated in a model of experimental subcutaneous sporotrichosis in normal and gp60-preimmunized C57BL/6 and BALB/c mice strains which were then infected with S. schenckii conidia. Results showed that both mice strains use different cytokine profiles in order to fight S. schenckii infection; C57BL/6 mice seem to use a Th17 response while BALB/c mice tend to depend on a Th1 profile. Preimmunization with gp60 showed a downregulatory effect on the immune response since cytokines levels were diminished in both strains. There were no significant differences in the magnitude of dorsoplantar inflammation between gp60-preimmunized and nonimmunized mice of both strains. However, skin lesions due to the infection in gp60-preimmunized mice were more severe in BALB/c than in C57BL/6 mice, suggesting that the antigen exerts a higher downregulatory effect on the Th1 response.

  3. Complex assembly, crystallization and preliminary X-ray crystallographic studies of rhesus macaque MHC Mamu-A*01 complexed with an immunodominant SIV-Gag nonapeptide

    International Nuclear Information System (INIS)

    Chu, Fuliang; Lou, Zhiyong; Gao, Bin; Bell, John I.; Rao, Zihe; Gao, George F.

    2005-01-01

    Crystallization of the first rhesus macaque MHC class I complex. Simian immunodeficiency virus (SIV) infection in rhesus macaques has been used as the best model for the study of human immunodeficiency virus (HIV) infection in humans, especially in the cytotoxic T-lymphocyte (CTL) response. However, the structure of rhesus macaque (or any other monkey model) major histocompatibility complex class I (MHC I) presenting a specific peptide (the ligand for CTL) has not yet been elucidated. Here, using in vitro refolding, the preparation of the complex of the rhesus macaque MHC I allele (Mamu-A*01) with human β 2 m and an immunodominant peptide, CTPYDINQM (Gag-CM9), derived from SIV Gag protein is reported. The complex (45 kDa) was crystallized; the crystal belongs to space group I422, with unit-cell parameters a = b = 183.8, c = 155.2 Å. The crystal contains two molecules in the asymmetric unit and diffracts X-rays to 2.8 Å resolution. The structure is being solved by molecular replacement and this is the first attempt to determined the crystal structure of a peptide–nonhuman primate MHC complex

  4. Identification of galactose as the immunodominant sugar of leishmanial excreted factor and subsequent labeling with galactose oxidase and sodium boro[3H]hydride.

    Science.gov (United States)

    Slutzky, G M; Greenblatt, C L

    1982-01-01

    Inhibition by low-molecular-weight sugars of precipitin line formation between a polysaccharide (EF) excreted by Leishmania tropica subsp. major, Leishmania enriettii, and rabbit antileishmanial antibodies on double gel diffusion plates revealed that galactose residues, possibly as components of lactosyl groups, were the critical immunodominant sugars mediating antibody recognition of EF. The galactose residues of the EF of L. tropica subsp. major were specifically labeled with tritium via galactose oxidase and sodium boro[3H]hydride. The radioactive EF had an apparent molecular weight of about 85,000 on sodium dodecyl sulfate-polyacrylamide gels and was precipitated by antileishmanial antibodies as well as Ricinus communis lectins I and II (galactose specific). Lectins specific for glucose-mannose residues, fucose, N-acetylglucosamine, and N-acetylgalactosamine did not precipitate the labeled EF. Treatment of [3H]EF with proteolytic (trypsin, papain, protease) or glycosidic (alpha-amylase, beta-galactosidase) enzymes had no effect on either the electrophoretic pattern of the material or on its recognition by antileishmanial antibodies or R. communis lectin. This resistance to enzyme activity suggests that EF may be a useful marker for the presence of the parasite in vivo if it can be detected in minute quantities. PMID:6179874

  5. The immunodominant influenza matrix t cell epitope recognized in human induces influenza protection in HLA-A2/Kb transgenic mice

    International Nuclear Information System (INIS)

    Plotnicky, H.; Cyblat-Chanal, D.; Aubry, J.-P.; Derouet, F.; Klinguer-Hamour, C.; Beck, A.; Bonnefoy, J.-Y.; Corvaiea, N.

    2003-01-01

    The protective efficacy of the influenza matrix protein epitope 58-66 (called M1), recognized in the context of human HLA-A2 molecules, was evaluated in a HLA-A2/K b transgenic mouse model of lethal influenza infection. Repeated subcutaneous immunizations with M1 increased the percentage of survival. This effect was mediated by T cells since protection was abolished following in vivo depletion of all T lymphocytes, CD8 + , or CD4 + T cells. The survival correlated with the detection of memory CD8 + splenocytes able to proliferate in vitro upon stimulation with M1 and to bind M1-loaded HLA-A2 dimers, as well as with M1-specific T cells in the lungs, which were directly cytotoxic to influenza-infected cells following influenza challenge. These results demonstrated for the first time that HLA-A2-restricted cytotoxic T cells specific for the major immunodominant influenza matrix epitope are protective against the infection. They encourage further in vivo evaluation of T cell epitopes recognized in the context of human MHC molecules

  6. Presence of the acute phase protein, bikunin, in the endometrium of gilts during estrous cycle and early pregnancy.

    Science.gov (United States)

    Hettinger, A M; Allen, M R; Zhang, B R; Goad, D W; Malayer, J R; Geisert, R D

    2001-08-01

    Noninvasive, epitheliochorial placental attachment in the pig is regulated through endometrial production of protease inhibitors. The objective of the present study was to determine if the light-chain serine protease inhibitor of the inter-alpha-trypsin inhibitor family, bikunin, is produced by the porcine endometrium during the estrous cycle and early pregnancy. Western blot analysis revealed the presence of bikunin in uterine flushings of gilts collected during the luteal phase of the estrous cycle and early pregnancy (Days 12-18). However, bikunin unbound to the inter-alpha-trypsin heavy chains was detected only in endometrial explant culture medium obtained from estrus and pregnant (Days 12, 15, and 18) gilts. Endometrial bikunin gene expression was lowest on Day 10 of the estrous cycle and pregnancy, followed by a 30- to 77-fold increase on Day 15 of the estrous cycle and pregnancy. Bikunin gene expression decreased on Day 18 of the estrous cycle, whereas endometrial bikunin gene expression continued to increase in pregnant gilts. Bikunin mRNA was localized to the uterine glands between Days 15 and 18 of the estrous cycle and pregnancy. In addition to its role as a protease inhibitor, bikunin functions in stabilization of the extracellular matrix, which suggests that bikunin could be involved with facilitating placental attachment to the uterine epithelial surface in the pig.

  7. Single-portal-phase low-tube-voltage dual-energy CT for short-term follow-up of acute pancreatitis: evaluation of CT severity index, interobserver agreement and radiation dose

    Energy Technology Data Exchange (ETDEWEB)

    Wichmann, Julian L. [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany); Universitaetsklinikum Frankfurt, Institut fuer Diagnostische und Interventionelle Radiologie, Frankfurt am Main (Germany); Majenka, Pawel; Beeres, Martin; Kromen, Wolfgang; Schulz, Boris; Bauer, Ralf W.; Kerl, J.M.; Gruber-Rouh, Tatjana; Hammerstingl, Renate; Vogl, Thomas J.; Lehnert, Thomas [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany); Wesarg, Stefan [Fraunhofer IGD, Cognitive Computing and Medical Imaging, Darmstadt (Germany)

    2014-11-15

    To intra-individually compare single-portal-phase low-tube-voltage (100-kVp) computed tomography (CT) with 120-kVp images for short-term follow-up assessment of CT severity index (CTSI) of acute pancreatitis, interobserver agreement and radiation dose. We retrospectively analysed 66 patients with acute pancreatitis who underwent initial dual-contrast-phase CT (unenhanced, arterial, portal phase) at admission and short-term (mean interval 11.4 days) follow-up dual-contrast-phase dual-energy CT. The 100-kVp and linearly blended images representing 120-kVp acquisition follow-up CT images were independently evaluated by three radiologists using a modified CTSI assessing pancreatic inflammation, necrosis and extrapancreatic complications. Scores were compared with paired t test and interobserver agreement was evaluated using intraclass correlation coefficients (ICC). Mean CTSI scores on unenhanced, portal- and dual-contrast-phase images were 4.9, 6.1 and 6.2 (120 kVp) and 5.0, 6.0 and 6.1 (100 kVp), respectively. Contrast-enhanced series showed a higher CTSI compared to unenhanced images (P < 0.05) but no significant differences between single- and dual-contrast-phase series (P > 0.7). CTSI scores were comparable for 100-kVp and 120-kVp images (P > 0.05). Interobserver agreement was substantial for all evaluated series and subcategories (ICC 0.67-0.93). DLP of single-portal-phase 100-kVp images was reduced by 41 % compared to 120-kVp images (363.8 versus 615.9 mGy cm). Low-tube-voltage single-phase 100-kVp CT provides sufficient information for follow-up evaluation of acute pancreatitis and significantly reduces radiation exposure. (orig.)

  8. A Phase I Study of CPI-613 in Combination with High-Dose Cytarabine and Mitoxantrone for Relapsed or Refractory Acute Myeloid Leukemia.

    Science.gov (United States)

    Pardee, Timothy S; Anderson, Rebecca G; Pladna, Kristin M; Isom, Scott; Ghiraldeli, Lais P; Miller, Lance D; Chou, Jeff W; Jin, Guangxu; Zhang, Wei; Ellis, Leslie R; Berenzon, Dmitriy; Howard, Dianna S; Hurd, David D; Manuel, Megan; Dralle, Sarah; Lyerly, Susan; Powell, Bayard L

    2018-05-01

    Purpose: CPI-613, a lipoate analogue that inhibits pyruvate dehydrogenase (PDH) and α-ketogluterate dehydrogenase (KGDH), has activity in patients with myeloid malignancies. This study explored the role of mitochondrial metabolism in chemotherapy response and determined the MTD, efficacy, and safety of CPI-613 combined with high-dose cytarabine and mitoxantrone in patients with relapsed or refractory acute myeloid leukemia. Experimental Design: The role of mitochondrial response to chemotherapy was assessed in cell lines and animal models. A phase I study of CPI-613 plus cytarabine and mitoxantrone was conducted in patients with relapsed or refractory AML. Results: Exposure to chemotherapy induced mitochondrial oxygen consumption that depended on PDH. CPI-613 sensitized AML cells to chemotherapy indicating that mitochondrial metabolism is a source of resistance. Loss of p53 did not alter response to CPI-613. The phase I study enrolled 67 patients and 62 were evaluable for response. The overall response rate was 50% (26CR+5CRi/62). Median survival was 6.7 months. In patients over 60 years old, the CR/CRi rate was 47% (15/32) with a median survival of 6.9 months. The response rate for patients with poor-risk cytogenetics also was encouraging with 46% (11/24 patients) achieving a CR or CRi. RNA sequencing analysis of a subset of baseline bone marrow samples revealed a gene expression signature consistent with the presence of B cells in the pretreatment marrow of responders. Conclusions: The addition of CPI-613 to chemotherapy is a promising approach in older patients and those with poor-risk cytogenetics. Clin Cancer Res; 24(9); 2060-73. ©2018 AACR . ©2018 American Association for Cancer Research.

  9. The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

    International Nuclear Information System (INIS)

    Vuong, Te; Waschke, Kevin; Niazi, Tamim; Richard, Carole; Parent, Josee; Liberman, Sender; Mayrand, Serge; Loungnarath, Rasmy; Stein, Barry; Devic, Slobodan

    2011-01-01

    Purpose: Acute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT). Methods and Materials: Fifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receive the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT. Results: At the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078). Conclusions: This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results.

  10. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study.

    Science.gov (United States)

    Ravandi, Farhad; Ritchie, Ellen K; Sayar, Hamid; Lancet, Jeffrey E; Craig, Michael D; Vey, Norbert; Strickland, Stephen A; Schiller, Gary J; Jabbour, Elias; Erba, Harry P; Pigneux, Arnaud; Horst, Heinz-August; Recher, Christian; Klimek, Virginia M; Cortes, Jorge; Roboz, Gail J; Odenike, Olatoyosi; Thomas, Xavier; Havelange, Violaine; Maertens, Johan; Derigs, Hans-Günter; Heuser, Michael; Damon, Lloyd; Powell, Bayard L; Gaidano, Gianluca; Carella, Angelo-Michele; Wei, Andrew; Hogge, Donna; Craig, Adam R; Fox, Judith A; Ward, Renee; Smith, Jennifer A; Acton, Gary; Mehta, Cyrus; Stuart, Robert K; Kantarjian, Hagop M

    2015-09-01

    Safe and effective treatments are urgently needed for patients with relapsed or refractory acute myeloid leukaemia. We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed or refractory acute myeloid leukaemia. This phase 3, double-blind, placebo-controlled trial was undertaken at 101 international sites. Eligible patients with acute myeloid leukaemia were aged 18 years of age or older and had refractory disease or were in first relapse after one or two cycles of previous induction chemotherapy, including at least one cycle of anthracycline (or anthracenedione) plus cytarabine. Patients were randomly assigned 1:1 to vosaroxin (90 mg/m(2) intravenously on days 1 and 4 in a first cycle; 70 mg/m(2) in subsequent cycles) plus cytarabine (1 g/m(2) intravenously on days 1-5) or placebo plus cytarabine through a central interactive voice system with a permuted block procedure stratified by disease status, age, and geographical location. All participants were masked to treatment assignment. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day and 60-day all-cause mortality. Efficacy analyses were done by intention to treat; safety analyses included all treated patients. This study is registered with ClinicalTrials.gov, number NCT01191801. Between Dec 17, 2010, and Sept 25, 2013, 711 patients were randomly assigned to vosaroxin plus cytarabine (n=356) or placebo plus cytarabine (n=355). At the final analysis, median overall survival was 7·5 months (95% CI 6·4-8·5) in the vosaroxin plus cytarabine group and 6·1 months (5·2-7·1) in the placebo plus cytarabine group (hazard ratio 0·87, 95% CI 0·73-1·02; unstratified log-rank p=0·061; stratified p=0·024). A higher proportion of patients achieved complete remission in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group (107 [30%] of 356 patients vs 58 [16%] of 355

  11. A study of acute phase and transport protein synthesis in undernourished men using simulated infection and uniformly 15N-labelled Spirulina Platenses

    International Nuclear Information System (INIS)

    Kurpad, A.V.; Soares, M.J.; Sekhar, R.V.; Reeds, P.J.; Fjeld, C.R.

    1994-01-01

    This study was conducted to test the hypothesis that acute phase protein synthesis is accelerated and transport protein synthesis is decelerated in adult men in whom the stress of infection is superimposed upon undernutrition. As a pilot study, four chronically undernourished men and two well-nourished controls were studied on two occasions separated by four days; the second session was conducted 24 hours after the administration of typhoid vaccine. Basal urine and blood samples were collected and then subjects were given priming oral doses of 15 N-Spirulina (13.5mg/kg body weight) and oral doses (3.5mg/kg body weight) every 30 min for the next six hours. Meals were aliquoted during the dosing period. Blood samples were collected at four, five and six hours. 15 N enrichment in different fractions of plasma i.e., albumin, non-albumin and amino acids, was measured by combustion GC-IRMS. Total urinary nitrogen was measured by Kjeldahl. 5 refs, 2 figs, 3 tabs

  12. Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial.

    Science.gov (United States)

    Brune, Mats; Castaigne, Sylvie; Catalano, John; Gehlsen, Kurt; Ho, Anthony D; Hofmann, Wolf-Karsten; Hogge, Donna E; Nilsson, Bo; Or, Reuven; Romero, Ana I; Rowe, Jacob M; Simonsson, Bengt; Spearing, Ruth; Stadtmauer, Edward A; Szer, Jeff; Wallhult, Elisabeth; Hellstrand, Kristoffer

    2006-07-01

    The primary objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.5 mg); both compounds were administered by subcutaneous injection twice daily. Study arms were balanced for age, sex, previous treatment, leukemic karyotypes, time from CR to inclusion, and frequency of secondary leukemia. Three years after enrollment of the last patient, treatment with HDC/IL-2 was found to improve LFS over control in the study population (CR1 + CR > 1, n = 320; P < .01, log-rank test). For patients in CR1 (n = 261), treatment significantly improved LFS (P = .01) with 3-year LFS estimates of 40% (HDC/IL-2) compared with 26% (control). Side effects were typically mild to moderate. These results indicate that HDC/IL-2 treatment offers an efficacious and tolerable treatment for patients with AML in remission.

  13. Facilitated beam-walking recovery during acute phase by kynurenic acid treatment in a rat model of photochemically induced thrombosis causing focal cerebral ischemia.

    Science.gov (United States)

    Abo, Masahiro; Yamauchi, Hideki; Suzuki, Masahiko; Sakuma, Mio; Urashima, Mitsuyoshi

    We previously demonstrated the presence of activated areas in the non-injured contralateral sensorimotor cortex in addition to the ipsilateral sensorimotor cortex of the area surrounding a brain infarction, using a rat model of focal photochemically induced thrombosis (PIT) and functional magnetic resonance imaging. Using this model, we next applied gene expression profiling to screen key molecules upregulated in the activated area. RNA was extracted from the ipsilateral and contralateral sensorimotor cortex to the focal brain infarction and from the sham controlled cortex, and hybridized to gene-expression profiling arrays containing 1,322 neurology-related genes. Results showed that glycine receptors were upregulated in both the ipsilateral and contralateral cortex to the focal ischemic lesion. To prove the preclinical significance of upregulated glycine receptors, kynurenic acid, an endogenous antagonist to glycine receptors on neuronal cells, was administered intrathecally. As a result, the kynurenic acid significantly improved behavioral recovery within 10 days from paralysis induced by the focal PIT (p beam walking. These results suggest that intrathecal administration of a glycine receptor antagonist may facilitate behavioral recovery during the acute phase after brain infarction. Copyright (c) 2006 S. Karger AG, Basel.

  14. Acute-phase proteins investigation based on lectins affinity capture prior to 2-DE separation: application to serum from multiple sclerosis patients.

    Science.gov (United States)

    Robotti, Andrea; Natale, Massimo; Albo, Alessandra Giuliano; Lis, Katarzyna; Perga, Simona; Marnetto, Fabiana; Gilli, Francesca; Bertolotto, Antonio

    2010-09-01

    Plasma acute-phase proteins (APPs) glyco-isoforms are important biomarkers of inflammatory processes such as those occurring in multiple sclerosis (MS). Specific analysis of these proteins is often hampered by sample biochemical complexity. The aim of our study was to set up a method to accurately visualize, identify and quantify APPs glyco-isoforms in human serum. An enrichment strategy based on affinity chromatography using the carbohydrate-binding proteins concanavalin A (ConA) and erythrina cristagalli lectin (ECL) was applied to pooled serum samples from 15 patients and 9 healthy individuals. Image analysis of 2-DE detected 30 spots with a fold change higher than 1.5. A total of 14 were statistically significant (p valuewell known. Performing galectin-3 binding and Western blotting, we were able to demonstrate a correlation between hybrid type glyco-isoforms of β-haptoglobin and MS. In conclusion, although the patho-physiological role of the identified species still remains unclear and further validations are needed, these findings may have a relevant impact on disease-specific marker identification approaches.

  15. Platelet reactivity in the early and late phases of acute coronary syndromes according to cytochrome P450 2C19 phenotypes.

    Science.gov (United States)

    Nagashima, Zenko; Tsukahara, Kengo; Morita, Satoshi; Endo, Tsutomu; Sugano, Teruyasu; Hibi, Kiyoshi; Himeno, Hideo; Fukui, Kazuki; Umemura, Satoshi; Kimura, Kazuo

    2013-09-01

    It remains unknown whether the time course of the antiplatelet effects of clopidogrel differs according to cytochrome P450 (CYP) 2C19 phenotype in Japanese patients with acute coronary syndromes (ACS). Platelet reactivity was serially assessed by VerifyNow-P2Y12 assay (Accumetrics, San Diego, CA, USA). Results were expressed as P2Y12-reaction-units (PRU) in 177 patients with ACS who underwent stent implantation and received aspirin plus a 300-mg loading dose of clopidogrel followed by 75 mg/day. High on-clopidogrel treatment platelet reactivity (HTPR) was defined as PRU>235. On the basis of the CYP2C19*2 and *3 alleles, 46 patients (26.0%) were classified as extensive metabolizers (EM), 103 (58.2%) as intermediate metabolizers (IM), and 28 (15.8%) as poor metabolizers (PM). At fashion (168±99 vs. 213±77 vs. 278±69, pJapanese patients with ACS carried CYP2C19 variant alleles. The majority of IM and PM had increased platelet reactivity during the early phase of ACS. Although HTPR was frequently observed even 14-28 days after standard maintenance doses of clopidogrel in PM, the incidence of adverse outcomes did not differ, irrespective of CYP2C19 genotype. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  16. Effects of preoperative feeding with a whey protein plus carbohydrate drink on the acute phase response and insulin resistance. A randomized trial

    Directory of Open Access Journals (Sweden)

    Dock-Nascimento Diana B

    2011-06-01

    Full Text Available Abstract Background Prolonged preoperative fasting increases insulin resistance and current evidence recommends carbohydrate (CHO drinks 2 hours before surgery. Our hypothesis is that the addition of whey protein to a CHO-based drink not only reduces the inflammatory response but also diminish insulin resistance. Methods Seventeen patients scheduled to cholecystectomy or inguinal herniorraphy were randomized and given 474 ml and 237 ml of water (CO group or a drink containing CHO and milk whey protein (CHO-P group respectively, 6 and 3 hours before operation. Blood samples were collected before surgery and 24 hours afterwards for biochemical assays. The endpoints of the study were the insulin resistance (IR, the prognostic inflammatory and nutritional index (PINI and the C-reactive protein (CRP/albumin ratio. A 5% level for significance was established. Results There were no anesthetic or postoperative complications. The post-operative IR was lower in the CHO-P group when compared with the CO group (2.75 ± 0.72 vs 5.74 ± 1.16; p = 0.03. There was no difference between the two groups in relation to the PINI. The CHO-P group showed a decrease in the both CRP elevation and CRP/albumin ratio (p Conclusions Shortening the pre-operative fasting using CHO and whey protein is safe and reduces insulin resistance and postoperative acute phase response in elective moderate operations. Trial registration ClinicalTrail.gov NCT01354249

  17. Production of thyrotropin receptor antibodies in acute phase of infectious mononucleosis due to Epstein-Barr virus primary infection: a case report of a child.

    Science.gov (United States)

    Nagata, Keiko; Okuno, Keisuke; Ochi, Marika; Kumata, Keisuke; Sano, Hitoshi; Yoneda, Naohiro; Ueyama, Jun-Ichi; Matsushita, Michiko; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Kanzaki, Susumu; Hayashi, Kazuhiko

    2015-01-01

    Various autoantibodies have been reported to be detected during the progression of infectious mononucleosis. We observed a case of infectious mononucleosis due to Epstein-Barr virus primary infection for 2 months, and noticed the transiently increased titer of thyrotropin receptor autoantibodies detected at the acute phase on the 3rd day after admission. At that time, real-time quantitative PCR also revealed the mRNA expressions of an immediate early lytic gene, BZLF1, and a latent gene, EBNA2. The expression of BZLF1 mRNA means that Epstein-Barr virus infects lytically, and EBNA2 protein has an important role in antibody production as well as the establishment of Epstein-Barr virus latency. These results suggest that Epstein-Barr virus lytic infection is relevant to thyrotropin receptor autoantibody production. Thyrotropin receptor autoantibodies stimulate thyroid follicular cells to produce excessive thyroid hormones and cause Graves' disease. Recently, we reported the thyrotropin receptor autoantibody production from thyrotropin receptor autoantibody-predisposed Epstein-Barr virus-infected B cells by the induction of Epstein-Barr virus lytic infection in vitro. This case showed in vivo findings consistent with our previous reports, and is important to consider the pathophysiology of Graves' disease and one of the mechanisms of autoimmunity.

  18. Metabolic Cost of the Activation of Immune Response in the Fish-Eating Myotis (Myotis vivesi: The Effects of Inflammation and the Acute Phase Response.

    Directory of Open Access Journals (Sweden)

    Aída Otálora-Ardila

    Full Text Available Inflammation and activation of the acute phase response (APR are energetically demanding processes that protect against pathogens. Phytohaemagglutinin (PHA and lipopolysaccharide (LPS are antigens commonly used to stimulate inflammation and the APR, respectively. We tested the hypothesis that the APR after an LPS challenge was energetically more costly than the inflammatory response after a PHA challenge in the fish-eating Myotis bat (Myotis vivesi. We measured resting metabolic rate (RMR after bats were administered PHA and LPS. We also measured skin temperature (Tskin after the LPS challenge and skin swelling after the PHA challenge. Injection of PHA elicited swelling that lasted for several days but changes in RMR and body mass were not significant. LPS injection produced a significant increase in Tskin and in RMR, and significant body mass loss. RMR after LPS injection increased by 140-185% and the total cost of the response was 6.50 kJ. Inflammation was an energetically low-cost process but the APR entailed a significant energetic investment. Examination of APR in other bats suggests that the way in which bats deal with infections might not be uniform.

  19. Voxel-by-voxel analysis of ECD-brain SPECT can separate penumbra from irreversibly damaged tissue at the acute phase of stroke

    International Nuclear Information System (INIS)

    Darcourt, J.; Migneco, O.; David, O.; Bussiere, F.; Mahagne, M.H.; Dunac, A.; Baron, J.C.

    2002-01-01

    Aim. At the acute phase of ischemic stroke, the target of treatment is still salvageable hypoperfused cerebral tissue; so called penumbra. We tested the possibility of separating on early ECD brain SPECT penumbral voxels (P) from irreversibly damaged damaged tissue (IDT). We used ECD which is not only a perfusion tracer but also a metabolic marker. Materials and methods. We prospectively studied 18 patients who underwent ECD-SPECT within the 12 hours following a first-ever acute middle cerebral artery stroke. Neurological evaluation was performed using the Orgogozo's scale at admission and 3 months later in order to calculate and evolution index (IE%) (Martinez-Vila et al.). SPECT data were obtained using a triple head camera equipped with fan beam collimators one hour after injection of 1000 MBq of 99mTc-ECD. On reconstructed images gray matter voxels were automatically segmented. Contralateral healthy hemisphere was used as reference leading to the identification of 3 cortical voxel types: normal (N-SPECT) above 80%; penumbra (P-SPECT) between 80% and 40% and IDT (IDT-SPECT) below 40%. 10 patients also underwent a T2 weighted 3D MRI study at 3 months. Cortical voxels with hypersignal served as reference for IDT (IDT-MRI) the others were considered normal (N-MRI). SPECT and MRI data were co-registered. Therefore each voxel belonged to one of 6 categories (3 SPECT x 2 MRI). Results. (1) The SPECT thresholds were validated on the MRI subgroup. 99% of the N-SPECT voxels were normal on late MRI. 84% of IDT-SPECT voxels corresponded to IDT-MRI. 89% of P-SPECT voxels were normal on late MRI and 11% corresponded to IDT on late MRI. Other categories of voxels (N-SPECT IDT-MRI and IDT-SPECT N-MRI) represented less than 5%. (2) Percentages of each voxel SPECT type was correlated with the EI% on the entire population (Spearman test). P-SPECT extent correlated with EI% improvement (p<0.001) and IDT-SPECT with EI% worsening (p<0.001). Conclusion. Analysis of ECD cortical

  20. Safety and efficacy of uric acid in patients with acute stroke (URICO-ICTUS): a randomised, double-blind phase 2b/3 trial.

    Science.gov (United States)

    Chamorro, Angel; Amaro, Sergio; Castellanos, Mar; Segura, Tomás; Arenillas, Juan; Martí-Fábregas, Joan; Gállego, Jaime; Krupinski, Jurek; Gomis, Meritxell; Cánovas, David; Carné, Xavier; Deulofeu, Ramón; Román, Luis San; Oleaga, Laura; Torres, Ferran; Planas, Anna M

    2014-05-01

    Uric acid is an antioxidant with neuroprotective effects in experimental models of stroke. We assessed whether uric acid therapy would improve functional outcomes at 90 days in patients with acute ischaemic stroke. URICO-ICTUS was a randomised, double-blind, placebo-controlled, phase 2b/3 trial that recruited patients with acute ischaemic stroke admitted to ten Spanish stroke centres. Patients were included if they were aged 18 years or older, had received alteplase within 4·5 h of symptom onset, and had an eligible National Institutes of Health Stroke Scale (NIHSS) score (>6 and ≤25) and premorbid (assessed by anamnesis) modified Rankin Scale (mRS) score (≤2). Patients were randomly allocated (1:1) to receive uric acid 1000 mg or placebo (both infused intravenously in 90 min during the infusion of alteplase), stratified by centre and baseline stroke severity. The primary outcome was the proportion of patients with excellent outcome (ie, an mRS score of 0-1, or 2 if premorbid score was 2) at 90 days, analysed in the target population (all randomly assigned patients who had been correctly diagnosed with ischaemic stroke and had begun study medication). The study is registered with ClinicalTrials.gov, number NCT00860366. Between July 1, 2011, and April 30, 2013, we randomly assigned 421 patients, of whom 411 (98%) were included in the target population (211 received uric acid and 200 received placebo). 83 (39%) patients who received uric acid and 66 (33%) patients who received placebo had an excellent outcome (adjusted risk ratio 1·23 [95% CI 0·96-1·56]; p=0·099). No clinically relevant or statistically significant differences were reported between groups with respect to death (28 [13%] patients who received uric acid vs 31 [16%] who received placebo), symptomatic intracerebral haemorrhage (nine [4%] vs six [3%]), and gouty arthritis (one [<1%] vs four [2%]). 516 adverse events occurred in the uric acid group and 532 in the placebo group, of which 61 (12

  1. Impact of post operative intensity modulated radiotherapy on acute gastro-intestinal toxicity for patients with endometrial cancer: Results of the phase II RTCMIENDOMETRE French multicentre trial

    International Nuclear Information System (INIS)

    Barillot, Isabelle; Tavernier, Elsa; Peignaux, Karine; Williaume, Danièle; Nickers, Philippe; Leblanc-Onfroy, Magali; Lerouge, Delphine

    2014-01-01

    Purpose/objective: Whole “conventional” pelvic irradiation (up to 45–50 Gy) following hysterectomy is associated with a high rate of adverse gastro-intestinal (GI) adverse events, of which around 60% correspond to acute grade 2 toxicity. The phase II RTCMIENDOMETRE trial was designed to test the hypothesis that IMRT could reduce the incidence of grade 2 or more acute GI toxicity to less than 30% in patients irradiated post-operatively for an endometrial cancer. Materials/methods: Patients with post-operative stage Ib G3, Ic or II endometrial carcinomas with no history of chronic inflammatory bowel disease were eligible. Guidelines for volume delineation and dose prescription were detailed in the protocol. The investigators were advised to use a web-based atlas developed for the RTOG 0418 study. The dose of the vaginal and nodal PTV was 45 Gy in 25 fractions. To assess the ability of the participating centres to comply with the protocol guidelines, they were requested to complete a dummy run procedure before inclusion of their 1st patient. GI and genito-urinary (GU) toxicity were graded according to the CTCAE V 3.0 classification and were prospectively recorded every week during irradiation, as well as at time of brachytherapy insertions and during the follow-up visit at week 15 (W15). Special attention was given to note any changes to the grade of adverse events between W5 and W15. Results: From May 2008 to April 2010, 49 patients from 6 centres were recruited for the trial. One patient could not be treated, one patient died of vascular stroke at W3 without toxicity, and 1 patient refused to be followed-up after treatment. Thus, 46 cases were available for analysis at W15. The distribution by stage was as follows: Ib 16.3%, Ic 64.2%, II 20.4%. Thirty six patients (75%) received an additional vaginal vault boost of 6–10 Gy delivered by HDR brachytherapy in 1 or 2 fractions. Among the 47 patients who completed IMRT, 27% (95% CI 14.5–39.7%) developed at

  2. Effect of a prostaglandin - given rectally for prevention of radiation-induced acute proctitis - on late rectal toxicity. Results of phase III randomized, placebo-controlled, double-blind study

    International Nuclear Information System (INIS)

    Kertesz, Tereza; Herrmann, Markus K.A.; Christiansen, Hans; Hermann, Robert M.; Hess, Clemens F.; Hille, Andrea; Zapf, Antonia; Pradier, Olivier; Schmidberger, Heinz

    2009-01-01

    Background and purpose: to assess the late effect of a prostaglandin, given rectally during irradiation, on late rectal toxicity. In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol, however, significantly more rectal bleeding had been reported. Patients and methods: a total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale. Results: the median follow-up was 50 months. 20 patients suffered from grade 1, four patients from grade 2 as well, and three patients only from grade 2 toxicity. Frequency, bleeding and urgency were the most commonly reported symptoms. In keeping with other studies and clinical experience, the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity (p = 0.03). Any acute rectal bleeding was significant correlated with any late rectal bleeding (p = 0.017). Conclusion: misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no negative impact on the incidence and severity of late rectal bleeding, in contrast to acute rectal bleeding. The routine clinical use of misoprostol suppositories cannot be recommended. (orig.)

  3. Effect of a prostaglandin - given rectally for prevention of radiation-induced acute proctitis - on late rectal toxicity. Results of phase III randomized, placebo-controlled, double-blind study

    Energy Technology Data Exchange (ETDEWEB)

    Kertesz, Tereza; Herrmann, Markus K.A.; Christiansen, Hans; Hermann, Robert M.; Hess, Clemens F.; Hille, Andrea [Dept. of Radiotherapy and Radiooncology, Univ. of Goettingen (Germany); Zapf, Antonia [Dept. of Medical Statistics, Univ. of Goettingen (Germany); Pradier, Olivier [Dept. of Radiotherapy and Radiooncology, Univ. of Brest (France); Schmidberger, Heinz [Dept. of Radiotherapy and Radiooncology, Univ. of Mainz (Germany)

    2009-09-15

    Background and purpose: to assess the late effect of a prostaglandin, given rectally during irradiation, on late rectal toxicity. In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol, however, significantly more rectal bleeding had been reported. Patients and methods: a total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale. Results: the median follow-up was 50 months. 20 patients suffered from grade 1, four patients from grade 2 as well, and three patients only from grade 2 toxicity. Frequency, bleeding and urgency were the most commonly reported symptoms. In keeping with other studies and clinical experience, the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity (p = 0.03). Any acute rectal bleeding was significant correlated with any late rectal bleeding (p = 0.017). Conclusion: misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no negative impact on the incidence and severity of late rectal bleeding, in contrast to acute rectal bleeding. The routine clinical use of misoprostol suppositories cannot be recommended. (orig.)

  4. Acyclovir Therapy Reduces the CD4+ T Cell Response against the Immunodominant pp65 Protein from Cytomegalovirus in Immune Competent Individuals.

    Directory of Open Access Journals (Sweden)

    Annette Pachnio

    Full Text Available Cytomegalovirus (CMV infects the majority of the global population and leads to the development of a strong virus-specific immune response. The CMV-specific CD4+ and CD8+ T cell immune response can comprise between 10 and 50% of the T cell pool within peripheral blood and there is concern that this may impair immunity to other pathogens. Elderly individuals with the highest magnitude of CMV-specific immune response have been demonstrated to be at increased risk of mortality and there is increasing interest in interventions that may serve to moderate this. Acyclovir is an anti-viral drug with activity against a range of herpes viruses and is used as long term treatment to suppress reactivation of herpes simplex virus. We studied the immune response to CMV in patients who were taking acyclovir to assess if therapy could be used to suppress the CMV-specific immune response. The T cell reactivity against the immunodominant late viral protein pp65 was reduced by 53% in people who were taking acyclovir. This effect was seen within one year of therapy and was observed primarily within the CD4+ response. Acyclovir treatment only modestly influenced the immune response to the IE-1 target protein. These data show that low dose acyclovir treatment has the potential to modulate components of the T cell response to CMV antigen proteins and indicate that anti-viral drugs should be further investigated as a means to reduce the magnitude of CMV-specific immune response and potentially improve overall immune function.

  5. Construction and immunological evaluation of truncated hepatitis B core particles carrying HBsAg amino acids 119–152 in the major immunodominant region (MIR)

    Energy Technology Data Exchange (ETDEWEB)

    Su, Qiudong; Yi, Yao [National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing 102206 (China); Guo, Minzhuo [Beijing Entry-Exit Inspection and Quarantine Beureau, Tianshuiyuan Lane 6, Chaoyang District, Beijing 100026 (China); Qiu, Feng; Jia, Zhiyuan; Lu, Xuexin; Meng, Qingling [National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing 102206 (China); Bi, Shengli, E-mail: shengli_bi@163.com [National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Changbai Road 155, Changping District, Beijing 102206 (China)

    2013-09-13

    Highlights: •The conformational HBV neutralization antigen domain was successfully displayed on the surface of truncated HBc particles. •Appropriate dialysis procedures to support the renaturing environment for the protein refolding. •Efficient purification procedures to obtain high purity and icosahedral particles of mosaic HBV antigen. •Strong immune responses not only including neutralization antibody response but also Th1 cell response were induced in mice. -- Abstract: Hepatitis B capsid protein expressed in Escherichia coli can reassemble into icosahedral particles, which could strongly enhance the immunogenicity of foreign epitopes, especially those inserted into its major immunodominant region. Herein, we inserted the entire ‘α’ antigenic determinant amino acids (aa) 119–152 of HBsAg into the truncated HBc (aa 1–144), between Asp{sup 78} and Pro{sup 79}. Prokaryotic expression showed that the mosaic HBc was mainly in the form of inclusion bodies. After denaturation with urea, it was dialyzed progressively for protein renaturation. We observed that before and after renaturation, mosaic HBc was antigenic as determined by HBsAg ELISA and a lot of viruslike particles were observed after renaturation. Thus, we further purified the mosaic viruslike particles by (NH{sub 4}){sub 2}SO{sub 4} precipitation, DEAE chromatography, and Sepharose 4FF chromatography. Negative staining electron microscopy demonstrated the morphology of the viruslike particles. Immunization of Balb/c mice with mosaic particles induced the production of anti-HBs antibody and Th1 cell immune response supported by ELISPOT and CD4/CD8 proportions assay. In conclusion, we constructed mosaic hepatitis core particles displaying the entire ‘α’ antigenic determinant on the surface and laid a foundation for researching therapeutic hepatits B vaccines.

  6. Diverse Epitope Specificity, Immunodominance Hierarchy, and Functional Avidity of Effector CD4 T Cells Established During Priming Is Maintained in Lung After Influenza A Virus Infection.

    Science.gov (United States)

    Richards, Katherine A; DiPiazza, Anthony T; Rattan, Ajitanuj; Knowlden, Zackery A G; Yang, Hongmei; Sant, Andrea J

    2018-01-01

    One of the major contributions to protective immunity to influenza viruses that is provided by virus-specific CD4 T cells is delivery of effector function to the infected lung. However, there is little known about the selection and breadth of viral epitope-specific CD4 T cells that home to the lung after their initial priming. In this study, using a mouse model of influenza A infection and an unbiased method of epitope identification, the viral epitope-specific CD4 T cells elicited after infection were identified and quantified. We found that a very diverse specificity of CD4 T cells is primed by infection, including epitopes from hemagglutinin, neuraminidase, matrix protein, nucleoprotein, and non-structural protein-1. Using peptide-specific cytokine EliSpots, the diversity and immunodominance hierarchies established in the lung-draining lymph node were compared with specificities of CD4 T cells that home to the lung. Our studies revealed that CD4 T cells of all epitope specificities identified in peripheral lymphoid tissue home back to the lung and that most of these lung-homing cells are localized within the tissue rather than the pulmonary vasculature. There is a striking shift of CD4 T cell functionality that enriches for IFN-γ production as cells are primed in the lymph node, enter the lung vasculature, and finally establish residency in the tissue, but with no apparent shifts in their functional avidity. We conclude that CD4 T cells of broad viral epitope specificity are recruited into the lung after influenza infection, where they then have the opportunity to encounter infected or antigen-bearing antigen-presenting cells.

  7. Acute phase nutritional screening tool associated with functional outcomes of hip fracture patients: A longitudinal study to compare MNA-SF, MUST, NRS-2002 and GNRI.

    Science.gov (United States)

    Inoue, Tatsuro; Misu, Shogo; Tanaka, Toshiaki; Kakehi, Tetsuya; Ono, Rei

    2018-02-15

    Several hip fracture patients are malnourished, but no study has attempted to determine the optimal nutritional screening tool for predicting functional outcomes. We investigated the association between each nutritional status assessed by four nutritional screening tools at admission and functional outcomes during the postoperative acute phase in hip fracture patients. The Mini Nutritional Assessment-Short Form (MNA-SF), the Malnutrition Universal Screening Tool (MUST), the Nutritional Risk Score 2002 (NRS-2002) and the Geriatric Nutritional Risk Index (GNRI) were assessed at admission before surgery. We evaluated the motor domain of the functional independence measure (motor-FIM) score at discharge, efficiency on the motor-FIM (change in the motor-FIM score after postoperative rehabilitation divided by postoperative length of hospital stay), and 10-m walking speed at postoperative 14 days as functional outcomes. Two hundred and five patients (mean patient age, 83.5 ± 7.0 years; range, 65-100 years; 82% female) were included. The MNA-SF evaluation classified 56 patients as well-nourished, 103 as at risk of malnutrition and 46 as malnourished. The MUST evaluation classified 97 patients as low risk, 42 as medium risk and 66 as high risk. The NRS-2002 evaluation classified 89 patients as well-nourished, 69 as medium risk and 47 as nutritionally at risk. The GNRI evaluation classified 44 patients as no risk, 74 as low risk and 87 as a major risk. Multiple linear regression analysis revealed that MNA-SF had a significant association with discharge motor-FIM (well-nourished vs. at risk of malnutrition, standardised β = -0.06, p = 0.04; vs. malnourished, standardised β = -0.32, p hip fracture patients. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  8. Yield of atrial fibrillation detection with Textile Wearable Holter from the acute phase of stroke: Pilot study of Crypto-AF registry.

    Science.gov (United States)

    Pagola, Jorge; Juega, Jesus; Francisco-Pascual, Jaume; Moya, Angel; Sanchis, Mireia; Bustamante, Alejandro; Penalba, Anna; Usero, Maria; Cortijo, Elisa; Arenillas, Juan F; Calleja, Ana I; Sandin-Fuentes, Maria; Rubio, Jeronimo; Mancha, Fernando; Escudero-Martinez, Irene; Moniche, Francisco; de Torres, Reyes; Pérez-Sánchez, Soledad; González-Matos, Carlos E; Vega, Ángela; Pedrote, Alonso A; Arana-Rueda, Eduardo; Montaner, Joan; Molina, Carlos A

    2018-01-15

    We describe the feasibility of monitoring with a Textile Wearable Holter (TWH) in patients included in Crypto AF registry. We monitored cryptogenic stroke patients from stroke onset (<3days) continuously during 28days. We employed a TWH composed by a garment and a recorder. We compared two garments (Lead and Vest) to assess rate of undiagnosed Atrial Fibrillation (AF) detection, monitoring compliance, comfortability (1 to 5 points), skin lesions, and time analyzed. We describe the timing of AF detection in three periods (0-3, 4-15 and 16-28days). The rate of undiagnosed AF detection with TWH was 21.9% (32 out of 146 patients who completed the monitoring). Global time compliance was 90% of the time expected (583/644h). The level of comfortability was 4 points (IQR 3-5). We detected reversible skin lesions in 5.47% (8/146). The comfortability was similar but time compliance (in hours) was longer in Vest group 591 (IQR [521-639]) vs. Lead 566 (IQR [397-620]) (p=0.025). Also, time analyzed was more prolonged in Vest group 497 (IQR [419-557]) vs. Lead (336h (IQR [140-520]) (p=0.001)). The incidence of AF increases from 5.6% (at 3days) to 17.5% (at 15th day) and up to 20.9% (at 28th day). The percentage of AF episodes detected only in each period was 12.5% (0-3days); 21.7% (4-15days) and 19% (16-28days). 28days Holter monitoring from the acute phase of the stroke was feasible with TWH. Following our protocol, only five patients were needed to screen to detected one case of AF. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Heat-tolerant versus heat-sensitive Bos taurus cattle: influence of air temperature and breed on the acute phase response to a provocative immune challenge.

    Science.gov (United States)

    Carroll, J A; Burdick Sanchez, N C; Chaffin, R; Chase, C C; Coleman, S W; Spiers, D E

    2013-10-01

    The difference in the acute phase response of a heat-tolerant and a heat-sensitive Bos taurus breed to a lipopolysaccharide (LPS) challenge when housed at different air temperatures (Ta) was studied. Angus (ANG; heat-sensitive; n = 11; 306 ± 26 kg BW) and Romosinuano (RO; heat-tolerant; n = 10; 313 ± 32 kg BW) heifers were transported from the USDA Agricultural Research Service SubTropical Agricultural Research Station in Florida to the Brody Environmental Chambers at the University of Missouri, Columbia. Heifers were housed in stanchions in 4 temperature-controlled environmental chambers. Initially, Ta in the 4 chambers was cycling at thermoneutrality (TN; 18.5°C-23.5°C) for a 1-wk adjustment period, followed by an increase in 2 of the 4 chambers to cycling heat stress (HS; 24°C-38°C) for 2 wk. On day 19, heifers were fitted with jugular catheters and rectal temperature (RT) recording devices. On day 20, heifers were challenged with LPS (0.5 μg/kg BW; 0 h), sickness behavior scores (SBSs) were recorded, and blood samples were collected at 0.5-h intervals from -2 to 8 h and again at 24 h relative to LPS challenge at 0 h. Serum was isolated and stored at -80°C until analyzed for cortisol and cytokine concentrations. A breed by Ta interaction (P heat-tolerant RO and heat-sensitive ANG heifers under different Ta which may aid in elucidating differences in productivity, disease resistance, and longevity among cattle breeds. Published by Elsevier Inc.

  10. Feeding common carp Cyprinus carpio with β-glucan supplemented diet stimulates C-reactive protein and complement immune acute phase responses following PAMPs injection.

    Science.gov (United States)

    Pionnier, Nicolas; Falco, Alberto; Miest, Joanna J; Shrive, Annette K; Hoole, Dave

    2014-08-01

    The effect of β-glucan as a feed additive on the serum and gene profile of C-reactive protein (CRP) and complement acute phase responses was ascertained in common carp Cyprinus carpio. In addition effects of subsequent intraperitoneal injections of pathogen-associated molecular patterns (PAMPs), i.e. LPS or poly(I:C), to mimic bacterial or viral infection respectively, were studied. Carp were first orally fed with β-glucan (MacroGard®) with a daily β-glucan intake of 6 mg per kg body weight or with control food for 25 days and then injected with PBS containing either LPS (4 mg/kg) or poly(I:C) (5 mg/kg) or PBS alone. Fish were sampled during the 25 days of the feeding period and up to 7 days post-PAMPs injections for serum and liver, head kidney and mid-gut tissues. Oral administration of β-glucan for 25 days significantly increased serum CRP levels and alternative complement activity (ACP). In addition, the subsequent LPS and poly(I:C) challenges significantly affected CRP and complement related gene expression profiles (crp1, crp2, c1r/s, bf/c2, c3 and masp2), with the greatest effects observed in the β-glucan fed fish. However, in fish fed β-glucan the PAMPs injections had less effects on CRP levels and complement activity in the serum than in control fed fish, suggesting that the 25 days of β-glucan immunostimulation was sufficient enough to reduce the effects of LPS and poly(I:C) injections. Results suggest that MacroGard® stimulated CRP and complement responses to PAMPs immunological challenges in common carp thus highlighting the beneficial β-glucan immunostimulant properties. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2.

    Science.gov (United States)

    Holkova, Beata; Supko, Jeffrey G; Ames, Matthew M; Reid, Joel M; Shapiro, Geoffrey I; Perkins, Edward Brent; Ramakrishnan, Viswanathan; Tombes, Mary Beth; Honeycutt, Connie; McGovern, Renee M; Kmieciak, Maciej; Shrader, Ellen; Wellons, Martha D; Sankala, Heidi; Doyle, Austin; Wright, John; Roberts, John D; Grant, Steven

    2013-04-01

    This phase I study was conducted to identify the maximum-tolerated dose (MTD) of alvocidib when combined with vorinostat in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Secondary objectives included investigating the pharmacokinetic and pharmacodynamic effects of the combination. Patients received vorinostat (200 mg orally, three times a day, for 14 days) on a 21-day cycle, combined with 2 different alvocidib administration schedules: a 1-hour intravenous infusion, daily × 5; or a 30-minute loading infusion followed by a 4-hour maintenance infusion, weekly × 2. The alvocidib dose was escalated using a standard 3+3 design. Twenty-eight patients were enrolled and treated. The alvocidib MTD was 20 mg/m(2) (30-minute loading infusion) followed by 20 mg/m(2) (4-hour maintenance infusion) on days one and eight, in combination with vorinostat. The most frequently encountered toxicities were cytopenias, fatigue, hyperglycemia, hypokalemia, hypophosphatemia, and QT prolongation. Dose-limiting toxicities (DLT) were cardiac arrhythmia-atrial fibrillation and QT prolongation. No objective responses were achieved although 13 of 26 evaluable patients exhibited stable disease. Alvocidib seemed to alter vorinostat pharmacokinetics, whereas alvocidib pharmacokinetics were unaffected by vorinostat. Ex vivo exposure of leukemia cells to plasma obtained from patients after alvocidib treatment blocked vorinostat-mediated p21(CIP1) induction and downregulated Mcl-1 and p-RNA Pol II for some specimens, although parallel in vivo bone marrow responses were infrequent. Alvocidib combined with vorinostat is well tolerated. Although disease stabilization occurred in some heavily pretreated patients, objective responses were not obtained with these schedules. ©2013 AACR.

  12. Effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690].

    NARCIS (Netherlands)

    D.W.J. Dippel (Diederik); E.J. van Breda (Eric); H.B. van der Worp (Bart); H.M.A. van Gemert (Maarten); R.J. Meijer (Ron); L.J. Kappelle (Jaap); P.J. Koudstaal (Peter Jan)

    2003-01-01

    textabstractBACKGROUND: Body temperature is a strong predictor of outcome in acute stroke. In a previous randomized trial we observed that treatment with high-dose acetaminophen (paracetamol) led to a reduction of body temperature in patients with acute ischemic stroke, even when

  13. Monozygotic twin pairs discordant for Hashimoto's thyroiditis share a high proportion of thyroid peroxidase autoantibodies to the immunodominant region A. Further evidence for genetic transmission of epitopic “fingerprints”

    DEFF Research Database (Denmark)

    Brix, Thomas Heiberg; Hegedüs, Laszlo; Gardas, Andrzej

    2010-01-01

    Thyroid peroxidase antibodies (TPOAbs) in patients with Hashimoto's thyroiditis (HT) predominantly react with two immunodominant regions (IDR-A, IDR-B). Theoretically, as shown for the level of TPOAbs, the autoantibody epitopic recognition of the IDRs could be under genetic control. To examine this......, we compared the distribution of TPOAb epitopic fingerprints between healthy monozygotic (MZ) co-twins and siblings to patients with clinically overt HT with a control group of euthyroid subjects, matched for sex and age, but without autoimmune thyroid disease (AITD) among their first-degree relatives...

  14. Effectiveness of three commonly used transition phase diets in the inpatient management of children with severe acute malnutrition : A pilot randomized controlled trial in Malawi

    NARCIS (Netherlands)

    Versloot, Christian J.; Voskuijl, Wieger; van Vliet, Sara J.; van den Heuvel, Meta; Carter, Jane C.; Phiri, Ajib; Kerac, Marko; Heikens, Geert Tom; van Rheenen, Patrick F.; Bandsma, Robert H. J.

    2017-01-01

    Background: The case fatality rate of severely malnourished children during inpatient treatment is high and mortality is often associated with diarrhea. As intestinal carbohydrate absorption is impaired in severe acute malnutrition (SAM), differences in dietary formulations during nutritional

  15. Efficacy and safety profile of combination of tramadol-diclofenac versus tramadol-paracetamol in patients with acute musculoskeletal conditions, postoperative pain, and acute flare of osteoarthritis and rheumatoid arthritis: a Phase III, 5-day open-label study

    Science.gov (United States)

    Chandanwale, Ajay S; Sundar, Subramanian; Latchoumibady, Kaliaperumal; Biswas, Swati; Gabhane, Mukesh; Naik, Manoj; Patel, Kamlesh

    2014-01-01

    Objective We aimed to evaluate the safety and efficacy of a fixed-dose combination (FDC) of tramadol and diclofenac versus a standard approved FDC of tramadol and paracetamol, in patients with acute moderate to severe pain. Methods A total of 204 patients with moderate to severe pain due to acute musculoskeletal conditions (n=52), acute flare of osteoarthritis (n=52), acute flare of rheumatoid arthritis (n=50), or postoperative pain (n=50) were enrolled in the study at baseline. Each disease category was then randomized to receive either of two treatments for 5 days: group A received an FDC of immediate-release tramadol hydrochloride (50 mg) and sustained-release diclofenac sodium (75 mg) (one tablet, twice daily), and group B received an FDC of tramadol hydrochloride (37.5 mg) and paracetamol (325 mg) (two tablets every 4–6 hours, up to a maximum of eight tablets daily). The primary efficacy end points were reductions in pain intensity from baseline at day 3 and day 5 as assessed by a Visual Analog Scale (VAS) score. Results Group A showed a significant reduction in the VAS score for overall pain from baseline on day 3 (P=0.001) and day 5 (Ppain, and gastritis), which required minimal management, without any treatment discontinuation. The number of adverse events in group A was nine (8.82%) compared with 22 (21.78%) in group B, after 5 days of treatment. Conclusion An FDC of tramadol-diclofenac showed a significantly greater reduction in pain intensity and was well tolerated compared with tramadol-paracetamol, resulting in better analgesia in patients suffering from moderate to severe pain due to acute musculoskeletal conditions, postoperative pain following orthopedic surgery, or acute flare of osteoarthritis and rheumatoid arthritis. PMID:25152629

  16. Intraocular Hemorrhages and Retinopathy of Prematurity in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study.

    Science.gov (United States)

    Daniel, Ebenezer; Ying, Gui-Shuang; Siatkowski, R Michael; Pan, Wei; Smith, Eli; Quinn, Graham E

    2017-03-01

    To describe the clinical characteristics of intraocular hemorrhages (IOHs) in infants in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study and to evaluate their potential use for prediction of disease severity. Secondary data analysis from a prospective study. Preterm infants with birth weight (BW) ≤1250 g. Infants underwent serial digital retinal imaging in both eyes starting at 32 weeks' postmenstrual age. Nonphysician trained readers (TRs) evaluated all image sets from eyes that ever had IOHs documented on image evaluation or eye examination for the presence, location, type, area, and relation of the IOH to the junction between vascularized and avascular retina. Associations of IOH with demographic and neonatal factors, and with the presence and severity of retinopathy of prematurity (ROP) were investigated by univariate and multivariate analyses. Sensitivity and specificity of the telemedicine system for detecting referral-warranted ROP (RW-ROP) were calculated with and without incorporating hemorrhage into the standardized grading protocol. Retinal and vitreous hemorrhage. Among 1239 infants (mean [standard deviation] BW = 864 [212] g; gestational age [GA] = 27 [2.2] weeks) who underwent an average of 3.2 imaging sessions, 22% had an IOH in an eye on at least 1 of the e-ROP visits. Classification of IOH was preretinal (57%), blot (57%), dot (38%), flame-shaped (16%), and vitreous (8%); most IOHs were unilateral (70%). The IOH resolved in 35% of eyes by the next imaging session and in the majority (76%) of cases by 8 weeks after initial detection. Presence of IOH was inversely associated with BW and GA and significantly associated (P < 0.0001) with the presence and severity of ROP (BW and GA adjusted odds ratios [ORs] of 2.46 for any ROP, 2.88 for stage 3, and 3.19 for RW-ROP). Incorporating IOH into the grading protocol minimally altered the sensitivity of the system (94% vs. 95%). Approximately 1 in 5 preterm

  17. In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria.

    Directory of Open Access Journals (Sweden)

    Henrique Borges da Silva

    2015-02-01

    Full Text Available Dendritic cells (DCs are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip, with Plasmodium chabaudi AS (Pc parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.

  18. In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria.

    Science.gov (United States)

    Borges da Silva, Henrique; Fonseca, Raíssa; Cassado, Alexandra Dos Anjos; Machado de Salles, Érika; de Menezes, Maria Nogueira; Langhorne, Jean; Perez, Katia Regina; Cuccovia, Iolanda Midea; Ryffel, Bernhard; Barreto, Vasco M; Marinho, Cláudio Romero Farias; Boscardin, Silvia Beatriz; Álvarez, José Maria; D'Império-Lima, Maria Regina; Tadokoro, Carlos Eduardo

    2015-02-01

    Dendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip), with Plasmodium chabaudi AS (Pc) parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs) by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.

  19. A Simple Proteomics-Based Approach to Identification of Immunodominant Antigens from a Complex Pathogen: Application to the CD4 T Cell Response against Human Herpesvirus 6B.

    Directory of Open Access Journals (Sweden)

    Aniuska Becerra-Artiles

    Full Text Available Most of humanity is chronically infected with human herpesvirus 6 (HHV-6, with viral replication controlled at least in part by a poorly characterized CD4 T cell response. Identification of viral epitopes recognized by CD4 T cells is complicated by the large size of the herpesvirus genome and a low frequency of circulating T cells responding to the virus. Here, we present an alternative to classical epitope mapping approaches used to identify major targets of the T cell response to a complex pathogen like HHV-6B. In the approach presented here, extracellular virus preparations or virus-infected cells are fractionated by SDS-PAGE, and eluted fractions are used as source of antigens to study cytokine responses in direct ex vivo T cell activation studies. Fractions inducing significant cytokine responses are analyzed by mass spectrometry to identify viral proteins, and a subset of peptides from these proteins corresponding to predicted HLA-DR binders is tested for IFN-γ production in seropositive donors with diverse HLA haplotypes. Ten HHV-6B viral proteins were identified as immunodominant antigens. The epitope-specific response to HHV-6B virus was complex and variable between individuals. We identified 107 peptides, each recognized by at least one donor, with each donor having a distinctive footprint. Fourteen peptides showed responses in the majority of donors. Responses to these epitopes were validated using in vitro expanded cells and naturally expressed viral proteins. Predicted peptide binding affinities for the eight HLA-DRB1 alleles investigated here correlated only modestly with the observed CD4 T cell responses. Overall, the response to the virus was dominated by peptides from the major capsid protein U57 and major antigenic protein U11, but responses to other proteins including glycoprotein H (U48 and tegument proteins U54 and U14 also were observed. These results provide a means to follow and potentially modulate the CD4 T-cell immune

  20. Design, synthesis and evaluation of an anthraquinone derivative conjugated to myelin basic protein immunodominant (MBP85-99) epitope: Towards selective immunosuppression.

    Science.gov (United States)

    Tapeinou, Anthi; Giannopoulou, Efstathia; Simal, Carmen; Hansen, Bjarke E; Kalofonos, Haralabos; Apostolopoulos, Vasso; Vlamis-Gardikas, Alexios; Tselios, Theodore

    2018-01-01

    Anthraquinone type compounds, especially di-substituted amino alkylamino anthraquinones have been widely studied as immunosuppressants. The anthraquinone ring is part of mitoxandrone that has been used for the treatment of multiple sclerosis (MS) and several types of tumors. A desired approach for the treatment of MS would be the immunosuppression and elimination of specific T cells that are responsible for the induction of the disease. Herein, the development of a peptide compound bearing an anthraquinone derivative with the potential to specifically destroy the encephalitogenic T cells responsible for the onset of MS is described. The compound consists of the myelin basic protein (MBP) 85-99 immunodominant epitope (MBP 85-99 ) coupled to an anthraquinone type molecule (AQ) via a disulfide (S-S) and 6 amino hexanoic acid (Ahx) residues (AQ-S-S-(Ahx) 6 MBP 85-99 ). AQ-S-S-(Ahx) 6 MBP 85-99 could bind to HLA II DRB1*-1501 antigen with reasonable affinity (IC 50 of 56 nM) The compound was localized to the nucleus of Jurkat cells (an immortalized line of human T lymphocytes) 10 min after its addition to the medium and resulted in lowered Bcl-2 levels (apoptosis). Entrance of the compound was abolished when cells were pre-treated with cisplatin, an inhibitor of thioredoxin reductase. Accordingly, levels of free thiols were elevated in the culture supernatants of Jurkat cells exposed to N-succinimidyl 3-(2-pyridyldithio) propionate coupled to (Ahx) 6 MBP 85-99 via a disulphide (SPDP-S-S-(Ahx) 6 MBP 85-99 ) but returned to normal after exposure to cisplatin. These results raise the possibility of AQ-S-S-(Ahx) 6 MBP 85-99 being used as an eliminator of encephalitogenic T cells via implication of the thioredoxin system for the generation of the toxic, thiol-containing moiety (AQ-SH). Future experiments would ideally determine whether SPDP-S-S-(Ahx) 6 MBP 85-99 could incorporate into HLA II DRB1*-1501 tetramers and neutralize encephalitogenic T cell lines sensitized to

  1. Identification of an immunodominant epitope in glycoproteins B and G of herpes simplex viruses (HSVs) using synthetic peptides as antigens in assay of antibodies to HSV in herpes simplex encephalitis patients.

    Science.gov (United States)

    Bhullar, S S; Chandak, N H; Baheti, N N; Purohit, H J; Taori, G M; Daginawala, H F; Kashyap, R S

    2014-01-01

    Herpes simplex encephalitis (HSE) is a severe viral infection of the central nervous system (CNS). Assay of antibody response is widely used in diagnostics of HSE. The aim of this study was to identify an immunodominant epitope determining the antibody response to herpes simplex viruses (HSVs) in cerebrospinal fluid (CSF) of HSE patients. The synthetic peptides that resembled type-common as well as type-specific domains of glycoproteins B (gB) and G (gG) of these viruses were evaluated for binding with IgM and IgG antibodies in CSF samples from HSE and non-HSE patients in ELISA. The QLHDLRF peptide, derived from gB of HSV was found to be an immunodominant epitope in the IgM and IgG antibody response. The patients with confirmed and suspected HSE showed in ELISA against this peptide 26% and 23% positivities for IgM, 43% and 37% positivities for IgG and 17% and 15% for both IgM and IgG antibodies, respectively. The total positivities of 86% and 75% for both IgM and IgG antibodies were obtained in the patients with confirmed and suspected HSE, respectively. These results demonstrate that a synthetic peptide-based diagnostics of HSE can be an efficient and easily accessible alternative. This is the first report describing the use of synthetic peptides derived from HSVs in diagnostics of HSE using patientsʹ CSF samples.

  2. Cytogenetic study of preleukemic phases and of acute leukemia secondary to chemo- and/or radiotherapy. Review of the literature (102 cases)

    International Nuclear Information System (INIS)

    Smadja, N.; Krulik, M.; Debray, J.

    1982-01-01

    A review of the literature upon 102 cases with cytogenetic study of preleukemic states (Prel.) and/or acute secondary leukemia (ASL) following chemotherapy and/or radiotherapy treatment has been made. The karyotype was almost always abnormal (91% of cases). There was a predominance of hypodiploidy with abnormalities including chromosome number 5 (-5 ou 5q-) and/or number 7 (7- or 7q-) (chromosomes studied with banding). The abnormalities were present in preleukemia state. The pattern of the acute secondary leukemia was particularly different from that acute leukemia de novo: high frequency of preleukemia state, ANLL type of leukemia, very bad prognosis, importance of cytogenetic abnormalities. There was a great interest in the study of the karyotype for the previous detection in ASL: this allowed their discovery as soon as the preleukemia state [fr

  3. Activation of the protein tyrosine phosphatase SHP2 via the interleukin-6 signal transducing receptor protein gp130 requires tyrosine kinase Jak1 and limits acute-phase protein expression.

    Science.gov (United States)

    Schaper, F; Gendo, C; Eck, M; Schmitz, J; Grimm, C; Anhuf, D; Kerr, I M; Heinrich, P C

    1998-11-01

    Stimulation of the interleukin-6 (IL-6) signalling pathway occurs via the IL-6 receptor-glycoprotein 130 (IL-6R-gp130) receptor complex and results in the regulation of acute-phase protein genes in liver cells. Ligand binding to the receptor complex leads to tyrosine phosphorylation and activation of Janus kinases (Jak), phosphorylation of the signal transducing subunit gp130, followed by recruitment and phosphorylation of the signal transducer and activator of transcription factors STAT3 and STAT1 and the src homology domain (SH2)-containing protein tyrosine phosphatase (SHP2). The tyrosine phosphorylated STAT factors dissociate from the receptor, dimerize and translocate to the nucleus where they bind to enhancer sequences of IL-6 target genes. Phosphorylated SHP2 is able to bind growth factor receptor bound protein (grb2) and thus might link the Jak/STAT pathway to the ras/raf/mitogen-activated protein kinase pathway. Here we present data on the dose-dependence, kinetics and kinase requirements for SHP2 phosphorylation after the activation of the signal transducer, gp130, of the IL-6-type family receptor complex. When human fibrosarcoma cell lines deficient in Jak1, Jak2 or tyrosine kinase 2 (Tyk2) were stimulated with IL-6-soluble IL-6R complexes it was found that only in Jak1-, but not in Jak 2- or Tyk2-deficient cells, SHP2 activation was greatly impaired. It is concluded that Jak1 is required for the tyrosine phosphorylation of SHP2. This phosphorylation depends on Tyr-759 in the cytoplasmatic domain of gp130, since a Tyr-759-->Phe exchange abrogates SHP2 activation and in turn leads to elevated and prolonged STAT3 and STAT1 activation as well as enhanced acute-phase protein gene induction. Therefore, SHP2 plays an important role in acute-phase gene regulation.

  4. Concentrations of the acute phase reactants high-sensitive C-reactive protein and YKL-40 and of interleukin-6 before and after treatment in patients with acromegaly and growth hormone deficiency

    DEFF Research Database (Denmark)

    Andreassen, Mikkel; Vestergaard, Henrik; Kristensen, Lars Østergaard

    2007-01-01

    Acromegaly is accompanied by increased cardiovascular mortality and a cluster of proatherogenic risk factors. In the general population, ischaemic heart disease (IHD) is associated with elevated levels of inflammatory markers. The acute phase reactant (APR) C-reactive protein (CRP) has been...... reported to be reduced in acromegaly and increase after treatment, suggesting that excess of GH/IGF-I could have anti-inflammatory effects. This is in accordance with results obtained in patients with growth hormone deficiency (GHD), where increased levels of CRP have been reported....

  5. Risk Score for Predicting Treatment-Requiring Retinopathy of Prematurity (ROP) in the Telemedicine Approaches to Evaluating Acute-Phase ROP Study.

    Science.gov (United States)

    Ying, Gui-Shuang; VanderVeen, Deborah; Daniel, Ebenezer; Quinn, Graham E; Baumritter, Agnieshka

    2016-10-01

    To develop a risk score for predicting treatment-requiring retinopathy of prematurity (TR-ROP) in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) study. Second analyses of an observational cohort study. Infants with birth weight (BW) prematurity (ROP) examination for determining TR-ROP by study-certified ophthalmologists. Nonphysician trained readers evaluated wide-field retinal image sets for characteristics of ROP, pre-plus/plus disease, and retinal hemorrhage. Risk score points for predicting TR-ROP were derived from the regression coefficients of significant predictors in a multivariate logistic regression model. TR-ROP. Eighty-five of 771 infants (11.0%) developed TR-ROP. In a multivariate model, significant predictors for TR-ROP were gestational age (GA) (odds ratio [OR], 5.7; 95% confidence interval [CI], 1.7-18.9 for ≤25 vs. ≥28 weeks), need for respiratory support (OR, 7.0; 95% CI, 1.3-37.1 for high-frequency oscillatory ventilation vs. no respiratory support), slow weight gain (OR, 2.4; 95% CI, 1.2-4.6 for weight gain ≤12 g/day vs. >15 g/day), and image findings at the first image session including number of quadrants with pre-plus (OR, 3.8; 95% CI, 1.5-9.7 for 4 pre-plus quadrants vs. no pre-plus), stage and zone of ROP (OR, 4.7; 95% CI, 2.1-11.8 for stage 1-2 zone I, OR, 5.9; 95% CI, 2.1-16.6 for stage 3 zone I vs. no ROP), and presence of blot hemorrhage (OR, 3.1; 95% CI, 1.4-6.7). Image findings predicted TR-ROP better than GA (area under receiver operating characteristic curve [AUC] = 0.82 vs. 0.75, P = 0.03). The risk of TR-ROP steadily increased with higher risk score and predicted TR-ROP well (AUC = 0.88; 95% CI, 0.85-0.92). Risk score ≥3 points for predicting TR-ROP had a sensitivity of 98.8%, specificity of 40.1%, and positive and negative predictive values of 17.0% and 99.6%, respectively. Image characteristics at 34 PMA weeks or earlier independently predict TR-ROP. If externally validated in

  6. Predictors for the development of referral-warranted retinopathy of prematurity in the telemedicine approaches to evaluating acute-phase retinopathy of prematurity (e-ROP) study.

    Science.gov (United States)

    Ying, Gui-Shuang; Quinn, Graham E; Wade, Kelly C; Repka, Michael X; Baumritter, Agnieshka; Daniel, Ebenezer

    2015-03-01

    Detection of treatment-requiring retinopathy of prematurity (ROP) involves serial eye examinations. An ROP prediction model using predictive factors could identify high-risk infants and reduce required eye examinations. To determine predictive factors for the development of referral-warranted (RW) ROP. This multicenter observational cohort study included secondary analysis of data from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity Study. Infants included in the study had a birth weight (BW) of less than 1251 g. Serial ROP examinations of premature infants who had 2 or more ROP examinations. Incidence of RW-ROP (defined as the presence of plus disease, zone I ROP, or ROP stage 3 or greater in either eye) and associations with predictive factors. Among 979 infants without RW-ROP at first study-related eye examination (median postmenstrual age, 33 weeks; range, 29-40 weeks) who underwent at least 2 eye examinations, 149 (15.2%) developed RW-ROP. In a multivariate model, significant predictors for RW-ROP were male sex (odds ratio [OR], 1.80; 95% CI, 1.13-2.86 vs female), nonblack race (OR, 2.76; 95% CI, 1.50-5.08 for white vs black race and OR, 4.81; 95% CI, 2.19-10.6 for other vs black race), low BW (OR, 5.16; 95% CI, 1.12-7.20 for ≤500 g vs >1100 g), younger gestational age (OR, 9.79; 95% CI, 3.49-27.5 for ≤24 weeks vs ≥28 weeks), number of quadrants with preplus disease (OR, 7.12; 95% CI, 2.53-20.1 for 1-2 quadrants and OR, 18.4; 95% CI, 4.28-79.4 for 3-4 quadrants vs no preplus disease), stage 2 ROP (OR, 4.13; 95% CI, 2.13-8.00 vs no ROP), the presence of retinal hemorrhage (OR, 4.36; 95% CI, 1.57-12.1 vs absence), the need for respiratory support (OR, 4.99; 95% CI, 1.89-13.2 for the need for controlled mechanical ventilator; OR, 11.0; 95% CI, 2.26-53.8 for the need for high-frequency oscillatory ventilation vs no respiratory support), and slow weight gain (OR, 2.44; 95% CI, 1.22-4.89 for weight gain ≤12 g/d vs >18 g

  7. Management of severe acute malnutrition

    African Journals Online (AJOL)

    age are attributed to undernutrition, especially in developing countries. ... General principles for inpatient management of acute malnutrition can be divided into two phases, i.e. the .... malnourished child: Perspective from developing countries.

  8. Unreliability of three commercial Coxiella burnetii phase II IgM ELISA kits for the seroscreening of acute Q fever in human cases

    Directory of Open Access Journals (Sweden)

    Selvaraj Stephen

    2017-01-01

    Interpretation & conclusions: The three different ELISA kits exhibited poor agreement amongst them and unacceptable level of false positivity. IFA remains to be the only option for diagnosing acute QF. Discrepancy between the clinical findings and IFA/ELISA results needs confirmation by C. burnetii DNA detection in real-time polymerase chain reaction.

  9. CHANGES OF BUOYANT DENSITY DURING THE S-PHASE OF THE CELL-CYCLE - DIRECT EVIDENCE DEMONSTRATED IN ACUTE MYELOID-LEUKEMIA BY FLOW-CYTOMETRIC

    NARCIS (Netherlands)

    DAENEN, S; HUIGES, W; MODDERMAN, E; HALIE, MR

    Studies with synchronized or exponentially growing bacteria and mammalian cell lines are not able to demonstrate small changes in buoyant density during the cell cycle. Flowcytometric analysis of density separated acute myeloid leukemia cells, a system not dependent on time-related variables, shows

  10. Pharmacokinetics, pharmacodynamics, efficacy, and safety of a new recombinant asparaginase preparation in children with previously untreated acute lymphoblastic leukemia: A randomized phase 2 clinical trial

    NARCIS (Netherlands)

    R. Pieters (Rob); I.M. Appel (Inge); H.J. Kuehnel; I. Tetzlaff-Fohr (Iris); U. Pichlmeier (Uwe); I. van der Vaart (Inekee); E. Visser (Eline); R.L. Stigter

    2008-01-01

    textabstractThe pharmacokinetics, pharmacodynam-ics, efficacy, and safety of a new recom-binant Escherichia coli - asparaginase preparation was compared withAsparagi-nase medac. Thirty-two children with acute lymphoblastic leukemia were randomized to receive one of both agents at a dose of 5000

  11. RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Carcinoma of the Anal Canal

    Energy Technology Data Exchange (ETDEWEB)

    Kachnic, Lisa A., E-mail: lisa.kachnic@bmc.org [Department of Radiation Oncology, Boston University Medical Center, Boston, Massachusetts (United States); Winter, Kathryn [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Myerson, Robert J. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Goodyear, Michael D. [Department of Medicine, Dalhousie University, Halifax (Canada); Willins, John [Department of Radiation Oncology, Boston University Medical Center, Boston, Massachusetts (United States); Esthappan, Jacqueline [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Haddock, Michael G. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Rotman, Marvin [Department of Radiation Oncology, State University of New York—Downstate Medical Center, Brooklyn, New York (United States); Parikh, Parag J. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Safran, Howard [Department of Medicine, Brown University, Providence, Rhode Island (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States)

    2013-05-01

    Purpose: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator’s ability to perform DP-IMRT. Results: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. Conclusions: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.

  12. The use of acute phase proteins for monitoring animal health and welfare in the pig production chain: the validation of an immunochromatographic method for the detection of elevated levels of pig-MAP.

    Science.gov (United States)

    Piñeiro, Matilde; Morales, Joaquín; Vizcaíno, Elena; Murillo, José Alberto; Klauke, Thorsten; Petersen, Brigitte; Piñeiro, Carlos

    2013-11-01

    The serum concentration of acute phase proteins (APPs) increases in the presence of disease or stress, which makes APPs notable parameters for the global assessment of animal health and welfare. A rapid, immunochromatographic test (ICT) for the detection of elevated levels of pig Major Acute-phase Protein (pig-MAP), one of the main APPs in pigs, was evaluated in more than 1400 pig serum samples obtained from commercial farms. The ICT showed a good performance with a relative sensitivity (Sn) and specificity (Sp) of 94 and 97%, respectively, for a threshold of 1.5mg/mL (comparison with ELISA). Differences in the pig-MAP levels and the number of positive samples with the ICT were observed within the season of sampling, farms, and age groups at one farm, according to the presence of disease or lesions. The ICT was also evaluated in blood samples obtained at slaughter in association with the carcase inspection. The results from this study indicate that the ICT may be used for the evaluation of groups of pigs, after analysing one sub-sample of these pigs, and might be a useful tool in routine health and welfare monitoring programmes aimed to improve the quality of pig production. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial

    OpenAIRE

    Márta, Katalin; Szabó, Anikó N; Pécsi, Dániel; Varjú, Péter; Bajor, Judit; Gódi, Szilárd; Sarlós, Patrícia; Mikó, Alexandra; Szemes, Kata; Papp, Mária; Tornai, Tamás; Vincze, Áron; Márton, Zsolt; Vincze, Patrícia A; Lankó, Erzsébet

    2017-01-01

    Introduction Acute pancreatitis (AP) is an inflammatory disease with no specific treatment. Mitochondrial injury followed by ATP depletion in both acinar and ductal cells is a recently discovered early event in its pathogenesis. Importantly, preclinical research has shown that intracellular ATP delivery restores the physiological function of the cells and protects from cell injury, suggesting that restoration of energy levels in the pancreas is therapeutically beneficial. Despite several high...

  14. Effect of paracetamol (acetaminophen and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690

    Directory of Open Access Journals (Sweden)

    Meijer Ron J

    2003-02-01

    Full Text Available Abstract Background Body temperature is a strong predictor of outcome in acute stroke. In a previous randomized trial we observed that treatment with high-dose acetaminophen (paracetamol led to a reduction of body temperature in patients with acute ischemic stroke, even when they had no fever. The purpose of the present trial was to study whether this effect of acetaminophen could be reproduced, and whether ibuprofen would have a similar, or even stronger effect. Methods Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 1000 mg acetaminophen, 400 mg ibuprofen, or placebo, given 6 times daily during 5 days. Treatment was started within 24 hours from the onset of symptoms. Body temperatures were measured at 2-hour intervals during the first 24 hours, and at 6-hour intervals thereafter. Results No difference in body temperature at 24 hours was observed between the three treatment groups. However, treatment with high-dose acetaminophen resulted in a 0.3°C larger reduction in body temperature from baseline than placebo treatment (95% CI: 0.0 to 0.6 °C. Acetaminophen had no significant effect on body temperature during the subsequent four days compared to placebo, and ibuprofen had no statistically significant effect on body temperature during the entire study period. Conclusions Treatment with a daily dose of 6000 mg acetaminophen results in a small, but potentially worthwhile decrease in body temperature after acute ischemic stroke, even in normothermic and subfebrile patients. Further large randomized clinical trials are needed to study whether early reduction of body temperature leads to improved outcome.

  15. Human Placenta-Derived Mesenchymal Stem Cells Reduce Mortality and Hematoma Size in a Rat Intracerebral Hemorrhage Model in an Acute Phase

    Directory of Open Access Journals (Sweden)

    Bo Young Choi

    2018-01-01

    Full Text Available Intracerebral hemorrhage (ICH is a critical disease, highly associated with mortality and morbidity. Several studies have demonstrated the beneficial effect of mesenchymal stem cells (MSCs on ICH, mostly focused on their mid-to-long-term effect. Acute hematoma expansion is one of the most important prognostic factors of ICH. We hypothesized that MSCs would decrease mortality and hematoma size in acute ICH, based on the findings of a few recent researches reporting their effect on blood-brain barrier and endothelial integrity. Rat ICH models were made using bacterial collagenase. One hour after ICH induction, the rats were randomly divided into MSC-treated and control groups. Mortality, hematoma volume, ventricular enlargement, brain edema, and degenerating neuron count were compared at 24 hours after ICH induction. Expression of tight junction proteins (ZO-1, occludin and coagulation factor VII mRNA was also compared. Mortality rate (50% versus 8.3%, hematoma size, ventricular size, hemispheric enlargement, and degenerating neuron count were significantly lower in the MSC-treated group (p=0.034, 0.038, 0.001, 0.022, and <0.001, resp., while the expression of ZO-1 and occludin was higher (p=0.007 and 0.012. Administration of MSCs may prevent hematoma expansion in the hyperacute stage of ICH and decrease acute mortality by enhancing the endothelial integrity of cerebral vasculature.

  16. Myelin Basic Protein-Induced Production of Tumor Necrosis Factor-α and Interleukin-6, and Presentation of the Immunodominant Peptide MBP85-99 by B Cells from Patients with Relapsing-Remitting Multiple Sclerosis

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Börnsen, Lars; Sellebjerg, Finn

    2016-01-01

    to study cytokine production by B cells, but here we used the physiologically relevant self-antigen myelin basic protein (MBP) to stimulate B cells from untreated patients with RRMS and healthy donors. Moreover, we took advantage of the unique ability of the monoclonal antibody MK16 to recognize...... the immunodominant peptide MBP85-99 presented on HLA-DR15, and used it as a probe to directly study B-cell presentation of self-antigenic peptide. The proportions of B cells producing TNF-α or IL-6 after stimulation with MBP were higher in RRMS patients than in healthy donors, indicating a pro-inflammatory profile...... for self-reactive patient B cells. In contrast, polyclonal stimulation with PMA + ionomycin and MBP revealed no difference in cytokine profile between B cells from RRMS patients and healthy donors. Expanded disability status scale (EDSS) as well as multiple sclerosis severity score (MSSS) correlated...

  17. Acute symptoms, not rectally administered sucralfate, predict for late radiation proctitis: longer term follow-up of a phase III trial--Trans-Tasman Radiation Oncology Group.

    Science.gov (United States)

    O'Brien, Peter C; Franklin, C Ian; Poulsen, Michael G; Joseph, David J; Spry, Nigel S; Denham, James W

    2002-10-01

    To assess the potential for sucralfate administered rectally to reduce the risk of late rectal morbidity in patients undergoing nonconformal radiotherapy (RT) for carcinoma of the prostate and to study the variables potentially contributing to late rectal morbidity and particularly to explore the relationship between acute and late toxicity. Eighty-six patients with localized prostate carcinoma were randomized in a double-blind, placebo-controlled study to a daily enema of 3 g of sucralfate in a 15-mL suspension or the same suspension without sucralfate. The enema began the first day of RT and was continued for 2 weeks after treatment completion. The primary end point of the study was acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) toxicity; however, the patients were followed for an additional 5 years on a 6-month basis. The evaluation included late RTOG/EORTC toxicity and a patient self-assessment questionnaire. With a median follow-up of 5 years, the Kaplan-Meier probability of late Grade 2 RTOG/EORTC toxicity was 12% (95% confidence interval [CI] 2-22%) for placebo and 5% (95% CI 0-12%) for sucralfate (p = 0.26). The probability of late rectal bleeding was 59% (95% CI 45-73%) for placebo and 54% (95% CI 40-68%) for sucralfate. No statistically significant difference was found between the treatment arms for the peak incidence of any of the other patient self-assessment variables. Cox proportional hazards modeling indicated acute RTOG/EORTC toxicity of Grade 2 or greater was associated with a hazard ratio of 2.74 (95% CI 1.31-5.73) for the development of late toxicity of Grade 1 or greater. Substituting the patient self-assessment variables for acute RTOG/EORTC toxicity revealed that rectal pain of a moderate or severe grade during RT was the best predictor of the subsequent development of late toxicity, with a hazard ratio of 3.44 (95% CI 1.68-7). The results of this study do not support the use of

  18. Acute symptoms, not rectally administered sucralfate, predict for late radiation proctitis: longer term follow-up of a phase III trial--Trans-Tasman Radiation Oncology Group

    International Nuclear Information System (INIS)

    O'Brien, Peter C.; Franklin, C. Ian; Poulsen, Michael G.; Joseph, David J.; Spry, Nigel S.; Denham, James W.

    2002-01-01

    Purpose: To assess the potential for sucralfate administered rectally to reduce the risk of late rectal morbidity in patients undergoing nonconformal radiotherapy (RT) for carcinoma of the prostate and to study the variables potentially contributing to late rectal morbidity and particularly to explore the relationship between acute and late toxicity. Methods and Materials: Eighty-six patients with localized prostate carcinoma were randomized in a double-blind, placebo-controlled study to a daily enema of 3 g of sucralfate in a 15-mL suspension or the same suspension without sucralfate. The enema began the first day of RT and was continued for 2 weeks after treatment completion. The primary end point of the study was acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) toxicity; however, the patients were followed for an additional 5 years on a 6-month basis. The evaluation included late RTOG/EORTC toxicity and a patient self-assessment questionnaire. Results: With a median follow-up of 5 years, the Kaplan-Meier probability of late Grade 2 RTOG/EORTC toxicity was 12% (95% confidence interval [CI] 2-22%) for placebo and 5% (95% CI 0-12%) for sucralfate (p=0.26). The probability of late rectal bleeding was 59% (95% CI 45-73%) for placebo and 54% (95% CI 40-68%) for sucralfate. No statistically significant difference was found between the treatment arms for the peak incidence of any of the other patient self-assessment variables. Cox proportional hazards modeling indicated acute RTOG/EORTC toxicity of Grade 2 or greater was associated with a hazard ratio of 2.74 (95% CI 1.31-5.73) for the development of late toxicity of Grade 1 or greater. Substituting the patient self-assessment variables for acute RTOG/EORTC toxicity revealed that rectal pain of a moderate or severe grade during RT was the best predictor of the subsequent development of late toxicity, with a hazard ratio of 3.44 (95% CI 1.68-7). Conclusion

  19. THE STUDY "REGISTER OF PATIENTS AFTER ACUTE STROKE (REGION." Part 1. Hospital Prospective Register of Patients after Acute Stroke (According to the Results of the Pilot Phase of the Study

    Directory of Open Access Journals (Sweden)

    S. A. Boytsov

    2016-01-01

    Full Text Available Aim. To assess the main features of the clinical course of acute cerebrovascular accident (ACVA, its short-term and long-term outcomes and quality of pharmacotherapy based on hospital register. Material and methods. The hospital register of acute stroke (AS was organized in one of the cardiovascular centers in Moscow city. The results of the pilot part of the study are presented (170 patients hospitalized from January 01, 2014 to September 30, 2014 with ACVA living in the service area of one of the closest outpatient clinics. Presence of cardiovascular diseases (CVD and their risk factors (RF, prehospital therapy, short-term complications including death and pharmacotherapy recommended to survived patients were analyzed using hospital medical records. During ambulatory follow-up (prospective part of the register the vital status and pharmacotherapy were assessed. Results. The majority of patients with AS had concomitant CVD (on average 2 per patient and non CVD (on average 1.2 per patient. Data on the risk factors of CVD and their complications were reflected insufficiently in the medical records. Most patients in the prehospital period did not receive adequate treatment for the reduction in the cardiovascular risk. 90 patients survived and were discharged. 1.5-2 years after discharge, information on the vital status was available for 78 (86.7% patients. 61 of them (78.2% were alive and 17 (21.8% died. Conclusion. The pilot part of the REGION register revealed that the majority of patients with AS have concomitant CVD and non-CVD. The overall quality of pharmacotherapy, primary and secondary prevention of ACVA was far from that recommended in clinical guidelines, especially during follow-up in outpatient clinic.

  20. Antioxidant responses to an acute ultra-endurance exercise: impact on DNA stability and indications for an increased need for nutritive antioxidants in the early recovery phase.

    Science.gov (United States)

    Neubauer, Oliver; Reichhold, Stefanie; Nics, Lukas; Hoelzl, Christine; Valentini, Judit; Stadlmayr, Barbara; Knasmüller, Siegfried; Wagner, Karl-Heinz

    2010-10-01

    Antioxidant requirements have neither been defined for endurance nor been defined for ultra-endurance athletes. To verify whether an acute bout of ultra-endurance exercise modifies the need for nutritive antioxidants, we aimed (1) to investigate the changes of endogenous and exogenous antioxidants in response to an Ironman triathlon; (2) to particularise the relevance of antioxidant responses to the indices of oxidatively damaged blood lipids, blood cell compounds and lymphocyte DNA and (3) to examine whether potential time-points of increased susceptibility to oxidative damage are associated with alterations in the antioxidant status. Blood that was collected from forty-two well-trained male athletes 2 d pre-race, immediately post-race, and 1, 5 and 19 d later was sampled. The key findings of the present study are as follows: (1) Immediately post-race, vitamin C, α-tocopherol, and levels of the Trolox equivalent antioxidant capacity, the ferric reducing ability of plasma and the oxygen radical absorbance capacity (ORAC) assays increased significantly. Exercise-induced changes in the plasma antioxidant capacity were associated with changes in uric acid, bilirubin and vitamin C. (2) Significant inverse correlations between ORAC levels and indices of oxidatively damaged DNA immediately and 1 d post-race suggest a protective role of the acute antioxidant responses in DNA stability. (3) Significant decreases in carotenoids and γ-tocopherol 1 d post-race indicate that the antioxidant intake during the first 24 h of recovery following an acute ultra-endurance exercise requires specific attention. Furthermore, the present study illustrates the importance of a diversified and well-balanced diet to maintain a physiological antioxidant status in ultra-endurance athletes in reference to recommendations.

  1. The anticancer drug tamoxifen is active against Trypanosoma cruzi in vitro but ineffective in the treatment of the acute phase of Chagas disease in mice

    Directory of Open Access Journals (Sweden)

    Danilo Ciccone Miguel

    2010-11-01

    Full Text Available The activity of the antineoplastic drug tamoxifen was evaluated against Trypanosoma cruzi. In vitro activity was determined against epimastigote, trypomastigote and amastigote forms of CL14, Y and Y benznidazole resistant T. cruzi strains. Regardless of the strain used, the drug was active against all life-cycle stages of the parasite with a half maximal effective concentration ranging from 0.7-17.9 µM. Two experimental models of acute Chagas disease were used to evaluate the in vivo efficacy of treatment with tamoxifen. No differences in parasitemia and mortality were observed between control mock-treated and tamoxifen-treated mice.

  2. Painful Vaso-occlusive Crisis as a  Prodromal Phase of Acute Chest Syndrome. Is Only One Chest X-ray Enough? A Case Report

    Directory of Open Access Journals (Sweden)

    Charalambos Neocleous

    2013-01-01

    Full Text Available The predominant pathophysiological feature of homozygous sickle cell anemia (SCA is the vaso-occlusion. Vaso-occlusion can be associated with painful crises, which are the primary reason for those patients to seek medical care. Vaso-occlusion is responsible for the acute chest syndrome (ACS with large morbidity and mortality or more rarely (and especially in adults for priapism and acute neurological events (strokes. A 10-year-old boy with homozygous SCA was admitted to the Pediatric Emergencies with painful vaso-occlusive crisis and fever. Initially he had normal chest X-ray but, after 24-hour-hospitalization, he developed  ACS with new chest X-ray findings. He was treated with broad spectrum antibiotics, blood transfusions and bronchodilators and after a  six-day treatment, he was significantly improved. The patient was discharged 13 days later with no other therapy at home. The possibility of  ACS development should be still considered, even when a  known patient with SCA presents a  painful vaso-occlusive crisis with an initial normal chest X-ray. Therefore, repeated clinical examination is required and possible changes in  the clinical status could indicate the necessity of a  new radiographic examination. In  this way, early  ACS could be recognized and the catastrophic consequences due to this syndrome could be avoided.

  3. The whole brain diffusion tensor imaging study on acute phase of the posttraumatic stress disorder resulting from the single-prolonged stress based on tract based spatial statistics

    International Nuclear Information System (INIS)

    Xi Yibin; Liu Kang; Zhe Xia; Mu Yunfeng; Yin Hong; Huan Yi; Yang Xiaobin; Du Ping

    2013-01-01

    Objective: To study the changes of the brain white matter microstructure at the acute stage of posttraumatic stress disorder (PTSD) resulting from a single-prolonged stress. Methods: DTI scans were performed on 17 survivors buried more than 190 h in Shanxi Wangjialing mine disaster and 17 cases of normal controls using Siemens 3.0 T MR. The differences of the FA values measured from the whole brain DTI between the two groups were analyzed based on tract based spatial statistics (TBSS). FA data were statistically compared between the two groups based on nonparametric random permutation test (RPT), and the brain areas of the PTSD patients with abnormal FA were defined. Results: Compared with control group, FA values in the PTSD (at acute stage) group decreased in genu, rostral body of corpus callosum, and increased in the left thalamic and corticospinal tract region of bilateral corona radiata and the posterior limb of the left internal capsule, the left cerebral peduncle. The differences were statistically significant (P < 0.01 TFCE-corrected). Conclusions: TBSS is a comprehensive and accurate method for evaluating the changes of whole brain DTI in PTSD cases. The fiber structural abnormalities in the genu, rostral body of bilateral corpus callosum, anterior radiation of left thalamic may be due to stress. TBSS can provide a more objective basis for the early diagnosis and intervention of PTSD. (authors)

  4. Correlation between the Efficacy of Lamotrigine and the Serum Lamotrigine Level during the Remission Phase of Acute Bipolar II Depression: A Naturalistic and Unblinded Prospective Pilot Study.

    Science.gov (United States)

    Kikkawa, Akiyoshi; Kitamura, Yoshihisa; Aiba, Tetsuya; Hiraki, Koichi; Sendo, Toshiaki

    2017-01-01

    Lamotrigine has acute antidepressant effects in patients with bipolar disorder. However, there is little information regarding appropriate serum levels of lamotrigine and the time until remission after the start of lamotrigine therapy in patients with bipolar II depression. This was a naturalistic and unblinded prospective pilot study. Twelve patients' depressive symptoms were evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS) at the start of treatment and at the time of remission, and blood samples were obtained at the time of remission. Mahalanobis distance was used to analyze the relationship between the MADRS improvement rate and the serum lamotrigine level. Furthermore, we calculated the Spearman's rank correlation coefficient for the relationship between the MADRS improvement rate and the serum lamotrigine level, and produced box plots of the serum lamotrigine level at remission and the time until remission. The Mahalanobis distance for the patient that was co-administered lamotrigine and valproic acid differed significantly from those of the other patients (p<0.001). There was no linear relationship between the serum lamotrigine level and the MADRS improvement rate among the patients that did not receive valproic acid. The median time from the start of lamotrigine therapy until remission was 6 weeks. The serum lamotrigine level does not have an important impact on the acute therapeutic effects of lamotrigine on bipolar II depression. In addition, we consider that different treatment options should be considered for non-responders who do not exhibit any improvement after the administration of lamotrigine for approximately 6 weeks.

  5. Acute nephritic syndrome

    Science.gov (United States)

    Glomerulonephritis - acute; Acute glomerulonephritis; Nephritis syndrome - acute ... Acute nephritic syndrome is often caused by an immune response triggered by an infection or other disease. Common causes in children ...

  6. Acute reperfusion without recanalization

    DEFF Research Database (Denmark)

    Makris, Nikolaos; Chamard, Leila; Mikkelsen, Irene K

    2017-01-01

    Acute reperfusion despite persistent arterial occlusion may occur in up to 30% of ischemic stroke patients. Recruitment of leptomeningeal collaterals may explain this phenomenon. Using dynamic susceptibility-contrast perfusion imaging (DSC-PI), we assessed acute changes in collateral flow among...... patients without recanalization. From a multicenter prospective database (I-KNOW), 46 patients with magnetic resonance angiography visible occlusion in whom both reperfusion and recanalization were assessed within 6 h of onset were identified. Maps of collateral flow at arterial, capillary and late venous...... phases were generated from DSC-PI through inter-frame registration, baseline signal subtraction and temporal summation, and graded blind to all other relevant clinical and radiological data using the Higashida scale. Flow direction and the acute evolution of collaterals were evaluated against...

  7. A phase II randomized study of topical intrarectal administration of amifostine for the prevention of acute radiation-induced rectal toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kouloulias, V.E. [Dept. of Radiation Oncology, Aretaieion Univ. Hospital, Univ. of Athens Medical School, Athens (Greece); Dept. of Electrical and Computer Engineering, National Technical Univ. of Athens, Athens (Greece); Center of Radiation Oncology, YGEIA Diagnostic and Therapeutic Center of Athens, Athens (Greece); Kouvaris, J.R.; Kokakis, J.D.; Antypas, C.; Mallas, E.; Vosdoganis, S.P.; Vlahos, L.J. [Dept. of Radiation Oncology, Aretaieion Univ. Hospital, Univ. of Athens Medical School, Athens (Greece); Pissakas, G. [Radiotherapy Dept., Agios Savvas Anticancer Hospital, Athens (Greece); Matsopoulos, G. [Dept. of Electrical and Computer Engineering, National Technical Univ. of Athens, Athens (Greece); Michopoulos, S. [Gastroenterology Unit, Alexandra General Hospital, Athens (Greece); Kostakopoulos, A. [Urology Dept., Sismanoglio Hospital, Univ. of Athens Medical School, Athens (Greece)

    2004-09-01

    Purpose: to investigate the cytoprotective effect of intrarectal amifostine administration on acute radiation-induced rectal toxicity. Patients and methods: 67 patients with T1b-2 NO MO prostate cancer were randomized to receive amifostine intrarectally (group A, n - 33) or not (group B, n = 34) before irradiation. Therapy was delivered using a four-field technique with three-dimensional conformal planning. In group A, 1,500 mg amifostine was administered intrarectally as an aqueous solution in a 40-ml enema. Two different toxicity scales were used: EORTC/RTOG rectal and urologic toxicity criteria along with a Subjective-RectoSigmoid (S-RS) scale based on the endoscopic terminology of the World Organization for Digestive Endoscopy. Objective measurements with rectosigmoidoscopy were performed at baseline and 1-2 days after the completion of radiotherapy. The area under curve for the time course of mucositis (RTOG criteria) during irradiation represented the mucositis index (MI). Results: intrarectal amifostine was feasible and well tolerated without any systemic or local side effects. According to the RTOG toxicity scale, five out of 33 patients showed grade 1 mucositis in group A versus 15 out of 34 patients with grade 1/2 in group B (p = 0.026). Mean rectal MI was 0.3 {+-} 0.1 in group A versus 2.2 {+-} 0.4 in group B (p < 0.001), while S-RS score was 3.9 {+-} 0.5 in group A versus 6.3 {+-} 0.7 in group B (p < 0.001). The incidence of urinary toxicity was the same in both groups. Conclusion: intrarectal administration of amifostine seems to have a cytoprotective efficacy in acute radiation-induced rectal mucositis. Further randomized studies are needed for definitive therapeutic decisions. (orig.)

  8. Ação do prebiótico sobre as proteínas de fase aguda de pacientes com neoplasia hematológica Action of prebiotics on proteins in the acute phase of hematologic neoplasia

    Directory of Open Access Journals (Sweden)

    Telma Búrigo

    2007-06-01

    developed in the Bone Marrow Transplantation Unit of the Oncology Research Center in Florianopolis and was aimed at studying the action of prebiotic agents on protein response in the acute phase of hematologic neoplastic patients submitted to chemotherapy. A double-blind randomized clinical trial was performed involving 25 patients divided into two groups. Patients received 12 g FOS (n=14 or placebo (maltdextrine (n=11 over 15 days. All the variables were determined before and after supplementation. The serum levels of negative acute phase proteins, albumin and pre-albumin, and positive acute phase proteins, C-reactive protein, were evaluated. The presence of diarrhea and constipation are reported, as are the quantity of bifidobacteria and fecal pH measurements. Reductions in the serum levels of negative acute phase proteins (albumin and pre-albumin show intense proteic catabolism thereby, favoring the synthesis of protein in the positive acute phase. The supplemented group presented with a significant increase in the quantity of bifidobacteria. The fecal pH levels were affected in both groups. The serum levels of positive acute phase proteins were statistically higher in the control group indicating the occurrence of inflammatory processes and a higher metabolic demand suggesting that the quantity of bifidobacteria may favor a reduction of these adverse conditions in the supplemented group as was confirmed by the negative correlation between variables.

  9. A Phase II single-arm trial of palonosetron for the prevention of acute and delayed chemotherapy-induced nausea and vomiting in malignant glioma patients receiving multidose irinotecan in combination with bevacizumab

    Directory of Open Access Journals (Sweden)

    Affronti ML

    2016-12-01

    Full Text Available Mary Lou Affronti,1–3 Sarah Woodring,1,2 Katherine B Peters,1,4 James E Herndon II,5 Frances McSherry,5 Patrick N Healy,5 Annick Desjardins,1,4 James J Vredenburgh,6 Henry S Friedman1,2 1The Preston Robert Tisch Brain Tumor Center at Duke, South Hospital, Duke University Medical Center, 2Department of Neurosurgery, Duke University Health System, 3Duke University School of Nursing, 4Department of Neurology, 5Department of Biostatistics and Bioinformatics, Duke University Health System, Durham, NC, 6Saint Francis Cancer Center, Hartford, CT, USA Purpose: Given that the prognosis of recurrent malignant glioma (MG remains poor, improving quality of life (QoL through symptom management is important. Meta-analyses establishing antiemetic guidelines have demonstrated the superiority of palonosetron (PAL over older 5-hydroxytryptamine 3-receptor antagonists in chemotherapy-induced nausea and vomiting (CINV prevention, but excluded patients with gliomas. Irinotecan plus bevacizumab is a treatment frequently used in MG, but is associated with low (55% CINV complete response (CR; no emesis or use of rescue antiemetic with commonly prescribed ondansetron. A single-arm Phase II trial was conducted in MG patients to determine the efficacy of intravenous PAL (0.25 mg and dexamethasone (DEX; 10 mg received in conjunction with biweekly irinotecan–bevacizumab treatment. The primary end point was the proportion of subjects achieving acute CINV CR (no emesis or antiemetic ≤24 hours postchemotherapy. Secondary end points included delayed CINV CR (days 2–5, overall CINV CR (days 1–5, and QoL, fatigue, and toxicity.Materials and methods: A two-stage design of 160 patients was planned to differentiate between CINV CR of 55% and 65% after each dose of PAL–DEX. Validated surveys assessed fatigue and QoL.Results: A total of 63 patients were enrolled, after which enrollment was terminated due to slow accrual; 52 patients were evaluable for the primary outcome

  10. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  11. Double-blind randomized phase III study comparing a mixture of natural agents versus placebo in the prevention of acute mucositis during chemoradiotherapy for head and neck cancer.

    Science.gov (United States)

    Marucci, Laura; Farneti, Alessia; Di Ridolfi, Paolo; Pinnaro, Paola; Pellini, Raul; Giannarelli, Diana; Vici, Patrizia; Conte, Mario; Landoni, Valeria; Sanguineti, Giuseppe

    2017-09-01

    There is no widely accepted intervention in the prevention of acute mucositis during chemoradiotherapy for head and neck carcinoma. In the present double-blind study, we tested 4 natural agents, propolis, aloe vera, calendula, and chamomile versus placebo. Patients undergoing concomitant chemo-intensity-modulated radiotherapy (IMRT) were given natural agent or matched placebo; grade 3 mucositis on physical examination according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was the primary endpoint. Various covariates were tested at logistic regression, including the individual amount of mucosa receiving at least 9.5 Gy per week (V9.5w). One hundred seven patients were randomized from January 2011 to July 2014, and 104 were assessable (51%-49% were assigned to the placebo group and 53%-51% were assigned to the natural agent). Overall, 61 patients developed peak grade 3 mucositis with no difference between arms (P = .65). Conversely, V9.5w (P = .007) and primary site (P = .037) were independent predictors. The selected natural agents do not prevent mucositis, whereas the role of V9.5w is confirmed. © 2017 Wiley Periodicals, Inc.

  12. Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study.

    Science.gov (United States)

    Swords, Ronan T; Erba, Harry P; DeAngelo, Daniel J; Bixby, Dale L; Altman, Jessica K; Maris, Michael; Hua, Zhaowei; Blakemore, Stephen J; Faessel, Hélène; Sedarati, Farhad; Dezube, Bruce J; Giles, Francis J; Medeiros, Bruno C

    2015-05-01

    This trial was conducted to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the first in class NEDD8-activating enzyme (NAE) inhibitor, pevonedistat, and to investigate pevonedistat pharmacokinetics and pharmacodynamics in patients with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Pevonedistat was administered via a 60-min intravenous infusion on days 1, 3 and 5 (schedule A, n = 27), or days 1, 4, 8 and 11 (schedule B, n = 26) every 21-days. Dose escalation proceeded using a standard '3 + 3' design. Responses were assessed according to published guidelines. The MTD for schedules A and B were 59 and 83 mg/m(2) , respectively. On schedule A, hepatotoxicity was dose limiting. Multi-organ failure (MOF) was dose limiting on schedule B. The overall complete (CR) and partial (PR) response rate in patients treated at or below the MTD was 17% (4/23, 2 CRs, 2 PRs) for schedule A and 10% (2/19, 2 PRs) for schedule B. Pevonedistat plasma concentrations peaked after infusion followed by elimination in a biphasic pattern. Pharmacodynamic studies of biological correlates of NAE inhibition demonstrated target-specific activity of pevonedistat. In conclusion, administration of the first-in-class agent, pevonedistat, was feasible in patients with MDS and AML and modest clinical activity was observed. © 2015 John Wiley & Sons Ltd.

  13. Mitoxantrone, etoposide and cytarabine following epigenetic priming with decitabine in adults with relapsed/refractory acute myeloid leukemia or other high-grade myeloid neoplasms: a phase 1/2 study.

    Science.gov (United States)

    Halpern, A B; Othus, M; Huebner, E M; Buckley, S A; Pogosova-Agadjanyan, E L; Orlowski, K F; Scott, B L; Becker, P S; Hendrie, P C; Chen, T L; Percival, M-E M; Estey, E H; Stirewalt, D L; Walter, R B

    2017-12-01

    DNA methyltransferase inhibitors sensitize leukemia cells to chemotherapeutics. We therefore conducted a phase 1/2 study of mitoxantrone, etoposide and cytarabine following 'priming' with 5-10 days of decitabine (dec/MEC) in 52 adults (median age 55 (range: 19-72) years) with relapsed/refractory acute myeloid leukemia (AML) or other high-grade myeloid neoplasms. During dose escalation in cohorts of 6-12 patients, all dose levels were well tolerated. As response rates appeared similar with 7 and 10 days of decitabine, a 7-day course was defined as the recommended phase 2 dose (RP2D). Among 46 patients treated at/above the RP2D, 10 (22%) achieved a complete remission (CR), 8 without measurable residual disease; five additional patients achieved CR with incomplete platelet recovery, for an overall response rate of 33%. Seven patients (15%) died within 28 days of treatment initiation. Infection/neutropenic fever, nausea and mucositis were the most common adverse events. While the CR rate compared favorably to a matched historic control population (observed/expected CR ratio=1.77), CR rate and survival were similar to two contemporary salvage regimens used at our institution (G-CLAC (granulocyte colony-stimulating factor (G-CSF); clofarabine; cytarabine) and G-CLAM (G-CSF; cladribine; cytarabine; mitoxantrone)). Thus, while meeting the prespecified efficacy goal, we found no evidence that dec/MEC is substantially better than other cytarabine-based regimens currently used for relapsed/refractory AML.

  14. Three-phase bone scintigraphy with Tc-99m MDP in the diagnosis and management of acute osteoarticular infections in children; Cintigrafia osea trifasica con Tc-99m MDP en el diagnostico y manejo de infecciones osteoarticulares agudas en ninos

    Energy Technology Data Exchange (ETDEWEB)

    Coll C, Claudia [Hospital Clinico de la Universidad de Chile, Departamento de Medicina, Medicina Nuclear, Santiago (Chile); Cifras V, Jose Luis [Hospital Felix Bulnes C, Servicio de Ortopedia y Traumatologia Infantil, Santiago (Chile); Massardo V, Teresa [Hospital Clinico de la Universidad de Chile, Departamento de Medicina, Medicina Nuclear, Santiago (Chile); Moya S, Hernan [Hospital Roberto del Rio, Servicio de Ortopedia y Traumatologia Infantil, Santiago (Chile)

    2002-07-01

    One of the most important causes of residual damage in skeleton is incompletely treated osteoarticular infections (OAI). Goal: to assess the value of emergency three-phase bone scan (3FBS) in the evaluation of OAI. Methods: Thirty-eight children were studied with 54 3FBS. Results: Global analysis: 76% of the cases were principally articular; staphylococcus germs and hip's affection were the common. Nine patients with preoperative scan were positive with 16 foci, 86% confirmed by surgery cultivate. Seven children had negative 3FBS without posterior clinical symptomatology; in 5 of them it was demonstrated soft tissue involvement with normal osteoblastic phase. In 14/17 cases evaluated after surgical intervention, there was a relation between the scan and the clinical course. In two of those cases, in the 3FBS a new location was found. Conclusion: 3FBS is a helpful tool in the diagnosis and assessment of acute OAI in pediatric population. A positive 3FBS is highly accurate for OAI and a negative one rules it out securely (au)

  15. Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ringbaek, T.; Lange, P.; Mogensen, T.

    2008-01-01

    Acute exacerbation of COPD is a major cause of hospitalisation in Denmark. Most of the patients require supplemental oxygen in the acute phase and some patients continue oxygen therapy at home after discharge. In this paper we discuss the physiological mechanisms of respiratory failure seen...... in acute exacerbations of COPD. The principles for oxygen therapy in the acute phase are described and recommendations for oxygen therapy are suggested Udgivelsesdato: 2008/5/5...

  16. Hemometabolismo cerebral: variações na fase aguda do coma traumático Cerebral hemometabolism: variability in the acute phase of traumatic coma

    Directory of Open Access Journals (Sweden)

    ANTONIO L. E. FALCÃO

    2000-09-01

    Full Text Available OBJETIVO: avaliar as interrelações entre as alterações hemometabólicas cerebrais e sistêmicas em pacientes com traumatismo craniencefálico (TCE grave submetidos a um protocolo terapêutico padronizado. DESENHO: estudo prospectivo, intervencionista em pacientes com coma traumático. LOCAL: uma UTI geral em hospital universitário. PACIENTES E MÉTODOS: vinte e sete pacientes (21M e 6F, idade 14-58 anos, com TCE grave, com três a oito pontos na escala de coma de Glasgow, foram avaliados prospectivamente segundo um protocolo cumulativo padronizado para tratamento da hipertensão intracraniana aguda, o qual incluía medidas rotineiras da pressão intracraniana (PIC e da extração cerebral de oxigênio (ECO2. Foram analisadas as interrelações hemometabólicas envolvendo: pressão arterial média (PAM, PIC, pressão parcial de gás carbônico arterial (PaCO2, ECO2, pressão de perfusão cerebral (PPC e extração sistêmica de oxigênio (ESO2. INTERVENÇÕES: apenas as padronizadas no protocolo terapêutico. RESULTADOS: não houve correlação entre a ECO2 e a PPC (r = -0,07; p = 0,41. Houve correlação inversa entre a PaCO2 e a ECO2 (r = -0,24; p = 0,005 e direta entre a ESO2 e a ECO2 (r = 0,24; p = 0,01. A mortalidade geral dos pacientes foi de 25,9% (7/27. CONCLUSÃO: 1 a PPC não se correlaciona com a ECO2 em quaisquer níveis de PIC; 2 a ECO2 está estreitamente relacionada aos diferentes níveis de PaCO2 ; e 3 durante a hiperventilação otimizada existe um acoplamento entre a ECO2 e a ESO2.OBJECTIVE: to evaluate the interrelationships between cerebral and systemic hemometabolic alterations in patients with severe traumatic brain injury managed according to a standardized therapeutic protocol. DESIGN: prospective, interventional study in patients with traumatic coma. SETTING: a general Intensive Care Unit in a teaching hospital. PATIENTS AND METHODS: twenty-seven patients (21M e 6F, aging 14--58 years, with severe acute brain trauma

  17. Acute pancreatitis.

    Science.gov (United States)

    Talukdar, Rupjyoti; Vege, Santhi S

    2015-09-01

    To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality.

  18. Time to Angiographic Reperfusion and Clinical Outcome after Acute Ischemic Stroke in the Interventional Management of Stroke Phase III (IMS III) Trial: A Validation Study

    Science.gov (United States)

    Khatri, Pooja; Yeatts, Sharon D.; Mazighi, Mikael; Broderick, Joseph P.; Liebeskind, David S.; Demchuk, Andrew M.; Amarenco, Pierre; Carrozzella, Janice; Spilker, Judith; Foster, Lydia D.; Goyal, Mayank; Hill, Michael D.; Palesch, Yuko Y.; Jauch, Edward C.; Haley, E. Clarke; Vagal, Achala; Tomsick, Thomas A.

    2014-01-01

    BACKGROUND The IMS III Trial did not demonstrate clinical benefit of the endovascular approach compared to IV rt-PA alone for moderate or severe ischemic strokes (NIHSS≥8) enrolled within three hours of stroke onset. Late reperfusion of tissue that is no longer salvageable may be one explanation, as suggested by prior exploratory studies showing an association between time to reperfusion and good clinical outcome. We sought to validate this relationship in the large-scale IMS III trial, and consider its implications for future endovascular trials. METHODS The analysis consisted of the endovascular cohort with proximal arterial occlusions in the anterior circulation that achieved angiographic reperfusion (TICI 2–3) during the endovascular procedure (within 7 hours from the onset of symptoms). Logistic regression was used to model good clinical outcome (90-day modified Rankin 0–2) as a function of the time to reperfusion, and prespecified variables were considered for adjustment. FINDINGS Among 240 proximal vessel occlusions, angiographic reperfusion (TICI 2–3) was achieved in 182 (76%). Mean time to reperfusion was 325 minutes (range 180–418 minutes). Longer time for reperfusion was associated with a decreased likelihood of good clinical outcome (RR [95% CI] for every 30 minute delay: unadjusted 0·85 [0·77–0·94]; adjusted 0·88 [0·80–0·98]). INTERPRETATION We confirm that delay in time to angiographic reperfusion leads to a decreased likelihood of good clinical outcome. Achieving rapid reperfusion may be critical for the successes of future acute endovascular trials. FUNDING: NIH/NINDS (study sponsor), Genentech Inc. (study drug - intra-arterial t-PA), EKOS Corp. (device), Concentric Inc. (device), Cordis Neurovascular, Inc. (device), and Boehringer Ingelheim (European Investigator Meeting support). PMID:24784550

  19. Two-Stage Priming of Allogeneic Natural Killer Cells for the Treatment of Patients with Acute Myeloid Leukemia: A Phase I Trial.

    Directory of Open Access Journals (Sweden)

    Panagiotis D Kottaridis

    Full Text Available Human Natural Killer (NK cells require at least two signals to trigger tumor cell lysis. Absence of ligands providing either signal 1 or 2 provides NK resistance. We manufactured a lysate of a tumour cell line which provides signal 1 to resting NK cells without signal 2. The tumor-primed NK cells (TpNK lyse NK resistant Acute Myeloid Leukemia (AML blasts expressing signal 2 ligands. We conducted a clinical trial to determine the toxicity of TpNK cell infusions from haploidentical donors. 15 patients with high risk AML were screened, 13 enrolled and 7 patients treated. The remaining 6 either failed to respond to re-induction chemotherapy or the donor refused to undergo peripheral blood apheresis. The conditioning consisted of fludarabine and total body irradiation. This was the first UK trial of a cell therapy regulated as a medicine. The complexity of Good Clinical Practice compliance was underestimated and led to failures requiring retrospective independent data review. The lessons learned are an important aspect of this report. There was no evidence of infusional toxicity. Profound myelosuppression was seen in the majority (median neutrophil recovery day 55. At six months follow-up, three patients treated in Complete Remission (CR remained in remission, one patient infused in Partial Remission had achieved CR1, two had relapsed and one had died. One year post-treatment one patient remained in CR. Four patients remained in CR after treatment for longer than their most recent previous CR. During the 2 year follow-up six of seven patients died; median overall survival was 400 days post infusion (range 141–910. This is the first clinical trial of an NK therapy in the absence of IL-2 or other cytokine support. The HLA-mismatched NK cells survived and expanded in vivo without on-going host immunosuppression and appeared to exert an anti-leukemia effect in 4/7 patients treated.ISRCTN trial registry ISRCTN11950134.

  20. Inclusion of anti-phospholipase A2 antibody to backgrounding diets on performance, feed efficiency, in vitro fermentation, and the acute-phase response of growing beef calves.

    Science.gov (United States)

    Mercadante, V R G; Waters, K M; Marquezini, G H L; Henry, D D; Ciriaco, F M; Arthington, J D; DiLorenzo, N; Lamb, G C

    2015-01-01

    In Exp. 1, individual performance and daily DMI was measured on 70 crossbred weaned calves during a 70-d period using a GrowSafe system (GrowSafe Systems Ltd., Airdrie, AB, Canada) at the University of Florida North Florida Research and Education Center Feed Efficiency Facility (FEF). Calves were fed a low-concentrate (LC) growing diet, blocked by weight and sex, and then randomly assigned to pens to receive either no additional supplement (CON; n = 35) or receive a supplement of anti-phospholipase A2 antibody (aPLA2) at an inclusion rate of 0.6% of the diet DM (n = 35). After the 70-d feed efficiency (FE) trial (Phase 1), calves were loaded into a commercial livestock trailer and were driven for approximately 1,600 km during 24 h. Upon return to the FEF (Phase 2), calves were relocated to the same pens and groups and received the same diets and treatments for 28 d. Blood samples from each calf were collected on d 0, 1, 3, 5, 7, 14, 21, and 28 relative to initiation of transportation and were analyzed for determination of concentrations of plasma ceruloplasmin and haptoglobin. In Phase 1, initial BW (242.0 ± 3.7 kg; P = 0.92), BW at d 70 (313.0 ± 4.1 kg; P = 0.79), and ADG (1.01 ± 0.02 kg; P = 0.95) were similar between treatments. However, daily DMI was greater (P = 0.01) for CON (9.18 ± 0.15 kg) than aPLA2 (8.53 ± 0.15 kg). In addition, residual feed intake was greater (P = 0.002) for CON (0.389 ± 0.110 kg/d) than aPLA2 calves (-0.272 ± 0.110 kg/d). In Phase 2, after transportation, there were no differences between treatments on BW loss due to transportation shrink (26.0 ± 0.6 kg; P = 0.86), BW at d 28 (339.0 ± 4.1 kg; P = 0.72), ADG (1.28 ± 0.03 kg/d; P = 0.72), G:F (0.164 ± 0.004; P = 0.83), and concentrations of plasma haptoglobin (0.08 ± 0.02 mg/mL; P = 0.41). However, concentrations of plasma ceruloplasmin were greater (P calves (14.3 ± 0.3 mg/dL) compared to aPLA2 calves (13.0 ± 0.3 mg/dL). In Exp. 2, the effects of aPLA2 inclusion on LC and

  1. Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial

    Energy Technology Data Exchange (ETDEWEB)

    But-Hadzic, Jasna, E-mail: jbut@onko-i.si [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Anderluh, Franc [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Brecelj, Erik; Edhemovic, Ibrahim [Division of Surgery, Institute of Oncology, Ljubljana (Slovenia); Secerov-Ermenc, Ajra; Hudej, Rihard; Jeromen, Ana [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Kozelj, Miran; Krebs, Bojan [Division of Surgery, University Medical Centre Maribor, Maribor (Slovenia); Oblak, Irena [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Omejc, Mirko [Division of Surgery, University Medical Centre Lubljana, Ljubljana (Slovenia); Vogrin, Andrej [Division of Diagnostics, Institute of Oncology, Ljubljana (Slovenia); Velenik, Vaneja [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia)

    2016-12-01

    Background and Purpose: This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. Methods and Materials: Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m{sup 2}/12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). Results: Fifty patients completed preoperative treatment according to the protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. Conclusions: Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging.

  2. N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy

    International Nuclear Information System (INIS)

    Miller, Robert C.; Petereit, Daniel G.; Sloan, Jeff A.; Liu, Heshan; Martenson, James A.; Bearden, James D.; Sapiente, Ronald; Seeger, Grant R.; Mowat, Rex B.; Liem, Ben; Iott, Matthew J.; Loprinzi, Charles L.

    2016-01-01

    Purpose: To provide confirmatory evidence on the use of sulfasalazine to reduce enteritis during pelvic radiation therapy (RT), following 2 prior single-institution trials suggestive that benefit existed. Methods and Materials: A multi-institution, randomized, double-blind, placebo-controlled phase 3 trial was designed to assess the efficacy of sulfasalazine versus placebo in the treatment of RT-related enteritis during RT including the posterior pelvis (45.0-53.5 Gy) and conducted through a multicenter national cooperative research alliance. Patients received 1000 mg of sulfasalazine or placebo orally twice daily during and for 4 weeks after RT. The primary endpoint was maximum severity of diarrhea (Common Terminology Criteria for Adverse Events version 4.0). Toxicity and bowel function were assessed by providers through a self-administered bowel function questionnaire taken weekly during RT and for 6 weeks afterward. Results: Eighty-seven patients were enrolled in the trial between April 29, 2011, and May 13, 2013, with evenly distributed baseline factors. At the time of a planned interim toxicity analysis, more patients with grade ≥3 diarrhea received sulfasalazine than received placebo (29% vs 11%, P=.04). A futility analysis showed that trial continuation would be unlikely to yield a positive result, and a research board recommended halting study treatment. Final analysis of the primary endpoint showed no significant difference in maximum diarrhea severity between the sulfasalazine and placebo arms (P=.41). Conclusions: Sulfasalazine does not reduce enteritis during pelvic RT and may be associated with a higher risk of adverse events than placebo. This trial illustrates the importance of confirmatory phase 3 trials in the evaluation of symptom-control agents.

  3. N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Robert C., E-mail: miller.robert@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Petereit, Daniel G. [Rapid City Regional Oncology Group, Rapid City, South Dakota (United States); Sloan, Jeff A.; Liu, Heshan [Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota (United States); Martenson, James A. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Bearden, James D. [Upstate Carolina Community Clinical Oncology Program, Spartanburg, South Carolina (United States); Sapiente, Ronald [Carle Cancer Center CCOP, Urbana, Illinois (United States); Seeger, Grant R. [Altru Health Systems, Grand Forks, North Dakota (United States); Mowat, Rex B. [Toledo Community Hospital Oncology Program CCOP, Toledo, Ohio (United States); Liem, Ben [University of New Mexico, Albuquerque, New Mexico (United States); Iott, Matthew J. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Loprinzi, Charles L. [Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota (United States)

    2016-07-15

    Purpose: To provide confirmatory evidence on the use of sulfasalazine to reduce enteritis during pelvic radiation therapy (RT), following 2 prior single-institution trials suggestive that benefit existed. Methods and Materials: A multi-institution, randomized, double-blind, placebo-controlled phase 3 trial was designed to assess the efficacy of sulfasalazine versus placebo in the treatment of RT-related enteritis during RT including the posterior pelvis (45.0-53.5 Gy) and conducted through a multicenter national cooperative research alliance. Patients received 1000 mg of sulfasalazine or placebo orally twice daily during and for 4 weeks after RT. The primary endpoint was maximum severity of diarrhea (Common Terminology Criteria for Adverse Events version 4.0). Toxicity and bowel function were assessed by providers through a self-administered bowel function questionnaire taken weekly during RT and for 6 weeks afterward. Results: Eighty-seven patients were enrolled in the trial between April 29, 2011, and May 13, 2013, with evenly distributed baseline factors. At the time of a planned interim toxicity analysis, more patients with grade ≥3 diarrhea received sulfasalazine than received placebo (29% vs 11%, P=.04). A futility analysis showed that trial continuation would be unlikely to yield a positive result, and a research board recommended halting study treatment. Final analysis of the primary endpoint showed no significant difference in maximum diarrhea severity between the sulfasalazine and placebo arms (P=.41). Conclusions: Sulfasalazine does not reduce enteritis during pelvic RT and may be associated with a higher risk of adverse events than placebo. This trial illustrates the importance of confirmatory phase 3 trials in the evaluation of symptom-control agents.

  4. A randomized phase II/III study of adverse events between sequential (SEQ) versus simultaneous integrated boost (SIB) intensity modulated radiation therapy (IMRT) in nasopharyngeal carcinoma; preliminary result on acute adverse events.

    Science.gov (United States)

    Songthong, Anussara P; Kannarunimit, Danita; Chakkabat, Chakkapong; Lertbutsayanukul, Chawalit

    2015-08-08

    To investigate acute and late toxicities comparing sequential (SEQ-IMRT) versus simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) in nasopharyngeal carcinoma (NPC) patients. Newly diagnosed stage I-IVB NPC patients were randomized to receive SEQ-IMRT or SIB-IMRT, with or without chemotherapy. SEQ-IMRT consisted of two sequential radiation treatment plans: 2 Gy x 25 fractions to low-risk planning target volume (PTV-LR) followed by 2 Gy x 10 fractions to high-risk planning target volume (PTV-HR). In contrast, SIB-IMRT consisted of only one treatment plan: 2.12 Gy and 1.7 Gy x 33 fractions to PTV-HR and PTV-LR, respectively. Toxicities were evaluated according to CTCAE version 4.0. Between October 2010 and November 2013, 122 eligible patients were randomized between SEQ-IMRT (54 patients) and SIB-IMRT (68 patients). With median follow-up time of 16.8 months, there was no significant difference in toxicities between the two IMRT techniques. During chemoradiation, the most common grade 3-5 acute toxicities were mucositis (15.4% vs 13.6%, SEQ vs SIB, p = 0.788) followed by dysphagia (9.6% vs 9.1%, p = 1.000) and xerostomia (9.6% vs 7.6%, p = 0.748). During the adjuvant chemotherapy period, 25.6% and 32.7% experienced grade 3 weight loss in SEQ-IMRT and SIB-IMRT (p = 0.459). One-year overall survival (OS) and progression-free survival (PFS) were 95.8% and 95.5% in SEQ-IMRT and 98% and 90.2% in SIB-IMRT, respectively (p = 0.472 for OS and 0.069 for PFS). This randomized, phase II/III trial comparing SIB-IMRT versus SEQ-IMRT in NPC showed no statistically significant difference between both IMRT techniques in terms of acute adverse events. Short-term tumor control and survival outcome were promising.

  5. A randomized phase II/III study of adverse events between sequential (SEQ) versus simultaneous integrated boost (SIB) intensity modulated radiation therapy (IMRT) in nasopharyngeal carcinoma; preliminary result on acute adverse events

    International Nuclear Information System (INIS)

    Songthong, Anussara P.; Kannarunimit, Danita; Chakkabat, Chakkapong; Lertbutsayanukul, Chawalit

    2015-01-01

    To investigate acute and late toxicities comparing sequential (SEQ-IMRT) versus simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) in nasopharyngeal carcinoma (NPC) patients. Newly diagnosed stage I-IVB NPC patients were randomized to receive SEQ-IMRT or SIB-IMRT, with or without chemotherapy. SEQ-IMRT consisted of two sequential radiation treatment plans: 2Gy x 25 fractions to low-risk planning target volume (PTV-LR) followed by 2Gy x 10 fractions to high-risk planning target volume (PTV-HR). In contrast, SIB-IMRT consisted of only one treatment plan: 2.12Gy and 1.7Gy x 33 fractions to PTV-HR and PTV-LR, respectively. Toxicities were evaluated according to CTCAE version 4.0. Between October 2010 and November 2013, 122 eligible patients were randomized between SEQ-IMRT (54 patients) and SIB-IMRT (68 patients). With median follow-up time of 16.8 months, there was no significant difference in toxicities between the two IMRT techniques. During chemoradiation, the most common grade 3–5 acute toxicities were mucositis (15.4 % vs 13.6 %, SEQ vs SIB, p = 0.788) followed by dysphagia (9.6 % vs 9.1 %, p = 1.000) and xerostomia (9.6 % vs 7.6 %, p = 0.748). During the adjuvant chemotherapy period, 25.6 % and 32.7 % experienced grade 3 weight loss in SEQ-IMRT and SIB-IMRT (p = 0.459). One-year overall survival (OS) and progression-free survival (PFS) were 95.8 % and 95.5 % in SEQ-IMRT and 98 % and 90.2 % in SIB-IMRT, respectively (p = 0.472 for OS and 0.069 for PFS). This randomized, phase II/III trial comparing SIB-IMRT versus SEQ-IMRT in NPC showed no statistically significant difference between both IMRT techniques in terms of acute adverse events. Short-term tumor control and survival outcome were promising

  6. Effects of dietary energy level and intake of corn by-product-based diets on newly received growing cattle: antibody production, acute phase protein response, stress, and immunocompetency of healthy and morbid animals.

    Science.gov (United States)

    Spore, Tyler J; Montgomery, Sean P; Titgemeyer, Evan C; Hanzlicek, Gregg A; Vahl, Chris I; Nagaraja, Tiruvoor G; Cavalli, Kevin T; Hollenbeck, William R; Wahl, Ross A; Blasi, Dale A

    2018-04-14

    Effects of dietary energy level and intake of corn by-product-based diets on antibody production, acute phase protein response, stress, and immunocompetency of healthy and morbid newly received growing cattle were evaluated. Four dietary treatments were formulated to supply 0.99, 1.10, 1.21, and 1.32 Mcal NEg/ kg DM and were offered at 100%, 95%, 90%, and 85% of ad libitum based on 0.99/100 treatment intake, respectively. Thirty-two pens were utilized with approximately 12 animals/pen. Four animals from each pen (32/dietary treatment) were randomly selected and used to serve as a subset to monitor immune function and acute phase proteins following a split-plot design. In addition, two animals were randomly and independently selected from each pen (16/dietary treatment) and used to measure fecal cortisol metabolite. Additionally, animals removed from the pen one (M1), two (M2), or three (M3) times and classified as morbid were bled in conjunction with a healthy control (H) removed at the same time and the serum analyzed for the same parameters. A quadratic response to time (P bovine viral diarrhea type 1 (BVD-I) and infectious bovine rhinotracheitis (IBR; P levels by day 27. Titer levels for BVD-I and IBR were lowest on arrival, higher on day 14, and significantly higher on day 27. Titers for bovine viral diarrhea type 2 (BVD-II) responded linearly (P levels on arrival and highest levels on day 27. Haptoglobin was elevated in morbid animals compared to healthy pen mates (P levels for BVD-I and IBR were also higher in healthy animals compared to animals pulled for morbidity (P energy receiving diets based on fermentable fiber from by-products can be fed to newly received growing cattle without negative effects on antibody production toward vaccines, inflammation, or overall stress. In addition, haptoglobin concentrations and titer levels for BVD-I and IBR viruses are higher in healthy animals compared to sick animals.

  7. Acute phase protein mRNA expressions and enhancement of antioxidant defense system in Black-meated Silkie Fowls supplemented with clove (Eugenia caryophyllus extracts under the influence of chronic heat stress

    Directory of Open Access Journals (Sweden)

    Alhassan Usman Bello

    2016-11-01

    Full Text Available Abstract Background The current study investigates the anti-stress effects of clove (Eugenia caryophyllus extracts (0, 200, 400, and 600 mg/kg on serum antioxidant biomarkers, immune response, immunological organ growth index, and expression levels of acute phase proteins (APPs; ovotransferrin (OVT, ceruloplasmin (CP, ceruloplasmin (AGP, C-reactive protein (CRP, and serum amyloid-A (SAA mRNA in the immunological organs of 63-d-old male black-meated Silkie fowls subjected to 21 d chronic heat stress at 35 ± 2 °C. Results The results demonstrated that clove extract supplementation in the diet of Silkie fowls subjected to elevated temperature (ET improve growth performance, immune responses, and suppressed the activities of glutathion peroxidase (GSH-Px, superoxide dismutase (SOD, catalase (CAT, and thioredoxin reductase (TXNRD; reduced serum malonaldehyde (MDA and glutathione (GSH concentrations when compared with fowls raised under thermoneutral condition (TC. Upon chronic heat stress and supplementation of clove extracts, the Silkie fowls showed a linear increase in GSH-Px, SOD, CAT, and TXNRD activities (P = 0.01 compared with fowls fed diets without clove extract. ET decreased (P < 0.05 the growth index of the liver, spleen, bursa of Fabricius and thymus. However, the growth index of the liver, spleen, bursa of Fabricius and thymus increased significantly (P < 0.05 which corresponded to an increase in clove supplemented levels. The expression of OVT, CP, AGP, CRP, and SAA mRNA in the liver, spleen, bursa of Fabricius and thymus were elevated (P < 0.01 by ET compared with those maintained at TC. Nevertheless, clove mitigates heat stress-induced overexpression of OVT, CP, AGP, CRP and SAA mRNA in the immune organs of fowls fed 400 mg clove/kg compared to other groups. Conclusions The results showed that clove extracts supplementation decreased oxidative stress in the heat-stressed black-meated fowls by alleviating

  8. Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix.

    Science.gov (United States)

    Ali, Neserin; Ljunggren, Stefan; Karlsson, Helen M; Wierzbicka, Aneta; Pagels, Joakim; Isaxon, Christina; Gudmundsson, Anders; Rissler, Jenny; Nielsen, Jörn; Lindh, Christian H; Kåredal, Monica

    2018-01-01

    Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m 3 ) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC-MS/MS and a targeted selected reaction monitoring LC-MS/MS analyzing 130 proteins and four in vivo peptide degradation products. The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The

  9. DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial.

    Science.gov (United States)

    Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob; Abrahamsson, Jonas; Lund, Bendik; Kanerva, Jukka; Jónsson, Ólafur Gísli; Vaitkeviciene, Goda; Pruunsild, Kaie; Hjalgrim, Lisa Lyngsie; Schmiegelow, Kjeld

    2017-04-01

    Adjustment of mercaptopurine and methotrexate maintenance therapy of acute lymphoblastic leukaemia by leucocyte count is confounded by natural variations. Cytotoxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to establish whether DNA-TGN concentrations in blood leucocytes during maintenance therapy are associated with relapse-free survival. In this substudy of the NOPHO ALL2008 phase 3 trial done in 23 hospitals in seven European countries (Denmark, Estonia, Finland, Iceland, Lithuania, Norway, and Sweden), we analysed data from centralised and blinded analyses of 6-mercaptopurine and methotrexate metabolites in blood samples from patients with non-high-risk childhood acute lymphoblastic leukaemia. Eligible patients were aged 1·0-17·9 years; had been diagnosed with non-high-risk precursor B-cell or T-cell leukaemia; had been treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol; and had reached maintenance therapy in first remission. Maintenance therapy was (mercaptopurine 75 mg/m 2 once per day and methotrexate 20 mg/m 2 once per week, targeted to a leucocyte count of 1·5-3·0 × 10 9 cells per L). We measured DNA-TGN and erythrocyte concentrations of TGN nucleotides, methylated mercaptopurine metabolites, and methotrexate polyglutamates. The primary objective was the association of DNA-TGN concentrations and 6-mercaptopurine and methotrexate metabolites with relapse-free survival. The secondary endpoint was the assessment of DNA-TGN concentration and 6-mercaptopurine and methotrexate metabolites during maintenance therapy phase 2. Between Nov 26, 2008 and June 14, 2016, 1509 patients from the NOPHO ALL2008 study were assessed for eligibility in the DNA-TGN substudy, of which 918 (89%) of 1026 eligible patients had at least one DNA-TGN measurement and were included in the analyses. Median follow-up was 4·6 years (IQR 3·1-6·1). Relapse-free survival was

  10. Acute Pancreatitis

    DEFF Research Database (Denmark)

    Bertilsson, Sara; Håkansson, Anders; Kalaitzakis, Evangelos

    2017-01-01

    Aims: We aimed to evaluate the potential relation between the incidence of (alcoholic and non-alcoholic) acute pancreatitis (AP) and alcohol consumption in the general population, and whether the occurrence of AP shows any seasonal variation, particularly in relation to periods with expected...... consumption in the general population do not appear to be related to changes in the incidence of AP and there are no significant seasonal differences in the occurrence of AP in Sweden. Short summary: The incidence of acute pancreatitis (AP) is increasing, and alcohol is still recognized as one of the most...

  11. A Pooled Analysis of the Phase 3 REVIVE Trials: Randomized, Double-blind Studies to EValuate the Safety and Efficacy of Iclaprim Versus Vancomycin for trEatment of Acute Bacterial Skin and Skin Structure Infections.

    Science.gov (United States)

    Huang, David B; Corey, G Ralph; Holland, Thomas L; Lodise, Thomas; O'Riordan, William; Wilcox, Mark H; File, Thomas M; Dryden, Matthew; Balser, Barbara; Desplats, Eve; Torres, Antoni

    2018-05-18

    Iclaprim, a diaminopyrimidine antibiotic, was compared with vancomycin for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) in two studies (REVIVE-1 and REVIVE-2). We explored the efficacy and tolerability of iclaprim in a pooled analysis of results from both studies. REVIVE-1 and REVIVE-2 were Phase 3, double-blind, randomized (1:1), multicenter, active-controlled, non-inferiority (margin of 10%) trials, each designed to enroll 600 patients a piece with ABSSSI. The studies used identical study protocols. Iclaprim 80 mg and vancomycin 15 mg/kg were administered IV every 12 hours for 5-14 days. The primary endpoint was a ≥20% reduction from baseline in lesion size (early clinical response [ECR]) at the early time point (48 to 72 hours after the start of study drug) in the intent-to-treat population. In REVIVE-1, ECR at the early time point was 80.9% with iclaprim vs. 81.0% with vancomycin (treatment difference, -0.13%; 95% confidence interval, -6.42% to 6.17%). In REVIVE-2, ECR was 78.3% with iclaprim vs. 76.7% with vancomycin (treatment difference: 1.58%, 95% CI: -5.10% to 8.26%). The pooled ECR was 79.6% with iclaprim vs. 78.8% with vancomycin (treatment difference: 0.75%, 95% CI: -3.84 to 5.35%). Iclaprim and vancomycin were comparable for the incidence of mostly mild adverse events, except for a higher incidence of elevated serum creatinine with vancomycin (n=7) compared with iclaprim (n=0). Iclaprim achieved noninferiority compared with vancomycin for early clinical response at the early time point and secondary endpoints with a similar safety profile in two Phase 3 studies for the treatment of ABSSSI suspected or confirmed to be caused by Gram-positive pathogens. NCT02600611 and NCT02607618. Copyright © 2018. Published by Elsevier B.V.

  12. The Australian National Sub-Acute and Non-Acute Patient casemix classification.

    Science.gov (United States)

    Eagar, K

    1999-01-01

    The Australian National Sub-Acute and Non-Acute Patient (AN-SNAP) Version 1 casemix classification was completed in 1997. AN-SNAP is designed for the classification of sub-acute and non-acute care provided in both inpatient and ambulatory settings and is intended to be useful for both funding and clinical management purposes. The National Sub-Acute and Non-Acute Casemix Classification study has produced the first version of a national classification of sub-acute and non-acute care. Ongoing refinement (leading to Version 2) will be possible through further analysis of the existing data set in combination with analysis of the results of a carefully planned and phased implementation.

  13. Exploring the impact of visual and movement based priming on a motor intervention in the acute phase post-stroke in persons with severe hemiparesis of the upper extremity

    Science.gov (United States)

    Patel, Jigna; Qiu, Qinyin; Yarossi, Mathew; Merians, Alma; Massood, Supriya; Tunik, Eugene; Adamovich, Sergei; Fluet, Gerard

    2016-01-01

    Purpose Explore the potential benefits of using priming methods prior to an active hand task in the acute phase post-stroke in persons with severe upper extremity hemiparesis. Methods Five individuals were trained using priming techniques including virtual reality (VR) based visual mirror feedback and contralaterally controlled passive movement strategies prior to training with an active pinch force modulation task. Clinical, kinetic, and neurophysiological measurements were taken pre and post the training period. Clinical measures were taken at six months post training. Results The two priming simulations and active training were well tolerated early after stroke. Priming effects were suggested by increased maximal pinch force immediately after visual and movement based priming. Despite having no clinically observable movement distally, the subjects were able to volitionally coordinate isometric force and muscle activity (EMG) in a pinch tracing task. The Root Mean Square Error (RMSE) of force during the pinch trace task gradually decreased over the training period suggesting learning may have occurred. Changes in motor cortical neurophysiology were seen in the unaffected hemisphere using Transcranial Magnetic Stim