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Sample records for acute phase markers

  1. Circulating Microbial Products and Acute Phase Proteins as Markers of Pathogenesis in Lymphatic Filarial Disease

    PubMed Central

    Anuradha, R.; George, P. Jovvian; Pavan Kumar, N.; Fay, Michael P.; Kumaraswami, V.; Nutman, Thomas B.; Babu, Subash

    2012-01-01

    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. PMID:22685406

  2. Effects of competition on acute phase proteins and lymphocyte subpopulations - oxidative stress markers in eventing horses.

    PubMed

    Valle, E; Zanatta, R; Odetti, P; Traverso, N; Furfaro, A; Bergero, D; Badino, P; Girardi, C; Miniscalco, B; Bergagna, S; Tarantola, M; Intorre, L; Odore, R

    2015-10-01

    The aim of the study was to evaluate markers of the acute phase response (APR) in eventing horses by measuring acute phase proteins (APP) (haptoglobin, Hp, and serum amyloid A, SAA), lysozyme, protein adducts such as pentosidine-like adducts (PENT), malondialdehyde adducts (MDA), hydroxynonenal adducts (HNE) and total advanced glycation/glycoxidation end products (AGEs), complete blood count and lymphocyte subpopulations (CD4+, CD8+ and CD21+) both at rest and at the end of an eventing competition. Blood samples were collected from eight Warmblood horses (medium age 10 ± 3) during an official national 2-day event competition at rest (R) and 10 min after the arrival of the cross-country test on the second day. Exercise caused a significant increase in red blood cell number, haemoglobin, packed cell volume, neutrophils, white blood cell and lymphocyte number; however, these values remained within the normal range. The CD4+ and CD8+ cells significantly increased, whereas the CD21+ lymphocytes decreased; a significant increase in serum SAA, lysozyme and protein carbonyl derivates was also observed. Two-day event causes significant changes in APR markers such as lysozyme, protein carbonyl derivates (HNE, AGEs, PENT) and lymphocyte subpopulations. The data support the hypothesis that 2-day event may alter significantly APR markers. Limitations of the study were the relatively small sample size and sampling time conditioned by the official regulations of the event. Therefore, further studies are needed to investigate the time required for recovery to basal values in order to define the possible effects on the immune function of the athlete horse.

  3. Acute phase reaction and acute phase proteins*

    PubMed Central

    Gruys, E.; Toussaint, M.J.M.; Niewold, T.A.; Koopmans, S.J.

    2005-01-01

    A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes, negative and positive acute phase proteins (APPs) with function and associated pathology is given. It appears that APPs represent appropriate analytes for assessment of animal health. Whereas they represent non-specific markers as biological effect reactants, they can be used for assessing nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. When such acute phase index is applied to separate healthy animals from animals with some disease, much better results are obtained than with single analytes and statistically acceptable results for culling individual animals may be reached. Unfortunately at present no cheap, comprehensive and easy to use system is available for assessing various acute phase proteins in serum or blood samples at the same time. Protein microarray or fluid phase microchip technology may satisfy this need; and permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease specific variables. Applying such technology may help to solve health problems in various countries not only in animal husbandry but also in human populations. PMID:16252337

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

    PubMed

    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 (P<0.05) and IL-8 (P<0.01) responses to T-cell activation. Hierarchical clustering revealed 2 distinct inflammatory clusters associated with previous preeclampsia: 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.

  5. Peripheral Inflammatory Markers and Antioxidant Response during the Post-Acute and Chronic Phase after Severe Traumatic Brain Injury

    PubMed Central

    Licastro, Federico; Hrelia, Silvana; Porcellini, Elisa; Malaguti, Marco; Di Stefano, Cristina; Angeloni, Cristina; Carbone, Ilaria; Simoncini, Laura; Piperno, Roberto

    2016-01-01

    Traumatic brain injury (TBI) is a mechanical insult to the brain caused by external forces and associated with inflammation and oxidative stress. The patients may show different profiles of neurological recovery and a combination of oxidative damage and inflammatory processes can affect their courses. It is known that an overexpression of cytokines can be seen in peripheral blood in the early hours/days after the injury, but little is known about the weeks and months encompassing the post-acute and chronic phases. In addition, no information is available about the antioxidant responses mediated by the major enzymes that regulate reactive oxygen species levels: superoxide dismutase, catalase, peroxidases, and GSH-related enzymes. This study investigates the 6-month trends of inflammatory markers and antioxidant responses in 22 severe TBI patients with prolonged disorders of consciousness, consecutively recruited in a dedicated neurorehabilitation facility. Patients with a high degree of neurological impairment often show an uncertain outcome. In addition, the profiles of plasma activities were related to the neurological recovery after 12 months. Venous peripheral blood samples were taken blindly as soon as clinical signs and laboratory markers confirmed the absence of infections, 3 and 6 months later. The clinical and neuropsychological assessment continued up to 12 months. Nineteen patients completed the follow-up. In the chronic phase, persistent high plasma levels of cytokines can interfere with cognitive functioning and higher post-acute levels of cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL1b, IL6] are associated with poorer cognitive recoveries 12 months later. Moreover, higher IFN-γ, higher TNF-α, and lower glutathione peroxidase activity are associated with greater disability. The results add evidence of persistent inflammatory response, provide information about long-term imbalance of antioxidant activity, and suggest that

  6. Peripheral Inflammatory Markers and Antioxidant Response during the Post-Acute and Chronic Phase after Severe Traumatic Brain Injury.

    PubMed

    Licastro, Federico; Hrelia, Silvana; Porcellini, Elisa; Malaguti, Marco; Di Stefano, Cristina; Angeloni, Cristina; Carbone, Ilaria; Simoncini, Laura; Piperno, Roberto

    2016-01-01

    Traumatic brain injury (TBI) is a mechanical insult to the brain caused by external forces and associated with inflammation and oxidative stress. The patients may show different profiles of neurological recovery and a combination of oxidative damage and inflammatory processes can affect their courses. It is known that an overexpression of cytokines can be seen in peripheral blood in the early hours/days after the injury, but little is known about the weeks and months encompassing the post-acute and chronic phases. In addition, no information is available about the antioxidant responses mediated by the major enzymes that regulate reactive oxygen species levels: superoxide dismutase, catalase, peroxidases, and GSH-related enzymes. This study investigates the 6-month trends of inflammatory markers and antioxidant responses in 22 severe TBI patients with prolonged disorders of consciousness, consecutively recruited in a dedicated neurorehabilitation facility. Patients with a high degree of neurological impairment often show an uncertain outcome. In addition, the profiles of plasma activities were related to the neurological recovery after 12 months. Venous peripheral blood samples were taken blindly as soon as clinical signs and laboratory markers confirmed the absence of infections, 3 and 6 months later. The clinical and neuropsychological assessment continued up to 12 months. Nineteen patients completed the follow-up. In the chronic phase, persistent high plasma levels of cytokines can interfere with cognitive functioning and higher post-acute levels of cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL1b, IL6] are associated with poorer cognitive recoveries 12 months later. Moreover, higher IFN-γ, higher TNF-α, and lower glutathione peroxidase activity are associated with greater disability. The results add evidence of persistent inflammatory response, provide information about long-term imbalance of antioxidant activity, and suggest that

  7. Leptin role in advanced lung cancer. A mediator of the acute phase response or a marker of the status of nutrition?

    PubMed

    Alemán, María Remedios; Santolaria, Francisco; Batista, Norberto; de La Vega, María; González-Reimers, Emilio; Milena, Antonio; Llanos, Marta; Gómez-Sirvent, Juan Luis

    2002-07-07

    Leptin is an anorexia inductor peptide produced by adipocytes and related to fat mass. Leptin is also produced by fat under proinflammatory cytokine action. Our objective is to study serum leptin levels in relation to nutritional status and acute phase response in advanced-stage non-small cell lung cancer.Seventy-six patients newly diagnosed of non surgical non-small cell lung cancer before chemotherapy treatment and 30 healthy controls were included. BMI, serum leptin and cholesterol levels and lymphocyte count were decreased in lung cancer patients. Cytokine IL-6, TNF-alpha, sTNF-RII, sIL-2R, IL-12, IL-10 and IFN-gamma, and other acute phase reactants as alpha1 antitrypsin, ferritin, CRP and platelets were all raised in patients, whereas the IL-2 was decreased. We found a direct relationship between leptin and other indicators of the status of nutrition, especially total fat mass. We also found a close relationship between the status of nutrition and the performance status (Karnofsky index). However, serum leptin and nutritional status were inversely correlated with acute phase proteins and proinflammatory cytokines, suggesting a stress-type malnutrition. Although serum leptin levels, nutritional status and Karnofsky index are related to survival, at multivariate analysis they all were displaced by the acute phase reaction markers. These results suggest that cancer anorexia and cachexia are not due to a dysregulation of leptin production. Circulating leptin concentrations are not elevated in weight-losing cancer patients and are inversely related to the intensity of the inflammatory response. In advanced lung cancer patients serum leptin concentrations only depend on the total amount of fat.

  8. Prognostic markers in acute pancreatitis.

    PubMed

    Gomatos, Ilias P; Xiaodong, Xu; Ghaneh, Paula; Halloran, Christopher; Raraty, Michael; Lane, Brian; Sutton, Robert; Neoptolemos, John P

    2014-04-01

    Acute pancreatitis has a mortality rate of 5-10%. Early deaths are mainly due to multiorgan failure and late deaths are due to septic complications from pancreatic necrosis. The recently described 2012 Revised Atlanta Classification and the Determinant Classification both provide a more accurate description of edematous and necrotizing pancreatitis and local complications. The 2012 Revised Atlanta Classification uses the modified Marshall scoring system for assessing organ dysfunction. The Determinant Classification uses the sepsis-related organ failure assessment scoring system for organ dysfunction and, unlike the 2012 Revised Atlanta Classification, includes infected necrosis as a criterion of severity. These scoring systems are used to assess systemic complications requiring intensive therapy unit support and intra-abdominal complications requiring minimally invasive interventions. Numerous prognostic systems and markers have been evaluated but only the Glasgow system and serum CRP levels provide pragmatic prognostic accuracy early on. Novel concepts using genetic, transcriptomic and proteomic profiling and also functional imaging for the identification of specific disease patterns are now required.

  9. The acute phase protein ceruloplasmin as a non-invasive marker of pseudopregnancy, pregnancy, and pregnancy loss in the giant panda.

    PubMed

    Willis, Erin L; Kersey, David C; Durrant, Barbara S; Kouba, Andrew J

    2011-01-01

    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.

  10. Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

    PubMed Central

    Raffray, Loic; Giry, Claude; Vandroux, David; Kuli, Barbara; Randrianjohany, Andry; Pequin, Anne-Marie; Renou, Frédéric; Jaffar-Bandjee, Marie-Christine; Gasque, Philippe

    2016-01-01

    It has long been known that pathogenic Leptospira can mobilize the immune system but the specific contribution of neutrophils to control the infectious challenge remains to be clarified. We herein analyzed the phenotype of circulating neutrophils of patients with leptospirosis and healthy controls for the expression of toll-like receptor (TLR) type 2 (TLR2, to sense the leptospiral LPS) and several activation markers: interleukin 8 chemokine receptor CD182 (CXCR2), CD11b of the integrin/opsonin complement receptor type 3 (CR3) and CD15 (ligand of the selectin). The plasmatic level of the main CD182 ligand, interleukin 8 (CXCL8), was measured by ELISA. Hospitalized leptospirosis cases showed marked neutrophilia, particularly in the most severe cases. Interestingly, TLR2 was significantly increased in leptospirosis but identical levels of CD182 and CD11b were detected when compared to controls. CD15 was significantly decreased on neutrophils in leptospirosis but returned to normal within 1 month. Basal levels of IL-8 were measured in control subjects and were not increased in leptospirosis cases at the initial stage of the disease. In conclusion, we observed that neutrophils failed to regulate the expression of several of the receptors involved in cell activation and recruitment. This study further emphasizes the paradigm that neutrophils may be impaired in their overall capacity to thwart bacterial infection in leptospirosis patients. PMID:27802348

  11. N-terminal pro-brain natriuretic peptide can be an adjunctive diagnostic marker of hyper-acute phase of Kawasaki disease.

    PubMed

    Kwon, Hyuksool; Lee, Jin Hee; Jung, Jae Yun; Kwak, Young Ho; Kim, Do Kyun; Jung, Jin Hee; Chang, Ikwan; Kim, Kyuseok

    2016-12-01

    The purpose of this study was to determine whether the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level could be a useful marker for Kawasaki disease in the pediatric emergency department (PED) and in the presence of fever duration of 4 days or less (hyper-acute phase of Kawasaki disease). Medical records of patients who were 1 month to 15 years old of age and presented at the PED with suspected Kawasaki disease from January 1, 2010, to December 31, 2014, were collected retrospectively. Two hundred thirty-nine patients with a history of fever for 4 days or less were diagnosed with Kawasaki disease, as well as 111 patients with other febrile diseases, and were enrolled. The NT-proBNP level was significantly higher in patients with Kawasaki disease (Kawasaki disease vs. other febrile disease group, 444.8 (189.7-951.5) vs. 153.4 (68.9-287.6) pg/mL; p < 0.001), and a cutoff value of 244.7 pg/mL yielded a sensitivity and specificity of 68.6 and 70.3 %, respectively. The area under the curve of the NT-proBNP for predicting Kawasaki disease was 0.763 (95 % CI 0.712-0.814).

  12. Regulation of T lymphocyte apoptotic markers is associated to cell activation during the acute phase of dengue.

    PubMed

    Torrentes-Carvalho, Amanda; Marinho, Cintia Ferreira; de Oliveira-Pinto, Luzia Maria; de Oliveira, Débora Batista; Damasco, Paulo Vieira; Cunha, Rivaldo Venâncio; de Souza, Luiz José; de Azeredo, Elzinandes Leal; Kubelka, Claire Fernandes

    2014-05-01

    Dengue fever, a public health problem in Brazil, may present severe clinical manifestations as result of an increased vascular permeability and coagulation disorders. T cell activation is a critical event for an effective immune response against infection, including the production of cytokines. We aim to reveal mechanisms that modulate the virus-cell interaction, with an emphasis on cell death. Apoptosis is involved in lymphocyte homeostasis, contributes to the clearance of virus-infected cells but also may play a role in the pathogenesis. Phosphatidylserine exposure on CD8T lymphocytes from dengue patients support early apoptotic processes and loss of genomic integrity, observed by DNA fragmentation in T lymphocytes and indicating late apoptosis. These T cells express activation and cytotoxic phenotypes as revealed by CD29 and CD107a upregulation. Higher frequencies of CD95 were detected in T lymphocytes mainly in those with the cytotoxic profile (CD107a+) and lower levels of anti-apoptotic molecule Bcl-2, suggesting that both CD4+ and CD8+ T cell subsets are more susceptible to apoptosis during acute dengue. The analysis of apoptosis-related protein expression profile showed that not only molecules with pro- but also those with anti-apoptotic functions are overexpressed, indicating that survival mechanisms could be possibly protecting cells against apoptosis caused by viral, immune, oxidative and/or genotoxic stresses. These observations led us to propose that in dengue patients there is an association between T cell susceptibility to apoptosis and the activation state. The mechanisms for understanding the immunopathogenesis during dengue infection are discussed.

  13. Lymphocyte surface markers in acute rheumatic fever and post-streptococcal acute glomerulonephritis.

    PubMed Central

    Williams, R C; Zabriskie, J B; Mahros, F; Hassaballa, F; Abdin, Z H

    1977-01-01

    Lymphocyte cell-surface markers were examined in forty children with acute rheumatic fever (ARF) and twelve with acute post-streptococal glomerulonephritis (AGN) and compared to thirty-six normal controls of similar age. Cell-surface-marker studies included surface Ig using fluorescein-labelled F(ab)2 anti-F(AB')2, IgG aggregate binding cells, and EAC rosettes. T cells were identified both as 'active' rosettes and total E-binding cells. Proportions and absolute numbers of cells bearing surface Ig and Fc receptors were elevated in subjects with AGN (Pless than0-01-0-5), whereas proportions of cells producing EAC rosettes were diminished. Patients with acute rheumatic carditis or chorea showed a substantial elevation in proportions and numbers of active T-cell rosettes (Pless than0-01). Streptococcal antigen binding cells capable of forming rosettes with autologous cells coated with group A streptococcal membranes were elevated in the acute phase of both rheumatic fever and acute glomerulonephritis(Pless than0-01). The majority of such cells were removed by passage over insolubilized Ig-anti-IgG columns and appeared to be B cells. PMID:300301

  14. Salivary Markers of Inflammation in Response to Acute Stress

    PubMed Central

    Slavish, Danica C.; Graham-Engeland, Jennifer E.; Smyth, Joshua M.; Engeland, Christopher G.

    2014-01-01

    There is burgeoning interest in the ability to detect inflammatory markers in response to stress within naturally occurring social contexts and/or across multiple time points per day within individuals. Salivary collection is a less invasive process than current methods of blood collection and enables intensive naturalistic methodologies, such as those involving extensive repeated measures per day over time. Yet the reliability and validity of saliva-based to blood-based inflammatory biomarkers in response to stress remains unclear. We review and synthesize the published studies that have examined salivary markers of inflammation following exposure to an acute laboratory stressor. Results from each study are reviewed by analyte (IL-1β, TNF-α, IL-6, IL-2, IL-4, IL-10, IL-12, CRP) and stress type (social-cognitive and exercise-physical), after which methodological issues and limitations are addressed. Although the literature is limited, several inflammatory markers (including IL-1β, TNF-α, and IL-6) have been reliably determined from saliva and have increased significantly in response to stress across multiple studies, with effect sizes ranging from very small to very large. Although CRP from saliva has been associated with CRP in circulating blood more consistently than other biomarkers have been associated with their counterparts in blood, evidence demonstrating it reliably responds to acute stress is absent. Although the current literature is presently too limited to allow broad assertion that inflammatory biomarkers determined from saliva are valuable for examining acute stress responses, this review suggests that specific targets may be valid and highlights specific areas of need for future research. PMID:25205395

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

    PubMed

    Kristensen, Lena; Buhl, Rikke; Nostell, Katarina; Bak, Lars; Petersen, Ellen; Lindholm, Maria; Jacobsen, Stine

    2014-04-01

    The purpose of the study was to investigate whether acute strenuous exercise (1600- to 2500-m race) would elicit an acute phase response (APR) in Standardbred trotters. Blood levels of several inflammatory markers [serum amyloid A (SAA), haptoglobin, fibrinogen, white blood cell count (WBC), 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 have been caused by exercise-induced hemolysis, which indicates that horses might experience a condition similar to athlete's anemia in humans. The pathogenesis and clinical implications of the hematological and blood-biochemical changes elicited by acute exercise in Standardbred trotters in the present study warrant further investigation.

  16. Markers of gluten sensitivity in acute mania: a longitudinal study.

    PubMed

    Dickerson, Faith; Stallings, Cassie; Origoni, Andrea; Vaughan, Crystal; Khushalani, Sunil; Yolken, Robert

    2012-03-30

    Increased levels of antibodies to gliadin, which is derived from the wheat protein gluten, have been reported in schizophrenia and bipolar disorder in cross-sectional studies. We examined longitudinally the levels of antibody reactivity to gliadin in acute mania. The sample included 60 individuals assessed during a hospital stay for acute mania, 39 at a 6-month follow-up, and a sample of 143 non-psychiatric controls. Antibodies to gliadin were measured by enzyme immunoassay. The relationship of the antibodies to the clinical course of mania was analyzed by the use of regression models. Individuals with mania had significantly increased levels of IgG antibodies to gliadin, but not other markers of celiac disease, at baseline compared with controls in multivariate analyses. However, these levels were not significantly different from those of controls at the six month follow-up. Among the individuals with mania, elevated levels at follow-up were significantly associated with re-hospitalization in the 6-month follow-up period. The monitoring and control of gluten sensitivity may have significant effects on the management of individuals hospitalized with acute mania.

  17. [Acute-phase proteins in inflammation].

    PubMed

    Engler, R

    1995-01-01

    The acute phase proteins (APPs) have been empirically defined as those whose plasma concentration changes following inflammatory reaction. Those proteins whose concentrations increase are referred to as positive APP, while those whose levels decline are termed negative APP. In man, positive APP are: alpha 1 acid glycoprotein, alpha 1 protease inhibitor, alpha 1 antichymotrypsin, haptoglobin, ceruloplasmin, fibrinogen, C-reactive protein, serum amyloid A. Great variability in the APP response between different species is observed. The principal functions of APP, result from the interaction of these proteins with ligands of various origins which give "protein-ligands" complexes. These complexes are cleared by the RES or by the hepatocyte. The results are protease inhibition, neutralization of toxic molecules such as hemoglobin or the superoxide anion, clearance of cell membranes and chromatin. The drop of the plasma concentration of negative APP during an inflammatory reaction carries a rise of free ligands (fatty acids, hormones, vitamins, trace elements). IL6 has been recognized as the principal regulator of most APP genes. The response of the hepatic cell to IL6 is characterized by the enhanced production of type 2 or IL6 specific APPs. The biochemical process of signal transduction is IL6--JAK2--APRF The set of APP genes regulated by IL1 type cytokines (type 1 APPs) is distinct from that regulated by IL6 type cytokine. IL1 and TNF alpha mediated stimulation of type 1 APP genes is synergistically enhanced by IL6 type cytokines. The biochemical process of signal transduction is IL1, IL6--Ras--MAP kinase--NFIL6 The targeted inflammatory proteic profile including the assay of C-reactive protein, haptoglobin and alpha 1 acid glycoprotein produces a "biological tool" to the clinician in order to manage an inflammatory response. IL6, a proteic marker for the future, connected with CRP, will be assayed during early inflammatory reaction.

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

    PubMed

    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.

  19. Markers of criticality in phase synchronization

    PubMed Central

    Botcharova, Maria; Farmer, Simon F.; Berthouze, Luc

    2014-01-01

    The concept of the brain as a critical dynamical system is very attractive because systems close to criticality are thought to maximize their dynamic range of information processing and communication. To date, there have been two key experimental observations in support of this hypothesis: (i) neuronal avalanches with power law distribution of size and (ii) long-range temporal correlations (LRTCs) in the amplitude of neural oscillations. The case for how these maximize dynamic range of information processing and communication is still being made and because a significant substrate for information coding and transmission is neural synchrony it is of interest to link synchronization measures with those of criticality. We propose a framework for characterizing criticality in synchronization based on an analysis of the moment-to-moment fluctuations of phase synchrony in terms of the presence of LRTCs. This framework relies on an estimation of the rate of change of phase difference and a set of methods we have developed to detect LRTCs. We test this framework against two classical models of criticality (Ising and Kuramoto) and recently described variants of these models aimed to more closely represent human brain dynamics. From these simulations we determine the parameters at which these systems show evidence of LRTCs in phase synchronization. We demonstrate proof of principle by analysing pairs of human simultaneous EEG and EMG time series, suggesting that LRTCs of corticomuscular phase synchronization can be detected in the resting state and experimentally manipulated. The existence of LRTCs in fluctuations of phase synchronization suggests that these fluctuations are governed by non-local behavior, with all scales contributing to system behavior. This has important implications regarding the conditions under which one should expect to see LRTCs in phase synchronization. Specifically, brain resting states may exhibit LRTCs reflecting a state of readiness facilitating

  20. Diagnostic value of blood inflammatory markers for detection of acute appendicitis in children

    PubMed Central

    Sack, Ulrich; Biereder, Birgit; Elouahidi, Tino; Bauer, Katrin; Keller, Thomas; Tröbs, Ralf-Bodo

    2006-01-01

    Background Acute appendicitis (AA) is a common surgical problem that is associated with an acute-phase reaction. Previous studies have shown that cytokines and acute-phase proteins are activated and may serve as indicators for the severity of appendicitis. The aim of this study was to compare diagnostic value of different serum inflammatory markers in detection of phlegmonous or perforated appendicitis in children. Methods Data were collected prospectively on 211 consecutive children. Laparotomy was performed for suspected AA for 189 patients. Patients were subdivided into groups: nonsurgical abdominal pain, early appendicitis, phlegmonous or gangrenous appendicitis, perforated appendicitis. White blood cell count (WBC), serum C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), acid α1-glycoprotein (α1GP), endotoxin, and erythrocyte sedimentation reaction (ESR) were estimated ad the time of admission. The diagnostic performance was analyzed using receiver operating characteristic (ROC) curves. Results WBC count, CRP and IL-6 correlated significantly with the severity of appendiceal inflammation. Identification of children with severe appendicitis was supported by IL-6 or CRP but not WBC. Between IL-6 and CRP, there were no significant differences in diagnostic use. Conclusion Laboratory results should be considered to be integrated within the clinical assessment. If used critically, CRP and IL-6 equally provide surgeons with complementary information in discerning the necessity for urgent operation. PMID:17132173

  1. Prognostic markers in acute pancreatitis: can pancreatic necrosis be predicted?

    PubMed Central

    Leese, T.; Shaw, D.; Holliday, M.

    1988-01-01

    The value of six prognostic markers was assessed prospectively in 198 attacks of acute pancreatitis with specific attention to their ability to predict pancreatic necrosis. The Imrie Prognostic Score (IPS) was recorded within 48 h of diagnosis. The serum C-reactive protein (CRP) alpha 1 antiprotease (A1AP), alpha 2 macroglobulin (A2M), amylase and white cell count (WCC) were measured on days 1, 3 and 7. When comparing all severe clinical outcomes to mile outcomes, serum CRP concentrations were higher on all three days (P less than 0.02, less than 0.001, less than 0.001), A1AP concentrations were higher on day 3 (P less than 0.05), A2M concentrations were lower on day 7 (P less than 0.01) and WCC was higher on all three days (P less than 0.001, less than 0.001, less than 0.001). Serum amylase concentrations showed no significant differences. None of the measured parameters were helpful in distinguishing patients who subsequently developed pancreatic necrosis from patients who had other severe outcomes. Multivariate analysis revealed that the initial IPS showed greatest independent significance in predicting severe outcome followed by the WCC (days 1 and 7) and CRP (day 3). CRP and WCC may be clinically useful predictors of severe outcome to supplement the initial IPS. These methods are unlikely to distinguish pancreatic necrosis from other severe outcomes, but they may supplement clinical judgment in selecting a high risk group of patients for contrast enhanced computed tomography. PMID:2458063

  2. Regulation of the acute phase and immune responses

    SciTech Connect

    Sehgal, P.B.; Grieninger, G.; Tosato, G.

    1989-01-01

    This book contains the conference entitled Regulation of the acute phase and immune responses: Interleukin-L. Topics covered include: Interferon-B{sub 2}/26kDa Protein, Regulation of acute phase liver gene expression, and Genetics and regulation of expression of IL-6.

  3. Acute Phase Reactants as Novel Predictors of Cardiovascular Disease

    PubMed Central

    Ahmed, M. S.; Jadhav, A. B.; Hassan, A.; Meng, Qing H.

    2012-01-01

    Acute phase reaction is a systemic response which usually follows a physiological condition that takes place in the beginning of an inflammatory process. This physiological change usually lasts 1-2 days. However, the systemic acute phase response usually lasts longer. The aim of this systemic response is to restore homeostasis. These events are accompanied by upregulation of some proteins (positive acute phase reactants) and downregulation of others (negative acute phase reactants) during inflammatory reactions. Cardiovascular diseases are accompanied by the elevation of several positive acute phase reactants such as C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, white blood cell count, secretory nonpancreatic phospholipase 2-II (sPLA2-II), ferritin, and ceruloplasmin. Cardiovascular disease is also accompanied by the reduction of negative acute phase reactants such as albumin, transferrin, transthyretin, retinol-binding protein, antithrombin, and transcortin. In this paper, we will be discussing the biological activity and diagnostic and prognostic values of acute phase reactants with cardiovascular importance. The potential therapeutic targets of these reactants will be also discussed. PMID:24049653

  4. Discovery and validation of urine markers of acute pediatric appendicitis using high accuracy mass spectrometry

    PubMed Central

    Kentsis, Alex; Lin, Yin Yin; Kurek, Kyle; Calicchio, Monica; Wang, Yan Yan; Monigatti, Flavio; Campagne, Fabien; Lee, Richard; Horwitz, Bruce; Steen, Hanno; Bachur, Richard

    2015-01-01

    Study Objective Molecular definition of disease has been changing all aspects of medical practice, from diagnosis and screening to understanding and treatment. Acute appendicitis is among many human conditions that are complicated by the heterogeneity of clinical presentation and shortage of diagnostic markers. Here, we sought to profile the urine of patients with appendicitis with the goal of identifying new diagnostic markers. Methods Candidate markers were identified from the urine of children with histologically proven appendicitis by using high accuracy mass spectrometry proteome profiling. These systemic and local markers were used to assess the probability of appendicitis in a blinded, prospective study of children being evaluated for acute abdominal pain in our emergency department. Tests of performance of the markers were evaluated against the pathologic diagnosis and histologic grade of appendicitis. Results Test performance of 57 identified candidate markers was studied in 67 patients, with median age of 11 years, 37% of whom had appendicitis. Several exhibited favorable diagnostic performance, including calgranulin A (S100-A8), α-1-acid glycoprotein 1 (orosomucoid), and leucine-rich α-2-glycoprotein (LRG), with the ROC AUC and values of 0.84 (95 % CI 0.72-0.95), 0.84 (0.72-0.95), and 0.97 (0.93-1.0), respectively. LRG was enriched in diseased appendices and its abundance correlated with severity of appendicitis. Conclusions High accuracy mass spectrometry urine proteome profiling allowed identification of diagnostic markers of acute appendicitis. Usage of LRG and other identified biomarkers may improve the diagnostic accuracy of clinical evaluations of appendicitis. PMID:19556024

  5. Pixel-by-pixel absolute phase retrieval using three phase-shifted fringe patterns without markers

    NASA Astrophysics Data System (ADS)

    Jiang, Chufan; Li, Beiwen; Zhang, Song

    2017-04-01

    This paper presents a method that can recover absolute phase pixel by pixel without embedding markers on three phase-shifted fringe patterns, acquiring additional images, or introducing additional hardware component(s). The proposed three-dimensional (3D) absolute shape measurement technique includes the following major steps: (1) segment the measured object into different regions using rough priori knowledge of surface geometry; (2) artificially create phase maps at different z planes using geometric constraints of structured light system; (3) unwrap the phase pixel by pixel for each region by properly referring to the artificially created phase map; and (4) merge unwrapped phases from all regions into a complete absolute phase map for 3D reconstruction. We demonstrate that conventional three-step phase-shifted fringe patterns can be used to create absolute phase map pixel by pixel even for large depth range objects. We have successfully implemented our proposed computational framework to achieve absolute 3D shape measurement at 40 Hz.

  6. Apoptotic markers and DNA damage are related to late phase of stroke: Involvement of dyslipidemia and inflammation.

    PubMed

    Pascotini, Eduardo Tanuri; Flores, Ariane Ethur; Kegler, Aline; Gabbi, Patricia; Bochi, Guilherme Vargas; Algarve, Thais Doeler; Prado, Ana Lucia Cervi; Duarte, Marta M M F; da Cruz, Ivana B M; Moresco, Rafael Noal; Royes, Luiz Fernando Freire; Fighera, Michele Rechia

    2015-11-01

    Oxidative stress and brain inflammation are thought to contribute to the pathophysiology of cerebral injury in acute stroke, leading to apoptosis and cell death. Lipid accumulation may lead to progression of carotid plaques and inflammation, contributing to increased acute stroke risk. However, little is known about these events and markers in the late stroke (>6 months) and if dyslipidemia could contribute to disease's pathophysiology in a later phase. In this case-control study, we recruited patients in the late stroke phase (n=40) and health subjects (control group; n = 40). Dichlorodihydrofluorescein (DCFH), nitrite/nitrate (NOx), Tumor necrosis factor-alpha (TNF-α), Acetylcholinesterase (AChE), Caspase 8 (CASP 8), Caspase 3 (CASP 3) and Picogreen (PG) were measured in periphery blood samples. Furthermore, a correlation among all measured markers (DCFH, NOx, TNF-α, AChE, CASP 8, CASP 3 and PG) was realized. The marker levels were also compared to triglycerides (TG), total (CHO), LDL and HDL cholesterol levels and medications used. Statistical analyses showed that stroke patients presented an increase of DCFH, NOx, TNF-α and AChE levels when compared to control subjects. In addition, we observed that stroke patients had significantly higher CASP 8, CASP 3 and PG levels than control group. A significant correlation between TNF-α with CASP 8 (r = 0.4) and CASP 3 (r = 0.4) levels was observed, but not with oxidative/nitrosative markers. Moreover, we observed that stroke patients with dyslipidemia had significantly higher TNF-α, CASP 8 and CASP 3 levels than stroke without dyslipidemia and control groups. Our findings suggest that oxidative and inflammatory markers may be still increased and lead to caspase activation and DNA damage even after 6 months to cerebral injury. Furthermore, it is plausible to propose that dyslipidemia may contribute to worsen proinflammatory state in a later phase of stroke and an increased risk to new neurovascular events.

  7. C-reactive protein and the acute phase reaction in geriatric patients.

    PubMed

    Bertsch, Thomas; Triebel, Jakob; Bollheimer, Cornelius; Christ, Michael; Sieber, Cornel; Fassbender, Klaus; Heppner, Hans Jürgen

    2015-10-01

    The C-reactive protein (CRP), first described as a serum component capable of precipitating the C-polysaccharide of pneumococci, is one of the most important proteins because the serum concentration rises in the acute phase reaction. The acute phase reaction is the nonspecific reaction of the body to noxious stimuli of the most varied kinds, such as infections, burns, neoplasms and tissue trauma. The CRP is synthesized in liver parenchymal cells by cytokines which are derived from stimulated leucocytes and released into the circulation. Because of its molecular structure and in synergy with the complement system, it is able to precipitate and/or lyse microorganisms, thereby rendering them harmless. Measurement of the serum CRP concentration can provide important information with respect to the diagnosis and monitoring of treatment. Due to immunosenescence in geriatric patients the synthesis of CRP appears to be limited to inflammatory stimuli; however, this phenomenon does not appear to be of major clinical relevance. Despite the introduction of new parameters of the acute phase reaction, sometimes with better performance, such as interleukin-6, procalcitonin and the soluble endotoxin receptor sCD14, measurement of CRP for diagnosis and treatment monitoring is still justified even in geriatric patients as testing is rapid, economic and nearly ubiquitously available round the clock. Biochemical markers of the acute phase reaction should always be interpreted together with the clinical picture and their specific limitations.

  8. Monitoring the acute phase response to vaso-occlusive crisis in sickle cell disease.

    PubMed Central

    Stuart, J; Stone, P C; Akinola, N O; Gallimore, J R; Pepys, M B

    1994-01-01

    AIMS--To identify suitable acute phase proteins as objective markers of tissue ischaemia during painful vaso-occlusive crises in sickle cell disease. METHODS--The prodromal and established phases of 14 vaso-occlusive crises were studied longitudinally in 10 patients with sickle cell anaemia. Automated solid phase enzyme immunoassays were used to measure the fast responding acute phase proteins C-reactive protein and serum amyloid A protein. Slower responding glycoproteins (fibrinogen, orosomucoid, sialic acid and concanavalin-A binding) were measured in parallel. RESULTS--C-reactive protein and serum amyloid A protein increased early in crisis, sometimes within the early (prodromal) phase. Crises that resolved within 24 hours in hospital showed a minor and transient rise compared with crises that required treatment for four days or more. In eight crises treated by patients at home the acute phase response ranged from minor to a level consistent with extensive tissue ischaemia. CONCLUSIONS--Sensitive enzyme immunoassays for C-reactive protein and serum amyloid A protein are of potential value for monitoring the onset of tissue ischaemia in sickle cell crisis and for confirming subsequent resolution. PMID:7510726

  9. Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

    PubMed Central

    la Garza, Francisco Javier Guzmán-de; Ibarra-Hernández, Juan Manuel; Cordero-Pérez, Paula; Villegas-Quintero, Pablo; Villarreal-Ovalle, Claudia Ivette; Torres-González, Liliana; Oliva-Sosa, Norma Edith; Alarcón-Galván, Gabriela; Fernández-Garza, Nancy Esthela; Muñoz-Espinosa, Linda Elsa; Cámara-Lemarroy, Carlos Rodrigo; Carrillo-Arriaga, José Gerardo

    2013-01-01

    OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion. PMID:23917671

  10. Markers of coagulation activation and acute kidney injury in patients after hematopoietic cell transplantation

    PubMed Central

    Hingorani, Sangeeta R; Seidel, Kristy; Pao, Emily; Lawler, Rick; McDonald, George B.

    2015-01-01

    Acute kidney injury (AKI) is common after hematopoietic cell transplant (HCT). The etiology of AKI is unknown because biopsies are rarely performed. The pathophysiology of injury is inferred from clinical data. Thrombotic microangiopathy (TMA) is often invoked as the cause of renal injury. Patients > 2 years undergoing their first HCT at Fred Hutchinson Cancer Research Center (FHCRC) participated in this study. We prospectively measured plasma markers of coagulation activation, (PAI-1 and tPA) and fibrinolyis (D-dimer) weekly in 149 patients during the first 100 days post-transplant. Cox proportional hazards modeling was used to determine associations between these markers and AKI (doubling of baseline serum creatinine). Kruskal-Wallis test was used to determine associations between day 100 urinary albumin to creatinine ratios (ACR) and these markers. Thirty one percent of patients developed AKI. Though elevations in these markers occurred frequently, neither PAI-1 nor tPA were associated with development of AKI. D-dimer was associated with a slightly increased risk of AKI (RR=1.76; p-value 0.04). None of these markers were associated with micro- or macroalbuminuria at day 100. The lack of an association with AKI suggests that endothelial injury in the form of TMA is not a common cause of AKI early after transplant. PMID:25665045

  11. Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase

    ClinicalTrials.gov

    2015-04-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Blastic Phase; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  12. Markers

    ERIC Educational Resources Information Center

    Healthy Schools Network, Inc., 2011

    2011-01-01

    Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…

  13. Comparison of five cardiac markers in the detection of reperfusion after thrombolysis in acute myocardial infarction.

    PubMed Central

    Lavin, F.; Kane, M.; Forde, A.; Gannon, F.; Daly, K.

    1995-01-01

    OBJECTIVE--To investigate and compare the clinical usefulness of serial measurements of five cardiac marker proteins, namely creatine kinase (CK), CK-MB mass, myoglobin, troponin T, and myosin light chain 1, in the early detection of reperfusion after thrombolytic treatment. METHOD--Serial blood samples were taken from 26 patients presenting with acute myocardial infarction. Concentrations of the five markers were assayed in each sample. Thrombolytic treatment was given to the patients who were divided into those who reperfused (n = 17, group A) and those who failed to reperfuse (n = 9, group B) on the basis of clinical signs and angiography within 24 h. RESULTS--The release profiles of CK, CK-MB mass, myoglobin, and troponin T for patients in group A differed from those of patients in group B. No difference was observed in the release profile of myosin light chain 1 between the two groups. The time to peak concentration of CK, CK-MB mass, myoglobin, and troponin T occurred significantly earlier in patients of group A than in those of group B, with myoglobin peaking earlier than the other markers. An index, defined as the ratio of the concentration of each marker immediately before and 2 h after the start of thrombolytic treatment, was calculated for each marker in groups A and B. The 2 h myoglobin and troponin T indices were significantly different between groups A and B. The diagnostic efficiency of the myoglobin index, however, was best at 85%. CONCLUSIONS--These studies suggest that myoglobin has greater potential than the other markers examined in the detection of reperfusion after thrombolytic treatment. PMID:7786656

  14. Waterlow score as a surrogate marker for predicting adverse outcome in acute pancreatitis

    PubMed Central

    Gillick, K; Elbeltagi, H; Bhattacharya, S

    2016-01-01

    Introduction Introduced originally to stratify risk for developing decubitus ulcers, the Waterlow scoring system is recorded routinely for surgical admissions. It is a composite score, reflecting patients’ general condition and co-morbidities. The aim of this study was to investigate whether the Waterlow score can be used as an independent surrogate marker to predict severity and adverse outcome in acute pancreatitis. Methods In this retrospective analysis, a consecutive cohort was studied of 250 patients presenting with acute pancreatitis, all of whom had their Waterlow score calculated on admission. Primary outcome measures were length of hospital stay and mortality. Secondary outcome measures included rate of intensive care unit (ICU) admission and development of complications such as peripancreatic free fluid, pancreatic necrosis and pseudocyst formation. Correlation of the Waterlow score with some known markers of disease severity and outcomes was also analysed. Results The Waterlow score correlated strongly with the most commonly used marker of disease severity, the Glasgow score (analysis of variance, p=0.0012). Inpatient mortality, rate of ICU admission and length of hospital stay increased with a higher Waterlow score (Mann–Whitney U test, p=0.0007, p=0.049 and p=0.0002 respectively). There was, however, no significant association between the Waterlow score and the incidence of three known complications of pancreatitis: presence of peripancreatic fluid, pancreatic pseudocyst formation and pancreatic necrosis. Receiver operating characteristic curve analysis demonstrated good predictive power of the Waterlow score for mortality (area under the curve [AUC]: 0.73), ICU admission (AUC: 0.65) and length of stay >7 days (AUC: 0.64). This is comparable with the predictive power of the Glasgow score and C-reactive protein. Conclusions The Waterlow score for patients admitted with acute pancreatitis could provide a useful tool in prospective assessment of

  15. Cytokine levels in pleural fluid as markers of acute rejection after lung transplantation*

    PubMed Central

    de Camargo, Priscila Cilene León Bueno; Afonso, José Eduardo; Samano, Marcos Naoyuki; Acencio, Milena Marques Pagliarelli; Antonangelo, Leila; Teixeira, Ricardo Henrique de Oliveira Braga

    2014-01-01

    Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4). The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients. PMID:25210966

  16. Pathophysiological mechanisms of acute pancreatitis define inflammatory markers of clinical prognosis.

    PubMed

    Minkov, Georgi A; Halacheva, Krasimira S; Yovtchev, Yovcho P; Gulubova, Maya V

    2015-07-01

    Development of acute pancreatitis illustrates the need to understand the basic mechanisms of disease progression to drive the exploration of therapeutic options. Cytokines play a major role in the pathogenesis of acute pancreatitis as underlying systemic inflammatory response, tissue damage, and organ dysfunction. However, little is known about circulating concentrations of these inflammatory markers and their real impact on clinical practice. Experimental studies have suggested that the prognosis for acute pancreatitis depends on the degree of pancreatic necrosis and the intensity of multisystem organ failure generated by the systemic inflammatory response. This suggests an intricate balance between localized tissue damage with proinflammatory cytokine production and a systemic anti-inflammatory response that restricts the inappropriate movement of proinflammatory agents into the circulation. Implication of such mediators suggests that interruption or blunting of an inappropriate immune response has the potential to improve outcome. A detailed understanding of pathophysiological processes and immunological aspects in patients with acute pancreatitis is the basis for the development of therapeutic strategies that will provide significant reductions in morbidity and mortality.

  17. Presence of an acute phase response in sheep with clinical classical scrapie

    PubMed Central

    2012-01-01

    Background Work with experimental scrapie in sheep has been performed on-site for many years including studies on PrPSc dissemination and histopathology of organs and tissues both at preclinical and clinical stages. In this work serum was sampled at regular intervals from lambs which were infected immediately after birth and from parallel healthy controls, and examined for acute phase proteins. In contrast to earlier experiments, which extensively studied PrPSc dissemination and histopathology in peripheral tissues and brain, this experiment is focusing on examination of serum for non-PrPSc markers that discriminates the two groups, and give insight into other on-going processes detectable in serum samples. Results There was clear evidence of an acute phase response in sheep with clinical scrapie, both experimental and natural. All the three proteins, ceruloplasmin, haptoglobin and serum amyloid A, were increased at the clinical stage of scrapie. Conclusion There was evidence of a systemic measurable acute phase response at the clinical terminal end-stage of classical scrapie. PMID:22805457

  18. Serial profile of vitamins and trace elements during the acute phase of allogeneic stem cell transplantation.

    PubMed

    Nannya, Yasuhito; Shinohara, Akihito; Ichikawa, Motoshi; Kurokawa, Mineo

    2014-03-01

    Currently, we utilize vitamins and trace elements formulations that are not prepared specifically for patients receiving hematopoietic stem cell transplantation (HSCT), and adequacy of this strategy has not been evaluated. We prospectively measured blood level of vitamins and trace elements in 15 patients once per week at 6 time points around the acute phase of allogeneic HSCT. We provided standard nutrition support, including administration of parenteral nutrition with vitamin and trace elements formulation in case of impairment of oral intake. Most patients had vitamin B1 deficiency from the start of preparative regimens. Vitamin C deficiency was prominent throughout the acute phase of HSCT and this was significantly associated with high inflammatory markers, C-reactive protein and ferritin. Remarkable vitamin K overload associated with administration of parenteral supplementation and ferritin overload caused by repeated transfusions was observed. Moderate deficiency of zinc was at least partially linked to gastrointestinal loss by diarrhea. We revealed several features of vitamin and trace element status in the acute phase of HSCT and provided a basis for attempts to improve the nutritional condition in HSCT recipients.

  19. Acute-phase protein concentration and metabolic status affect the outcome of treatment in cows with clinical and subclinical endometritis.

    PubMed

    Heidarpour, M; Mohri, M; Fallah-Rad, A H; Dehghan Shahreza, F; Mohammadi, M

    2012-09-01

    The aim of this study was to investigate the role of acute-phase protein concentration and metabolic status in the establishment and resistance of clinical endometritis (CE) and subclinical endometritis (SE) in dairy cows. We also characterised the treatment-related changes in the concentration of acute-phase proteins and metabolic variables in dairy cows affected by CE and SE. Cows of the SE and CE groups presented a significantly higher β-hydroxybutyrate (BHB), haptoglobin and total sialic acid (TSA) concentrations compared with a healthy group of animals. A significantly lower serum calcium concentration, and a significantly higher serum aspartate aminotransferase activity in the CE group, were observed when compared with SE and healthy groups. The comparison of parameters before treatment indicated that cows suffering from CE or SE with lower concentrations of hepatic and inflammatory markers showed a better response to further treatment, and endometritis was not detected in the second examination. Moreover, decreased concentrations of BHB, acute-phase proteins and hepatic markers were observed after successful treatment for endometritis in CE and SE cows. The results obtained in this study suggest that improved liver function and a decrease in the acute-phase protein concentration might favour the resolution of endometritis after treatment.

  20. Investigation of suitable biopsy markers for grating-based phase contrast mammography

    NASA Astrophysics Data System (ADS)

    Arboleda, C.; Wang, Z.; Forte, S.; Kubik-Huch, R. A.; Stampanoni, M.

    2017-01-01

    Phase-contrast mammography is a rising technology where, in addition to X-ray absorption, images show phase and dark-field contrast. Although the use of biopsy markers constitutes a fundamental task in breast examinations, there has not been any investigation concerning appropriate clips for this technology. We studied the suitability of three markers (Tumark, Somatex Medical Technologies; Hydromark, Mammotome; and Mammostar, Mammotome) for this modality on a laboratory source setup using a chicken breast phantom. The first two clips appeared to be innocuous, whereas Mammostar showed the potential that the non-metallic portion only could be used as a marker for this technique.

  1. Normal Caloric Responses during Acute Phase of Vestibular Neuritis

    PubMed Central

    Lee, Sun-Uk; Park, Seong-Ho; Kim, Hyo-Jung; Koo, Ja-Won

    2016-01-01

    Background and Purpose We report a novel finding of caloric conversion from normal responses into unilateral paresis during the acute phase of vestibular neuritis (VN). Methods We recruited 893 patients with a diagnosis of VN at Dizziness Clinic of Seoul National University Bundang Hospital from 2003 to 2014 after excluding 28 patients with isolated inferior divisional VN (n=14) and those without follow-up tests despite normal caloric responses initially (n=14). We retrospectively analyzed the neurotological findings in four (0.5%) of the patients who showed a conversion from initially normal caloric responses into unilateral paresis during the acute phase. Results In those four patients, the initial caloric tests were performed within 2 days of symptom onset, and conversion into unilateral caloric paresis was documented 1–4 days later. The clinical and laboratory findings during the initial evaluation were consistent with VN in all four patients except for normal findings in bedside head impulse tests in one of them. Conclusions Normal findings in caloric tests should be interpreted with caution during the acute phase of suspected VN. Follow-up evaluation should be considered when the findings of the initial caloric test are normal, but VN remains the most plausible diagnosis. PMID:26932259

  2. Acute phase protein response in the capybara (Hydrochoerus hydrochaeris).

    PubMed

    Bernal, Luis; Feser, Mariane; Martínez-Subiela, Silvia; García-Martínez, Juan D; Cerón, José J; Tecles, Fernando

    2011-10-01

    We evaluated the acute phase protein response in capybaras (Hydrochoerus hydrochaeris). Three animal groups were used: 1) healthy animals (n=30), 2) a group in which experimental inflammation with turpentine was induced (n=6), and 3) a group affected with sarcoptic scabies (n=14) in which 10 animals were treated with ivermectin. Haptoglobin (Hp), acid-soluble glycoprotein (ASG) and albumin were analyzed in all animals. In those treated with turpentine, Hp reached its maximum value at 2 wk with a 2.7-fold increase, whereas ASG increased 1.75-fold and albumin decreased 0.87-fold 1 wk after the induction of inflammation. Capybaras affected with sarcoptic scabies presented increases in Hp and ASG of 4.98- and 3.18-fold, respectively, and a 0.87-fold decrease in albumin, compared with healthy animals. Haptoglobin and ASG can be considered as moderate, positive acute phase proteins in capybaras because they showed less than 10-fold increases after an inflammatory process and reached their peak concentrations 1 wk after the induction of inflammation. Conversely, albumin can be considered a negative acute phase protein in capybaras because it showed a reduction in concentration after inflammatory stimulus.

  3. Acute and subchronic toxicity of inhaled toluene in male Long Evans rats: oxidative stress markers in brain

    EPA Pesticide Factsheets

    Research interested in oxidative stress markers following exposure to VOCsThis dataset is associated with the following publication:Kodavanti , P., J. Royland , D.A. Moore-Smith, J. Beas, J. Richards , T. Beasley , P. Evansky , and P.J. Bushnell. Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain. NEUROTOXICOLOGY. Elsevier B.V., Amsterdam, NETHERLANDS, 51: 10-19, (2015).

  4. Elimination Half-Lives of Acute Phase Proteins in Rats and Beagle Dogs During Acute Inflammation.

    PubMed

    Kuribayashi, Takashi; Seita, Tetsuro; Momotani, Eiichi; Yamazaki, Shunsuke; Hagimori, Kohei; Yamamoto, Shizuo

    2015-08-01

    The half-lives of typical acute phase proteins in rats and beagle dogs during acute inflammation were investigated. Acute inflammation was induced by injection of turpentine oil in rats and administration of indomethacin in beagle dogs. Serum concentrations of α2-macroglobulin (α2M) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay and α1-acid glycoprotein (AAG) was measured by single radial immunodiffusion. Half-life was calculated as 0.693/elimination rate constant (K). The mean half-lives in the terminal elimination phase of α2M and AAG were 68.1 and 164.8 h, respectively. The half-life of AAG was significantly longer than that of α2M. Mean half-lives in the terminal elimination phase of CRP and AAG were 161.9 and 304.4 h, respectively. The half-life of AAG was significantly longer than that of CRP in beagle dogs. No significant differences in the half-life of AAG were observed between rats and beagle dogs. Furthermore, serum concentrations in the terminal elimination phase could be simulated with the K data acquired in this study.

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

    SciTech Connect

    Shannahan, Jonathan H.; Alzate, Oscar; Winnik, Witold M.; Andrews, Debora; Schladweiler, Mette C.; Ghio, Andrew J.; Gavett, Stephen H.; Kodavanti, Urmila P.

    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

  6. DNA-binding antibodies and hepatitis B markers in acute and chronic liver disease.

    PubMed Central

    Kingham, J G; Rassam, S; Ganguly, N; Mcguire, M J; Nasrat, B; Holgate, S T; Triger, D R; Wright, R

    1978-01-01

    A Farr technique has been used to assay antibodies to double-stranded DNA in the serum of patients with acute and chronic liver disease and carriers of HBsAg from the United Kingdom and Iraq. These antibodies were found in all groups from both countries. The highest levels were found in chronic active hepatitis and cirrhosis. In the Iraqi patients there was a strongly positive correlation between DNA-binding antibody levels and the presence of hepatitis B markers but not with disease activity. In the patients from the United Kingdom there was little correlation with disease activity and none with autoantibodies. Ninety-five per cent of asymptomatic carriers of HBsAG had elevated DNA-binding antibodies. It is suggested that hepatitis B-specific DNA might be one trigger to DNA antibody formation, though in liver disease a variety of factors are clearly operative. PMID:309808

  7. Tetraspanin CD81 is an adverse prognostic marker in acute myeloid leukemia

    PubMed Central

    Roumier, Christophe; Peyrouze, Pauline; Gonzales, Fanny; Berthon, Céline; Quesnel, Bruno; Preudhomme, Claude; Behal, Hélène; Duhamel, Alain; Roche-Lestienne, Catherine; Cheok, Meyling

    2016-01-01

    CD81 is a cell surface protein which belongs to the tetraspanin family. While in multiple myeloma its expression on plasma cells is associated with worse prognosis, this has not yet been explored in acute myeloid leukemia (AML). We measured membrane expression of CD81 on AML cells at diagnosis, evaluated its association with AML characteristics and its influence on patient outcome after intensive chemotherapy in a cohort of 134 patients. CD81 was detected in 92/134 (69%) patients. Patients with AML expressing CD81 had elevated leukocyte count (P=0.02) and were more likely classified as intermediate or adverse-risk by cytogenetics (P<0.001). CD81 expression had a negative impact on survival (event-free survival, overall survival and relapse-free survival) in univariate (P<0.001) and in multivariate analyses (P=0.003, 0.002 and <0.001, respectively). CD81 has a negative impact on OS in patients with NPM1 mutation (P=0.01) and in patients ELN-favorable (P=0.002). In conclusion, this cell surface marker may be a new prognostic marker for diagnostic risk classification and a potential therapeutic target for drug development in AML. PMID:27566555

  8. Early phase of acute pancreatitis: Assessment and management

    PubMed Central

    Phillip, Veit; Steiner, Jörg M; Algül, Hana

    2014-01-01

    Acute pancreatitis (AP) is a potentially life-threatening disease with a wide spectrum of severity. The overall mortality of AP is approximately 5%. According to the revised Atlanta classification system, AP can be classified as mild, moderate, or severe. Severe AP often takes a clinical course with two phases, an early and a late phase, which should both be considered separately. In this review article, we first discuss general aspects of AP, including incidence, pathophysiology, etiology, and grading of severity, then focus on the assessment of patients with suspected AP, including diagnosis and risk stratification, followed by the management of AP during the early phase, with special emphasis on fluid therapy, pain management, nutrition, and antibiotic prophylaxis. PMID:25133018

  9. Correlation between the serum and tissue levels of oxidative stress markers and the extent of inflammation in acute appendicitis

    PubMed Central

    Dumlu, Ersin Gürkan; Tokaç, Mehmet; Bozkurt, Birkan; Yildirim, Murat Baki; Ergin, Merve; Yalçin, Abdussamed; Kiliç, Mehmet

    2014-01-01

    OBJECTIVES: To determine the serum and tissue levels of markers of impaired oxidative metabolism and correlate these levels with the histopathology and Alvarado score of acute appendicitis patients. METHOD: Sixty-five acute appendicitis patients (mean age, 31.4±12.06 years; male/female, 30/35) and 30 healthy control subjects were studied. The Alvarado score was recorded. Serum samples were obtained before surgery and 12 hours postoperatively to examine the total antioxidant status, total oxidant status, paraoxonase, stimulated paraoxonase, arylesterase, catalase, myeloperoxidase, ceruloplasmin, oxidative stress markers (advanced oxidized protein products and total thiol level) and ischemia-modified albumin. Surgical specimens were also evaluated. RESULTS: The diagnoses were acute appendicitis (n = 37), perforated appendicitis (n = 8), phlegmonous appendicitis (n = 12), perforated+phlegmonous appendicitis (n = 4), or no appendicitis (n = 4). The Alvarado score of the acute appendicitis group was significantly lower than that of the perforated+phlegmonous appendicitis group (p = 0.004). The serum total antioxidant status, total thiol level, advanced oxidized protein products, total oxidant status, catalase, arylesterase, and ischemia-modified albumin levels were significantly different between the acute appendicitis and control groups. There was no correlation between the pathological extent of acute appendicitis and the tissue levels of the markers; additionally, there was no correlation between the tissue and serum levels of any of the parameters. CONCLUSIONS: The imbalance of oxidant/antioxidant systems plays a role in the pathogenesis acute appendicitis. The Alvarado score can successfully predict the presence and extent of acute appendicitis. PMID:25518019

  10. [Plasmapheresis in acute phase of multiple sclerosis and neuromyelitis optica].

    PubMed

    Matsuo, Hidenori

    2014-11-01

    In acute phase of multiple sclerosis (MS) and neuromyelitis optica (NMO), plasmapheresis (PP) should be considered as the 2nd choice treatment when corticosteroid pulse therapy results in unsuccessful. It is believed that the beneficial effects of PP occur through the elimination of pathogenic humoral and plasma factors, including autoantibodies, complement components, and cytokines. In MS, several clinical trials have shown the efficacy. However, there have been no randomized controlled trials that demonstrated the efficacy of PP in NMO. There are three methods of PP, plasma exchange, double filtration plasmapheresis and immunoadsorption plasmapheresis, available in Japan. But the difference of efficacy among these 3 methods has not been fully evaluated.

  11. Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke: A Randomized Trial.

    PubMed

    Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Della Corte, Vittoriano; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

    2016-03-01

    Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile.

  12. Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke

    PubMed Central

    Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Corte, Vittoriano Della; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

    2016-01-01

    Abstract Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile. PMID:27043681

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

    PubMed

    Shannahan, Jonathan H; Alzate, Oscar; Winnik, Witold M; Andrews, Debora; Schladweiler, Mette C; Ghio, Andrew J; Gavett, Stephen H; Kodavanti, Urmila P

    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.

  14. Acute phase response in cattle infected with Anaplasma marginale.

    PubMed

    Nazifi, S; Razavi, S M; Kaviani, F; Rakhshandehroo, E

    2012-03-23

    This study was undertaken to evaluate the acute phase responses via the assessment of the concentration of serum sialic acids (total, lipid bound and protein bound), inflammatory mediators (IFN-γ and TNF-α) and acute phase proteins (Hp and SAA) in 20 adult crossbred cattle naturally infected by Anaplasma marginale. The infected animals were divided into 2 subgroups on the basis of parasitemia rate (<20% and >20%). Also, as a control group, 10 clinically healthy cattle from the same farms were sampled. Our data revealed significant decreases in red blood cell count (RBC), hematocrite (PCV) and hemoglobine (Hb) in infected cattle compared to healthy ones. Conversely, the concentrations of Hp, SAA, ceruloplasmin, fibrinogen, serum sialic acids and the circulatory IFN-γ and TNF-α were increased in the diseased cattle (P<0.05). In addition, it was evident that the progression of parasitemia in infected cattle did not induce any significant alterations in the hematological indices (RBCs, PCV and Hb) and the concentrations of Hp, SAA, ceruloplasmin and fibrinogen. SAA was the most sensitive factor to change in the diseased cattle. Therefore, increase in SAA concentration may be a good indicator of inflammatory process in cattle naturally infected with Anaplasma marginale.

  15. ACUTE PHASE PROTEIN AND ELECTROPHORESIS PROTEIN FRACTION VALUES FOR CAPTIVE AMERICAN FLAMINGOS (PHOENICOPTERUS RUBER).

    PubMed

    Delk, Katie W; Wack, Raymund F; Burgdorf-Moisuk, Anne; Kass, Philip H; Cray, Carolyn

    2015-12-01

    Protein electrophoresis has recognized applications in determining the health status of various species. While reference intervals for electrophoresis have been determined for psittacine and raptor species, there are none reported for Phoenicopteriformes species. Reference intervals for haptoglobin and protein fractions obtained by electrophoresis were determined for the American flamingo (Phoenicopterus ruber) based on plasma samples from 39 captive birds. The reference intervals were as follows: haptoglobin, 0.17-0.8 mg/ml; total protein, 3.65-6.38 g/dl; prealbumin, 0.26-1.9 g/dl; albumin, 1.51-3.12 g/dl; α-1 globulin, 0.06-0.38 g/dl; α-2 globulin, 0.17-0.67 g/dl; β globulin, 0.38-1.33 g/dl; γ globulin, 0.26-0.68 g/dl; albumin : globulin ratio, 0.93-2.17. As captive flamingos often suffer from pododermatitis, feet of all flamingos were scored to determine if pododermatitis would be reflected in the acute phase proteins. Spearman rank correlation was performed on each of the protein fractions and pododermatitis scores, and only albumin had a significant correlation. This indicates that albumin, as a negative acute phase protein, may be a marker for this disease process.

  16. Mean Platelet Volume and Platelet Distribution Width as Markers in the Diagnosis of Acute Gangrenous Appendicitis

    PubMed Central

    Fan, Zhe; Pan, Jiyong; Zhang, Yingyi; Wang, Ziyi; Zhu, Ming; Yang, Baoshun; Shi, Lei; Jing, Huirong

    2015-01-01

    Introduction. Acute gangrenous appendicitis (AGA) is a common medical condition; however, the grade of appendicitis usually cannot be established preoperatively. We have attempted to identify some indicators, such as the mean platelet volume (MPV) and the platelet distribution width (PDW), to diagnose AGA. Aims. To evaluate whether or not the MPV and PDW are suitable markers to diagnose AGA. Methods. A retrospective study of 160 patients with AGA and 160 healthy patients was undertaken. Disease diagnosis was confirmed based on the pathologic examination of surgical specimens. Patient white blood cell (WBC) count, neutrophil ratio (NR), platelet (PLT) count, MPV, PDW, and hematocrit (HCT) were analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the sensitivity and specificity of these indices in AGA. Results. There were no significant differences between the AGA and control groups in age and gender. Compared to the control group, the WBC count, NR, and PDW were significantly higher (P < 0.001, resp.) and the MPV and HCT were significantly lower (P < 0.001, resp.) in the AGA group. The diagnostic specificities of the WBC count, NR, PLT count, MPV, PDW, and HCT were 86.3%, 92.5%, 58.1%, 81.7%, 83.9%, and 66.3%, respectively. Therefore, the NR had the highest diagnostic specificity for the diagnosis of AGA. Conclusions. This is the first study to assess the MPV and PDW in patients with AGA. Our present study showed that the MPV is reduced and the PDW is increased in patients with AGA; the sensitivity of PDW was superior to the MPV. A decreased MPV value and an increased PDW could serve as two markers to diagnose AGA. The NR had the highest specificity for the diagnosis of AGA. PMID:26688600

  17. Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis

    PubMed Central

    Vujasinovic, Miroslav; Tepes, Bojan; Makuc, Jana; Rudolf, Sasa; Zaletel, Jelka; Vidmar, Tjasa; Seruga, Maja; Birsa, Bostjan

    2014-01-01

    AIM: To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP). METHODS: Patients with AP were invited to participate in the study. Severity of AP was determined by the Atlanta classification and definitions revised in 2012. Pancreatic exocrine insufficiency (PEI) was diagnosed by the concentration of fecal elastase-1. An additional work-up, including laboratory testing of serum nutritional markers for determination of malnutrition, was offered to all patients with low levels of fecal elastase-1 FE. Hemoglobin A1c or oral glucose tolerance tests were also performed in patients without prior diabetes mellitus, and type 3c diabetes mellitus (T3cDM) was diagnosed according to American Diabetes Association criteria. RESULTS: One hundred patients were included in the study: 75% (75/100) of patients had one attack of AP and 25% (25/100) had two or more attacks. The most common etiology was alcohol. Mild, moderately severe and severe AP were present in 67, 15 and 18% of patients, respectively. The mean time from attack of AP to inclusion in the study was 2.7 years. PEI was diagnosed in 21% (21/100) of patients and T3cDM in 14% (14/100) of patients. In all patients with PEI, at least one serologic nutritional marker was below the lower limit of normal. T3cDM was more frequently present in patients with severe AP (P = 0.031), but was also present in some patients with mild and moderately severe AP. PEI was present in all degrees of severity of AP. There were no statistically significantly differences according to gender, etiology and number of AP attacks. CONCLUSION: As exocrine and endocrine pancreatic insufficiency can develop after AP, routine follow-up of patients is necessary, for which serum nutritional panel measurements can be useful. PMID:25561813

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

    PubMed Central

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

    2015-01-01

    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 < 0.05), and 3.1% of the variations in these occurrence over the study period were explained by these factors. Meteorological variables may predict occurrence of acute phase of chronic periodontitis. PMID:26251916

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

    PubMed

    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 < 0.05), and 3.1% of the variations in these occurrence over the study period were explained by these factors. Meteorological variables may predict occurrence of acute phase of chronic periodontitis.

  20. The effect of Prometheus device on laboratory markers of inflammation and tissue regeneration in acute liver failure management.

    PubMed

    Rocen, M; Kieslichova, E; Merta, D; Uchytilova, E; Pavlova, Y; Cap, J; Trunecka, P

    2010-11-01

    Prometheus, based on modified fractionated plasma separation and adsorption (FPSA) method, is used in the therapy of acute liver failure as a bridge to liver transplantation. As the therapeutic effect of Prometheus is caused not only by the elimination of terminal metabolites, the aim of the study was to identify the effect of FPSA on the levels of cytokines and markers of inflammation and liver regeneration. Previous studies assessing cytokine levels involved mostly acute-on-chronic liver failure patients. Data concerning markers of inflammation and liver regeneration are not published yet. Eleven patients (three males, eight females) with acute liver failure were investigated. These patients underwent 37 therapeutic sessions on Prometheus device. Before and after each treatment, the plasma levels of selected cytokines, tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), procalcitonin (PCT), hepatocyte growth factor (HGF), and α(1) fetoprotein, were measured, and the kinetics of their plasma concentrations was evaluated. Before the therapy, elevated levels of interleukin (IL)-6, IL-8, IL-10, TNFα, CRP, and PCT were detected. The level of TNFα, CRP, PCT, and α(1) fetoprotein decreased significantly during the therapy. In contrast, an increase of HGF was detected. The decline of IL-6, IL-8, and IL-10 concentrations was not significant. Our results show that Prometheus is highly effective in clearing inflammatory mediators responsible for systemic inflammatory response syndrome and affects the serum levels of inflammatory and regeneration markers important for management of acute liver failure.

  1. Identification of novel molecular prognostic markers for paediatric T-cell acute lymphoblastic leukaemia.

    PubMed

    Gottardo, Nicholas G; Hoffmann, Katrin; Beesley, Alex H; Freitas, Joseph R; Firth, Martin J; Perera, Kanchana U; de Klerk, Nicolas H; Baker, David L; Kees, Ursula R

    2007-05-01

    In the last four decades the survival of patients with newly diagnosed childhood T-cell acute lymphoblastic leukaemia (T-ALL) has improved dramatically. In sharp contrast, relapsed T-ALL continues to confer a dismal prognosis. We sought to determine if gene expression profiling could uncover a signature of outcome for children with T-ALL. Using 12 patient specimens obtained before therapy started, we examined the gene expression profile by oligonucleotide microarrays. We identified three genes, CFLAR, NOTCH2 and BTG3, whose expression at the time of diagnosis accurately distinguished the patients according to disease outcome. These genes are involved in the regulation of apoptosis and cellular proliferation. The prognostic value of the three predictive genes was assessed in an independent cohort of 25 paediatric T-ALL patients using quantitative real-time reverse transcription polymerase chain reaction. Patients assigned to the adverse outcome group had a significantly higher cumulative incidence of relapse compared with patients assigned to the favourable outcome group (46% vs. 8%, P = 0.029). Five-year overall survival was also significantly worse in the patients assigned to the adverse outcome group (P = 0.0039). The independent influence of the 3-gene predictor was confirmed by multivariate analysis. Our study provides proof of principle that genome-wide expression profiling can detect novel molecular prognostic markers in paediatric T-ALL.

  2. Value of plasmatic membrane attack complex as a marker of severity in acute kidney injury.

    PubMed

    Rodríguez, Eva; Riera, Marta; Barrios, Clara; Pascual, Julio

    2014-01-01

    The aim of this study was to determine if complement pathway is activated in AKI; for this purpose, we measured, through ELISA sandwich, the terminal lytic fraction of the complement system, called membrane attack complex (C5b-C9), in AKI patients compared with patients with similar clinical conditions but normal renal function. Our data showed that complement system is activated in AKI. Plasmatic MAC concentrations were significantly higher in AKI patients than in those with normal renal function; this difference is maintained independently of the AKI etiology and is proportional to the severity of AKI, measured by ADQI classification. In addition, we found that plasmatic MAC concentrations were significantly higher in patients who did not recover renal function at time of hospitalization discharge, in patients who died during the acute process, and in patients who need renal replacement therapy during hospitalization, but in this last group, the differences did not reach statistical significance. In conclusion, plasmatic MAC concentration seems valuable as a marker of AKI severity.

  3. Cellular markers that distinguish the phases of hemangioma during infancy and childhood.

    PubMed Central

    Takahashi, K; Mulliken, J B; Kozakewich, H P; Rogers, R A; Folkman, J; Ezekowitz, R A

    1994-01-01

    Hemangiomas, localized tumors of blood vessels, appear in approximately 10-12% of Caucasian infants. These lesions are characterized by a rapid proliferation of capillaries for the first year (proliferating phase), followed by slow, inevitable, regression of the tumor over the ensuing 1-5 yr (involuting phase), and continual improvement until 6-12 yr of age (involuted phase). To delineate the clinically observed growth phases of hemangiomas at a cellular level, we undertook an immunohistochemical analysis using nine independent markers. The proliferating phase was defined by high expression of proliferating cell nuclear antigen, type IV collagenase, and vascular endothelial growth factor. Elevated expression of the tissue inhibitor of metalloproteinase, TIMP 1, an inhibitor of new blood vessel formation, was observed exclusively in the involuting phase. High expression of basic fibroblast growth factor (bFGF) and urokinase was present in the proliferating and involuting phases. There was coexpression of bFGF and endothelial phenotypic markers CD31 and von Willebrand factor in the proliferating phase. These results provide an objective basis for staging hemangiomas and may be used to evaluate pharmacological agents, such as corticosteroids and interferon alfa-2a, which accelerate regression of hemangiomas. By contrast, vascular malformations do not express proliferating cell nuclear antigen, vascular endothelial growth factor, bFGF, type IV collagenase, and urokinase. These data demonstrate immunohistochemical differences between proliferating hemangiomas and vascular malformations which reflect the biological distinctions between these vascular lesions. Images PMID:7911127

  4. Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have an acute-phase response

    PubMed Central

    Rivory, L P; Slaviero, K A; Clarke, S J

    2002-01-01

    Inflammatory disease states (infection, arthritis) are associated with reduced drug oxidation by the cytochrome P450 3A system. Many chemotherapy agents are metabolised through this pathway, and disease may therefore influence inter-individual differences in drug pharmacokinetics. The purpose of this study was to assess cytochrome P450 3A function in patients with advanced cancer, and its relation to the acute-phase response. We evaluated hepatic cytochrome P450 3A function in 40 patients with advanced cancer using the erythromycin breath test. Both the traditional C20min measure and the recently proposed 1/TMAX values were estimated. The marker of acute-phase response, C-reactive protein and the pro-inflammatory cytokines IL-6, IL-1β, TNFα and IL-8 were measured in serum or plasma at baseline. Cancer patients with an acute phase response (C-reactive protein >10 mg l−1, n=26) had reduced metabolism as measured with the erythromycin breath test 1/TMAX (Kruskal–Wallis Anova, P=0.0062) as compared to controls (C-reactive protein ⩽10 mg l−1, n=14). Indeed, metabolism was significantly associated with C-reactive protein over the whole concentration range of this acute-phase marker (r=−0.64, Spearman Rank Correlation, P<0.00001). C-reactive protein serum levels were significantly correlated with those of IL-6 (Spearman coefficient=0.58, P<0.0003). The reduction in cytochrome P450 3A function with acute-phase reaction was independent of the tumour type and C-reactive protein elevation was associated with poor performance status. This indicates that the sub-group of cancer patients with significant acute-phase response have compromised drug metabolism, which may have implications for the safety of chemotherapy in this population. British Journal of Cancer (2002) 87, 277–280. doi:10.1038/sj.bjc.6600448 www.bjcancer.com © 2002 Cancer Research UK PMID:12177794

  5. Cardiac troponins I and T: molecular markers for early diagnosis, prognosis, and accurate triaging of patients with acute myocardial infarction.

    PubMed

    Tiwari, Ram P; Jain, Anubhav; Khan, Zakir; Kohli, Veena; Bharmal, R N; Kartikeyan, S; Bisen, Prakash S

    2012-12-01

    Acute myocardial infarction (AMI) is the leading cause of death worldwide, with early diagnosis still being difficult. Promising new cardiac biomarkers such as troponins and creatine kinase (CK) isoforms are being studied and integrated into clinical practice for early diagnosis of AMI. The cardiac-specific troponins I and T (cTnI and cTnT) have good sensitivity and specificity as indicators of myocardial necrosis and are superior to CK and its MB isoenzyme (CK-MB) in this regard. Besides being potential biologic markers, cardiac troponins also provide significant prognostic information. The introduction of novel high-sensitivity troponin assays has enabled more sensitive and timely diagnosis or exclusion of acute coronary syndromes. This review summarizes the available information on the potential of troponins and other cardiac markers in early diagnosis and prognosis of AMI, and provides perspectives on future diagnostic approaches to AMI.

  6. Acute phase response in lame crossbred dairy cattle

    PubMed Central

    Bagga, A.; Randhawa, Swaran Singh; Sharma, S.; Bansal, B. K.

    2016-01-01

    Aim: The study was undertaken to study acute phase response based on acute phase proteins (APPs) such as C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA), and fibrinogen in lame crossbred dairy cattle. Materials and Methods: Lame animals (n=30) were selected within 3-7 days of being noticed as lame by the farm veterinarian, from a local dairy farm in southeast Ludhiana over a period of 6 months, stratified proportionately with respect to stage of lactation with non-lame healthy cows (n=10). All the cows were otherwise healthy and did not have any other inflammatory problems such as pneumonia, enteritis, mastitis, or any kind of acute uterine inflammation. Blood samples were collected from all the animals; serum and plasma samples were separated and stored at −20°C. The levels of CRP, Hp, and SAA were estimated using Sandwich ELISA, whereas fibrinogen was estimated by heat precipitation method. Results: SAA levels in lame cows were significantly higher (22.19±0.85 µg/ml), approximately 3 times as compared to non-lame cows (8.89±0.72 µg/ml), whereas serum Hp concentration was approximately 20 times higher in the lame cattle (21.71±3.32 mg/dl) as compared to non-lame cows (1.17±0.07 mg/dl). Fibrinogen also increased in the lame cattle (3.97±0.22 g/L) as compared to non-lame group (1.40±0.17 g/L). Serum CRP levels analyzed in the lame cattle for the first time in the present study, and significant high concentration was appreciated in lame cattle (4.41±0.33 mg/L) as compared to non-lame cattle (0.61±0.14 mg/L). Lame cattle were having more of sole hemorrhages, sole ulcers, and white line lesions as compared to non-lame cattle. Conclusion: It can be concluded that lame cattle exhibit high levels of APPs including CRP, Hp, SAA, and fibrinogen as compared to non-lame cattle. PMID:27956769

  7. Oxidative Status and Acute Phase Reactants in Patients with Environmental Asbestos Exposure and Mesothelioma

    PubMed Central

    Sezgi, Cengizhan; Taylan, Mahsuk; Selimoglu Sen, Hadice; Evliyaoğlu, Osman; Kaya, Halide; Abakay, Ozlem; Abakay, Abdurrahman; Tanrıkulu, Abdullah Cetin; Senyiğit, Abdurrahman

    2014-01-01

    Background and Objectives. The aim of this study was to investigate inflammatory indicators and oxidative status in patients with asbestos exposure with and without mesothelioma and to compare results with data from healthy subjects. Methods. Eighty people with exposure to environmental asbestos and without any disease, 46 mesothelioma patients, and a control group of 50 people without exposure to environmental asbestos were enrolled in this prospective study. Serum total oxidant level (TOL), total antioxidant capacity (TAC), and oxidative stress index (OSI), CRP, transferrin, ceruloplasmin, α-1 antitrypsin, ferritin, and copper levels were measured. Results. Mesothelioma group exhibited higher TOL, OSI, α1-antitrypsin, ferritin and copper levels as compared to the other groups (P < 0.001, P = 0.007, P < 0.0001, P < 0.001, and P < 0.001, resp.). Transferrin was lower in the mesothelioma group than in the other two groups (P < 0.001). The asbestos group had higher TOL, TAC, α1-antitrypsin, and transferrin levels (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, resp.), as well as lower OSI and ferritin levels as compared to the control group (P < 0.001 and P < 0.001). Conclusions. We believe that elevated acute phase reactants and oxidative stress markers (TOL and OSI) in the mesothelioma group can be used as predictive markers for the development of asbestos-related malignancy. PMID:24592197

  8. Two genes controlling acute phase responses by the antitumor polysacch aride, lentinan.

    PubMed

    Maeda, Y Y; Takahama, S; Kohara, Y; Yonekawa, H

    1996-01-01

    Lentinan, a beta-1,6;1,3-glucan, is tumor-specific for transplantable mouse solid-type tumors and it also stimulates the production of acute phase proteins (APPs). The APP response to lentinan is of the delayed type (DT-APR) and differs from that to lipopolysaccharide, which is acute. We found that the responses were genetically controlled in mice and that low responsiveness is dominant (Maeda et al. 1991). Using 123 segregants of crosses between SWR/J (a high responder) and Mus spretus (a low responder), we analyzed the linkage between DT-APR responsiveness and the DNA polymerase chain reaction-simple sequence length polymorphism (PCR-SSLP) phenotype using 80 chromosome-specific microsatellite markers. We identified two loci (ltn1.1 and ltn1.2) responsible for DT-APR. ltn1.1 is closely linked to D3Mit11 on chromosome 3 and ltn1.2 to D11Nds9 on chromosome 11 (P <0.001). The linkage analysis also suggested that ltn1.2 is the major determinant for DT-APR. Correlation between lentinan-specific IL-6 mRNA expression (the late expression) controlled recessively and DT-APR induction suggests that the ltn1 loci control some process(es) of IL-6 expression in the regulation step before NF-IL6.

  9. Cystatin C as a Marker of Acute Kidney Injury in the Emergency Department

    PubMed Central

    Coelho, Silvia; Rodrigues, Bruno; Martins, Henrique; Frade, Francisca; Lopes, Stela; Cunha, Luis; Papoila, Ana Luisa

    2010-01-01

    Background and objectives: The diagnosis of acute kidney injury (AKI) is usually based on changes in serum creatinine, which is a poor marker of early renal dysfunction. The discriminative and predictive abilities of serum and urinary cystatin C were examined for the prediction of AKI. Design, setting, participants, & measurements: In this prospective cohort study, serum and urinary cystatin C were serially measured in a heterogeneous group of patients (n = 616) presenting to a tertiary care emergency department. The primary outcome was AKI, classified according to RIFLE and AKIN criteria. The secondary outcome was an adjudication based on clinical criteria to AKI, prerenal azotemia, chronic kidney disease (CKD), and normal kidney function. Results: Patients were adjudicated to have AKI in 21.1%, prerenal azotemia in 25.8%, CKD in 2.4%, and normal kidney function in 50.7%. For the diagnosis of AKI, the discriminatory ability of urinary creatinine and cystatin C was marginal. Both serum cystatin C and serum creatinine (at presentation and 6 hours later) showed high discriminatory ability for the diagnosis of AKI. However, only serum cystatin C attained a significant early predictive power (Hosmer-Lemeshow P value > 0.05). Serum cystatin C could differentiate between AKI and prerenal azotemia, but not between AKI and CKD. Conclusions: Serum cystatin C is an early, predictive biomarker of AKI, which outperforms serum creatinine in the heterogeneous emergency department setting. However, neither biomarker discriminated between AKI and CKD. Additional biomarkers continue to be needed for improved specificity in the diagnosis of community-acquired AKI. PMID:20576828

  10. Serum Procalcitonin as a Useful Serologic Marker for Differential Diagnosis between Acute Gouty Attack and Bacterial Infection

    PubMed Central

    Song, Jung-Soo

    2016-01-01

    Purpose Patients with gout are similar to those with bacterial infection in terms of the nature of inflammation. Herein we compared the differences in procalcitonin (PCT) levels between these two inflammatory conditions and evaluated the ability of serum PCT to function as a clinical marker for differential diagnosis between acute gouty attack and bacterial infection. Materials and Methods Serum samples were obtained from 67 patients with acute gouty arthritis and 90 age-matched patients with bacterial infection. Serum PCT levels were measured with an enzyme-linked fluorescent assay. Results Serum PCT levels in patients with acute gouty arthritis were significantly lower than those in patients with bacterial infection (0.096±0.105 ng/mL vs. 4.94±13.763 ng/mL, p=0.001). However, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels showed no significant differences between the two groups. To assess the ability of PCT to discriminate between acute gouty arthritis and bacterial infection, the areas under the curves (AUCs) of serum PCT, uric acid, and CRP were 0.857 [95% confidence interval (CI), 0.798–0.917, p<0.001], 0.808 (95% CI, 0.738–0.878, p<0.001), and 0.638 (95% CI, 0.544–0.731, p=0.005), respectively. There were no significant differences in ESR and white blood cell counts between these two conditions. With a cut-off value of 0.095 ng/mL, the sums of sensitivity and specificity of PCT were the highest (81.0% and 80.6%, respectively). Conclusion Serum PCT levels were significantly lower in patients with acute gouty attack than in patients with bacterial infection. Thus, serum PCT can be used as a useful serologic marker to differentiate between acute gouty arthritis and bacterial infections. PMID:27401644

  11. Resistin is not an appropriate biochemical marker to predict severity of acute pancreatitis: A case-controlled study

    PubMed Central

    Al-Maramhy, Hamdi; Abdelrahman, Abdelrahman I; Sawalhi, Samer

    2014-01-01

    AIM: To assess levels of serum resistin upon hospital admission as a predictor of acute pancreatitis (AP) severity. METHODS: AP is both a common and serious disease, with severe cases resulting in a high mortality rate. Several predictive inflammatory markers have been used clinically to assess severity. This prospective study collected data from 102 patients who were diagnosed with an initial acute biliary pancreatitis between March 2010 and February 2013. Measurements of body mass index (BMI) and waist circumference (WC) were obtained and serum resistin levels were analyzed at the time of hospital admission using enzyme-linked immunosorbent assay. Additionally, resistin levels were measured from a control group after matching gender, BMI and age. RESULTS: A total of 102 patients (60 females and 42 males) were diagnosed with acute gallstone-induced pancreatitis. The mean age was 45 years, and mean BMI value was 30.5 kg/m2 (Obese, class I). Twenty-two patients (21.6%) had severe AP, while eighty-eight patients had mild pancreatitis (78.4%). Our results showed that BMI significantly correlated with pancreatitis severity (P = 0.007). Serum resistin did not correlate with BMI, weight or WC. Furthermore, serum resistin was significantly higher in patients with AP compared to control subjects (P < 0.0001). The mean resistin values upon admission were 17.5 ng/mL in the severe acute biliary pancreatitis group and 16.82 ng/mL in the mild AP group (P = 0.188), indicating that resistin is not an appropriate predictive marker of clinical severity. CONCLUSION: We demonstrate that obesity is a risk factor for developing severe AP. Further, although there is a correlation between serum resistin levels and AP at the time of hospital admission, resistin does not adequately serve as a predictive marker of clinical severity. PMID:25386084

  12. [Acute phase reaction and immunocompetence in sepsis and SIRS].

    PubMed

    Burdon, Dan; Zabel, Peter

    2002-01-01

    The incidence of sepsis and SIRS, respectively is still rising. Mortality is 40 to 70% and, thus, remains very high in spite of major advances in intensive care medicine. Numerous experimental data have helped to explain isolated aspects of the pathophysiology of these disease states but the complex patho-mechanism remains to be elucidated. The discovery of the toll-like receptors and of the endotoxin-binding proteins LBP and BPI have substantially contributed to the understanding of the bacterial toxin-host interactions and may stimulate the development of new therapeutic strategies in the future. Pro- and anti-inflammatory cytokines play a central role in disease evolution, however the concept of organ-derived and organ-specific damage is gaining importance. Both inflammation and counter-regulation can occur at the same time in the circulation thus, making the evaluation of the patients' immunological status difficult. Additionally, several gene polymorphisms have been detected for example within the toll-like receptor genes and TNF genes. These polymorphisms document the existence of pre-disposing factors, which influence acute phase reaction as well as immuno-competence in sepsis. Both genes and gender will play an important role in the future to identify patients at risk and potentially, to design a specific and individualized immuno-therapies.

  13. [Occurrence of acute infectious diarrhea during the lunar phases].

    PubMed

    Mikulecký, M; Schréter, I

    1993-08-23

    A chronobiometric analysis of 753 cases of acute infectious diarrhoea in adults in 1981-1990 in Kosice confirmed to a surprising extent recently reached conclusions of an investigation made by authors from Bratislava. The Kosice group comprised 352 cases of bacillary dysentery, 305 patients with salmonellosis, 72 with campylobacteriosis and 24 with yersiniosis. Statistically significantly fewer patients (p < 0.0001) were hospitalized during full moon, moon quarterly and new moon. In the intervals there were periods with a short-term increase of the daily admissions by cca 25%. This 7.38-day periodicity cannot be explained by the influence of the social 7-day week, as during observations extending over several years this rhythm is eliminated by a gradual shift across different phases of the moon. The authors did not find similar reports in the literature. For explanation, not only the organism of the host (variable immunity?) but also the infectious agent must be taken into account. More profound understanding of the mechanism may open the road to practical application of the described lunar relationship. Its knowledge can help already now to improve the organization of the health service.

  14. Alterations in oxidant/antioxidant balance, high-mobility group box 1 protein and acute phase response in cross-bred suckling piglets suffering from rotaviral enteritis.

    PubMed

    Kumar De, Ujjwal; Mukherjee, Reena; Nandi, Sukdeb; Patel, Bhimnere Hanumatnagouda Manjunatha; Dimri, Umesh; Ravishankar, Chintu; Verma, Ashok Kumar

    2014-10-01

    Rotaviral enteritis has emerged as a major cause of morbidity and mortality in piglets during their post-natal life. The present study was carried out to examine high-mobility group box 1 (HMGB1) protein, acute phase response and oxidative stress indices in the serum of suckling piglets suffering from enteritis with or without association of porcine group A rotavirus infection. The present investigation utilized 23 clinical cases with signs of acute enteritis and 12 more healthy piglets of a similar age group as control animals. Out of 23 enteritis cases, 12 cases were found to be positive for porcine group A rotavirus infection as confirmed by reverse transcription-polymerase chain reaction (RT-PCR) using specific primers for group A rotavirus, and the rest were found negative. The acute enteritis cases in piglets were associated with an elevated level of HMGB1 protein and serum haptoglobin and ceruloplasmin suggestive of an acute phase response. Among the oxidative stress indices, the concentrations of malondialdehyde (MDA) and nitric oxide (NO) in serum were significantly increased. A pronounced drop of total antioxidant capacity and the activity of antioxidant enzymes such as catalase and superoxide dismutase in the serum of piglets suffering from acute enteritis compared to healthy ones were also noticed. The alterations in HMGB1 protein, acute phase response and oxidative stress indices were more pronounced in cases with the involvement of porcine rotavirus as compared to rotavirus-negative cases. It is concluded that HMGB1 protein, markers of oxidative stress and acute phase proteins might play an important role in the aetiopathogenesis of porcine diarrhoea caused by rotavirus and might be true markers in diagnosing the conditions leading to the extension of the prompt and effective therapeutic care.

  15. Phase I/II study of the hypoxia-activated prodrug PR104 in refractory/relapsed acute myeloid leukemia and acute lymphoblastic leukemia.

    PubMed

    Konopleva, Marina; Thall, Peter F; Yi, Cecilia Arana; Borthakur, Gautam; Coveler, Andrew; Bueso-Ramos, Carlos; Benito, Juliana; Konoplev, Sergej; Gu, Yongchuan; Ravandi, Farhad; Jabbour, Elias; Faderl, Stefan; Thomas, Deborah; Cortes, Jorge; Kadia, Tapan; Kornblau, Steven; Daver, Naval; Pemmaraju, Naveen; Nguyen, Hoang Q; Feliu, Jennie; Lu, Hongbo; Wei, Caimiao; Wilson, William R; Melink, Teresa J; Gutheil, John C; Andreeff, Michael; Estey, Elihu H; Kantarjian, Hagop

    2015-07-01

    We previously demonstrated vast expansion of hypoxic areas in the leukemic microenvironment and provided a rationale for using hypoxia-activated prodrugs. PR104 is a phosphate ester that is rapidly hydrolyzed in vivo to the corresponding alcohol PR-104A and further reduced to the amine and hydroxyl-amine nitrogen mustards that induce DNA cross-linking in hypoxic cells under low oxygen concentrations. In this phase I/II study, patients with relapsed/refractory acute myeloid leukemia (n=40) after 1 or 2 prior treatments or acute lymphoblastic leukemia (n=10) after any number of prior treatments received PR104; dose ranged from 1.1 to 4 g/m(2). The most common treatment-related grade 3/4 adverse events were myelosuppression (anemia 62%, neutropenia 50%, thrombocytopenia 46%), febrile neutropenia (40%), infection (24%), and enterocolitis (14%). Ten of 31 patients with acute myeloid leukemia (32%) and 2 of 10 patients with acute lymphoblastic leukemia (20%) who received 3 g/m(2) or 4 g/m(2) had a response (complete response, n=1; complete response without platelet recovery, n=5; morphological leukemia-free state, n=6). The extent of hypoxia was evaluated by the hypoxia tracer pimonidazole administered prior to a bone marrow biopsy and by immunohistochemical assessments of hypoxia-inducible factor alpha and carbonic anhydrase IX. A high fraction of leukemic cells expressed these markers, and PR104 administration resulted in measurable decrease of the proportions of hypoxic cells. These findings indicate that hypoxia is a prevalent feature of the leukemic microenvironment and that targeting hypoxia with hypoxia-activated prodrugs warrants further evaluation in acute leukemia. The trial is registered at clinicaltrials.gov identifier: 01037556.

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

    PubMed

    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 < 0.001) serum amyloid A, alpha2-globulin, and haptoglobin concentrations compared with the healthy subgroup. Moreover, serum amyloid A (P = 0.020), alpha2-globulin (P < 0.001) and haptoglobin (P = 0.001) concentrations in 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.

  17. Senescence marker protein-30/gluconolactonase deletion worsens glucose tolerance through impairment of acute insulin secretion.

    PubMed

    Hasegawa, Goji; Yamasaki, Masahiro; Kadono, Mayuko; Tanaka, Muhei; Asano, Mai; Senmaru, Takafumi; Kondo, Yoshitaka; Fukui, Michiaki; Obayashi, Hiroshi; Maruyama, Naoki; Nakamura, Naoto; Ishigami, Akihito

    2010-02-01

    Senescence marker protein-30 (SMP30) is an androgen-independent factor that decreases with age. We recently identified SMP30 as the lactone-hydrolyzing enzyme gluconolactonase (GNL), which is involved in vitamin C biosynthesis in animal species. To examine whether the age-related decrease in SMP30/GNL has effects on glucose homeostasis, we used SMP30/GNL knockout (KO) mice treated with L-ascorbic acid. In an ip glucose tolerance test at 15 wk of age, blood glucose levels in SMP30/GNL KO mice were significantly increased by 25% at 30 min after glucose administration compared with wild-type (WT) mice. Insulin levels in SMP30/GNL KO mice were significantly decreased by 37% at 30 min after glucose compared with WT mice. Interestingly, an insulin tolerance test showed a greater glucose-lowering effect in SMP30/GNL KO mice. High-fat diet feeding severely worsened glucose tolerance in both WT and SMP30/GNL KO mice. Morphometric analysis revealed no differences in the degree of high-fat diet-induced compensatory increase in beta-cell mass and proliferation. In the static incubation study of islets, insulin secretion in response to 20 mm glucose or KCl was significantly decreased in SMP30/GNL KO mice. On the other hand, islet ATP content at 20 mm in SMP30/GNL KO mice was similar to that in WT mice. Collectively, these data indicate that impairment of the early phase of insulin secretion due to dysfunction of the distal portion of the secretion pathway underlies glucose intolerance in SMP30/GNL KO mice. Decreased SMP30/GNL may contribute to the worsening of glucose tolerance that occurs in normal aging.

  18. Detecting Acute Myocardial Infarction by Diffusion-Weighted versus T2-Weighted Imaging and Myocardial Necrosis Markers.

    PubMed

    Jin, Jiyang; Chen, Min; Li, Yongjun; Wang, YaLing; Zhang, Shijun; Wang, Zhen; Wang, Lin; Ju, Shenghong

    2016-10-01

    We used a porcine model of acute myocardial infarction to study the signal evolution of ischemic myocardium on diffusion-weighted magnetic resonance images (DWI). Eight Chinese miniature pigs underwent percutaneous left anterior descending or left circumflex coronary artery occlusion for 90 minutes followed by reperfusion, which induced acute myocardial infarction. We used DWI preprocedurally and hourly for 4 hours postprocedurally. We acquired turbo inversion recovery magnitude T2-weighted images (TIRM T2WI) and late gadolinium enhancement images from the DWI slices. We measured the serum myocardial necrosis markers myoglobin, creatine kinase-MB isoenzyme, and cardiac troponin I at the same time points as the magnetic resonance scanning. We used histochemical staining to confirm injury. All images were analyzed qualitatively. Contrast-to-noise ratio (the contrast between infarcted and healthy myocardium) and relative signal index were used in quantitative image analysis. We found that DWI identified myocardial signal abnormity early (<4 hr) after acute myocardial infarction and identified the infarct-related high signal more often than did TIRM T2WI: 7 of 8 pigs (87.5%) versus 3 of 8 (37.5%) (P=0.046). Quantitative image analysis yielded a significant difference in contrast-to-noise ratio and relative signal index between infarcted and normal myocardium on DWI. However, within 4 hours after infarction, the serologic myocardial injury markers were not significantly positive. We conclude that DWI can be used to detect myocardial signal abnormalities early after acute myocardial infarction-identifying the infarction earlier than TIRM T2WI and widely used clinical serologic biomarkers.

  19. Detecting Acute Myocardial Infarction by Diffusion-Weighted versus T2-Weighted Imaging and Myocardial Necrosis Markers

    PubMed Central

    Chen, Min; Li, Yongjun; Wang, YaLing; Zhang, Shijun; Wang, Zhen; Wang, Lin; Ju, Shenghong

    2016-01-01

    We used a porcine model of acute myocardial infarction to study the signal evolution of ischemic myocardium on diffusion-weighted magnetic resonance images (DWI). Eight Chinese miniature pigs underwent percutaneous left anterior descending or left circumflex coronary artery occlusion for 90 minutes followed by reperfusion, which induced acute myocardial infarction. We used DWI preprocedurally and hourly for 4 hours postprocedurally. We acquired turbo inversion recovery magnitude T2-weighted images (TIRM T2WI) and late gadolinium enhancement images from the DWI slices. We measured the serum myocardial necrosis markers myoglobin, creatine kinase-MB isoenzyme, and cardiac troponin I at the same time points as the magnetic resonance scanning. We used histochemical staining to confirm injury. All images were analyzed qualitatively. Contrast-to-noise ratio (the contrast between infarcted and healthy myocardium) and relative signal index were used in quantitative image analysis. We found that DWI identified myocardial signal abnormity early (<4 hr) after acute myocardial infarction and identified the infarct-related high signal more often than did TIRM T2WI: 7 of 8 pigs (87.5%) versus 3 of 8 (37.5%) (P=0.046). Quantitative image analysis yielded a significant difference in contrast-to-noise ratio and relative signal index between infarcted and normal myocardium on DWI. However, within 4 hours after infarction, the serologic myocardial injury markers were not significantly positive. We conclude that DWI can be used to detect myocardial signal abnormalities early after acute myocardial infarction—identifying the infarction earlier than TIRM T2WI and widely used clinical serologic biomarkers. PMID:27777517

  20. 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.

    NASA Astrophysics Data System (ADS)

    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

  1. Induction of acute phase gene expression by brain irradiation

    SciTech Connect

    Hong, Ji-Hong |; Sun, Ji-Rong; Withers, H.R.

    1995-10-15

    To investigate the in vivo acute phase molecular response of the brain to ionizing radiation, C3Hf/Sed/Kam mice were given midbrain or whole-body irradiation. Cerebral expression of interleukins (IL-1{alpha}, IL-1{beta}, IL-2, IL-3, IL-4, IL-5, IL-6), interferon (IFN-{gamma}), tumor necrosis factors (TNF-{alpha} and TNF-{beta}), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthetase (iNOS), von Willebrand factor (vWF), {alpha}1-antichymotrypsin (EB22/5.3), and glial fibrillary acidic protein (GFAP) was measured at various times after various radiation doses by ribonuclease (RNase) protection assay. The effects of dexamethasone or pentoxifylline treatment of mice on radiation-induced gene expression were also examined. Levels of TNF-{alpha}, IL-1{beta}, ICAM-1, EB22/5.3, and to a lesser extent IL-1{alpha} and GFAP, messenger RNA were increased in the brain after irradiation, whether the dose was delivered to the whole body or only to the midbrain. Responses were radiation dose dependent, but were not found below 7 Gy; the exception being ICAM-1, which was increased by doses as low as 2 Gy. Most responses were rapid, peaking within 4-8 h, but antichymotrypsin and GFAP responses were delayed and still elevated at 24 h, by which time the others had subsided. Pretreatment of mice with dexamethasone or pentoxifylline suppressed radiation-induced gene expression, either partially or completely. Dexamethasone was more inhibitory than pentoxifylline at the doses chosen. The initial response of the brain to irradiation involves expression of inflammatory gene products, which are probably responsible for clinically observed early symptoms of brain radiotherapy. This mechanism explains the beneficial effects of the clinical use of steroids in such circumstances. 64 refs., 4 figs.

  2. [Management of coronary artery disease at the acute phase].

    PubMed

    Chatot, Marion; Schiele, François

    2015-03-01

    In patients with acute coronary syndrome (ACS), early management is of prime importance. However, the median time taken by the patient to call the emergency services is often very long, up to 2 hours. The presence of a physician as first responder ensures good quality resuscitation in case of cardiac arrest, and allows recording of a first ECG, which can be very informative, especially in ACS without ST segment elevation. Treatment at this stage is limited to sublingual nitroglycerin and aspirin. If the first ECG shows ST segment elevation, the patient should be immediately oriented for reperfusion, usually by percutaneous coronary intervention. in the absence of ST segment elevation, the diagnosis of ACS remains unconfirmed. This does not imply that the risk is lesser, but rather that the risk cannot be evaluated accurately in the pre-hospital setting. The use of risk scores can guide the choice of management towards an invasive strategy, including coronary angiography (immediately, or within 24-72 hours). Low-risk patients are candidates for an invasive strategy, provided non-invasive tests demonstrate the presence of ischemia. During the hospital phase, antiplatelet treatment should be initiated and must be adapted to the patient bleeding and thrombotic risk. Clopidogrel is recommended only in patients who are not amenable to prasugrel or ticagrelor. Statin therapy should be initiated from day one, regardless of the initial cholesterol level, preferably with 80 mg atorvastatin. Angiotensin-converting enzyme inhibitors and beta-blockers should also be prescribed to complete the medical prescription both in-hospital and in the long term.

  3. Prognostic markers of acute decompensated heart failure: the emerging roles of cardiac biomarkers and prognostic scores.

    PubMed

    Cohen-Solal, Alain; Laribi, Said; Ishihara, Shiro; Vergaro, Giuseppe; Baudet, Mathilde; Logeart, Damien; Mebazaa, Alexandre; Gayat, Etienne; Vodovar, Nicolas; Pascual-Figal, Domingo A; Seronde, Marie-France

    2015-01-01

    Rapidly assessing outcome in patients with acute decompensated heart failure is important but prognostic factors may differ from those used routinely for stable chronic heart failure. Multiple plasma biomarkers, besides the classic natriuretic peptides, have recently emerged as potential prognosticators. Furthermore, prognostic scores that combine clinical and biochemical data may also be useful. However, compared with the scores used in chronic heart failure, scores for acute decompensated heart failure have not been validated. This article reviews potential biomarkers, with a special focus on biochemical biomarkers, and possible prognostic scores that could be used by the clinician when assessing outcome in patients with acute heart failure.

  4. Assessment of circulating biochemical markers and antioxidative status in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients.

    PubMed

    Rasool, Mahmood; Farooq, Shahzad; Malik, Arif; Shaukat, Aysha; Manan, Abdul; Asif, Muhammad; Sani, Suleman; Qazi, Mahmood Husain; Kamal, Mohammad Amjad; Iqbal, Zafar; Hussain, Abrar

    2015-01-01

    Various circulating biochemical markers are indicators of pathological state in leukemia and its subtypes. Increased oxidative stress and decreased antioxidant factors portray clear image associated with malignancies during subtypes of leukemia. In this research work we investigated the inter-relationship among the subtypes of leukemia with circulating biochemical markers and oxidative stress in the Pakistani population. This research work was conducted on a total number of 70 subjects in which 20 were control participants and 50 were suffering from leukemia and divided into two subtypes (ALL and AML). Various circulating biomarkers were investigated including hematological, hepatic and renal profiles as well as oxidative stress markers, electrolytes and vitamins C and E. Results show that vitamin E was found to be decreased in diseased sub-types (P < 0.05). Malondialdehyde (MDA) levels were very high in disease sub-types (ALL-B = 8.69 ± 1.59; ALL-T = 8.78 ± 0.97; AML = 8.50 ± 1.29) compared to controls (1.22 ± 0.10; P < 0.05) while the levels of antioxidants [superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), catalase (CAT)], platelets, as well as electrolytes (Ca and Mg) were reduced in patients suffering from leukemia (sub-types). Enhanced levels of oxidative stress (MDA) and decreased levels of enzymatic and non-enzymatic antioxidants reflect the pathological state and impaired cell control in patients suffering from leukemia (subtypes) and show a strong correlation with oxidative stress, indicating that patients' biological systems are under oxidative stress.

  5. Acute Phase Proteins in Cerebrospinal Fluid from Dogs with Naturally-Occurring Spinal Cord Injury

    PubMed Central

    Anderson, Kimberly M.; Welsh, C. Jane; Young, Colin; Levine, Gwendolyn J.; Kerwin, Sharon C.; Boudreau, C. Elizabeth; Reyes, Ismael; Mondragon, Armando; Griffin, John F.; Cohen, Noah D.

    2015-01-01

    Abstract Spinal cord injury (SCI) affects thousands of people each year and there are no treatments that dramatically improve clinical outcome. Canine intervertebral disc herniation is a naturally-occurring SCI that has similarities to human injury and can be used as a translational model for evaluating therapeutic interventions. Here, we characterized cerebrospinal fluid (CSF) acute phase proteins (APPs) that have altered expression across a spectrum of neurological disorders, using this canine model system. The concentrations of C-reactive protein (CRP), haptoglobin (Hp), alpha-1-glycoprotein, and serum amyloid A were determined in the CSF of 42 acutely injured dogs, compared with 21 healthy control dogs. Concentrations of APPs also were examined with respect to initial injury severity and motor outcome 42 d post-injury. Hp concentration was significantly higher (p<0.0001) in the CSF of affected dogs, compared with healthy control dogs. Additionally, the concentrations of CRP and Hp were significantly (p=0.0001 and p=0.0079, respectively) and positively associated with CSF total protein concentration. The concentrations of CRP and Hp were significantly higher (p=0.0071 and p=0.0197, respectively) in dogs with severe injury, compared with those with mild-to-moderate SCI, but there was no significant correlation between assessed CSF APP concentrations and 42 d motor outcome. This study demonstrated that CSF APPs were dysregulated in dogs with naturally-occurring SCI and could be used as markers for SCI severity. As Hp was increased following severe SCI and is neuroprotective across a number of model systems, it may represent a viable therapeutic target. PMID:26186466

  6. Immunoadsorption therapy for neuromyelitis optica spectrum disorders long after the acute phase.

    PubMed

    Kobayashi, Masatake; Nanri, Kazunori; Taguchi, Takeshi; Ishiko, Tomoko; Yoshida, Masaharu; Yoshikawa, Noriko; Sugisaki, Kentaro; Tanaka, Nobuyuki

    2015-02-01

    Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease with exacerbations involving recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis. Pulse steroid therapy is recommended as the initial, acute-phase treatment for NMO. If ineffective, treatment with plasma exchange (PE) should commence. However, no evidence exists to support the effectiveness of PE long after the acute phase. Immunoadsorption therapy (IA) eliminates pathogenic antibodies while sparing other plasma proteins. With IA, side effects of PE resulting from protein substitution can be avoided. However, whether IA is effective for NMO remains unclear. We describe a patient with anti-aquaporin-4-positive myelitis who responded to IA using a tryptophan polyvinyl alcohol gel column that was begun 52 days after disease onset following the acute phase. Even long after the acute phase when symptoms appear to be stable, IA may be effective and should not be excluded as a treatment choice.

  7. Serum acute phase proteins as biomarkers of pleuritis and cranio-ventral pulmonary consolidation in slaughter-aged pigs.

    PubMed

    Saco, Yolanda; Fraile, Lorenzo; Giménez, Mercè; Alegre, Ana; López-Jimenez, Rosa; Cortey, Martí; Segalés, Joaquim; Bassols, Anna

    2011-08-01

    The purpose of this study was to investigate the relationship between the existence of lung lesions in pigs at slaughter and the concentration of the serum acute phase proteins (APP), haptoglobin (Hp), pig-major acute protein (Pig-MAP) and C-reactive protein (CRP). A total of 24 pig farms were selected out of a larger farm database previously screened to study risk factors associated with pleuritis and cranio-ventral pulmonary consolidation (CVPC) lesions at slaughter-aged pigs in Spain. The farms were classified as "pleuritis negative (P-) or positive (P+)" and as "CVPC negative (M-) or positive (M+)" and divided into four groups according to a 2X2 factorial design (P-M-, P-M+, P+M-, P+M+). Also at slaughter, blood from 20 randomly selected pigs from each farm was collected. Obtained serum samples were used to measure acute phase proteins. All APP concentrations were significantly higher for M+ farms than for M- ones. However, only Hp and Pig-MAP showed significantly higher concentrations for P+ farms than for P- ones. Pig-MAP was the most sensitive biomarker since it was able to clearly discriminate between P-/P+ and M-/M+ groups (p<0.001 in both cases). Hp was an excellent marker for pleuritis and good for CVPC lesions. CRP was able to discriminate for CVPC lesions but not for pleuritis. The present results indicate that Pig-MAP and, possibly Hp, may be used as potential markers to characterise and discriminate respiratory lesions in swine herds at slaughter.

  8. The Acute-Phase Proteins Serum Amyloid A and C Reactive Protein in Transudates and Exudates

    PubMed Central

    Okino, Alessandra M.; Bürger, Cristiani; Cardoso, Jefferson R.; Lavado, Edson L.; Lotufo, Paulo A.; Campa, Ana

    2006-01-01

    The distinction between exudates and transudates is very important in the patient management. Here we evaluate whether the acute-phase protein serum amyloid A (SAA), in comparison with C reactive protein (CRP) and total protein (TP), can be useful in this discrimination. CRP, SAA, and TP were determined in 36 exudate samples (27 pleural and 9 ascitic) and in 12 transudates (9 pleural and 3 ascitic). CRP, SAA, and TP were measured. SAA present in the exudate corresponded to 10% of the amount found in serum, that is, the exudate/serum ratio (E/S) was 0.10 ± 0.13. For comparison, the exudate/serum ratio for CRP and TP was 0.39 ± 0.37 and 0.68 ± 0.15, respectively. There was a strong positive correlation between serum and exudate SAA concentration (r = 0.764;p < 0.0001). The concentration of SAA in transudates was low and did not overlap with that found in exudates (0.02-0.21 versus 0.8–360.5 g/mL). SAA in pleural and ascitic exudates results mainly from leakage of the serum protein via the inflamed membrane. A comparison of the E/S ratio of SAA and CRP points SAA as a very good marker in discriminating between exudates and transudates. PMID:16864904

  9. Delta 9-tetrahydrocannabinol suppresses vomiting behavior and Fos expression in both acute and delayed phases of cisplatin-induced emesis in the least shrew.

    PubMed

    Ray, Andrew P; Griggs, Lisa; Darmani, Nissar A

    2009-01-03

    Cisplatin chemotherapy frequently causes severe vomiting in two temporally separated clusters of bouts dubbed the acute and delayed phases. Cannabinoids can inhibit the acute phase, albeit through a poorly understood mechanism. We examined the substrates of cannabinoid-mediated inhibition of both the emetic phases via immunolabeling for serotonin, Substance P, cannabinoid receptors 1 and 2 (CB(1), CB(2)), and the neuronal activation marker Fos in the least shrew (Cryptotis parva). Shrews were injected with cisplatin (10mg/kg i.p.), and one of vehicle, Delta(9)-THC, or both Delta(9)-THC and the CB(1) receptor antagonist SR141716A (2mg/kg i.p.), and monitored for vomiting. Delta(9)-THC-pretreatment caused concurrent decreases in the number of shrews expressing vomiting and Fos-immunoreactivity (Fos-IR), effects which were blocked by SR141716A-pretreatment. Acute phase vomiting induced Fos-IR in the solitary tract nucleus (NTS), dorsal motor nucleus of the vagus (DMNX), and area postrema (AP), whereas in the delayed phase Fos-IR was not induced in the AP at all, and was induced at lower levels in the other nuclei when compared to the acute phase. CB(1) receptor-IR in the NTS was dense, punctate labeling indicative of presynaptic elements, which surrounded Fos-expressing NTS neurons. CB(2) receptor-IR was not found in neuronal elements, but in vascular-appearing structures. All areas correlated with serotonin- and Substance P-IR. These results support published acute phase data in other species, and are the first describing Fos-IR following delayed phase emesis. The data suggest overlapping but separate mechanisms are invoked for each phase, which are sensitive to antiemetic effects of Delta(9)-THC mediated by CB(1) receptors.

  10. Predictors of Longitudinal Outcomes after Unstable Response to Acute Phase Cognitive Therapy for Major Depressive Disorder

    PubMed Central

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

    2015-01-01

    After patients with major depressive disorder (MDD) respond to acute-phase cognitive therapy (CT), continuation-phase treatments may be applied to improve long-term outcomes. We clarified which CT responders experience remission, recovery, relapse, and recurrence by testing baseline demographic, clinical, and personality variables. The sample of CT responders at higher risk of relapse (N = 241) was randomized to 8 months of continuation-phase CT (C-CT), double-blinded fluoxetine or pill placebo, and followed 24 months (Jarrett & Thase, 2010). Patients with lower positive emotionality and behavioral activation at the end of acute-phase CT showed increased risk for relapse/recurrence of MDD. In addition, patients with lower positive emotionality and behavioral activation, as well as higher residual depression (including emotional, cognitive, and social facets), showed decreased probability of remission (≥6 continuous weeks of minimal or absent symptoms) after acute-phase CT. Finally, patients with greater residual depression, as well as younger age and earlier MDD onset, showed decreased probability of recovery (≥35 continuous weeks of minimal or absent symptoms) after acute-phase CT. Moderator analyses did not reveal differential prediction across the continuation phase treatment arms. These results may help clinicians gauge the prognoses and need for continuation treatment among MDD patients who respond to acute-phase CT. PMID:25985046

  11. Acute phase response induced following tumor treatment by photodynamic therapy: relevance for the therapy outcome

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Merchant, Soroush; Stott, Brandon; Cecic, Ivana; Payne, Peter; Sun, Jinghai

    2006-02-01

    Acute phase response is an effector process orchestrated by the innate immune system for the optimal mobilization of the resources of the organism distant from the local insult site needed in the execution of a host-protecting reaction. Our research has shown that mice bearing tumors treated by photodynamic therapy (PDT) exhibit the three major hallmarks of acute phase response: release of acute phase reactants, neutrophilia, and pituitary/adrenal axis activation. Of particular interest in this study were acute phase proteins that have a pivotal role in the clearance of dead cells, since the occurrence of this process in PDT-treated tumors emerges as a critical event in the course of PDT-associated host response. It is shown that this type of acute phase reactants, including complement proteins (C3, C5, C9, mannose-binding lectin, and ficolin A) and related pentraxins (serum amyloid P component and PTX3), are upregulated following tumor PDT and accumulate in the targeted lesions. Based on the recently accumulated experimental evidence it is definitely established that the acute phase response is manifested in the hosts bearing PDT-treated tumors and it is becoming clear that this effector process is an important element of PDT-associated host response bearing in impact on the eventual outcome of this therapy.

  12. Acute restraint stress induces specific changes in nitric oxide production and inflammatory markers in the rat hippocampus and striatum.

    PubMed

    Chen, Hsiao-Jou Cortina; Spiers, Jereme G; Sernia, Conrad; Lavidis, Nickolas A

    2016-01-01

    Chronic mild stress has been shown to cause hippocampal neuronal nitric oxide synthase (NOS) overexpression and the resultant nitric oxide (NO) production has been implicated in the etiology of depression. However, the extent of nitrosative changes including NOS enzymatic activity and the overall output of NO production in regions of the brain like the hippocampus and striatum following acute stress has not been characterized. In this study, outbred male Wistar rats aged 6-7 weeks were randomly allocated into 0 (control), 60, 120, or 240 min stress groups and neural regions were cryodissected for measurement of constitutive and inducible NOS enzymatic activity, nitrosative status, and relative gene expression of neuronal and inducible NOS. Hippocampal constitutive NOS activity increased initially but was superseded by the inducible isoform as stress duration was prolonged. Interestingly, hippocampal neuronal NOS and interleukin-1β mRNA expression was downregulated, while the inducible NOS isoform was upregulated in conjunction with other inflammatory markers. This pro-inflammatory phenotype within the hippocampus was further confirmed with an increase in the glucocorticoid-antagonizing macrophage migration inhibitory factor, Mif, and the glial surveillance marker, Ciita. This indicates that despite high levels of glucocorticoids, acute stress sensitizes a neuroinflammatory response within the hippocampus involving both pro-inflammatory cytokines and inducible NOS while concurrently modulating the immunophenotype of glia. Furthermore, there was a delayed increase in striatal inducible NOS expression while no change was found in other pro-inflammatory mediators. This suggests that short term stress induces a generalized increase in inducible NOS signaling that coincides with regionally specific increased markers of adaptive immunity and inflammation within the brain.

  13. Inflammatory markers following acute fuel oil exposure or bacterial lipopolysaccharide in mallard ducks (Anas platyrhynchos).

    PubMed

    Lee, Kelly A; Tell, Lisa A; Mohr, F Charles

    2012-12-01

    Adult mallard ducks (Anas platyrhynchos) were orally dosed with bunker C fuel oil for 5 days, and five different inflammatory markers (haptoglobin, mannan-binding lectin, ceruloplasmin, unsaturated iron-binding capacity, and plasma iron) were measured in blood plasma prior to and 8, 24, 48, and 72 hr following exposure. In order to contrast the response to fuel oil with that of a systemic inflammatory response, an additional five ducks were injected intramuscularly with bacterial lipopolysaccharide (LPS). Oil-treated birds had an inflammatory marker profile that was significantly different from control and LPS-treated birds, showing decreases in mannan-binding lectin-dependent hemolysis and unsaturated iron-binding capacity, but no changes in any of the other inflammatory markers. Birds treated with oil also exhibited increased liver weights, decreased body and splenic weights, and decreased packed cell volume.

  14. Renal Cortical Lactate Dehydrogenase: A Useful, Accurate, Quantitative Marker of In Vivo Tubular Injury and Acute Renal Failure

    PubMed Central

    Zager, Richard A.; Johnson, Ali C. M.; Becker, Kirsten

    2013-01-01

    Studies of experimental acute kidney injury (AKI) are critically dependent on having precise methods for assessing the extent of tubular cell death. However, the most widely used techniques either provide indirect assessments (e.g., BUN, creatinine), suffer from the need for semi-quantitative grading (renal histology), or reflect the status of residual viable, not the number of lost, renal tubular cells (e.g., NGAL content). Lactate dehydrogenase (LDH) release is a highly reliable test for assessing degrees of in vitro cell death. However, its utility as an in vivo AKI marker has not been defined. Towards this end, CD-1 mice were subjected to graded renal ischemia (0, 15, 22, 30, 40, or 60 min) or to nephrotoxic (glycerol; maleate) AKI. Sham operated mice, or mice with AKI in the absence of acute tubular necrosis (ureteral obstruction; endotoxemia), served as negative controls. Renal cortical LDH or NGAL levels were assayed 2 or 24 hrs later. Ischemic, glycerol, and maleate-induced AKI were each associated with striking, steep, inverse correlations (r, −0.89) between renal injury severity and renal LDH content. With severe AKI, >65% LDH declines were observed. Corresponding prompt plasma and urinary LDH increases were observed. These observations, coupled with the maintenance of normal cortical LDH mRNA levels, indicated the renal LDH efflux, not decreased LDH synthesis, caused the falling cortical LDH levels. Renal LDH content was well maintained with sham surgery, ureteral obstruction or endotoxemic AKI. In contrast to LDH, renal cortical NGAL levels did not correlate with AKI severity. In sum, the above results indicate that renal cortical LDH assay is a highly accurate quantitative technique for gauging the extent of experimental acute ischemic and toxic renal injury. That it avoids the limitations of more traditional AKI markers implies great potential utility in experimental studies that require precise quantitation of tubule cell death. PMID:23825563

  15. Relationship between Inflammatory Markers and New Cardiovascular Events in Patients with Acute Myocardial Infarction Who Underwent Primary Angioplasty

    PubMed Central

    Franca, Eluisa La; Caruso, Marco; Sansone, Angela; Iacona, Rosanna; Ajello, Laura; Mancuso, Dario; Castellano, Fabiana; Novo, Salvatore; Assennato, Pasquale

    2013-01-01

    Introduction: The determination of inflammation markers in circulation has enabled an important improvement in the study of cardiovascular diseases. It was tested the hypothesis that non-specific markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and fibrinogen may provide prognostic information in patients with acute myocardial infarction with persistent ST-segment elevation (STEMI) undergoing primary angioplasty (PCI). Methods: Patients: A cohort of 197 consecutive patients with STEMI undergoing primary PCI was enrolled, evaluating during hospitalization, the peak values of the following markers of inflammation: ESR, CRP and fibrinogen. A telephone follow-up has been made in order to investigate any possible new cardiovascular events after hospital discharge and the procedure performed. Results: Higher values of CRP were statistically associated with adverse future events as composite endpoint and with the single endpoint of death. Furthermore, higher age, presence of hypertension, history of previous cardiovascular events, were statistically significantly associated with cardiac events at follow up. In this group were also overrepresented subjects with anterior myocardial infarction in the anterior localization and with an EF ≤ 35% at discharge. Conclusions: CRP appears to be a predictor of future cardiovascular events, confirming that a pro-inflammatory state promotes the progression of atherosclerotic disease and its complications. PMID:23777720

  16. PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  17. The Anion Gap is a Predictive Clinical Marker for Death in Patients with Acute Pesticide Intoxication.

    PubMed

    Lee, Sun-Hyo; Park, Samel; Lee, Jung-Won; Hwang, Il-Woong; Moon, Hyung-Jun; Kim, Ki-Hwan; Park, Su-Yeon; Gil, Hyo-Wook; Hong, Sae-Yong

    2016-07-01

    Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na(+), K(+), Cl(-) HCO3 (-), Ca(++)), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication.

  18. HEV, TTV and GBV-C/HGV markers in patients with acute viral hepatitis.

    PubMed

    Lyra, A C; Pinho, J R R; Silva, L K; Sousa, L; Saraceni, C P; Braga, E L; Pereira, J E; Zarife, M A S; Reis, M G; Lyra, L G C; Silva, L C da; Carrilho, F J

    2005-05-01

    The aim of the present study was to evaluate the prevalence of HEV, TTV and GBV-C/GBV-C/HGV in patients with acute viral hepatitis A, B and non-A-C. We evaluated sera of 94 patients from a sentinel program who had acute hepatitis A (N = 40), B (N = 42) and non-A-C (N = 12); 71 blood donors served as controls. IgM and anti-HEV IgG antibodies were detected by enzyme immunoassay using commercial kits. TTV and GBV-C/HGV were detected by nested PCR; genotyping was done by sequencing and phylogenetic analysis. Anti-HEV IgG was present in 38, 10 and 17% of patients with hepatitis A, B and non-A-C. Four patients with hepatitis A and 1 with non-A-C hepatitis also had anti-HEV IgM detected in serum. TTV was detected in 21% of patients with acute hepatitis and in 31% of donors. GBV-C/HGV was detected in 9% of patients with hepatitis, and in 10% of donors. We found TTV isolates of genotypes 1, 2, 3, and 4 and GBV-C/HGV isolates of genotypes 1 and 2. Mean aminotransferase levels were lower in patients who were TTV or GBV-C/HGV positive. In conclusion, the detection of anti-HEV IgM in some acute hepatitis A cases suggests co-infection with HEV and hepatitis E could be the etiology of a few cases of sporadic non-A-C hepatitis in Salvador, Brazil. TTV genotype 1, 2, 3 and 4 isolates and GBV-C/HGV genotype 1 and 2 strains are frequent in the studied population. TTV and GBV-C/HGV infection does not appear to have a role in the etiology of acute hepatitis.

  19. Phase angle as bioelectrical marker to identify elderly patients at risk of sarcopenia.

    PubMed

    Basile, Claudia; Della-Morte, David; Cacciatore, Francesco; Gargiulo, Gaetano; Galizia, Gianluigi; Roselli, Mario; Curcio, Francesco; Bonaduce, Domenico; Abete, Pasquale

    2014-10-01

    Several markers have been associated with sarcopenia in the elderly, including bioelectrical indices. Phase angle (PhA) is an impedance parameter and it has been suggested as an indicator of cellular death. Thus, the relationship between PhA and muscle mass and strength was investigated in 207 consecutively elderly participants (mean age 76.2±6.7years) admitted for multidimensional geriatric evaluation. Muscle strength by grip strength using a hand-held dynamometer and muscle mass was measured by bioimpedentiometer. PhA was calculated directly with its arctangent (resistance/reactance×180°/π). Linear relationship among muscular mass and strength and with clinical and biochemical parameters, including PhA at uni- and multivariate analysis were performed. Linear regression analysis demonstrated that lower level of PhA is associated with reduction in grip strength (y=3.16+0.08x; r=0.49; p<0.001), and even more, with muscle mass (y=3.04+0.25x; r=0.60; p<0001). Multivariate analysis confirms these relationships (grip strength β=0.245, p=0.031; muscular mass β=0.623, p<0.01). Thus, PhA is inversely related to muscle mass and strength in elderly subjects and it may be considered a good bioelectrical marker to identify elderly patients at risk of sarcopenia.

  20. A new infrared spectroscopoic marker for cochleate phases in phosphatidylserine-containing model membranes.

    PubMed Central

    Flach, C R; Mendelsohn, R

    1993-01-01

    Fourier transform-infrared (IR) spectroscopic and electron microscopic studies are reported for 1,2-dimyristoylphosphatidylserine (DMPS) and for DMPS/1,2-dimyristoylphosphatidylcholine mixtures in the presence and absence of Ca2+ ion. The frequency of the methyl symmetric deformation mode near 1,378 cm-1, previously assumed insensitive to changes in lipid morphology, has been found to respond to cochleate phase formation by undergoing an approximately 8 cm-1 increase. The new IR spectroscopic marker at 1,386 cm-1 has been used to identify and verify structures suggested from the phase diagram of J. R. Silvius and J. Gagné (1984. Biochemistry. 23:3241-3247) for this system. In addition, the ability of Mg2+ ion to induce cochleate formation has been demonstrated. Higher Mg2+ than Ca2+ levels are required for this process. Finally, IR spectroscopy has been used to monitor dehydration of the lipid surface through changes in the asymmetric PO2- stretching mode. Dehydration precedes cochleate phase formation (i.e., occurs at a lower Ca2+/phosphatidylserine level). Images FIGURE 3 FIGURE 3 PMID:8494975

  1. THE ACUTE PHASE RESPONSE INDUCED BY BRONCHOSCOPY WITH LAVAGE

    EPA Science Inventory

    Bronchoscopy has been used to evaluate the inflammatory responses in vitro and in vivo. The procedure may affect acute inflammation in the lower respiratory tract. We reviewed consecutive bronchoscopies done in normal healthy non-smokers between April, 1998 and April, 2004. The...

  2. Validity of Sudden Gains in Acute Phase Treatment of Depression

    ERIC Educational Resources Information Center

    Vittengl, Jeffrey R.; Clark, Lee Anna; Jarrett, Robin B.

    2005-01-01

    The authors examined the validity of sudden gains identified with T. Z. Tang and R. J. DeRubeis's (1999) method in 2 clinical data sets that involved treatment of major depressive disorder (N=227). Sudden gains replicated among self- and clinician reports of depressive symptoms and predicted better psychosocial functioning at the acute phase…

  3. The acute phase reactant, fibrinogen, as a guide to plasma exchange therapy for acute Guillain-Barré syndrome.

    PubMed

    Sanjay, Rashmi; Flanagan, Janice; Sodano, Donata; Gorson, Kenneth C; Ropper, Allan H; Weinstein, Robert

    2006-07-01

    The Guillian Barré syndrome is an acute inflammatory disorder for which plasma exchange is effective treatment. Up to 10% relapse after plasma exchange suggesting that treatment sometimes finishes before disease activity has resolved. We studied whether plasma fibrinogen, an inflammatory marker, might be used to determine when to discontinue plasma exchange in patients with acute Guillain-Barré syndrome. We conducted a post-hoc analysis of apheresis database and hospital records of patients treated with plasma exchange for acute Guillain-Barré syndrome during 1999-2004. Data were analyzed from 28 patients who underwent a total of 29 courses of plasma exchange for acute Guillain-Barré syndrome. The mean (+/-SD) plasma fibrinogen concentration was 422.5 (+/-96.4) mg/dl at the time of presentation and, in 17 of the 29, it was above 400 mg/dl (reference range 200-400). Twenty of the 21 patients whose fibrinogen fell by more than 30% from baseline by the time of the final plasma exchange treatment had neurological improvement. There was improvement in only 3 of the 8 instances where fibrinogen decreased by less than 30% by the end of plasma exchange therapy. A > or =30% decrease in fibrinogen by the conclusion of plasma exchange was significantly associated with sustained neurological improvement (P = 0.0025). The plasma fibrinogen level appears to reflect disease activity in acute Guillain-Barré syndrome. A <30% fall in fibrinogen level despite plasma exchange may indicate the need to continue plasma exchange to maximize the benefit of treatment or minimize the risk of relapse. Therapeutic plasma exchange need not be extended when plasma fibrinogen remains > or =30% below its level at presentation by the time of the final planned plasma exchange procedure.

  4. The Anion Gap is a Predictive Clinical Marker for Death in Patients with Acute Pesticide Intoxication

    PubMed Central

    2016-01-01

    Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na+, K+, Cl- HCO3-, Ca++), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication. PMID:27366016

  5. Plasma D-lactic acid level: a useful marker to distinguish perforated from acute simple appendicitis.

    PubMed

    Demircan, Mehmet; Cetin, Selma; Uguralp, Sema; Sezgin, Nurzen; Karaman, Abdurrahman; Gozukara, Engin M

    2004-10-01

    Early diagnosis of perforated appendicitis is important for reducing morbidity rates. The aim of this study was to determine the value and utility of plasma D-lactic acid levels in identifying the type of appendicitis. In this clinical study, plasma D-lactic acid levels were assessed in 44 consecutive paediatric patients (23 with acute appendicitis, 21 with perforated appendicitis) before laparotomy. D-lactic acid levels were determined by an enzymatic spectrophotometric technique using a D-lactic acid dehydrogenase kit. Patients with perforated appendicitis had higher D-lactic acid levels (3.970 +/- 0.687 mg/dL) than patients in the control group (0.478 +/- 0.149 mg/dL) and patients with acute appendicitis (1.409 +/- 0.324 mg/dL; p < 0.05). For a plasma D-lactic acid level greater than 2.5 mg/dL, the sensitivity and specificity of the D-lactic acid assay were 96% and 87%, respectively. The positive predictive value was 87%, the negative predictive value was 96%, and the diagnostic value was 91%. These results suggest that the measurement of plasma D-lactic acid levels may be a useful adjunct to clinical and radiological findings in distinguishing perforated from acute non-perforated appendicitis in children.

  6. A reduced lymphocyte ratio as an early marker for predicting acute pancreatitis

    PubMed Central

    Qi, Xiuzhong; Yang, Fangyong; Huang, Haitao; Du, Yiqi; Chen, Yan; Wang, Meitang; Zhu, Dezeng; Yue, Xiaoqiang; Wang, Lina

    2017-01-01

    The early diagnosis and severity grading for acute pancreatitis (AP) are difficult to determine because of the complexity and differences in disease process. To date, few studies have investigated the role of lymphocyte ratio (LR) in AP. Therefore, the objective of the present study was to investigate the prognostic value of LR as an indicator in AP, as well as determine an optimal cut-off value for the severity prediction. There were two hundred four patients involved in this study, ninety-two of whom had severe acute pancreatitis (SAP). The LR was analyzed on admission and correlated with severity, which was determined using the Atlanta classification. The optimal cut-off value for LR was generated using receiving operator characteristic (ROC) curves. The results showed that the LR in the SAP group decreased significantly compared to the mild acute pancreatitis (MAP) group (8.82 vs. 13.43). The optimal cut-off value obtained from ROC curves was 0.081, with a sensitivity of 80.4%, a specificity of 53.3%, a positive likelihood ratio of 1.722, and a negative likelihood ratio of 0.368. In conclusion, the LR is obviously related to the condition of AP patients and is valuable for the differential diagnosis of SAP in early stages of AP. PMID:28266603

  7. Senescence marker protein 30 (SMP30)/regucalcin (RGN) expression decreases with aging, acute liver injuries and tumors in zebrafish

    SciTech Connect

    Fujisawa, Koichi; Terai, Shuji; Hirose, Yoshikazu; Takami, Taro; Yamamoto, Naoki; Sakaida, Isao

    2011-10-22

    Highlights: {yields} Zebrafish SMP30/RGN mRNA expression decreases with aging. {yields} Decreased expression was observed in liver tumors as compared to the surrounding area. {yields} SMP30/RGN is important for liver proliferation and tumorigenesis. -- Abstract: Senescence marker protein 30 (SMP30)/regucalcin (RGN) is known to be related to aging, hepatocyte proliferation and tumorigenesis. However, expression and function of non-mammalian SMP30/RGN is poorly understood. We found that zebrafish SMP30/RGN mRNA expression decreases with aging, partial hepatectomy and thioacetamide-induced acute liver injury. SMP30/RGN expression was also greatly decreased in a zebrafish liver cell line. In addition, we induced liver tumors in adult zebrafish by administering diethylnitrosamine. Decreased expression was observed in foci, hepatocellular carcinomas, cholangiocellular carcinomas and mixed tumors as compared to the surrounding area. We thus showed the importance of SMP30/RGN in liver proliferation and tumorigenesis.

  8. Coagulopathy in patients with acute pulmonary embolism: a pilot study of whole blood coagulation and markers of endothelial damage.

    PubMed

    Lehnert, Per; Johansson, Pär I; Ostrowski, Sisse R; Møller, Christian H; Bang, Lia E; Olsen, Peter Skov; Carlsen, Jørn

    2017-02-01

    Whole blood coagulation and markers of endothelial damage were studied in patients with acute pulmonary embolism (PE), and evaluated in relation to PE severity. Twenty-five patients were enrolled prospectively each having viscoelastical analysis of whole blood done using thrombelastography (TEG) and Multiplate aggregometry. Fourteen of these patients were investigated for endothelial damage by ELISA measurements of Syndecan-1 (endothelial glycocalyx degradation), soluble endothelial Selectin (endothelial cell activation), soluble Thrombomodulin (endothelial cell injury) and Histone Complexed DNA fragments (endothelial cytotoxic histones). The mean values of TEG and Multiplate parameters were all within the reference levels, but a significant difference between patients with high and intermediate risk PE was observed for Ly30 (lytic activity) 1.5% [0-10] vs. 0.2% [0-2.2] p = .04, and ADP (platelet reactivity) 92 U [20-145] vs. 59 U [20-111] p = .03. A similar difference was indicated for functional fibrinogen 21 mm [17-29] vs. 18 mm [3-23] p = .05. Analysis of endothelial markers identified a significant difference in circulating levels between high and intermediate risk PE patients for Syndecan-1 118.6 ng/mL [76-133] vs. 36.3 ng/mL [11.8-102.9] p = .008. In conclusion, patients with acute PE had normal whole blood coagulation, but high risk PE patients had signs of increased activity of the haemostatic system and significantly increased level of endothelial glycocalyx degradation.

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

    PubMed

    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.

  10. Bcl-2 associated with positive symptoms of schizophrenic patients in an acute phase.

    PubMed

    Tsai, Meng-Chang; Liou, Chia-Wei; Lin, Tsu-Kung; Lin, I-Mei; Huang, Tiao-Lai

    2013-12-30

    B cell lymphoma protein-2 (Bcl-2) may contribute to the pathophysiology of schizophrenia in the brain. The aim of this study was to investigate the serum levels of Bcl-2 in schizophrenic patients in an acute phase, and evaluate Bcl-2 level changes after antipsychotic treatment. We consecutively enrolled 41 schizophrenia patients in an acute phase; 28 were followed up with a 4-week antipsychotic treatment. Serum Bcl-2 levels were measured with assay kits. All patients were evaluated by examining the correlation between Bcl-2 levels and Positive and Negative Syndrome Scale (PANSS) scores, using Pearson correlation coefficients. In schizophrenic patients in an acute phase, positive PANSS subscores were significantly negatively correlated with Bcl-2 levels. In addition, we found Bcl-2 levels had a significantly negative correlation with PANSS total scores and positive subscores in male patients in an acute phase. Using the paired t-test, we found no significant changes in Bcl-2 levels in schizophrenia patients who had received the 4-week treatment with antipsychotic drugs (n=28). In conclusion, our results suggest that Bcl-2 might be an indicator of schizophrenia severity in the acute phase. In addition, Bcl-2 levels might be associated with positive symptoms in male patients with schizophrenia.

  11. Semiautomated quantitative image analysis of glomerular immunohistochemistry markers desmin, vimentin, podocin, synaptopodin and WT-1 in acute and chronic rat kidney disease models.

    PubMed

    Funk, J; Ott, V; Herrmann, A; Rapp, W; Raab, S; Riboulet, W; Vandjour, A; Hainaut, E; Benardeau, A; Singer, T; Jacobsen, B

    2016-03-01

    Five different glomerular immunohistochemistry markers were evaluated and compared in four different acute and chronic rat kidney disease models. Progression of glomerular or podocyte damage was shown in the puromycin aminonucleoside nephrosis (PAN) and Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model. Progression and prevention of glomerular damage was demonstrated in the Zucker diabetic fatty (ZDF) and Dahl salt-sensitive (Dahl SS) rat. Immunohistochemistry was performed for desmin, vimentin, podocin, synaptopodin and Wilms tumor protein-1 (WT-1), and evaluation of glomerular immunohistochemistry markers was done by semiautomated quantitative image analysis. We found desmin and WT-1 as the most sensitive markers for podocyte damage in both acute and chronic glomerular damage followed by vimentin, podocin and synaptopodin. We were able to demonstrate that early podocyte damage as shown by increased desmin and vimentin staining together with either a phenotypic podocyte change or podocyte loss (reduced numbers of WT-1-stained podocytes) drives the progression of glomerular damage. This is followed by a reduction in podocyte-specific proteins such as podocin and synaptopodin. Our report describes the different sensitivity of glomerular or podocyte markers and gives future guidance for the selection of the most sensitive markers for efficacy testing of new drugs as well as for the selection of tissue-based toxicity markers for glomerular or podocyte injury. In addition to functional clinical chemistry markers, desmin and WT-1 immunohistochemistry offers reliable and valuable data on the morphologic state of podocytes.

  12. Metabolic and clinical markers of prognosis in the era of CT imaging in children with acute epidural hematomas.

    PubMed

    Ben Abraham, R; Lahat, E; Sheinman, G; Feldman, Z; Barzilai, A; Harel, R; Barzilay, Z; Paret, G

    2000-08-01

    Acute epidural hematoma (AEH), a relatively common complication of head injury in children, persists in bearing high morbidity and mortality. Early establishment of prognosis could guide optimal patient allocation, and early identification of predictive signs could assist in choosing appropriate therapeutic interventions. This study aimed to delineate expeditiously obtainable prognostic markers for determining outcome in a subset of children with AEH. We reviewed our 11-year experience with 61 consecutive children <16 years old with head trauma and isolated AEH. Treatment followed a standard advanced trauma life support protocol. A medical history was obtained, and all patients underwent neurosurgical and physical evaluations. CT scans were performed, as were laboratory tests which included arterial blood gases, glucose, electrolytes (K(+), Na(+)), hemoglobin and coagulation studies. Evaluation of the data collected on cause of injury, interval between trauma occurrence and presentation, clinical symptoms, Glasgow Coma Scale (GCS) scores, vital signs, laboratory test results, physical findings and surgical versus conservative management revealed that the best single predictors of outcome following AEH were the GCS and focal neurological deficits. Of all laboratory data obtained on admission, the blood potassium, pH and glucose test results correlated significantly with prognosis. Prognosis can be adequately and expeditiously estimated by selected markers within a comprehensive evaluation of children with AEH.

  13. Comparison of Virulence Markers of Peritoneal and Fallopian Tube Isolates with Endocervical Neisseria gonorrhoeae Isolates from Women with Acute Salpingitis

    PubMed Central

    Draper, D. L.; James, J. F.; Brooks, G. F.; Sweet, R. L.

    1980-01-01

    Neisseria gonorrhoeae strains which cause acute salpingitis are presumed to ascend the genital tract from the cervix. Previous studies utilized isolates obtained from endocervical canal cultures, although it was not known if the isolates truly represented the organisms present in the fallopian tubes. In this study, we compared N. gonorrhoeae isolates from endocervical canal cultures with fallopian tube or peritoneal cul-de-sac isolates or isolates from both sites obtained at laparoscopy. Potential virulence markers were studied, including colony phenotype, auxotype, antimicrobial agent susceptibility, protein patterns on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and susceptibility to normal human serum. Six of seven cervical isolates had the same antibiograms and molecular weight for major outer membrane proteins as those of the corresponding peritoneal isolates. Auxotypes also were the same and included prototrophic, proline-requiring, and proline-and-arginine-requiring isolates. The isolates as a group appeared to be very susceptible to the bactericidal action of pooled serum from normal women. Colony phenotypes varied between sites; the fallopian tubecul-de-sac isolates were predominantly of transparent phenotype and piliated. The cervical isolates were either mixtures of equal quantities of opaque and transparent phenotypes or predominantly opaque phenotype. By these markers, patients' N. gonorrhoeae cervical isolates appeared to be the same as their isolates from fallopian tubes except for a difference or shift in colony phenotype. Images Fig. 1 PMID:6769811

  14. Acute changes of serum markers for tissue damage after ESWL of kidney stones.

    PubMed

    Apostolov, I; Minkov, N; Koycheva, M; Isterkov, M; Abadjyev, M; Ondeva, V; Trendafilova, T

    1991-01-01

    Seventeen serum markers (including 9 enzyme activities) for eventual tissue damage were studied after ESWL in 40 patients with unilateral kidney calculosis. No changes were established in the 8 non-enzymic parameters and the activities of amylase, lipase, AST (GOT), ALT (GPT) and CK-MB. A statistically significant increase was found in LDH, alpha-HBDH, CK (twice) and glutamate dehydrogenase (3 times). The slight elevation of LDH and alpha-HBDH could be due to haemolysis caused by the shock waves. Increased activity of CK suggested myolysis and that of GlDH a hepatocellular damage.

  15. Predictive value of inflammatory markers for irrigation and debridement of acute TKA infection.

    PubMed

    Stryker, Louis S; Abdel, Matthew P; Hanssen, Arlen D

    2013-06-01

    The roles of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are well established in the diagnosis of total joint infection. However, it is not entirely clear what value preoperative CRP and ESR have in predicting outcomes following irrigation and debridement with insert exchange for acute hematogenous total knee arthroplasty infection. The total joint registry at the authors' institution was reviewed to identify all patients who underwent irrigation and debridement with insert exchange for a diagnosis of acute hematogenous infection of a primary total knee arthroplasty. Patient medical records were then reviewed for preoperative white blood cell count and CRP and ESR levels; interval from symptom onset to surgery; infecting organism; and any additional surgery for infection. Average patient age was 72 years (range, 51-91 years). Forty-four patients were men and 26 were women. Mean follow-up was 54 months (range, 12-176 months). Seventy-two procedures (69 patients) met the inclusion criteria. Of these, 20 (28%) additional procedures for infection were performed and were classified as treatment failures. Average CRP was 173.7 mg/L in the successful group and 159.0 mg/L in the failed group (P=.31). Mean ESR at the time of irrigation and debridement with insert exchange was 61.3 mm/hr in both groups (P=.49). Although CRP and ESR are well established in the diagnosis of infection, no role currently exists for them in predicting the outcomes of irrigation and debridement with insert exchange for the treatment of acute hematogenous total knee arthroplasty infection.

  16. Serum trace elements are associated with hemostasis, lipid spectrum and inflammatory markers in men suffering from acute ischemic stroke.

    PubMed

    Skalny, Anatoly V; Klimenko, Lydmila L; Turna, Aliya A; Budanova, Maria N; Baskakov, Ivan S; Savostina, Marina S; Mazilina, Aksana N; Deyev, Anatoly I; Skalnaya, Margarita G; Tinkov, Alexey A

    2017-02-20

    The primary objective of the study is investigation of the association between trace elements status and hemostasis, lipid spectrum and inflammatory markers in acute ischemic stroke (AIS). A total of 30 men suffering from AIS and 30 healthy controls were involved in the current survey. Blood count, serum lipid spectrum, complement components C4 and C3a, vascular endothelial growth factor (VEGF), S100B protein, NR2 antibodies (NR2Ab), and total antioxidant status (TAS), as well as plasma fibrinogen, and D-dimer levels and activated partial thromboplastin time (APTT) were assessed. Serum trace elements were analyzed using inductively coupled plasma mass spectrometry. AIS patients were characterized by significantly increased fibrinogen, D-dimer, TG, C3a, C4, NR2Ab, and VEGF levels. The leukocyte count, erythrocyte sedimentation rate and serum atherogenic index were also increased in stroke patients. Oppositely, TAS and APTT values, bleeding and blood coagulation time were decreased. AIS patients were characterized by significantly decreased serum Fe and Co concentrations, whereas the level of Cu, I, Li, Mn, Se, Zn, As, Pb, Ni, and especially V and B in serum was significantly increased. Serum V and B tightly correlated with the procoagulant state and inflammatory markers. Multiple regression analysis revealed a significant inverse association between serum Se levels and stroke markers after adjustment for covariates. Therefore, it is hypothesized that elements like vanadium and boron may be closely involved in stroke pathogenesis by modulation of hemostasis and inflammation, whereas the observed increase in Se levels may be considered as a compensatory reaction.

  17. Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome

    PubMed Central

    Forero-Castro, Maribel; Robledo, Cristina; Benito, Rocío; Abáigar, María; África Martín, Ana; Arefi, Maryam; Fuster, José Luis; de las Heras, Natalia; Rodríguez, Juan N.; Quintero, Jonathan; Riesco, Susana; Hermosín, Lourdes; de la Fuente, Ignacio; Recio, Isabel; Ribera, Jordi; Labrador, Jorge; Alonso, José M.; Olivier, Carmen; Sierra, Magdalena; Megido, Marta; Corchete-Sánchez, Luis A.; Ciudad Pizarro, Juana; García, Juan Luis; Ribera, José M.; Hernández-Rivas, Jesús M.

    2016-01-01

    Identifying additional genetic alterations associated with poor prognosis in acute lymphoblastic leukemia (ALL) is still a challenge. Aims: To characterize the presence of additional DNA copy number alterations (CNAs) in children and adults with ALL by whole-genome oligonucleotide array (aCGH) analysis, and to identify their associations with clinical features and outcome. Array-CGH was carried out in 265 newly diagnosed ALLs (142 children and 123 adults). The NimbleGen CGH 12x135K array (Roche) was used to analyze genetic gains and losses. CNAs were analyzed with GISTIC and aCGHweb software. Clinical and biological variables were analyzed. Three of the patients showed chromothripsis (cth6, cth14q and cth15q). CNAs were associated with age, phenotype, genetic subtype and overall survival (OS). In the whole cohort of children, the losses on 14q32.33 (p = 0.019) and 15q13.2 (p = 0.04) were related to shorter OS. In the group of children without good- or poor-risk cytogenetics, the gain on 1p36.11 was a prognostic marker independently associated with shorter OS. In adults, the gains on 19q13.2 (p = 0.001) and Xp21.1 (p = 0.029), and the loss of 17p (p = 0.014) were independent markers of poor prognosis with respect to OS. In summary, CNAs are frequent in ALL and are associated with clinical parameters and survival. Genome-wide DNA copy number analysis allows the identification of genetic markers that predict clinical outcome, suggesting that detection of these genetic lesions will be useful in the management of patients newly diagnosed with ALL. PMID:26872047

  18. Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-04-27

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  19. Cerebral Arterial Calcification Is an Imaging Prognostic Marker for Revascularization Treatment of Acute Middle Cerebral Arterial Occlusion

    PubMed Central

    Lee, Seong-Joon; Hong, Ji Man; Lee, Manyong; Huh, Kyoon; Choi, Jin Wook

    2015-01-01

    Background and Purpose To study the significance of intracranial artery calcification as a prognostic marker for acute ischemic stroke patients undergoing revascularization treatment after middle cerebral artery (MCA) trunk occlusion. Methods Patients with acute MCA trunk occlusion, who underwent intravenous and/or intra-arterial revascularization treatment, were enrolled. Intracranial artery calcification scores were calculated by counting calcified intracranial arteries among major seven arteries on computed tomographic angiography. Patients were divided into high (HCB; score ≥3) or low calcification burden (LCB; score <3) groups. Demographic, imaging, and outcome data were compared, and whether HCB is a prognostic factor was evaluated. Grave prognosis was defined as modified Rankin Scale 5-6 for this study. Results Of 80 enrolled patients, the HCB group comprised 15 patients, who were older, and more commonly had diabetes than patients in the LCB group. Initial National Institutes of Health Stroke Scale (NIHSS) scores did not differ (HCB 13.3±2.7 vs. LCB 14.6±3.8) between groups. The final good reperfusion after revascularization treatment (thrombolysis in cerebral infarction score 2b-3, HCB 66.7% vs. LCB 69.2%) was similarly achieved in both groups. However, the HCB group had significantly higher NIHSS scores at discharge (16.0±12.3 vs. 7.9±8.3), and more frequent grave outcome at 3 months (57.1% vs. 22.0%) than the LCB group. HCB was proven as an independent predictor for grave outcome at 3 months when several confounding factors were adjusted (odds ratio 4.135, 95% confidence interval, 1.045-16.359, P=0.043). Conclusions Intracranial HCB was associated with grave prognosis in patients who have undergone revascularization for acute MCA trunk occlusion. PMID:25692109

  20. Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.

    PubMed

    Seemungal, T; Harper-Owen, R; Bhowmik, A; Moric, I; Sanderson, G; Message, S; Maccallum, P; Meade, T W; Jeffries, D J; Johnston, S L; Wedzicha, J A

    2001-11-01

    The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV(1), 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD.

  1. Informatic interrogation of CSF proteomic profiles from HIV-infected subjects implicates acute phase and complement systems in shifting cognitive status.

    PubMed

    Ubaida-Mohien, Ceereena; Lamberty, Benjamin; Dickens, Alex M; Mielke, Michelle M; Marcotte, Thomas; Sacktor, Ned; Grant, Igor; Letendre, Scott; Franklin, D; Cibrowski, Pawel; Tharakan, Ravi; McArthur, Justin C; Fox, Howard; Haughey, Norman J

    2017-04-10

    The prevalence of HIV-Associated Neurocognitive Disorders (HAND) has not changed considerably in the last two decades. Potent antiretroviral therapy (ART) has shifted the severity of HAND to milder phenotypes, but excess morbidity and mortality continue to be associated with HAND. Changes in numerous markers of immune function, inflammation and cellular stress have been repeatedly associated with HAND but the underlying systems that drive these changes have not been identified. In this study we used systems informatics to interrogate the CSF proteomic content of longitudinal samples obtained from HIV-infected adults with stably unimpaired, stably impaired, worsening, or improving neurocognitive (NC) performance. The patterns of change in CSF protein content implicated the induction of acute phase and complement systems as important regulators of NC status. Worsening NC performance was preceded by induction of acute phase and complement systems, while improving NC performance was preceded by a downregulation of these systems.

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

    PubMed Central

    Manimaran, A.; Kumaresan, A.; Jeyakumar, S.; Mohanty, T. K.; Sejian, V.; Kumar, Narender; Sreela, L.; Prakash, M. Arul; Mooventhan, P.; Anantharaj, A.; Das, D. N.

    2016-01-01

    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. PMID:27051191

  3. Presence of acute phase changes in zinc, iron, and copper metabolism in turkey embryos

    SciTech Connect

    Klasing, K.C.; Richards, M.P.; Darcey, S.E.; Laurin, D.E.

    1987-01-01

    Acute phase changes in trace mineral metabolism were examined in turkey embryos. An endotoxin injection resulted in increased concentrations of serum copper and liver zinc and decreased concentrations of serum zinc in embryos incubated either in ovo or ex ovo. Changes in zinc and copper metabolism occurred when endotoxin either was injected intramuscularly, into the amnionic fluid, or administered onto the chorioallantoic membrane. Unlike poults, embryos did not respond to an inflammatory challenge with decreased serum iron concentrations. Acute phase changes in embryo serum zinc and copper as well as liver zinc concentrations were similar to those in poults. Increased liver zinc concentrations were associated with increased zinc in metallothionein (MT). An injection of a crude interleukin 1 preparation into embryos resulted in similar increases in hepatic zinc and MT concentrations as an endotoxin injection, suggesting a role for this cytokine in mediating the acute phase changes in embryonic zinc metabolism.

  4. Regulation of dopaminergic markers expression in response to acute and chronic morphine and to morphine withdrawal.

    PubMed

    García-Pérez, Daniel; Núñez, Cristina; Laorden, M Luisa; Milanés, M Victoria

    2016-03-01

    Dopamine (DA) is thought to represent a teaching signal and has been implicated in the induction of addictive behaviours. Dysfunction of DA homeostasis leading to high or low DA levels is causally linked to addiction. Previously, it has been proposed that the transcription factors Nurr1 and Pitx3, which are critical for transcription of a set of genes involved in DA metabolism in the mesolimbic pathway, are associated with addiction pathology. Using quantitative real-time polymerase chain reaction, immunofluorescence and Western blotting, we studied the effects of single morphine administration, morphine dependence and withdrawal on the DA markers DA transporters (DAT), vesicular monoamine transporters (VMAT2) and DA 2 receptor subtype (DRD2), DA 1 receptor subtype as well as tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and/or nucleus accumbens (NAc). In addition, Nurr1 and Pitx3 expression was also measured. Present data showed a high degree of colocalization of Nurr1 and Pitx3 with TH(+) neurons in the VTA. We found that the increased Nurr1 and/or Pitx3 levels during morphine dependence and in morphine-withdrawn rats were associated to an increase of DAT, VMAT2 and DRD2. Altogether, present data indicate that morphine dependence and withdrawal induced consistent alterations of most of the DA markers, which was correlated with transcription factors involved in the maintenance of DA neurons in drug-reward pathways, suggesting that Nurr1 and Pitx3 regulation might be associated with controlling adaptation to chronic morphine and to morphine withdrawal-induced alterations of DA neurons activity in the mesolimbic pathway.

  5. Poliomyelitis: immunoglobulin-containing cells in the central nervous system in acute and convalescent phases of the human disease.

    PubMed Central

    Esiri, M M

    1980-01-01

    The immunoperoxidase method has been used to demonstrate the presence of immunoglobulin-containing cells in the central nervous system in acute and convalescent phases of poliomyelitis. These cells were found in considerable numbers in the areas of damage during the acute phase, and persisted at the same sites, though in smaller numbers, during the convalescent phase for at least 8 months. Most of the positively stained cells were plasma cells. IgA was the commonest heavy chain type demonstrated, with lesser amounts also of IgG and, during the acute phase, IgM. In the acute phase more lambda than kappa light chain was demonstrated but in the convalescent phase this ratio was reversed. More light chain than heavy chain was demonstrable during the acute phase. The significance of these results is briefly discussed. Images Fig. 2 PMID:6771081

  6. Comparison of the prognostic values of inflammation markers in patients with acute pancreatitis: a retrospective cohort study

    PubMed Central

    Li, Yuanyuan; Zhao, Ying; Feng, Limin; Guo, Renyong

    2017-01-01

    Objectives Inflammation-based prognostic markers (neutrophil–lymphocyte ratio (NLR), prognostic nutritional index (PNI), red cell distribution width (RDW) and lymphocyte–monocyte ratio (LMR)) are associated with overall survival in some diseases. This study assessed their prognostic value in mortality and severity in acute pancreatitis (AP). Design A retrospective cohort study. Setting Patients with AP were recruited from the emergency department at our hospital. Participants A total of 359 patients with AP (31 non-survivors) were enrolled. Primary and secondary outcome measures Mortality and severity of AP were the primary and secondary outcome measures, respectively. Biochemistry and haematology results of the first test after admission were collected. Independent relationships between severe AP (SAP) and markers were assessed using multivariate logistic regression models. Mortality prediction ability was evaluated using receiver operating characteristic (ROC) curves. Overall survival was evaluated using the Kaplan-Meier method, with differences compared using the log-rank test. Independent relationships between mortality and each predictor were estimated using the Cox proportional hazard models. Results Compared with survivors of AP, non-survivors had higher RDW (p<0.001), higher NLR (p<0.001), lower LMR (p<0.001) and lower PNI (p<0.001) at baseline. C reactive protein (CRP; OR=8.251, p<0.001), RDW (OR=2.533, p=0.003) and PNI (OR=7.753, p<0.001) were independently associated with the occurrence of SAP. For predicting mortality, NLR had the largest area under the ROC curve (0.804, p<0.001), with a 16.64 cut-off value, 82.4% sensitivity and 75.6% specificity. RDW was a reliable marker for excluding death owing to its lowest negative likelihood ratio (0.11). NLR (HR=4.726, p=0.004), CRP (HR=3.503, p=0.003), RDW (HR=3.139, p=0.013) and PNI (HR=2.641, p=0.011) were independently associated with mortality of AP. Conclusions NLR was the most powerful marker of

  7. Phase I and Phase II Therapies for Acute Ischemic Stroke: An Update on Currently Studied Drugs in Clinical Research

    PubMed Central

    Reis, Cesar; Akyol, Onat; Ho, Wing Mann; Araujo, Camila; Huang, Lei; Applegate II, Richard

    2017-01-01

    Acute ischemic stroke is a devastating cause of death and disability, consequences of which depend on the time from ischemia onset to treatment, the affected brain region, and its size. The main targets of ischemic stroke therapy aim to restore tissue perfusion in the ischemic penumbra in order to decrease the total infarct area by maintaining blood flow. Advances in research of pathological process and pathways during acute ischemia have resulted in improvement of new treatment strategies apart from restoring perfusion. Additionally, limiting the injury severity by manipulating the molecular mechanisms during ischemia has become a promising approach, especially in animal research. The purpose of this article is to review completed and ongoing phases I and II trials for the treatment of acute ischemic stroke, reviewing studies on antithrombotic, thrombolytic, neuroprotective, and antineuroinflammatory drugs that may translate into more effective treatments. PMID:28286764

  8. Acute effects of superimposed electromyostimulation during cycling on myokines and markers of muscle damage

    PubMed Central

    Wahl, P.; Hein, M.; Achtzehn, S.; Bloch, W.; Mester, J.

    2015-01-01

    Objectives: The purpose of the present study was to evaluate the effects of superimposed electromyostimulation (E) during cycling on myokines and markers of muscle damage, as E might be a useful tool to induce a high local stimulus to skeletal muscle during endurance training without performing high external workloads. Methods: 13 subjects participated in three experimental trials each lasting 60 min in a randomized order. 1) Cycling (C), 2) Cycling with superimposed E (C+E) and 3) E. Interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), creatine kinase (CK) and myoglobin were determined before (pre) and 0’, 30’, 60’, 240’ and 24h after each intervention. Results: Only C+E caused significant increases in levels of CK and myoglobin. BDNF and IL-6 significantly increased after C and C+E, however increases for IL-6 were significantly higher after C+E compared to C. Conclusion: The present study showed that superimposed E during cycling might be a useful tool to induce a high local stimulus to skeletal muscle even when performing low to moderate external workloads. This effect might be due the activation of additional muscle fibers and mild eccentric work due to the concomitant activation of agonist and antagonist. However the higher load to skeletal muscle has to be taken into account. PMID:25730652

  9. Acute molecular markers of rodent hepatic carcinogenesis identified by transcription profiling.

    PubMed

    Kramer, Jeffrey A; Curtiss, Sandra W; Kolaja, Kyle L; Alden, Carl L; Blomme, Eric A G; Curtiss, William C; Davila, Julio C; Jackson, Carmen J; Bunch, Roderick T

    2004-04-01

    Currently, the only way to identify nongenotoxic hepatocarcinogens is through long-term repeat dose studies such as the 2 year rodent carcinogenicity assay. Such assays are both time consuming and expensive and require large amounts of active pharmaceutical or chemical ingredients. Thus, the results of the 2 year assay are not known until very late in the discovery and development process for new pharmaceutical entities. Although in many cases nongenotoxic carcinogenicity in rodents is considered to be irrelevant for humans, a positive finding in a 2 year carcinogenicity assay may increase the number of studies to demonstrate the lack of relevance to humans, delay final submission and subsequent registration of a product, and may result in a "black box" carcinogenicity warning on the label. To develop early identifiers of carcinogenicity, we applied transcription profiling using several prototype rodent genotoxic and nongenotoxic carcinogens, as well as two noncarcinogenic hepatotoxicants, in a 5 day repeat dose in vivo toxicology study. Fluorescent-labeled probes generated from liver mRNA prepared from male Sprague-Dawley rats treated with one of three dose levels of bemitradine, clofibrate, doxylamine, methapyrilene, phenobarbital, tamoxifen, 2-acetylaminofluorene, 4-acetylaminofluorene, or isoniazid were hybridized against rat cDNA microarrays. Correlation of the resulting data with an estimated carcinogenic potential of each compound and dose level identified several candidate molecular markers of rodent nongenotoxic carcinogenicity, including transforming growth factor-beta stimulated clone 22 and NAD(P)H cytochrome P450 oxidoreductase.

  10. Regional brain activation as a biological marker of affective responsivity to acute exercise: influence of fitness.

    PubMed

    Petruzzello, S J; Hall, E E; Ekkekakis, P

    2001-01-01

    Previous research has shown that regional brain activation, assessed via frontal electroencephalographic (EEG) asymmetry, predicts affective responsivity to aerobic exercise. To replicate and extend this work, in the present study we examined whether resting brain activation was associated with affective responses to an acute bout of aerobic exercise and the extent to which aerobic fitness mediated this relationship. Participants (high-fit, n = 22; low/moderate-fit, n = 45) ran on a treadmill for 30 min at 75% VO2max. EEG and affect were assessed pre- and 0-, 10-, 20-, and 30-min postexercise. Resting EEG asymmetry predicted positive affect (as measured by the energetic arousal subscale of the Activation Deactivation Adjective Check List) postexercise. Furthermore, resting frontal EEG asymmetry predicted affect only in the high-fit group, suggesting the effect might be mediated by some factor related to fitness. It was also shown that subjects with relatively greater left frontal activation had significantly more energy (i.e., activated pleasant affect) following exercise than subjects with relatively greater right frontal activation. In conclusion, aerobic fitness influenced the relationship between resting frontal asymmetry and exercise-related affective responsivity.

  11. Investigation of ischemia modified albumin, oxidant and antioxidant markers in acute myocardial infarction

    PubMed Central

    Hazini, Ahmet; Işıldak, İbrahim; Alpdağtaş, Saadet; Önül, Abdullah; Şenel, Ünal; Kocaman, Tuba; Dur, Ali; Iraz, Mustafa; Uyarel, Hüseyin

    2015-01-01

    Introduction Acute myocardial infarction (AMI) is still one of the most common causes of death worldwide. In recent years, for diagnosis of myocardial ischemia, a new parameter, called ischemia modified albumin (IMA), which is thought to be more advantageous than common methods, has been researched. Aim In this study, systematic analysis of parameters considered to be related to myocardial ischemia has been performed, comparing between control and myocardial ischemia groups. Material and methods We selected 40 patients with AMI and 25 healthy controls for this study. Ischemia modified albumin levels, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) antioxidant enzyme activities and non-enzymatic antioxidants such as retinol, α-tocopherol, β-carotene and ascorbic acid levels were investigated in both groups. Glutathione (GSH) and malondialdehyde (MDA) levels, which are indicators of oxidative stress, were compared between patient and control groups. Results Ischemia modified albumin levels were found significantly higher in the AMI diagnosed group when compared with controls. The MDA level was elevated in the patient group, whereas the GSH level was decreased. SOD, GPx and CAT enzyme levels were decreased in the patient group, where it could be presumed that oxidative stress causes the cardiovascular diseases. Conclusions Due to the increased oxidative stress, non-enzymatic and enzymatic antioxidant capacity was affected. Systematic investigation of parameters related to myocardial infarction has been performed, and it is believed that such parameters can contribute to protection and early diagnosis of AMI and understanding the mechanism of development of the disease. PMID:26677379

  12. Red cell distribution width to platelet ratio: New and promising prognostic marker in acute pancreatitis

    PubMed Central

    Çetinkaya, Erdinç; Şenol, Kazım; Saylam, Barış; Tez, Mesut

    2014-01-01

    AIM: To evaluate the accuracy of red cell distribution width (RDW) to platelet ratio (RPR) to predict in-hospital mortality in acute pancreatitis (AP). METHODS: Between January 2010 and June 2012, 102 patients with AP were recruited to the study. In this retrospective cohort study, for all subjects, demographic data on hospital admission, AP etiology, co-morbid diseases, organ failure assessment, laboratory parameters and length of hospital stay were examined. Additionally, we used a non-invasive prediction method in addition to the RPR to evaluate the disease severity. Multivariate logistic regression analyses were used to evaluate the impact of RPR on hospital admission to predict mortality. RESULTS: The male-female ratio (59/43) was 1.37 with a median age of 56.5 years (17-89 years). In both univariate and multivariate analyses, RDW and RPR were presented as independent and significant variables on admission to predict mortality. The RPR obtained on hospital admission was persistently higher among non-survivors than among survivors (P < 0.0001). The median RPR was 0.000087 in the non-survivor group and 0.000058 in the survivor group. RPR with a cutoff value of 0.000067 presented an area under the curve of 0.783 (95%CI: 0.688-0.878) in receiver operating characteristic curves and could predict the mortality of approximately 80% of the patients. CONCLUSION: We identified RPR as a valuable, novel laboratory test to predict mortality in AP. PMID:25339831

  13. Phosphatidylserine index as a marker of the procoagulant phenotype of acute myelogenous leukemia cells

    NASA Astrophysics Data System (ADS)

    Tormoen, Garth W.; Recht, Olivia; Gruber, András; Levine, Ross L.; McCarty, Owen J. T.

    2013-10-01

    Patients with acute myelogenous leukemia (AML) are at risk for thrombotic complications. Risk to develop thrombosis is closely tied to leukemia subtype, and studies have shown an association between leukocytosis and thrombosis in AML M3. We evaluated the relative roles of cell count and the surface expression of tissue factor (TF) and phosphatidylserine (PS) in the procoagulant phenotype of AML cell lines. The TF-positive AML M3 cell lines, NB4 and HL60, and AML M2 cell line, AML14, exhibited both extrinsic tenase and prothrombinase activity in a purified system and promoted experimental thrombus formation. In contrast, the TF-negative AML cell line, HEL, exhibited only prothrombinase activity and did not affect the rate of occlusive thrombus formation. In plasma, NB4, HL60 and AML14 shortened clotting times in a cell-count, PS- and TF-dependent manner. Exposure of cultured NB4, HL60, and AML14 cells to the chemotherapeutic agent daunorubicin increased their extrinsic tenase activity and PS expression. Clot initiation time inversely correlated with logarithm of PS index, defined as the product of multiplying leukocyte count with cell surface PS exposure. We propose that leukemia cell PS index may serve as a biomarker for procoagulant activity.

  14. Study of Aortic Valve Sclerosis as A Marker of Atherosclerosis in Acute Coronary Syndromes

    PubMed Central

    Picardo, Preeti Jane; Khariong, Peter Daniel S; Hajong, Debobratta; Naku, Narang; Anand, Madhur; Sharma, Girish; Singh, K Lenish

    2016-01-01

    Introduction Aortic valve sclerosis has been shown to be associated with increased incidence, chances of developing myocardial infarction and even death. The epidemiological risk factors causing calcification of aortic valves have also been found to cause atherosclerosis. Aim To analyse the epidemiological risk factors causing aortic valve sclerosis which have been studied in details and analysed to see whether they cause any significant increase in the incidence of cardiovascular events. Materials and Methods This prospective case-control study was conducted between 1st Jan 2015 to 31st Dec 2015 in NEIGRIHMS hospital and data for age, gender, socioeconomic status, hypertension, diabetes, tobacco use, Body Mass Iindex (BMI), cholesterol levels, Electrocardiography (ECG) changes and Ejection Fraction (EF) were collected and analysed by using SPSS software version 22. Results Hypertension, diabetes, weight, BMI, hyperglycaemia and hyperlipidemia were not found to be significantly associated with aortic valve sclerosis in patients presenting with acute coronary syndromes. The presence of aortic valve sclerosis was also not associated with increased risk of cardiovascular mortality and morbidity. Conclusion The risk factors for atherosclerosis were found to be associated with the presence of aortic valve sclerosis more in the control group and hence finding of a sclerosed aortic valve in the apparent normal population might identify those persons at increased risk of developing coronary artery disease and appropriate preventive measures should be taken before the disease sets in. PMID:28208902

  15. Preoperative Acute Inflammatory Markers as Predictors for Postoperative Complications in Primary Total Knee Arthroplasty

    PubMed Central

    Godoy, Gustavo; Sumarriva, Gonzalo; Ochsner, J. Lockwood; Chimento, George; Schmucker, Dana; Dasa, Vinod; Meyer, Mark

    2016-01-01

    Background: C-reactive protein (CRP) has been suggested as an independent risk factor for cardiovascular pathology in the nonsurgical setting. While postoperative CRP and erythrocyte sedimentation rate (ESR) have an established role in aiding the diagnosis of periprosthetic joint infections, some authors suggest a link between preoperative CRP and postoperative complications in patients undergoing total joint arthroplasty. Methods: We conducted a retrospective cohort study of 351 patients who underwent unilateral primary total knee arthroplasty by a single surgeon during a 28-month period (January 2013 through April 2015). Patient medical records were reviewed for the following complications occurring within 90 days postoperatively: myocardial infarction, arrhythmia, pulmonary embolism, wound infection, acute renal failure, and reoperation. Results: We found no statistically significant link between postoperative complications and preoperative CRP levels (P=0.5005) or ESR levels (P=0.1610). Conclusion: The results of this study do not support the routine inclusion of CRP and ESR analysis as part of the preoperative evaluation for elective total knee arthroplasty. PMID:27999506

  16. Kidney damage biomarkers detect acute kidney injury but only functional markers predict mortality after paraquat ingestion.

    PubMed

    Mohamed, Fahim; Buckley, Nicholas A; Jayamanne, Shaluka; Pickering, John W; Peake, Philip; Palangasinghe, Chathura; Wijerathna, Thilini; Ratnayake, Indira; Shihana, Fathima; Endre, Zoltan H

    2015-09-02

    Acute kidney injury (AKI) is common following paraquat ingestion. The diagnostic performance of injury biomarkers was investigated in serial blood and urine samples from patients from 5 Sri Lankan hospitals. Functional AKI was diagnosed using serum creatinine (sCr) or serum cystatin C (sCysC). The 95th centile in healthy subjects defined the urinary biomarker cutoffs for diagnosing structural AKI. 50 poisoned patients provided 2 or more specimens, 76% developed functional AKI [AKIN stage 1 (n=12), 2 (n=7) or 3 (n=19)]; 19/26 patients with AKIN stage 2/3 also had functional AKI by sCysC criteria (≥50% increase). Urinary cystatin C (uCysC), clusterin (uClu) and NGAL (uNGAL) increased within 24h of ingestion compared with NoAKI patients and healthy controls. Each biomarker demonstrated moderate diagnostic utility [AUC-ROC: uCysC 0.79, uNGAL 0.79, uClu 0.68] for diagnosis of functional AKI at 16h. Death occurred only in subjects with functional AKI. Structural biomarker-based definitions detected more AKI than did sCr or sCysC, but did not independently predict death. Renal injury biomarkers did not add clinical value to patients who died rapidly due to multi-organ failure. Use of injury biomarkers within 16-24h may guide early intervention for reno-protection in less severe paraquat poisoning.

  17. Two-dimensional paper chromatography-based fluorescent immunosensor for detecting acute myocardial infarction markers.

    PubMed

    Cho, Jung-Hwan; Kim, Min-Ha; Mok, Rak-Sun; Jeon, Jin-Woo; Lim, Guei-Sam; Chai, Chan-Young; Paek, Se-Hwan

    2014-09-15

    A novel washing scheme following antigen-antibody reactions with analyte was used during construction of a fluorescent immunosensor to resolve the background problem in the lateral flow assay with human serum. An immuno-membrane strip was devised to simultaneously measure cardiac troponin I (cTnI), creatinine kinase-MB isoform (CK-MB), and myoglobin to diagnose acute myocardial infarction. This strip was then installed within a cartridge containing a built-in washing solution tank, which was used to supply the solution across the signal generation pad of the strip after the immune reactions. Such cross-flow washing was initiated by onset-signaling from the internal control and began to run automatically upon sample addition. Under optimal conditions, the immunosensor displayed a stably suppressed background baseline, enabling us to attain a low detection limit for cTnI (0.05 ng/mL) as well as favorable reproducibility for repetitive measurements (relative standard deviation <10%). No interference was observed among the different complex formations at the respective analyte sites, and no artifacts were caused by sample matrices. We tested the performance relationship with the Pathfast reference system for positive serum samples (36 for cTnI, 58 for CK-MB, and 17 for myoglobin), and the correlation coefficients were >0.98. This result suggests that the new immunosensor system based on two-dimensional chromatography can be used for clinical testing.

  18. Pork, beef and chicken have similar effects on acute satiety and hormonal markers of appetite.

    PubMed

    Charlton, Karen E; Tapsell, Linda C; Batterham, Marijka J; Thorne, Rebecca; O'Shea, Jane; Zhang, Qingsheng; Beck, Eleanor J

    2011-02-01

    The effects of three different meat-containing breakfast meals (pork, beef or chicken) on acute satiety and appetite regulatory hormones were compared using a within-subjects study design. Thirty fasting non-smoking pre-menopausal women attended a research centre on three test days to consume, a meat-containing meal matched in energy (kJ) and protein content, palatability, and appearance. No difference was found between meat groups for either energy intake or macronutrient profile of food consumed at a subsequent ad libitum buffet lunch, or over the rest of the day. Visual Analogue Scale (VAS) ratings for hunger and satiety over an 180 min period did not differ between test meals. After consumption of the test meals, a significant difference was found in PYY response between pork and chicken meals (P=0.027) but not for levels of CCK, ghrelin, insulin or glucose. This study positions pork, beef, and chicken as equal in their effect on satiety and release of appetite-related intestinal hormones and of insulin.

  19. Elevated Circulating Levels of Inflammatory Markers in Patients with Acute Coronary Syndrome

    PubMed Central

    Al Shahi, Hamad; Shimada, Kazunori; Miyauchi, Katsumi; Yoshihara, Takuma; Sai, Eiryu; Shiozawa, Tomoyuki; Naito, Ryo; Aikawa, Tatsuro; Ouchi, Shohei; Kadoguchi, Tomoyasu; Miyazaki, Tetsuro; Daida, Hiroyuki

    2015-01-01

    Objective. We evaluated inflammatory cytokines and chemokine in peripheral blood mononuclear cells (PBMCs) in patients with either acute coronary syndrome (ACS) or stable coronary artery disease (CAD). Methods. We enrolled 20 ACS patients and 50 stable CAD patients without previous history of ACS who underwent cardiac catheterization. Patients with an estimated glomerular filtration rate of ≤30 mL/min/1.73 m2 and C-reactive protein of ≥1.0 mg/dL were excluded. Blood samples were collected from the patients just before catheterization, and PBMCs were isolated from the whole blood. The levels of inflammatory cytokines and chemokine were measured by using real-time quantitative polymerase chain reaction and immunoassays. Results. The expression of tumor necrosis factor alpha (TNF-α), interleukin- (IL-) 6, IL-10, IL-23A, IL-27, and IL-37 was significantly higher in the ACS group than in the CAD group (P < 0.05). In contrast, the expression of IL-33 was significantly lower in the ACS group than in the CAD group (P < 0.05). The ACS patients had higher plasma levels of TNF-α, IL-6, and IL-10 in the ACS group than in the CAD group. Conclusion. Circulating levels of pro-/anti-inflammatory cytokines, including IL-23A, IL-27, IL-33, and IL-37, may be associated with the pathogenesis of atherosclerosis in ACS patients. PMID:26504600

  20. The acute antinociceptive effect of hyperbaric oxygen is not accompanied by an increase in markers of oxidative stress

    PubMed Central

    Liu, Shulin; Shirachi, Donald Y.; Quock, Raymond M.

    2014-01-01

    Aims Exposure to hyperbaric oxygen (HBO2) causes an antinociceptive response in mice. However, breathing oxygen (O2) at an elevated pressure can potentially cause oxygen toxicity. The aim of this study was to identify the determinants of HBO2 antinociception and the toxicity profile of HBO2. Main methods Male NIH Swiss mice were assessed for acute antinociceptive responsiveness under room air or 100% O2 at 1.0 or 3.5 atmospheres absolute (ATA), using the acetic acid-induced abdominal constriction test. For the oxygen toxicity test, mice were exposed to 3.5 ATA oxygen for 11 min, 60 min, 60 min daily for 2 days (120 min) or 60 min daily for 4 days (240 min), then assessed by analyzing the levels of two oxidative stress markers, MDA (malondialdehyde) and protein carbonyl in brain, spinal cord and lung. Key Findings Only the combination of 100% O2 and 3.5 ATA caused significant antinociception. The antinociceptive effect of 100% O2 was pressure-dependent up to 3.5 ATA. In the oxygen toxicity test, mice exposed to HBO2 for different time intervals had levels of brain, spinal cord and lung MDA and protein carbonyl that were comparable to that of control animals exposed to room air. Significance Treatment with 100% O2 evokes a pressure-dependent antinociceptive effect. Since there was no significant increase in levels of the oxidative stress markers in the tested tissues, it is concluded HBO2 at 3.5 ATA produces antinociception in the absence of oxidative stress in mice. PMID:24418003

  1. Thresholds for the electrocardiographic change range of biochemical markers of acute myocardial infarction (GUSTO-IIa data).

    PubMed

    Bahit, Maria Cecilia; Criger, Douglas A; Ohman, E Magnus; Granger, Christopher B; Wagner, Galen S

    2002-08-01

    The definition of acute myocardial infarction (AMI) is increasingly dependent on levels of biochemical markers, including troponin. We aimed to determine the levels of biochemical markers associated with definite evolutionary electrocardiographic (ECG) changes in patients with ST-segment elevation myocardial infarction. By examining the database of 855 patients from the troponin substudy of GUSTO-IIa, we selected patients with ST-segment elevation at baseline, evidence of evolution of the QRS, T, and ST-segment waveforms on the predischarge electrocardiogram, and 3 measurements of > or =1 of the following: creatine kinase (CK)-MB, troponin T, or troponin I. We identified 222 patients with evolutionary ECG changes. The median QRS score for this population was 5 points; the fifth percentile was 1. For patients with 3 CK-MB measurements, the fifth percentile as a multiple of the upper limit of normal was 2.1 (upper limit of normal 7.0 ng/ml). For patients with troponin T measurements, the fifth percentile as a multiple of the upper limit of normal was 11.0 (upper limit of normal 0.1 ng/ml). For patients with troponin I measurements, the fifth percentile as a multiple of the upper limit of normal was 3.8 (upper limit of normal 1.5 ng/ml). This study revealed that 95% of the patients with definite ECG evidence of AMI had a more than twofold increase in CK-MB and more than a 3- to 11-fold increase in troponin.

  2. Oxidative stress markers in laparoscopic vs. open appendectomy for acute appendicitis: A double-blind randomized study

    PubMed Central

    Aktimur, Recep; Gokakin, Ali Kagan; Deveci, Koksal; Atabey, Mustafa; Topcu, Omer

    2016-01-01

    BACKGROUND: Oxidative stress is a complicated process, which was defined as an increase in prooxidants and decrease in antioxidants caused by various mechanisms, including inflammation and surgical trauma. The association between acute appendicitis and oxidative stress has been showed in previous studies. However, comparison of oxidative stress in laparoscopic or open appendectomy (OA) has not been established. PATIENTS AND METHODS: Patients who were diagnosed as acute appendicitis between October 2012 and January 2013 were randomized to open (OA, n = 50) and laparoscopic appendectomy (LA, n = 50). Blood samples for oxidative stress markers (total oxidant status [TOS] and total antioxidant status [TAS]), C-reactive protein (CRP) and white blood cells (WBC’s) were collected just before the surgery and 24 h after surgery. RESULTS: There were no differences in preoperative values of WBC and CRP between LA and OA groups (P = 0.523 and 0.424), however, in postoperative 24th h, CRP was reduced in LA group (P = 0.031). There were no differences in preoperative levels of TOS, TAS, and oxidative stress index (OSI) between LA and OA groups. In the postoperative 24th h, TOS and OSI were found to be significantly higher in OA group when compared to LA group (P = 0.017 and 0.002) whereas no difference was detected in TAS level in the postoperative 24th h (P = 0.172). CONCLUSIONS: This double-blind, randomized clinical trial provides evidence that LA for uncomplicated appendicitis is associated with significantly lower oxidative stress compared with OA. Some of the advantages of LA may be attributed to the significant reduction of oxidative stress in these patients. PMID:27073307

  3. Acute effects of plyometric jumping and intermittent running on serum bone markers in young males.

    PubMed

    Lin, Che-Fu; Huang, Tsang-hai; Tu, Kuo-Cheng; Lin, Linda L; Tu, Yi-Hsuan; Yang, Rong-Sen

    2012-04-01

    The purpose of this study was to investigate whether different modes of single-bout exercise would cause different responses in short-term bone metabolism. 24 untrained male college students (19.1 ± 0.1 years old) were recruited and randomly assigned to three groups: (1) a single-bout plyometric exercise group (the PL group, n = 8), (2) a 200-meter × 10 intermittent running group (the IR group, n = 8) and (3) a sedentary control group, which followed the same time schedule of experimentation without performing any exercise (the CON group, n = 8). Serial blood samples were collected before (baseline) and 5 min, 15 min, 1 h, 3 h, 6 h, 24 h, 48 h, and 72 h after exercise trials. Within 15 min of exercise, the PL and IR groups showed significantly higher serum phosphorus than did the control group (P < 0.05). Osteocalcin levels were significantly higher in the PL group at 5 min and 1 h after exercise (P < 0.05), while serum tartrate-resistant acid phosphatase (TRAP) showed no differences among groups. Exercises with different mechanical impact levels responded differently in serum bone formation markers as shown by osteocalcin. Because the increase in osteocalcin in the PL group was revealed shortly after the exercise bout, the changes might due to an exercise-induced mechanical impact rather than bone cellular activities.

  4. Glial markers and emotional memory in rats following acute cerebral radiofrequency exposures.

    PubMed

    Barthélémy, Amélie; Mouchard, Amandine; Bouji, Marc; Blazy, Kelly; Puigsegur, Renaud; Villégier, Anne-Sophie

    2016-12-01

    The widespread mobile phone use raises concerns on the possible cerebral effects of radiofrequency electromagnetic fields (RF EMF). Reactive astrogliosis was reported in neuroanatomical structures of adaptive behaviors after a single RF EMF exposure at high specific absorption rate (SAR, 6 W/kg). Here, we aimed to assess if neuronal injury and functional impairments were related to high SAR-induced astrogliosis. In addition, the level of beta amyloid 1-40 (Aβ 1-40) peptide was explored as a possible toxicity marker. Sprague Dawley male rats were exposed for 15 min at 0, 1.5, or 6 W/kg or for 45 min at 6 W/kg. Memory, emotionality, and locomotion were tested in the fear conditioning, the elevated plus maze, and the open field. Glial fibrillary acidic protein (GFAP, total and cytosolic fractions), myelin basic protein (MBP), and Aβ1-40 were quantified in six brain areas using enzyme-linked immunosorbent assay. According to our data, total GFAP was increased in the striatum (+114 %) at 1.5 W/kg. Long-term memory was reduced, and cytosolic GFAP was increased in the hippocampus (+119 %) and in the olfactory bulb (+46 %) at 6 W/kg (15 min). No MBP or Aβ1-40 expression modification was shown. Our data corroborates previous studies indicating RF EMF-induced astrogliosis. This study suggests that RF EMF-induced astrogliosis had functional consequences on memory but did not demonstrate that it was secondary to neuronal damage.

  5. Identification of serum endoglin as a novel prognostic marker after acute myocardial infarction

    PubMed Central

    Cruz-Gonzalez, Ignacio; Pabón, Pedro; Rodríguez-Barbero, Alicia; Martín-Moreiras, Javier; Pericacho, Miguel; Sánchez, Pedro L; Ramirez, Victor; Sánchez-Ledesma, María; Martín-Herrero, Francisco; Jiménez-Candil, Javier; Maree, Andrew O; Sánchez-Rodríguez, Angel; Martín-Luengo, Cándido; López-Novoa, José M

    2008-01-01

    Abstract Endoglin is a proliferation-associated and hypoxia-inducible protein expressed in endothelial cells. The levels of soluble circulating endoglin and their prognostic significance in patients with acute myocardial infarction (AMI) are not known. In this observational prospective study serum endoglin levels were measured by ELISA in 183 AMI patients upon admission to hospital and 48 hrs later and in 72 healthy controls. Endoglin levels in AMI patients on admission were significantly lower than in healthy controls (4.25 ± 0.99 ng/ml versus 4.59 ± 0.87 ng/ml; P= 0.013), and decreased further in the first 48 hours (3.65 ± 0.76 ng/ml, P < 0.001). Upon follow-up (median 319 days), patients who died had a significantly greater decrease in serum endoglin level over the first 48 hrs than those who survived (1.03 ± 0.91 versus 0.54 ± 0.55 ng/ml; P= 0.025). Endoglin decrease was an independent predictor of short-term (30 days) (hazard ratio 2.33;95% CI = 1.27–4.23; P= 0.006) cardiovascular mortality, and also predicts overall cardiovascular mortality during the follow-up (median 319 days) in AMI patients (hazard ratio 2.13;95% CI = 1.20–3.78; P= 0.01). In conclusion, early changes in serum endoglin may predict mortality after AMI. PMID:18494936

  6. Urine Albumin Excretion as a Marker of Acute Glycemic Changes in Isolated Postprandial Hyperglycemia

    PubMed Central

    Shilpasree, Alagilawada S; Patil, Vidya S; Patil, Vijayetha P; Ingleshwar, Deepti G

    2017-01-01

    Introduction: Postprandial hyperglycemia is a major risk factor for the development of cardiovascular diseases (CVDs), and Most of the times it occurs in patients with normal glycemic control diagnosed by fasting blood glucose (FBG) and glycated hemoglobin levels. Urine albumin excretion (UAE) is an independent predictor of CVD risk. Aim: To estimate UAE in isolated postprandial hyperglycemia (IPPHG) patients and to assess the relationship of UAE with FBG and postprandial blood glucose (PPBG) levels. Settings and Design: A cross-sectional study was carried out in 318 patients with Type II diabetes in the age group 30–60 years for 6 months. Materials and Methods: Patients were divided into five groups based on their FBG and PPBG values. UAE and lipid profile were measured in all the groups. Statistical Analysis: UAE and lipid profile in different groups were compared using ANOVA. Regression analysis was used to predict the variation of UAE with FBG, PPBG, and total cholesterol (TC). Results: Patients with IPPHG had significantly higher albumin excretion compared to normoglycemia (NG) group [P < 0.0001]. In impaired glucose tolerance and isolated fasting hyperglycemia groups, it did not differ significantly from NG group [P = 0.206 and P = 0.173]. Lipid profile did not show any significant difference between the groups. On regression analysis, PPBG but not FBG or TC correlated positively with UAE. Conclusion: UAE is easy, less expensive, and Widely available method done on spot urine samples which predicts the acute glycemic changes and increased risk of developing CVDs in patients with IPPHG. PMID:28042215

  7. Effects of acute aerobic and anaerobic exercise on blood markers of oxidative stress.

    PubMed

    Bloomer, Richard J; Goldfarb, Allan H; Wideman, Laurie; McKenzie, Michael J; Consitt, Leslie A

    2005-05-01

    The purpose of this study was to compare oxidative modification of blood proteins, lipids, DNA, and glutathione in the 24 hours following aerobic and anaerobic exercise using similar muscle groups. Ten cross-trained men (24.3 +/- 3.8 years, [mean +/- SEM]) performed in random order 30 minutes of continuous cycling at 70% of Vo(2)max and intermittent dumbbell squatting at 70% of 1 repetition maximum (1RM), separated by 1-2 weeks, in a crossover design. Blood samples taken before, and immediately, 1, 6, and 24 hours postexercise were analyzed for plasma protein carbonyls (PC), plasma malondialdehyde (MDA), and whole-blood total (TGSH), oxidized (GSSG), and reduced (GSH) glutathione. Blood samples taken before and 24 hours postexercise were analyzed for serum 8-hydroxy-2'-deoxyguanosine (8-OHdG). PC values were greater at 6 and 24 hours postexercise compared with pre-exercise for squatting, with greater PC values at 24 hours postexercise for squatting compared with cycling (0.634 +/- 0.053 vs. 0.359 +/- 0.018 nM.mg protein(-1)). There was no significant interaction or main effects for MDA or 8-OHdG. GSSG experienced a short-lived increase and GSH a transient decrease immediately following both exercise modes. These data suggest that 30 minutes of aerobic and anaerobic exercise performed by young, cross-trained men (a) can increase certain biomarkers of oxidative stress in blood, (b) differentially affect oxidative stress biomarkers, and (c) result in a different magnitude of oxidation based on the macromolecule studied. Practical applications: While protein and glutathione oxidation was increased following acute exercise as performed in this study, future research may investigate methods of reducing macromolecule oxidation, possibly through the use of antioxidant therapy.

  8. GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-12-03

    Acute Undifferentiated Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  9. Application of single nucleotide polymorphism markers to chum salmon Oncorhynchus keta: discovery, genotyping and linkage phase resolution.

    PubMed

    Garvin, M R; Gharrett, A J

    2010-12-01

    This study describes (1) the application of new methods to the discovery of informative single nucleotide polymorphism (SNP) markers in chum salmon Oncorhynchus keta, (2) a method to resolve the linkage phase of closely linked SNPs and (3) a method to inexpensively genotype them. Finally, it demonstrates that these SNPs provide information that discriminates among O. keta populations from different geographical regions of the northern Pacific Ocean. These informative markers can be used in conjunction with mixed-stock analysis to learn about the spatial and temporal marine distributions of O. keta and the factors that influence the distributions.

  10. Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response

    PubMed Central

    Ahyi, Ayele-Nati N.; Quinton, Lee J.; Jones, Matthew R.; Ferrari, Joseph D.; Pepper-Cunningham, Zachary A.; Mella, Juan R.; Remick, Daniel G.

    2013-01-01

    The acute-phase response is characteristic of perhaps all infections, including bacterial pneumonia. In conjunction with the acute-phase response, additional biological pathways are induced in the liver and are dependent on the transcription factors STAT3 and NF-κB, but these responses are poorly understood. Here, we demonstrate that pneumococcal pneumonia and other severe infections increase expression of multiple components of the cellular secretory machinery in the mouse liver, including the endoplasmic reticulum (ER) translocon complex, which mediates protein translation into the ER, and the coat protein complexes (COPI and COPII), which mediate vesicular transport of proteins to and from the ER. Hepatocyte-specific mutation of STAT3 prevented the induction of these secretory pathways during pneumonia, with similar results observed following pharmacological activation of ER stress by using tunicamycin. These findings implicate STAT3 in the unfolded protein response and suggest that STAT3-dependent optimization of secretion may apply broadly. Pneumonia also stimulated the binding of phosphorylated STAT3 to promoter regions of secretion-related genes in the liver, supporting a direct role for STAT3 in their transcription. Altogether, these results identify a novel function of STAT3 during the acute-phase response, namely, the induction of secretory machinery in hepatocytes. This may facilitate the processing and delivery of newly synthesized loads of acute-phase proteins, enhancing innate immunity and preventing liver injury during infection. PMID:23460517

  11. Feasibility and safety of acute phase rehabilitation after stroke using the hybrid assistive limb robot suit.

    PubMed

    Ueba, Tetsuya; Hamada, Omi; Ogata, Toshiyasu; Inoue, Tooru; Shiota, Etsuji; Sankai, Yoshiyuki

    2013-01-01

    Acute phase rehabilitation is an important treatment for improving the functional outcome of patients after stroke. The present cohort study analyzed the feasibility and safety of acute phase rehabilitation using the hybrid assistive limb robot suit in 22 patients, 7 males and 15 females (mean age 66.6 ± 17.7 years). Neurological deterioration, mortality, or other accidents were recorded as adverse events. Baseline characteristics of each patient were recorded at the first hybrid assistive limb rehabilitation. Hybrid assistive limb rehabilitation was conducted for 12.1 ± 7.0 days with the patients in stable condition. Acute phase hybrid assistive limb rehabilitation was performed a total of 84 times with no adverse events recorded except for orthostatic hypotension. Good functional outcomes were obtained in 14 patients. Orthostatic hypotension was observed during the first hybrid assistive limb rehabilitation in four patients, and was significantly associated with intracerebral hemorrhage (p = 0.007) and lower Brunnstrom stage (p = 0.033). Acute phase rehabilitation using the hybrid assistive limb suit is feasible and safe. Patients with intracerebral hemorrhage and lower Brunnstrom stage should be carefully monitored for orthostatic hypotension.

  12. Natural variations in the stress and acute phase responses of cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The initial response of the innate immune system upon activation has been defined as the acute phase response (APR). Activation of the APR results in several responses that include fever, metabolic adaptations, and changes in behavior. The APR can be modulated by many factors, with stress being th...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  14. Changes in the Neuropsychological Correlates of Clinical Dimensions between the Acute and Stable Phase of Schizophrenia

    ERIC Educational Resources Information Center

    Guillem, F.; Ganeva, E.; Pampoulova, T.; Stip, E.; Lalonde, P.; Sasseville, M.

    2005-01-01

    This study was designed to investigate whether the neuropsychological correlates of the symptom dimensions of schizophrenia vary with the clinical state in patients followed from the acute to stable the phase of the illness. Fifteen patients were assessed for symptoms (SAPS-SANS) and undergone a complete neuropsychological assessment at two…

  15. In Utero Exposure to Lipopolysaccharide Alters the Postnatal Acute Phase Response in Beef Heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine the potential effect of prenatal lipopolysaccharide (LPS) exposure on the postnatal acute phase response (APR) to an LPS challenge in heifers. Pregnant crossbred cows (n = 50) were separated into prenatal immune stimulation (PIS; n = 25; administered 0.1 microgr...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. The diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis

    PubMed Central

    Elmoslemany, Ahmed M.

    2016-01-01

    The goal of this study was to assess the diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis. Blood samples were collected from 56 sheep (36 naturally infected with Pasteurella multocida and 20 healthy controls) belonging to one farm in Eastern region, Saudi Arabia. Serum samples were evaluated for acute phase proteins (Haptoglobin (Hp), serum amyloid A (SAA) and fibrinogen (Fb)), and the proinflammatory cytokines (interleukins (IL-1α, IL-1β, and IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-ϒ)). Additionally, nasopharyngeal swabs and bronchoalveolar lavages were collected from all animals for bacteriological examinations. Receiver operating characteristic curve was used to assess the diagnostic performance of each parameter. All parameters showed moderate to high degree of positive correlation with case-control status. There was no significant difference in the area under the curve (AUC) among acute phase proteins; however, both Hp and SAA showed better sensitivity and specificity than Fb. The proinflammatory cytokines (IL1-α, IL1-β, and IL6) showed similar and highly accurate diagnostic performance (AUC > 0.9), whereas IFN-ϒ was moderately accurate (AUC = 0.79). In conclusion, this study confirms the value of acute phase proteins and cytokines as diagnostic biomarkers of naturally occuring pneumonic pasteurellosis in sheep. PMID:27547520

  18. Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke

    PubMed Central

    2011-01-01

    Background Neuroserpin has shown neuroprotective effects in animal models of cerebral ischemia and has been associated with functional outcome after ischemic stroke. Our aim was to study whether neuroserpin serum levels could be associated to biomarkers of excitotoxicity, inflammation and blood brain barrier disruption. Methods We prospectively included 129 patients with ischemic stroke (58.1% male; mean age, 72.4 ± 9.6 years) not treated with tPA within 12 hours (h) of symptoms onset (mean time, 4.7 ± 2.1 h). Poor functional outcome at 3 months was considered as a modified Rankin scale score >2. Serum levels of neuroserpin, Interleukin 6 (IL-6), Intercellular adhesion molecule-1 (ICAM-1), active Matrix metalloproteinase 9 (MMP-9), and cellular fibronectin (cFn) (determined by ELISA) and glutamate (determined by HPLC) were measured on admission, 24 and 72 h. The main variable was considered the decrease of neuroserpin levels within the first 24 h. ROC analysis was used to select the best predictive value for neuroserpin to predict poor functional outcome due to a lack of linearity. Results The decrease of neuroserpin levels within the first 24 h was negatively correlated with serum levels at 24 hours of glutamate (r = -0.642), IL-6 (r = -0.678), ICAM-1 (r = -0.345), MMP-9 (r = -0.554) and cFn (r = -0.703) (all P < 0.0001). In the multivariate analysis, serum levels of glutamate (OR, 1.04; CI95%, 1.01-1.06, p = 0.001); IL-6 (OR, 1.4; CI95%, 1.1-1.7, p = 0.001); and cFn (OR, 1.3; CI95%, 1.1-1.6, p = 0.002) were independently associated with a decrease of neuroserpin levels <70 ng/mL at 24 h after adjusting for confounding factors. Conclusions These findings suggest that neuroprotective properties of neuroserpin may be related to the inhibition of excitotoxicity, inflammation, as well as blood brain barrier disruption that occur after acute ischemic stroke. PMID:21569344

  19. Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-10-29

    B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  20. Clinical impact of circulating microRNAs as blood-based marker in childhood acute lymphoblastic leukemia.

    PubMed

    Swellam, Menha; El-Khazragy, Nashwa

    2016-08-01

    Aberrant microRNA (miRNA) expression participates in childhood acute lymphoblastic leukemia (ALL). This study aimed to investigate the expression of miRNA-100, miRNA-196a, and miRNA-146a among childhood ALL and study their correlation with other hematological parameters and different phenotypes. Peripheral blood mononuclear cells (PMNCs) were obtained from 85 childhood ALL and 25 healthy children for the detection of miRNA expression using quantitative real-time PCR. Significant higher median levels were reported for ALL compared to control children. The diagnostic efficacy for miRNA-146a was superior as both sensitivity and specificity were absolute. A significant correlation was observed between higher expression of miRNA-100 and lower platelet and lymphocyte counts; high expression of miRNA-146a showed significant correlation with low total leukocyte count (TLC) and lymphocyte counts. Significant relation was reported between studied miRNAs and different phenotyping. miRNA-100, miRNA-196a, and miRNA-146a have significant role in childhood ALL leukemogenesis, and they may be useful as biological diagnostic molecular markers.

  1. Effects of short-term propofol and dexmedetomidine on pulmonary morphofunction and biological markers in experimental mild acute lung injury.

    PubMed

    Cavalcanti, Vinícius; Santos, Cintia Lourenço; Samary, Cynthia Santos; Araújo, Mariana Neves; Heil, Luciana Boavista Barros; Morales, Marcelo Marcos; Silva, Pedro Leme; Pelosi, Paolo; Fernandes, Fatima Carneiro; Villela, Nivaldo; Rocco, Patricia Rieken Macedo

    2014-11-01

    We evaluated whether the short-term use of dexmedetomidine and propofol may attenuate inflammatory response and improve lung morphofunction in experimental acute lung injury (ALI). Thirty-six Wistar rats were randomly divided into five groups. Control (C) and ALI animals received sterile saline solution and Escherichia coli lipopolysaccharide by intraperitoneal injection respectively. After 24h, ALI animals were randomly treated with dexmedetomidine, propofol, or thiopental sodium for 1h. Propofol reduced static lung elastance and resistive pressure and was associated with less alveolar collapse compared to thiopental sodium and dexmedetomidine. Dexmedetomidine improved oxygenation, but did not modify lung mechanics or histology. Propofol was associated with lower IL (interleukin)-6 and IL-1β expression, whereas dexmedetomidine led to reduced inducible nitric oxide (iNOS) and increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression in lung tissue compared to thiopental sodium. In conclusion, in this model of mild ALI, short-term use of dexmedetomidine and propofol led to different functional effects and activation of biological markers associated with pulmonary inflammation.

  2. Development of Gene Expression Markers of Acute Heat-Light Stress in Reef-Building Corals of the Genus Porites

    PubMed Central

    Kenkel, Carly D.; Aglyamova, Galina; Alamaru, Ada; Bhagooli, Ranjeet; Capper, Roxana; Cunning, Ross; deVillers, Amanda; Haslun, Joshua A.; Hédouin, Laetitia; Keshavmurthy, Shashank; Kuehl, Kristin A.; Mahmoud, Huda; McGinty, Elizabeth S.; Montoya-Maya, Phanor H.; Palmer, Caroline V.; Pantile, Raffaella; Sánchez, Juan A.; Schils, Tom; Silverstein, Rachel N.; Squiers, Logan B.; Tang, Pei-Ciao; Goulet, Tamar L.; Matz, Mikhail V.

    2011-01-01

    Coral reefs are declining worldwide due to increased incidence of climate-induced coral bleaching, which will have widespread biodiversity and economic impacts. A simple method to measure the sub-bleaching level of heat-light stress experienced by corals would greatly inform reef management practices by making it possible to assess the distribution of bleaching risks among individual reef sites. Gene expression analysis based on quantitative PCR (qPCR) can be used as a diagnostic tool to determine coral condition in situ. We evaluated the expression of 13 candidate genes during heat-light stress in a common Caribbean coral Porites astreoides, and observed strong and consistent changes in gene expression in two independent experiments. Furthermore, we found that the apparent return to baseline expression levels during a recovery phase was rapid, despite visible signs of colony bleaching. We show that the response to acute heat-light stress in P. astreoides can be monitored by measuring the difference in expression of only two genes: Hsp16 and actin. We demonstrate that this assay discriminates between corals sampled from two field sites experiencing different temperatures. We also show that the assay is applicable to an Indo-Pacific congener, P. lobata, and therefore could potentially be used to diagnose acute heat-light stress on coral reefs worldwide. PMID:22046408

  3. Protective effect of resveratrol in endotoxemia-induced acute phase response in rats.

    PubMed

    Sebai, Hichem; Ben-Attia, Mossadok; Sani, Mamane; Aouani, Ezzedine; Ghanem-Boughanmi, Néziha

    2009-04-01

    Lipopolysaccharide (LPS), a glycolipid component of the cell wall of gram-negative bacteria can elicit a systemic inflammatory process leading to septic shock and death. Acute phase response is characterized by fever, leucocytosis, thrombocytopenia, altered metabolic responses and redox balance by inducing excessive reactive oxygen species (ROS) generation. Resveratrol (trans-3,5,4' trihydroxystilbene) is a natural polyphenol exhibiting antioxidant and anti-inflammatory properties. We investigated the protective effect of resveratrol on endotoxemia-induced acute phase response in rats. When acutely administered by i.p. route, resveratrol (40 mg/kg b.w.) counteracted the effect of a single injection of LPS (4 mg/kg b.w.) which induced fever, a decrease in white blood cells (WBC) and platelets (PLT) counts. When i.p. administered during 7 days at 20 mg/kg per day (subacute treatment), resveratrol abrogated LPS-induced erythrocytes lipoperoxidation and catalase (CAT) activity depression to control levels. In the plasma compartment, LPS increased malondialdehyde (MDA) via nitric monoxide (NO) elevation and decreased iron level. All these deleterious LPS effects were reversed by a subacute resveratrol pre-treatment via a NO independent way. Resveratrol exhibited potent protective effect on LPS-induced acute phase response in rats.

  4. ACUTE ETHANOL DISRUPTS PHOTIC AND SEROTONERGIC CIRCADIAN CLOCK PHASE-RESETTING IN THE MOUSE

    PubMed Central

    Brager, Allison J.; Ruby, Christina L.; Prosser, Rebecca A.; Glass, J. David

    2011-01-01

    Background Alcohol abuse is associated with impaired circadian rhythms and sleep. Ethanol administration disrupts circadian clock phase-resetting, suggesting a mode for the disruptive effect of alcohol abuse on the circadian timing system. In this study, we extend previous work in C57BL/6J mice to: 1) characterize the SCN pharmacokinetics of acute systemic ethanol administration; 2) explore the effects of acute ethanol on photic and non-photic phase-resetting; and 2) determine if the SCN is a direct target for photic effects. Methods First, microdialysis was used to characterize the pharmacokinetics of acute i.p. injections of 3 doses of ethanol (0.5, 1.0 and 2.0 g/kg) in the mouse suprachiasmatic (SCN) circadian clock. Second, the effects of acute i.p. ethanol administration on photic phase-delays and serotonergic ([+]8-OH-DPAT-induced) phase-advances of the circadian activity rhythm were assessed. Third, the effects of reverse-microdialysis ethanol perfusion of the SCN on photic phase-resetting were characterized. Results Peak ethanol levels from the 3 doses of ethanol in the SCN occurred within 20–40 min post-injection with half-lives for clearance ranging from 0.6–1.8 hr. Systemic ethanol treatment dose-dependently attenuated photic and serotonergic phase-resetting. This treatment also did not affect basal SCN neuronal activity as assessed by Fos expression. Intra-SCN perfusion with ethanol markedly reduced photic phase-delays. Conclusions These results confirm that acute ethanol attenuates photic phase-delay shifts and serotonergic phase-advance shifts in the mouse. This dual effect could disrupt photic and non-photic entrainment mechanisms governing circadian clock timing. It is also significant that the SCN clock is a direct target for disruptive effects of ethanol on photic shifting. Such actions by ethanol could underlie the disruptive effects of alcohol abuse on behavioral, physiological, and endocrine rhythms associated with alcoholism. PMID:21463340

  5. Influence of hypertension, obesity and nicotine abuse on quantitative and qualitative changes in acute-phase proteins in patients with essential hypertension

    PubMed Central

    Cymerys, Maciej; Bogdański, Paweł; Pupek-Musialik, Danuta; Jabłecka, Anna; Łącki, Jan; Korczowska, Izabela; Dytfeld, Joanna

    2012-01-01

    Summary Background Hypertension is a powerful risk factor for cardiovascular disease and frequently occurs in conjunction with obesity. Accumulative evidence suggests a link between inflammation and hypertension. The aim of study was to evaluate whether blood pressure, obesity and smoking may influence acute-phase response. Material/Methods Ninety-two patients with essential hypertension and 75 healthy volunteers as a control group were studied. In all subjects assessment of hsCRP, α1-acid glycoprotein (AGP), α1-antichymotrypsin, transferrin, α1-antitrypsin, and C3 and C4 complement were performed. Evaluation of glycosylation profile and reactivity coefficient (RC) for AGP was done by means of affinity immunoelectrophoresis with concanavalin A as a ligand. Results When compared to the controls, hypertensive subjects presented significantly higher hsCRP concentrations and lower transferrin level. Hypertensive patients had elevated AGP-AC. The intensification of the inflammatory reaction was greater in the subgroup of hypertensive patients smoking cigarettes. In obese hypertensives, elevated serum C3 complement level was found. Conclusions We conclude that arterial hypertension may evoke the acute-phase response in humans. Markers of acute-phase response are particularly strongly expressed in smokers. Serum C 3 complement, but not other APPs, is elevated in hypertension coexisting with obesity. PMID:22534714

  6. Systemic acute phase proteins response in calves experimentally infected with Eimeria zuernii.

    PubMed

    Lassen, Brian; Bangoura, Berit; Lepik, Triin; Orro, Toomas

    2015-09-15

    Acute phase proteins (APPs) have been demonstrated to be useful in evaluating general health stress and diseases in cattle. Serum amyloid A (SAA) and haptoglobin (Hp) are APPs that are produced during inflammation, and likely play a role in host immunological defence against Eimeria infection and the associated intestinal tissue damage. We investigated the involvement of SAA and HP in an experimental study, including three groups of calves: a control group (group 0, n=11), and two groups infected with either 150,000 or 250,000 Eimeria zuernii oocysts (group 1 (n=11) and group 2 (n=12), respectively). The calves were monitored for 28 days and data was collected on oocyst excretion, faecal score, animal weight, and SAA and Hp serum concentrations. Generalized linear mixed models showed that the clinical symptoms, indicated by an increase in the number of oocysts in the faeces and severe diarrhoea, manifested at patency for group 1 and 2. Serum Hp and SAA levels also increased during this period. Hp appeared to be a more sensitive marker than SAA, and differences between groups 1 and 2 were observed only for Hp. Linear regression models showed a negative association between weight gain and Hp concentrations, calculated as the area under the curve (AUC) during the overall experimental period and the patency period. A similar result was seen for SAA only during the patency period. This result supports the assumption that reduced weight gain due to E. zuernii infection is an immunologically driven process that involves an increase in APPs. A random intercept regression model of oocyst shedding groups showed that calves shedding 1-500 oocysts had reduced concentrations of Hp, indicating that a different immunological reaction occurs during mild shedding of E. zuernii oocysts than during more intensive shedding. A similar model was used to examine associations between faecal scores and Hp concentrations for each group. Group 2 calves with haemorrhagic diarrhoea displayed

  7. Proteogenomics of selective susceptibility to endotoxin using circulating acute phase biomarkers and bioassay development in sheep: a review

    PubMed Central

    2014-01-01

    Scientists have injected endotoxin into animals to investigate and understand various pathologies and novel therapies for several decades. Recent observations have shown that there is selective susceptibility to Escherichia coli lipopolysaccharide (LPS) endotoxin in sheep, despite having similar breed characteristics. The reason behind this difference is unknown, and has prompted studies aiming to explain the variation by proteogenomic characterisation of circulating acute phase biomarkers. It is hypothesised that genetic trait, biochemical, immunological and inflammation marker patterns contribute in defining and predicting mammalian response to LPS. This review discusses the effects of endotoxin and host responses, genetic basis of innate defences, activation of the acute phase response (APR) following experimental LPS challenge, and the current approaches employed in detecting novel biomarkers including acute phase proteins (APP) and micro-ribonucleic acids (miRNAs) in serum or plasma. miRNAs are novel targets for elucidating molecular mechanisms of disease because of their differential expression during pathological, and in healthy states. Changes in miRNA profiles during a disease challenge may be reflected in plasma. Studies show that gel-based two-dimensional electrophoresis (2-DE) coupled with either matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) or liquid chromatography–mass spectrometry (LC-MS/MS) are currently the most used methods for proteome characterisation. Further evidence suggests that proteomic investigations are preferentially shifting from 2-DE to non-gel based LC-MS/MS coupled with data extraction by sequential window acquisition of all theoretical fragment-ion spectra (SWATH) approaches that are able to identify a wider range of proteins. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and most recently proteomic methods have been used to

  8. Size distribution of particle-phase molecular markers during a severe winter pollution episode.

    PubMed

    Kleeman, Michael J; Riddle, Sarah G; Jakober, Chris A

    2008-09-01

    Airborne particulate matter was collected using filter samplers and cascade impactors in six size fractions below 1.8 microm during a severe winter air pollution event at three sites in the Central Valley of California. The smallest size fraction analyzed was 0.056 < Dp <0.1 microm particle diameter, which accounts for the majority of the mass in the ultrafine (PM0.1) size range. Separate samples were collected during the daytime (10 a.m. to 6 p.m. PST) and nighttime (8 p.m. to 8 a.m. PST) to characterize diurnal patterns. Each sample was extracted with organic solvents and analyzed using gas chromatography mass spectrometry for molecular markers that can be used for size-resolved source apportionment calculations. Colocated impactor and filter measurements were highly correlated (R8 > 0.8) for retene, benzo[ghi]flouranthene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[e]pyrene, benzo[a]pyrene, perylene, indeno[1,2,3-cd]pyrene, benzo[ghi]perylene, coronene, MW302 polycyclic aromatic hydrocarbon (PAHs), 17beta(H)-21alpha(H)-30-norhopane, 17alpha(H)-21beta(H)-hopane, alphabetabeta-20R-C29-ethylcholestane, levoglucosan, and cholesterol. Of these compounds, levoglucosan was present in the highest concentration (60-2080 ng m(-3)) followed by cholesterol (6-35 ng m(-3)), PAHs (2-38 ng m(-3)), and hopanes and steranes (0-2 ng m(-3)). Nighttime concentrations were higher than daytime concentrations in all cases. Organic compound size distributions were generally similar to the total carbon size distributions during the nighttime but showed greater variability during the daytime. This may reflect the dominance of fresh emission in the stagnant surface layer during the evening hours and the presence of aged organic aerosol at the surface during the daytime when the atmosphere is better mixed. All of the measured organic compound particle size distributions had a single mode that peaked somewhere between 0.18 and 0.56 microm, but the width of each distribution

  9. Nuclear factor erythroid-2 related factor 2 overexpressed mesenchymal stem cells transplantation, improves renal function, decreases injuries markers and increases repair markers in glycerol-induced Acute kidney injury rats

    PubMed Central

    Zhaleh, Fateme; Amiri, Fatemeh; Mohammadzadeh-Vardin, Mohammad; Bahadori, Marzie; Harati, Mitra Dehghan; Roudkenar, Mehryar Habibi; Saki, Sasan

    2016-01-01

    Objective(s): Recently cell therapy is a promising therapeutic modality for many types of disease including acute kidney injury (AKI). Due to the unique biological properties, mesenchymal stem cells (MSCs) are attractive cells in this regard. This study aims to transplant MSCs equipped with nuclear factor E2-related factor 2 (Nrf2) in rat experimental models of acute kidney and evaluate regeneration potential of injured kidney especially expression of injury and repaired biomarkers. Materials and methods: Nrf2 was overexpressed in bone marrow-derived MSCs by pcDNA.3.1 plasmid. AKI was induced using glycerol in rat models. The regenerative potential of Nrf2-overexpressed MSCs was evaluated in AKI-Induced animal models using biochemical and histological methods after transplantation. Expression of repaired genes, AQP1 and CK-18, as well as injury markers, Kim-1 and Cystatin C, was also assayed in engrafted kidney sections. Results: Our results revealed that transplantation of Nrf2-overexpressed MSCs into AKI-induced rats decreased blood urea nitrogen and creatinine and ameliorated kidney regeneration throughout 14 days. Upregulation of repaired markers and downregulation of injury markers were considerable 14 days after transplantation. Conclusions: Overexpression of Nrf2 in MSCs suggests a new strategy to increase efficiency of MSC-based cell therapy in AKI. PMID:27114803

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

    PubMed Central

    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

  11. Early downregulation of acute phase proteins after doxorubicin exposition in patients with breast cancer.

    PubMed

    Panis, Carolina; Pizzatti, Luciana; Bufalo, Aedra Carla; Herrera, Ana Cristina; Victorino, Vanessa Jacob; Cecchini, Rubens; Abdelhay, Eliana

    2016-03-01

    Chemotherapy remains the first-choice option for adjuvant therapy in breast cancer. Here, we investigated the impact of the first chemotherapic cycle of doxorubicin on the plasmatic-proteomic profiling of women diagnosed with breast cancer (n = 87). Blood samples were obtained from the same patient before and after doxorubicin infusion (1 h, 60 mg/m(2)) and processed for label-free LC-MS proteomic screening. A total of 80 proteins were downregulated after chemotherapy. In silico analysis revealed that the main biological process enrolled was inflammation and canonical pathways involving acute phase proteins. TNF-α, IL-1β, IL-12, TGF-β1, clusterin, and gelsolin were chosen as relevant for further validation. All selected targets presented reduced plasmatic levels after treatment. Our results indicate that doxorubicin downregulated acute phase proteins immediately after its infusion. Since such proteins are cancer promoting, its downregulation could support the effectiveness of doxorubicin along treatment.

  12. Levels of complement components, immunoglobulins and acute phase proteins in plasma during aging in Nigeria.

    PubMed

    Oyeyinka, G O; Salimonu, L S

    1999-01-01

    Plasma samples from Nigerians aged 6-95 years were examined for their content of complement components (C3, C4, factor B-Bf), immuloglobins (IgG, IgA, IgM IgD) and acute phase proteins (transferrin, albumin, C-reactive protein--CRP, alpha-2-macroglobulin). Albumin, was estimated colorimetrically and the other components by the single radial immunodiffusion techniques. No significant age-related changes in mean values of the four immunobulins and the four acute phase proteins could be demonstrated. Also, the mean values for C3 and Bf did not change significantly with age but C4 values rose significantly with increasing age (r -0.232: P < 0.01).

  13. A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD.

    PubMed

    Socié, Gérard; Vigouroux, Stéphane; Yakoub-Agha, Ibrahim; Bay, Jacques-Olivier; Fürst, Sabine; Bilger, Karin; Suarez, Felipe; Michallet, Mauricette; Bron, Dominique; Gard, Philippe; Medeghri, Zakaria; Lehert, Philippe; Lai, Chinglin; Corn, Tim; Vernant, Jean-Paul

    2017-02-02

    Treatment of steroid-resistant acute graft-versus-host disease (GVHD) remains an unmet clinical need. Inolimomab, a monoclonal antibody to CD25, has shown encouraging results in phase 2 trials. This phase 3 randomized, open-label, multicenter trial compared inolimomab vs usual care in adult patients with steroid-refractory acute GVHD. Patients were randomly selected to receive treatment with inolimomab or usual care (the control group was treated with antithymocyte globulin [ATG]). The primary objective was to evaluate overall survival at 1 year without changing baseline allocated therapy. A total of 100 patients were randomly placed: 49 patients in the inolimomab arm and 51 patients in the ATG arm. The primary criteria were reached by 14 patients (28.5%) in the inolimomab and 11 patients (21.5%) in the ATG arms, with a hazard ratio of 0.874 (P = .28). With a minimum follow-up of 1 year, 26 (53%) and 31 (60%) patients died in the inolimomab and ATG arms, respectively. Adverse events were similar in the 2 arms, with fewer viral infections in the inolimomab arm compared with the ATG arm. The primary end point of this randomized phase 3 trial was not achieved. The lack of a statistically significant effect confirms the need for development of more effective treatments for acute GVHD. This trial is registered to https://www.clinicaltrialsregister.eu/ctr-search/search as EUDRACT 2007-005009-24.

  14. The Kynurenine Pathway in the Acute and Chronic Phases of Cerebral Ischemia

    PubMed Central

    Cuartero, María Isabel; de la Parra, Juan; García-Culebras, Alicia; Ballesteros, Iván; Lizasoain, Ignacio; Moro, María Ángeles

    2016-01-01

    Kynurenines are a wide range of catabolites which derive from tryptophan through the “Kynurenine Pathway” (KP). In addition to its peripheral role, increasing evidence shows a role of the KP in the central nervous system (CNS), mediating both physiological and pathological functions. Indeed, an imbalance in this route has been associated with several neurodegenerative disorders such as Alzheimer’s and Huntington’s diseases. Altered KP catabolism has also been described during both acute and chronic phases of stroke; however the contribution of the KP to the pathophysiology of acute ischemic damage and of post-stroke disorders during the chronic phase including depression and vascular dementia, and the exact mechanisms implicated in the regulation of the KP after stroke are not well established yet. A better understanding of the regulation and activity of the KP after stroke could provide new pharmacological tools in both acute and chronic phases of stroke. In this review, we will make an overview of CNS modulation by the KP. We will detail the KP contribution in the ischemic damage, how the unbalance of the KP might trigger an alteration of the cognitive function after stroke as well as potential targets for the development of new drugs. PMID:25248805

  15. The effect of lunar phases on the occurrence of acute cardiovascular diseases

    NASA Astrophysics Data System (ADS)

    Chertoprud, V. E.; Gurfinkel', Yu. I.; Goncharova, E. E.; Ivanov-Kholodnyi, G. S.; Kanonidi, H. D.; Mitrofanova, T. A.; Trubina, M. A.

    2012-12-01

    This paper analyzes the possible impact of lunar phases on the dynamics of acute cardiovascular diseases: acute myocardial infarctions (MIs) and acute brain strokes (BSs) at different levels of heliogeomagnetic activity. The superposed epoch analysis (SEA) has been applied with dates of the new moon and full moon used as reference days. A statistical analysis of a 14-year-long (1992 to 2005) series of everyday medical data from the Central Clinical Hospital no. 1 of Russian Railways (Moscow) and the parameters of heliogeomagnetic activity was carried out. It was found that daily occurrences of MIs and BSs vary with the phase of the moon. These variations are significant; they continue at different levels of heliogeomagnetic activity and are not related to the variations in geomagnetic activity identified by the same method. The effect of lunar phases on MIs and BSs is quite different. New moons and full moons have qualitatively the same effect on MIs; however, there are significant differences in the incidence of BSs during new moons and full moons.

  16. Manifestation of Latent Left Ventricular Outflow Tract Obstruction in the Acute Phase of Takotsubo Cardiomyopathy

    PubMed Central

    Ozaki, Kazuyuki; Okubo, Takeshi; Tanaka, Komei; Hosaka, Yukio; Tsuchida, Keiichi; Takahashi, Kazuyoshi; Oda, Hirotaka; Minamino, Tohru

    2016-01-01

    Objective Left ventricular outflow tract (LVOT) obstruction is a complication in 15-25% of patients with Takotsubo cardiomyopathy and sometimes leads to catastrophic outcomes, such as cardiogenic shock or cardiac rupture. However, the underlying mechanisms have not been clarified. Methods and Results We experienced 22 cases of Takotsubo cardiomyopathy during 3 years, and 4 of these 22 cases were complicated with LVOT obstruction in the acute phase (mean age 79±5 years, 1 man, 21 women). The LVOT pressure gradient in the acute phase was 100±17 mmHg. Transthoracic echocardiogram (TTE) revealed left ventricular hypertrophy (LVH) in one case and sigmoid-shaped septum without LVH in three cases. The complete resolution of the LVOT obstruction was achieved in a few days with normalization of the left ventricular wall motion following administration of beta-blockers. A dobutamine provocation test after normalization of the left ventricular wall motion reproduced the LVOT obstruction in all cases and revealed the presence of latent LVOT obstruction. Conclusion The manifestation of latent LVOT obstruction in the acute phase of Takotsubo cardiomyopathy is one potential reason for the complication of LVOT obstruction with Takotsubo cardiomyopathy. PMID:27904102

  17. Insufficient secretion of atrial natriuretic peptide at acute phase of myocardial infarction.

    PubMed

    Maeda, K; Tsutamoto, T; Wada, A; Mabuchi, N; Hayashi, M; Hisanaga, T; Kamijo, T; Kinoshita, M

    2000-08-01

    To investigate the secretion of the plasma levels of atrial natriuretic peptide (ANP) in patients with acute myocardial infarction (AMI), we evaluated the relationship between plasma levels of ANP and pulmonary capillary wedge pressure (PCWP) in 45 consecutive patients during the acute phase of AMI ( approximately 12 h after the attack) (group 1) and compared data with those obtained after 1 mo (group 2). In both groups 1 and 2, plasma ANP levels significantly correlated with PCWP. The slope of the linear regression line between the PCWP and ANP in group 1 was significantly lower, by about one-third, than that in group 2. In addition, we examined changes in ANP levels and left ventricular end-diastolic pressure (LVEDP) over 180 min after AMI induced by injection of microspheres into the left coronary arteries of three dogs. The LVEDP and ANP levels 30 min after AMI were significantly higher than those before; however, despite the persistent high LVEDP during the 180 min after AMI, ANP levels decreased gradually and significantly to 63% of the peak level at 150 min. These findings suggest that the secretion of ANP during the acute phase of myocardial infarction may be insufficient relative to the chronic phase.

  18. Placental thrombosis in acute phase abortions during experimental Toxoplasma gondii infection in sheep

    PubMed Central

    2014-01-01

    After oral administration of ewes during mid gestation with 2000 freshly prepared sporulated oocysts of T. gondii isolate M4, abortions occurred between days 7 and 11 in 91.6% of pregnant and infected ewes. Afterwards, a further infection was carried out at late gestation in another group of sheep with 500 sporulated oocysts. Abortions happened again between days 9 and 11 post infection (pi) in 58.3% of the infected ewes. Classically, abortions in natural and experimental ovine toxoplasmosis usually occur one month after infection. Few experimental studies have reported the so-called acute phase abortions as early as 7 to 14 days after oral inoculation of oocysts, and pyrexia was proposed to be responsible for abortion, although the underline mechanism was not elucidated. In the present study, all placentas analysed from ewes suffering acute phase abortions showed infarcts and thrombosis in the caruncullar villi of the placentomes and ischemic lesions (periventricular leukomalacia) in the brain of some foetuses. The parasite was identified by PCR in samples from some placentomes of only one sheep, and no antigen was detected by immunohistochemical labelling. These findings suggest that the vascular lesions found in the placenta, and the consequent hypoxic damage to the foetus, could be associated to the occurrence of acute phase abortions. Although the pathogenesis of these lesions remains to be determined, the infectious dose or virulence of the isolate may play a role in their development. PMID:24475786

  19. Modification of hippocampal markers of synaptic plasticity by memantine in animal models of acute and repeated restraint stress: implications for memory and behavior.

    PubMed

    Amin, Shaimaa Nasr; El-Aidi, Ahmed Amro; Ali, Mohamed Mostafa; Attia, Yasser Mahmoud; Rashed, Laila Ahmed

    2015-06-01

    Stress is any condition that impairs the balance of the organism physiologically or psychologically. The response to stress involves several neurohormonal consequences. Glutamate is the primary excitatory neurotransmitter in the central nervous system, and its release is increased by stress that predisposes to excitotoxicity in the brain. Memantine is an uncompetitive N-methyl D-aspartate glutamatergic receptors antagonist and has shown beneficial effect on cognitive function especially in Alzheimer's disease. The aim of the work was to investigate memantine effect on memory and behavior in animal models of acute and repeated restraint stress with the evaluation of serum markers of stress and the expression of hippocampal markers of synaptic plasticity. Forty-two male rats were divided into seven groups (six rats/group): control, acute restraint stress, acute restraint stress with Memantine, repeated restraint stress, repeated restraint stress with Memantine and Memantine groups (two subgroups as positive control). Spatial working memory and behavior were assessed by performance in Y-maze. We evaluated serum cortisol, tumor necrotic factor, interleukin-6 and hippocampal expression of brain-derived neurotrophic factor, synaptophysin and calcium-/calmodulin-dependent protein kinase II. Our results revealed that Memantine improved spatial working memory in repeated stress, decreased serum level of stress markers and modified the hippocampal synaptic plasticity markers in both patterns of stress exposure; in ARS, Memantine upregulated the expression of synaptophysin and brain-derived neurotrophic factor and downregulated the expression of calcium-/calmodulin-dependent protein kinase II, and in repeated restraint stress, it upregulated the expression of synaptophysin and downregulated calcium-/calmodulin-dependent protein kinase II expression.

  20. Impact of acute water and feed deprivation events on growth performance, intestinal characteristics, and serum stress markers in weaned pigs.

    PubMed

    Horn, N; Ruch, F; Miller, G; Ajuwon, K M; Adeola, O

    2014-10-01

    The impact of acute stressors (24-h feed or water deprivation) on growth performance, intestinal characteristics, and serum stress markers in weaned pigs was evaluated. Pigs (6.21 ± 0.29 kg) were allotted in a randomized complete block design to 4 treatments on the basis of BW at the time of weaning. There were 8 mixed-sex pigs in each of 12 pens per treatment. Treatments were arranged as a 2 × 2 factorial and consisted of a feed or water stressor that included a 0- or 24-h deprivation period postweaning, and pigs were subsequently allowed access to feed and water. Growth performance was measured 1, 7, 14, and 28 d postweaning. Serum and intestinal samples were taken 1 and 7 d postweaning. Serum was analyzed for cortisol and corticotrophin-releasing factor, and villus height, crypt depth, and mast cell density were measured in the jejunum and the ileum. Expression of mucin (MUC2), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), claudin 1 (CL-1), occludin (OC), and zonula occludens 1 (ZO-1) genes were measured on d 1 and 7 postweaning in the jejunum and ileum by real-time PCR. There was a decrease (P < 0.05) in ADG with the water stressor 1 d postweaning, although subsequently, there were improvements (P < 0.05) in ADG and feed efficiency. Furthermore, the water stressor reduced ADFI during the last 14 d of the trial and cumulatively (P < 0.05). Seven days postweaning there was an increase (P < 0.05) in jejunal villous height to depth ratio due to the feed stressor and a decrease (P < 0.05) in the ileal villous height to depth ratio due to the water stressor. There was an increase (P < 0.05) in serum cortisol levels due to the water stressor both 1 and 7 d postweaning. Furthermore, there was an increase in serum corticotrophin-releasing factor 1 d but not 7 d postweaning due to the water stressor (P < 0.05). The feed stressor reduced (P < 0.05) TNF-α gene expression, and the water stressor reduced (P < 0.05) OC gene expression in the jejunum 1 d

  1. The Time Course of Markers of Neutrophil Extracellular Traps in Patients Undergoing Revascularisation for Acute Myocardial Infarction or Stable Angina Pectoris

    PubMed Central

    Arnesen, Harald; Opstad, Trine Baur

    2016-01-01

    Background and Aims. Neutrophil extracellular traps (NETs) have been identified in acute myocardial infarction. We assessed the time profile and association with infarct size for NETs markers in ST-elevation myocardial infarction (STEMI) and stable angina pectoris (AP). Methods. In 20 patients with STEMI and 10 with AP undergoing percutaneous coronary intervention (PCI), blood samples were collected before PCI (only AP group) and after 3 and 12 hours, days 1, 3, 5, 7, and 14 for measurement of NETs markers. Results. Double-stranded deoxyribonucleic acid (dsDNA) and nucleosome levels were higher in STEMI than AP until day 3 and 12 hours (p < 0.03, all). DsDNA declined after day 5 in both groups (p < 0.04, all), while nucleosomes declined until day 3 only in the AP group (p < 0.05, all). DsDNA correlated with peak troponin T and creatine kinase MB (CKMB) at day 5 (r = 0.48, p = 0.03, both) and with MRI-measured infarct size at days 5 and 7 (r = 0.61, p = 0.01 and r = 0.52, p = 0.04, resp.), while nucleosomes correlated with infarct size at day 5 (r = 0.58, p = 0.02). Conclusions. High levels of NETs markers were observed in STEMI shortly after revascularisation and were partly associated with infarct size. The decline thereafter in both groups indicates a role for NETs in both acute and chronic atherothrombosis. PMID:28074081

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

    PubMed

    Dumnicka, Paulina; Maduzia, Dawid; Ceranowicz, Piotr; Olszanecki, Rafał; Drożdż, Ryszard; Kuśnierz-Cabala, Beata

    2017-02-08

    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.

  3. Effect of Calendula officinalis Flower Extract on Acute Phase Proteins, Antioxidant Defense Mechanism and Granuloma Formation During Thermal Burns

    PubMed Central

    Chandran, Preethi K.; Kuttan, Ramadasan

    2008-01-01

    Effect of Calendula officinalis flower extract was investigated against experimentally induced thermal burns in rats. Burn injury was made on the shaven back of the rats under anesthesia and the animals were treated orally with different doses of the flower extract (20 mg, 100 mg and 200 mg/kg body weight). The animals treated with the extract showed significant improvement in healing when compared with the control untreated animals. The indicators of the wound healing such as collagen-hydroxyproline and hexosamine contents were significantly increased in the treated group indicating accelerated wound healing in the treated animals. The acute phase proteins—haptoglobin and orosomucoid which were increased due to burn injury were found to be decreased significantly in 200 mg/kg body weight extract treated animals. The antioxidant defense mechanism, which was decreased in the liver during burn injury, was found to be enhanced in treated animals. The lipid peroxidation was significantly lowered in the treated group when compared to control animals. Tissue damage marker enzymes- alkaline phosphatase, alanine and aspartate transaminases were significantly lowered in the treated groups in a dose dependant manner. The histopathological analyses of skin tissue also give the evidence of the increased healing potential of the extract after burn injury. PMID:18818737

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

    PubMed Central

    Dumnicka, Paulina; Maduzia, Dawid; Ceranowicz, Piotr; Olszanecki, Rafał; Drożdż, Ryszard; Kuśnierz-Cabala, Beata

    2017-01-01

    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. PMID:28208708

  5. Fibrinogen-like protein 1, a hepatocyte derived protein is an acute phase reactant

    SciTech Connect

    Liu Zhilin; Ukomadu, Chinweike

    2008-01-25

    Fibrinogen-like protein 1 (FGL1) is a hepatocyte derived protein that is upregulated in regenerating rodent livers following partial hepatectomy. It has been implicated as a mitogen for liver cell proliferation. In this study, we show that recombinant human IL-6 induces FGL1 expression in Hep G2 cells in a pattern similar to those of acute phase reactants. Following induction of acute inflammation in rats by subcutaneous injection of turpentine oil, serum FGL1 levels are also enhanced. Although, a recent report suggests that FGL1 associates almost exclusively with the fibrin matrix, we report here that approximately 20% of the total plasma FGL1 remains free. The enhancement of FGL1 levels in vitro by IL-6 and its induction after turpentine oil injection suggest that it is an acute phase reactant. Its presence in bound and free forms in the blood also implies biological roles that extend beyond the proposed autocrine effect it has on hepatocytes during regeneration.

  6. Pulmonary function of children with acute leukemia in maintenance phase of chemotherapy☆

    PubMed Central

    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

    2014-01-01

    OBJECTIVE: The aim of this study was to assess the pulmonary function of children with acute leukemia. METHODS: 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(r) in accordance with American Thoracic Society and European Respiratory Society guidelines. Maximal respiratory pressures were measured with an MVD300 digital manometer (Globalmed(r)). Maximal inspiratory pressures and maximal expiratory pressures were measured from residual volume and total lung capacity, respectively. RESULTS: 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. CONCLUSION: 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. PMID:25510995

  7. An accurate two-phase approximate solution to the acute viral infection model

    SciTech Connect

    Perelson, Alan S

    2009-01-01

    During an acute viral infection, virus levels rise, reach a peak and then decline. Data and numerical solutions suggest the growth and decay phases are linear on a log scale. While viral dynamic models are typically nonlinear with analytical solutions difficult to obtain, the exponential nature of the solutions suggests approximations can be found. We derive a two-phase approximate solution to the target cell limited influenza model and illustrate the accuracy using data and previously established parameter values of six patients infected with influenza A. For one patient, the subsequent fall in virus concentration was not consistent with our predictions during the decay phase and an alternate approximation is derived. We find expressions for the rate and length of initial viral growth in terms of the parameters, the extent each parameter is involved in viral peaks, and the single parameter responsible for virus decay. We discuss applications of this analysis in antiviral treatments and investigating host and virus heterogeneities.

  8. [Dynamics of interferon production during different phases of the pathological process in children with acute pneumonia and relapsing bronchitis].

    PubMed

    Koval'chuk, O L

    2001-01-01

    With the purpose of gaining further insight into regularities of changes that take place in indices for the interferon status in children with acute pneumonia and current bronchitis depending on the phase of the pathological process, 112 children were examined in whom the level of serum interferon was measured together with production of alpha- and gamma-interferon by leucocytes of the peripheral blood in vitro. It is shown that in the examined patients with acute pneumonia and relapsing bronchitis in the acute period and during the phase of reparation there are differences in functioning of indices for the system of interferon.

  9. Prognostic implications of cardiac scintigraphic parameters obtained in the early phase of acute myocardial infarction

    SciTech Connect

    Suzuki, A.; Matsushima, H.; Satoh, A.; Hayashi, H.; Sotobata, I.

    1988-06-01

    A cohort of 76 patients with acute myocardial infarction was studied with infarct-avid scan, radionuclide ventriculography, and thallium-201 myocardial perfusion scintigraphy. Infarct area, left ventricular ejection fraction, and defect score were calculated as radionuclide indices of the extent of myocardial infarction. The correlation was studied between these indices and cardiac events (death, congestive heart failure, postinfarction angina, and recurrence of myocardial infarction) in the first postinfarction year. High-risk patients (nonsurvivors and patients who developed heart failure) had a larger infarct area, a lower left ventricular ejection fraction, and a larger defect score than the others. Univariate linear discriminant analysis was done to determine the optimal threshold of these parameters for distinguishing high-risk patients from others. Radionuclide parameters obtained in the early phase of acute myocardial infarction were useful for detecting both patients with grave complications and those with poor late prognosis during a mean follow-up period of 2.6 years.

  10. Phase I Trial of AZD1775 and Belinostat in Treating Patients With Relapsed or Refractory Myeloid Malignancies or Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-02-03

    Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  11. Are the unenhanced and excretory CT phases necessary for the evaluation of acute pyelonephritis?

    PubMed

    Taniguchi, Lincoln S; Torres, Ulysses S; Souza, Saulo M; Torres, Lucas R; D'Ippolito, Giuseppe

    2017-05-01

    Background The most widely accepted computed tomography (CT) protocol for diagnosis of acute pyelonephritis (APN) includes at least a pre- and post-contrast scan, which may expose patients to higher doses of ionizing radiation. Purpose To establish the accuracy, reproducibility, and degree of confidence in CT diagnosis of acute pyelonephritis (APN) and urolithiasis using only images obtained during the nephrographic phase. Material and Methods A retrospective study of 100 consecutive patients (88 women; age range, 19-70 years) with clinical and laboratory suspicion of APN and who underwent triphasic abdominal CT scans (non-contrast, nephrographic, and excretory phases) was performed. Two readers first evaluated independently only the nephrographic phase of scans, and, in a second session, the entire study. The diagnostic reference standard was settled by a third experienced radiologist who reviewed all triphasic scans and clinical data. Results The accuracy of only nephrographic phase for diagnosis of APN and urolithiasis was in the range of 90.3-91.78% and 96.27-99.25%, respectively. There was no significant difference in comparison with the triphasic reading (z: -0.4 - 0.2; P = 0.34-0.83). The average degree of confidence for APN also showed no significant variation for both readers ( P = 0.4 and 0.08). Almost perfect inter-observer agreements for the diagnosis of APN (k = 0.86, P < 0.001) and for urolithiasis (k = 0.84, P < 0.001) were observed when considering only the nephrographic phase. Conclusion CT assessment of APN and urolithiasis can be accurately performed using only the late nephrographic phase, with consequent dose reduction.

  12. Restoration of energy level in the early phase of acute pediatric pancreatitis

    PubMed Central

    Mosztbacher, Dóra; Farkas, Nelli; Solymár, Margit; Pár, Gabriella; Bajor, Judit; Szűcs, Ákos; Czimmer, József; Márta, Katalin; Mikó, Alexandra; Rumbus, Zoltán; Varjú, Péter; Hegyi, Péter; Párniczky, Andrea

    2017-01-01

    Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better

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

    SciTech Connect

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

    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.

  14. Solid phase extraction cleanup for non-polar and moderately polar molecular markers of PM 2.5 sources

    NASA Astrophysics Data System (ADS)

    Turlington, John M.; McDow, Stephen R.

    2010-06-01

    A solid phase extraction cleanup step substantially improved analytical efficiency and data quality for measurements of non-polar and moderately polar organic molecular marker concentrations in airborne particulate matter. Rapid gas chromatography column deterioration was evident after very few samples in the absence of a cleanup step, resulting in the need for frequent recalibration. High molecular weight polycyclic aromatic hydrocarbons, were among the species most strongly impacted by the deterioration, exhibiting deviations as high as 30-40% from expected calibration verification standard values after only a few injections. Column deterioration and calibration verification failure were eliminated by introducing a solid phase extraction step prior to analysis and a total of 58 samples were analyzed with no unacceptable deviation of calibration verification standards from target values

  15. Scintigraphic evaluation of digital circulation during the developmental and acute phases of equine laminitis

    SciTech Connect

    Trout, D.R.

    1987-01-01

    Using nuclear isotopic imaging, digital circulation was sequentially evaluated at 24-hour intervals in 11 control horses and in 9 horses affected with acute laminitis, created by administration of a high-starch ration. Following intra-arterial injection of /sup 99m/Tc macroaggregated albumin into the brachiocephalic trunk, a gamma camera and dedicated nuclear medicine computer were used to acquire static images of the right front foot. Dynamic vascular-phase and static interstitial-phase images were also obtained after jugular vein injection of /sup 99m/Tc diethylenetriamine pentaacetic acid. These procedures were performed on standing horses, using either minimal or no tranquilization. The images were quantitatively analyzed for parameters indicative of circulation to the foot as a whole and to specific regions of interest within the foot. There was no evidence of reduced total blood flow to the lamellae during either the developmental or acute phases of laminitis. Although total flow tended to increase throughout the peripheral/external regions of the foot, statistically significant elevations were consistently present only within the lamellae. Changes indicative of decreased total blood flow were noted in the central/internal regions of the foot. These alterations usually occurred coincident with or after the onset of clinical lameness.

  16. Thromboembolism in the Sub-Acute Phase of Spinal Cord Injury: A Systematic Review of the Literature

    PubMed Central

    Belci, Maurizio; Van Middendorp, Joost J; Al Halabi, Ahmed; Meagher, Tom M

    2016-01-01

    To review the evidence of thromboembolism incidence and prophylaxis in the sub-acute phase of spinal cord injury (SCI) 3–6 months post injury. All observational and experimental studies with any length of follow-up and no limitations on language or publication status published up to March 2015 were included. Two review authors independently selected trials for inclusion and extracted data. Outcomes studied were incidence of pulmonary embolism (PE) and deep vein thrombosis (DVT) in the sub-acute phase of SCI. The secondary outcome was type of thromboprophylaxis. Our search identified 4305 references and seven articles that met the inclusion criteria. Five papers reported PE events and three papers reported DVT events in the sub-acute phase of SCI. Studies were heterogeneous in populations, design and outcome reporting, therefore a meta-analysis was not performed. The included studies report a PE incidence of 0.5%–6.0% and DVT incidence of 2.0%–8.0% in the sub-acute phase of SCI. Thromboprophylaxis was poorly reported. Spinal patients continue to have a significant risk of PE and DVT after the acute period of their injury. Clinicians are advised to have a low threshold for suspecting venous thromboembolism in the sub-acute phase of SCI and to continue prophylactic anticoagulation therapy for a longer period of time. PMID:27790330

  17. Cell cycle S phase markers are expressed in cerebral neuron nuclei of cats infected by the Feline Panleukopenia Virus.

    PubMed

    Poncelet, Luc; Garigliany, Mutien; Ando, Kunie; Franssen, Mathieu; Desmecht, Daniel; Brion, Jean-Pierre

    2016-12-16

    The cell cycle-associated neuronal death hypothesis, which has been proposed as a common mechanism for most neurodegenerative diseases, is notably supported by evidencing cell cycle effectors in neurons. However, in naturally occurring nervous system diseases, these markers are not expressed in neuron nuclei but in cytoplasmic compartments. In other respects, the Feline Panleukopenia Virus (FPV) is able to complete its cycle in mature brain neurons in the feline species. As a parvovirus, the FPV is strictly dependent on its host cell reaching the cell cycle S phase to start its multiplication. In this retrospective study on the whole brain of 12 cats with naturally-occurring, FPV-associated cerebellar atrophy, VP2 capsid protein expression was detected by immunostaining not only in some brain neuronal nuclei but also in neuronal cytoplasm in 2 cats, suggesting that viral mRNA translation was still occurring. In these cats, double immunostainings demonstrated the expression of cell cycle S phase markers cyclin A, cdk2 and PCNA in neuronal nuclei. Parvoviruses are able to maintain their host cells in S phase by triggering the DNA damage response. S139 phospho H2A1, a key player in the cell cycle arrest, was detected in some neuronal nuclei, supporting that infected neurons were also blocked into the S phase. PCR studies did not support a co-infection with an adeno or herpes virus. ERK1/2 nuclear accumulation was observed in some neurons suggesting that the ERK signaling pathway might be involved as a mechanism driving these neurons far into the cell cycle.

  18. Glutamate transporter type 3 mediates isoflurane preconditioning-induced acute phase of neuroprotection in mice.

    PubMed

    Li, Liaoliao; Deng, Jiao; Zuo, Zhiyi

    2013-09-01

    A pre-exposure to isoflurane reduces ischemic brain injury in rodents (isoflurane preconditioning). This neuroprotection has acute and delayed phases. Our previous in vitro studies suggest that the acute phase may involve excitatory amino acid transporters (EAATs). We determine whether this protection involves EAAT3, the major neuronal EAAT. Adult male EAAT3 knockout mice and their wild-type littermates were exposed or were not exposed to 1.5% isoflurane for 30 min. Sixty minutes later, they were subjected to a 90- or 60-min middle cerebral arterial occlusion (MCAO). Their neurological outcomes were evaluated 24h after the MCAO. In another experiment, cerebral cortex was harvested for Western blotting at 30 min after animals were exposed to 1.5% isoflurane for 30 min. Here, we showed that isoflurane reduced brain infarct volumes and improved neurological functions of wild-type mice after a 90-min MCAO. However, isoflurane pre-exposure did not change the neurological outcome of EAAT3 knockout mice no matter whether the MCAO was for 90 min or 60 min. Isoflurane increased phospho-Akt, a survival-promoting protein, in the wild-type mice but not in the EAAT3 knockout mice. The isoflurane-induced neuroprotection in the wild-type mice was abolished by LY294004, an Akt activation inhibitor. LY294004 alone did not affect the neurological outcome of the wild-type or EAAT3 knockout mice after focal brain ischemia. These results suggest that the isoflurane preconditioning-induced acute phase of neuroprotection involves EAAT3. The downstream event includes Akt activation.

  19. [Mechanism of thiol-dependence of acute phase proteins and serology of monospecific antisera in vitro].

    PubMed

    Kostiushov, V V; Kostiushova, N V; Pavlovich, S I; Sakhno, Iu P; Tymchyshyn, O L

    2001-01-01

    For the donors and for the patients with inflammatory processes is thiol-dependent the gear of immune responses in vitro an antigen--antibody on dynamics(changes) of change (+/- delta) of the contents SH- and S-S-group reaction mixtures. Thus, is conducted the analysis of interplay of proteins of an acute phase (CRP, orosomucoid and transferin) serums of a blood of the donors and patients with serology by related diagnostic (complementary) monospecific serums (MSS) against CRP (Anti-CRP), against Oroso (Anti-Oroso) i against Transf (Anti-Transf). Is established, that as against the donors, for the patients with inflammatory processes these reacting are accompanied by a phenomenon of a liberation of energy of Ag(+)-sensing non proteins SH-groups and they occur in supernatants of deprotheinized of reaction mixtures. At the same time, both for the donors, and for the patients, these reacting are accompanied modification by changes kept in repair (+/- delta) proteins SH- and S-S-rpy[symbol: see text], in integral reaction mixtures (in which one protein did not deposit). Such data testify, that the inflammatory process, apparently, can be accompanied by such rearrangement of a structurally functional condition of proteins of an acute phase, that under operating MSS in reaction mixtures descends labelised blended disulfide of communications between them and low molecular weight thiols. As a result of it there is a liberation of energy of Ag(+)-sensing non proteins SH-groups. This parameter can be used for an estimation of functional activity of proteins of an acute phase.

  20. Characterizing dynamic interactions between ultradian glucocorticoid rhythmicity and acute stress using the phase response curve.

    PubMed

    Rankin, James; Walker, Jamie J; Windle, Richard; Lightman, Stafford L; Terry, John R

    2012-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a dynamic oscillatory hormone signalling system that regulates the pulsatile secretion of glucocorticoids from the adrenal glands. In addition to regulation of basal levels of glucocorticoids, the HPA axis provides a rapid hormonal response to stress that is vitally important for homeostasis. Recently it has become clear that glucocorticoid pulses encode an important biological signal that regulates receptor signalling both in the central nervous system and in peripheral tissues. It is therefore important to understand how stressful stimuli disrupt the pulsatile dynamics of this system. Using a computational model that incorporates the crucial feed-forward and feedback components of the axis, we provide novel insight into experimental observations that the size of the stress-induced hormonal response is critically dependent on the timing of the stress. Further, we employ the theory of Phase Response Curves to show that an acute stressor acts as a phase-resetting mechanism for the ultradian rhythm of glucocorticoid secretion. Using our model, we demonstrate that the magnitude of an acute stress is a critical factor in determining whether the system resets via a Type 1 or Type 0 mechanism. By fitting our model to our in vivo stress-response data, we show that the glucocorticoid response to an acute noise stress in rats is governed by a Type 0 phase-resetting curve. Our results provide additional evidence for the concept of a deterministic sub-hypothalamic oscillator regulating the ultradian glucocorticoid rhythm, which constitutes a highly responsive peripheral hormone system that interacts dynamically with hypothalamic inputs to regulate the overall hormonal response to stress.

  1. Comparison of Tc-99m labeled liver and liver pate as markers for solid-phase gastric emptying

    SciTech Connect

    Christian, P.E.; Moore, J.G.; Datz, F.L.

    1984-03-01

    A radionuclide marker for studies of solid-phase gastric emptying should have a high labeling efficiency and remain relatively stable during gastric emptying. The availability of materials and the ease of preparation are also considerations in selecting radionuclide markers. The stability of intracellularly labeled chicken liver, surface-labeled chicken liver, and labeled pureed meat (liver pate) incubated with hydrochloric acid solution or gastric juice have been compared. Intracellularly labeled chicken liver and labeled liver pate were also compared in gastric emptying studies in humans. In vitro results demonstrated labeling efficiencies greater than 92% for both intracellularly labeled liver and labeled liver pate. The pate labeled with Tc-99m sulfur colloid was more stable than Tc-99m surface-labeled liver in vitro and its prepartion was easier than with the intracellular labeling technique. Gastric emptying studies on normal subjects demonstrated equal performance of the intracellularly labeled liver and the labeled liver pate. Labeled liver pate is thus an alternative to intracellularly labeled chicken liver in measuring solid-phase gastric emptying.

  2. Cytokine kinetics of Zika virus-infected patients from acute to reconvalescent phase.

    PubMed

    Tappe, Dennis; Pérez-Girón, José Vicente; Zammarchi, Lorenzo; Rissland, Jürgen; Ferreira, Davis F; Jaenisch, Thomas; Gómez-Medina, Sergio; Günther, Stephan; Bartoloni, Alessandro; Muñoz-Fontela, César; Schmidt-Chanasit, Jonas

    2016-06-01

    Zika virus is an emerging mosquito-borne flavivirus currently causing large epidemics in the Pacific Ocean region and Brazil. Clinically, Zika fever resembles dengue fever, but is less severe. Whereas the clinical syndrome and laboratory diagnostic procedures have been described, little attention was paid to the immunology of the disease and its possible use for clinical follow-up of patients. Here, we investigate the role of cytokines in the pathogenesis of Zika fever in travelers returning from Asia, the Pacific, and Brazil. Polyfunctional T cell activation (Th1, Th2, Th9, and Th17 response) was seen during the acute phase characterized by respective cytokine level increases, followed by a decrease in the reconvalescent phase.

  3. Sex differences in acute hormonal and subjective response to naltrexone: The impact of menstrual cycle phase.

    PubMed

    Roche, Daniel J O; King, Andrea C

    2015-02-01

    Women often exhibit larger hormonal and subjective responses to opioid receptor antagonists than men, but the biological mechanisms mediating this effect remain unclear. Among women, fluctuations in estradiol (E2) and progesterone (P4) across the menstrual cycle (MC) affect the endogenous opioid system. Therefore, the goal of the current study was to compare acute naltrexone response between women in the early follicular phase of the MC (low E2 and P4), women in the luteal phase of the MC (high E2 and P4), and men. Seventy healthy controls (n=46 women) participated in two morning sessions in which they received 50mg naltrexone or placebo in a randomized, counterbalanced order. Women were randomized to complete both sessions in either the early follicular (n=23) or luteal phase of the MC. Serum cortisol, salivary cortisol, prolactin, luteinizing hormone (LH), and subjective response were assessed upon arrival to the laboratory and at regular intervals after pill administration. In luteal and early follicular women but not men, naltrexone (vs. placebo) increased serum cortisol and prolactin levels from baseline; however, the naltrexone-induced increases in these hormones were significantly greater in luteal women than early follicular women. Additionally, only luteal women demonstrated an increase from baseline in salivary cortisol levels and the severity of adverse drug effects in response to naltrexone. In sum, the results indicate that luteal phase women are more sensitive to acute hormonal and subjective effects of naltrexone than early follicular women and men. These findings may have important implications for the use of naltrexone in women.

  4. Acute Radiation-Induced Nocturia in Prostate Cancer Patients Is Associated With Pretreatment Symptoms, Radical Prostatectomy, and Genetic Markers in the TGF{beta}1 Gene

    SciTech Connect

    De Langhe, Sofie; De Ruyck, Kim; Ost, Piet; Fonteyne, Valerie; Werbrouck, Joke; De Meerleer, Gert; De Neve, Wilfried; Thierens, Hubert

    2013-02-01

    Purpose: After radiation therapy for prostate cancer, approximately 50% of the patients experience acute genitourinary symptoms, mostly nocturia. This may be highly bothersome with a major impact on the patient's quality of life. In the past, nocturia is seldom reported as a single, physiologically distinct endpoint, and little is known about its etiology. It is assumed that in addition to dose-volume parameters and patient- and therapy-related factors, a genetic component contributes to the development of radiation-induced damage. In this study, we investigated the association among dosimetric, clinical, and TGF{beta}1 polymorphisms and the development of acute radiation-induced nocturia in prostate cancer patients. Methods and Materials: Data were available for 322 prostate cancer patients treated with primary or postoperative intensity modulated radiation therapy (IMRT). Five genetic markers in the TGF{beta}1 gene (-800 G>A, -509 C>T, codon 10 T>C, codon 25 G>C, g.10780 T>G), and a high number of clinical and dosimetric parameters were considered. Toxicity was scored using an symptom scale developed in-house. Results: Radical prostatectomy (P<.001) and the presence of pretreatment nocturia (P<.001) are significantly associated with the occurrence of radiation-induced acute toxicity. The -509 CT/TT (P=.010) and codon 10 TC/CC (P=.005) genotypes are significantly associated with an increased risk for radiation-induced acute nocturia. Conclusions: Radical prostatectomy, the presence of pretreatment nocturia symptoms, and the variant alleles of TGF{beta}1 -509 C>T and codon 10 T>C are identified as factors involved in the development of acute radiation-induced nocturia. These findings may contribute to the research on prediction of late nocturia after IMRT for prostate cancer.

  5. EEG oscillatory phase-dependent markers of corticospinal excitability in the resting brain.

    PubMed

    Berger, Barbara; Minarik, Tamas; Liuzzi, Gianpiero; Hummel, Friedhelm C; Sauseng, Paul

    2014-01-01

    Functional meaning of oscillatory brain activity in various frequency bands in the human electroencephalogram (EEG) is increasingly researched. While most research focuses on event-related changes of brain activity in response to external events there is also increasing interest in internal brain states influencing information processing. Several studies suggest amplitude changes of EEG oscillatory activity selectively influencing cortical excitability, and more recently it was shown that phase of EEG activity (instantaneous phase) conveys additional meaning. Here we review this field with many conflicting findings and further investigate whether corticospinal excitability in the resting brain is dependent on a specific spontaneously occurring brain state reflected by amplitude and instantaneous phase of EEG oscillations. We applied single pulse transcranial magnetic stimulation (TMS) over the left sensorimotor cortex, while simultaneously recording ongoing oscillatory activity with EEG. Results indicate that brain oscillations reflect rapid, spontaneous fluctuations of cortical excitability. Instantaneous phase but not amplitude of oscillations at various frequency bands at stimulation site at the time of TMS-pulse is indicative for brain states associated with different levels of excitability (defined by size of the elicited motor evoked potential). These results are further evidence that ongoing brain oscillations directly influence neural excitability which puts further emphasis on their role in orchestrating neuronal firing in the brain.

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

    PubMed Central

    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. T Helper Subsets, Peripheral Plasticity, and the Acute Phase Protein, α1-Antitrypsin

    PubMed Central

    Baranovski, Boris M.; Freixo-Lima, Gabriella S.; Lewis, Eli C.; Rider, Peleg

    2015-01-01

    The traditional model of T helper differentiation describes the naïve T cell as choosing one of several subsets upon stimulation and an added reciprocal inhibition aimed at maintaining the chosen subset. However, to date, evidence is mounting to support the presence of subset plasticity. This is, presumably, aimed at fine-tuning adaptive immune responses according to local signals. Reprograming of cell phenotype is made possible by changes in activation of master transcription factors, employing epigenetic modifications that preserve a flexible mode, permitting a shift between activation and silencing of genes. The acute phase response represents an example of peripheral changes that are critical in modulating T cell responses. α1-antitrypsin (AAT) belongs to the acute phase responses and has recently surfaced as a tolerogenic agent in the context of adaptive immune responses. Nonetheless, AAT does not inhibit T cell responses, nor does it shutdown inflammation per se; rather, it appears that AAT targets non-T cell immunocytes towards changing the cytokine environment of T cells, thus promoting a regulatory T cell profile. The present review focuses on this intriguing two-way communication between innate and adaptive entities, a crosstalk that holds important implications on potential therapies for a multitude of immune disorders. PMID:26583093

  8. Acute phase protein concentrations after limited distance and long distance endurance rides in horses.

    PubMed

    Cywińska, Anna; Szarska, Ewa; Górecka, Renata; Witkowski, Lucjan; Hecold, Mateusz; Bereznowski, Andrzej; Schollenberger, Antoni; Winnicka, Anna

    2012-12-01

    Acute phase proteins (APP) have been described as useful for assessing health in human and animal patients, as they closely reflect the acute phase reaction (APR). In humans and dogs a reaction analogous to APR has also been described after prolonged or strenuous exercise. The aim of this study was to determine, if similar reactions occur in endurance horses after limited and long distance rides. Seventeen horses that successfully completed various distance competitions were tested. Routine haematological and biochemical tests were performed and the concentrations of serum amyloid A (SAA), C-reactive protein (CRP) and haptoglobin were measured. Typical endurance exercise-induced haematological and biochemical changes were observed in all horses, regardless the distance. After long distance rides, the level of SAA markedly increased, but CRP and haptoglobin concentrations remained unchanged. After limited distance rides no changes in the levels of APPs were noted. Exercise-induced APR in horses occurred only after prolonged, strenuous exertion, and differed from APR in inflammation in that only SAA concentration was increased.

  9. Relationship between production of acute-phase proteins and strength of inflammatory stimulation in rats.

    PubMed

    Kuribayashi, Takashi; Tomizawa, Misaki; Seita, Tetsurou; Tagata, Kazutoshi; Yamamoto, Shizuo

    2011-07-01

    The relationship between intensity of inflammatory stimulation and production of α(2)-macroglobulin (α2M) and α(1)-acid glycoprotein (AAG) in rats was investigated. Sprague-Dawley rats were injected with turpentine oil at doses of 0.05, 0.2 or 0.4 mL/rat. Serum levels of α2M, interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) were measured by enzyme-linked immunosorbent assay, and AAG was measured by single radial immunodiffusion. Peak serum levels of α2M and AAG in rats injected at 0.05 mL/rat were significantly lower than those at 0.2 or 0.4 mL/rat. However, no significant differences were observed for peak serum levels of these acute-phase proteins between 0.2 and 0.4 mL/rat. Furthermore, peak serum levels of IL-6 and CINC-1 in rats injected at 0.05 mL/rat were significantly lower than those at 0.2 or 0.4 mL/rat. Thus, the production of these acute-phase proteins has upper limits, even under increased strength of inflammatory stimulation in rats injected with turpentine oil.

  10. Acute-phase responses vary with pathogen identity in house sparrows (Passer domesticus).

    PubMed

    Coon, Courtney A C; Warne, Robin W; Martin, Lynn B

    2011-06-01

    Pathogens may induce different immune responses in hosts contingent on pathogen characteristics, host characteristics, or interactions between the two. We investigated whether the broadly effective acute-phase response (APR), a whole body immune response that occurs in response to constitutive immune receptor activation and includes fever, secretion of immune peptides, and sickness behaviors such as anorexia and lethargy, varies with pathogen identity in the house sparrow (Passer domesticus). Birds were challenged with a subcutaneous injection of either a glucan at 0.7 mg/kg (to simulate fungal infection), a synthetic double-stranded RNA at 25 mg/kg (to simulate viral infection), or LPS at 1 mg/kg (to simulate a gram-negative bacterial infection), and then body mass, core body temperature changes, sickness behaviors, and secretion of an acute-phase protein, haptoglobin, were compared. Despite using what are moderate-to-high pyrogen doses for other vertebrates, only house sparrows challenged with LPS showed measurable APRs. Febrile, behavioral, and physiological responses to fungal and viral mimetics had minimal effects.

  11. The acute phase response of cod (Gadus morhua L.): expression of immune response genes.

    PubMed

    Audunsdottir, Sigridur S; Magnadottir, Bergljot; Gisladottir, Berglind; Jonsson, Zophonias O; Bragason, Birkir Th

    2012-02-01

    An acute phase response (APR) was experimentally induced in Atlantic cod (Gadus morhua L.) by intramuscular injection of turpentine oil. The change in the expression of immune related genes was monitored in the anterior kidney and the spleen over a period of 7 days. The genes examined were two types of pentraxins, apolipoprotein A1 (ApoA-I), the complement component C3, interleukin-1β (IL-1β), transferrin, cathelicidin, and hepcidin. All genes were constitutively expressed in both organs and their expression amplified by the turpentine injection. A pattern of response was observed both with respect to the organ preference and to the timing of a maximum response. The increased gene expression of the pentraxins, ApoA-I and C3 was restricted to the anterior kidney, the gene expression of IL-1β, cathelicidin, and transferrin increased in both organs, while hepcidin gene expression was only significantly increased in the spleen. The pentraxins and ApoA-I appear to be early mediators of APR in cod, possibly stimulating C3 and IL-1β response, while the antimicrobial peptides may play a minor role. The increase in transferrin gene expression in both organs, and apparent indifference to cortisol release associated with the turpentine injection, suggests that this could be a typical acute phase protein in cod.

  12. Neurohormonal activation in ischemic stroke: effects of acute phase disturbances on long-term mortality.

    PubMed

    Anne, Mäkikallio; Juha, Korpelainen; Timo, Mäkikallio; Mikko, Tulppo; Olli, Vuolteenaho; Kyösti, Sotaniemi; Heikki, Huikuri; Vilho, Myllylä

    2007-08-01

    A stress response consisting of elevated levels of cortisol and catecholamines is common after acute stroke. The plasma levels of natriuretic peptides are known to be elevated after ischemic stroke, but the relations of these neurohormonal systems in the acute phase of stroke and their impact on long-term prognosis have not been studied previously. A series of 51 consecutive patients (mean age 68+/-11 years) with an ischemic first-ever stroke underwent a comprehensive clinical investigation, scoring of their neurologic deficit by Scandinavian Stroke Scale (SSS), Barthel Index (BI) and Modified Ranking Scale (MRS) as well as measurements of plasma cortisol, norepinephrine, epinephrine, ACTH and atrial (N-ANP) and brain (N-BNP) natriuretic peptides on the 2nd and 7th days after ischemic stroke. The patients were followed up for 44+/-21 months. Higher levels of cortisol, ACTH and natriuretic peptides were observed in the stroke patients who died (n=22) during the follow-up than in the stroke survivors. Cortisol levels associated significantly with the 2nd and 7th day N-ANP and N-BNP levels, catecholamine levels (r= 0.55 - 0.94, p<0.01 for all) and measures of neurologic deficit (r= 0.36 - -0.44, p<0.05). High acute phase cortisol levels assessed either in the morning (RR=5.4, p<0.05) or in the evening (RR=5.8, p<0.05) predicted long-term mortality after stroke in multivariate analysis. Activation of the hypothalamus-pituitary-adrenal axis in ischemic stroke is associated with elevated levels of natriuretic peptides. High cortisol and natriuretic peptide values predict long-term mortality after ischemic stroke, suggesting that this profound neurohumoral disturbance is prognostically unfavourable.

  13. Acute-phase proteins in relation to neuropsychiatric symptoms and use of psychotropic medication in Huntington's disease.

    PubMed

    Bouwens, J A; Hubers, A A M; van Duijn, E; Cobbaert, C M; Roos, R A C; van der Mast, R C; Giltay, E J

    2014-08-01

    Activation of the innate immune system has been postulated in the pathogenesis of Huntington's disease (HD). We studied serum concentrations of C-reactive protein (CRP) and low albumin as positive and negative acute-phase proteins in HD. Multivariate linear and logistic regression was used to study the association between acute-phase protein levels in relation to clinical, neuropsychiatric, cognitive, and psychotropic use characteristics in a cohort consisting of 122 HD mutation carriers and 42 controls at first biomarker measurement, and 85 HD mutation carriers and 32 controls at second biomarker measurement. Significant associations were found between acute-phase protein levels and Total Functioning Capacity (TFC) score, severity of apathy, cognitive impairment, and the use of antipsychotics. Interestingly, all significant results with neuropsychiatric symptoms disappeared after additional adjusting for antipsychotic use. High sensitivity CRP levels were highest and albumin levels were lowest in mutation carriers who continuously used antipsychotics during follow-up versus those that had never used antipsychotics (mean difference for CRP 1.4 SE mg/L; P=0.04; mean difference for albumin 3 SE g/L; P<0.001). The associations found between acute-phase proteins and TFC score, apathy, and cognitive impairment could mainly be attributed to the use of antipsychotics. This study provides evidence that HD mutation carriers who use antipsychotics are prone to develop an acute-phase response.

  14. Iodothyronine-phospholipid interactions in the lipid gel phase probed by Raman spectral markers

    NASA Astrophysics Data System (ADS)

    Petruk, Ariel A.; Sosa Morales, Marcelo C.; Álvarez, Rosa M. S.

    2013-08-01

    A better understanding of the structural effects induced by thyroid hormones in model membranes is attained by Raman spectroscopy. The interactions of T3 and T4 with multilamellar vesicles of dipalmytoylphosphatidylcholine (DPPC) in the gel phase are characterized by analyzing the spectral behavior of the C-H and C-C stretching vibrations of the acyl chains. The spectra evidence an increase in the relative number of gauche conformation, which indicates the hormones are able to penetrate into the hydrophobic region of the bilayer and partially alter the lipid structure. In addition, the density packing of the acyl chains appears increased and the rotational mobility of the terminal methylene groups is slightly reduced in the iodothyronine/DPPC mixtures. These effects are interpreted in terms of the transition to an interdigitated phase due to the hormone incorporation to the membrane. The polar heads of the lipids also interact with the hormone, as evidenced by the PO2- symmetric stretching band.

  15. Early changes in oxidative stress markers in a rat model of acute stress: effect of l-carnitine on the striatum.

    PubMed

    Méndez-Cuesta, Luis A; Márquez-Valadez, Berenice; Pérez-De la Cruz, Verónica; Maldonado, Perla D; Santana, Ricardo A; Escobar-Briones, Carolina; Galván-Arzate, Sonia; Carrillo-Mora, Paul; Santamaría, Abel

    2011-08-01

    This work focuses on the effect of acute stress on different markers of oxidative stress and mitochondrial dysfunction in the rat striatum. In addition, the effect of a single dose of l-carnitine (l-CAR, 300 mg/kg, i.p.) was evaluated in these animals. Immobilization (restraint) stress was induced to rats for 24 hr. The levels of lipid peroxidation (LP) and mitochondrial function (MF), as well as the superoxide dismutase (SOD) activity and content and reduced glutathione (GSH) levels, were all measured in striatal samples of animals subjected to stress. Our results indicate that acute stress is able to increase the striatal LP and reduced the levels of MF, while significantly lowered the manganese superoxide dismutase (Mn-SOD) activity. No changes were observed in the total striatal content of SOD, nor in GSH levels, but serum corticosterone content was increased by stress. l-CAR exhibited partial protective effects on the immobilized group, reducing the striatal LP and recovering the striatal MF and Mn-SOD activity. Our results suggest that acute restraint stress brings an accurate model for early pro-oxidant responses that can be targeted by broad-spectrum antioxidants like l-CAR.

  16. Ischemia-Modified Albumin as a Marker of Acute Coronary Syndrome: The Case for Revising the Concept of "N-Terminal Modification" to "Fatty Acid Occupation" of Albumin.

    PubMed

    Oran, Ismail; Oran, Bulent

    2017-01-01

    Ischemia-modified albumin (IMA) is assumed "N-terminal modified" albumin which is generated immediately following myocardial ischemia. The diagnosis of IMA is based on reduced cobalt binding affinity to albumin which is attributed mainly to incapability of cobalt to bind at albumin's modified N-terminus. Although the albumin cobalt binding test was accepted as a potentially powerful marker for discriminating acute coronary syndrome from nonischemic chest pain, its usefulness has been brought into question in recent years. Patients with acutely ischemic myocardium exhibit a rapid increase in serum levels of fatty acids (FAs). Almost all released FAs are strongly bound to albumin which create conformational changes in the protein with resultant reduced cobalt binding affinity. There is a clear metabolic and temporal relationship between IMA measured via albumin cobalt binding testing and serum levels of FAs. In line with what has been suggested recently in the literature, we conclude that a shift from the concept of "N-terminal modified" to "FA-occupied" albumin is required, as this better describes IMA in patients with acute coronary syndrome. We also offer "oxidation modified albumin, OMA," which is conceptually different from the "FA-occupied" IMA, to describe modification of albumin in chronic disease associated with increased oxidative stress.

  17. Non-separative headspace solid phase microextraction-mass spectrometry profile as a marker to monitor coffee roasting degree.

    PubMed

    Liberto, Erica; Ruosi, Manuela R; Cordero, Chiara; Rubiolo, Patrizia; Bicchi, Carlo; Sgorbini, Barbara

    2013-02-27

    This study describes a non-separative headspace solid phase microextraction-mass spectrometry (HS-SPME-MS) approach, in view of its application to online monitoring of a roasting process. The system can quickly provide representative and diagnostic fingerprints of the volatile fraction of samples and, in combination with appropriate chemometric pattern recognition and regression techniques, can successfully be applied to characterize, discriminate, and/or correlate patterns with the roasting process. Eighty coffee samples of different varieties, geographical origins, and blends were analyzed. The experimental HS-SPME-MS results show that the TIC fingerprint can be used to discriminate the degree of roasting; diagnostic ion abundance(s) or ratios were closely correlated with the roasting process; both could successfully be used as markers or analytical decision makers, to monitor roasting processes online, and to define quality and safety of roasted coffee.

  18. Molecularly imprinted polymer of 5-methyluridine for solid-phase extraction of pyrimidine nucleoside cancer markers in urine.

    PubMed

    Jégourel, Damien; Delépée, Raphaël; Breton, Florent; Rolland, Antoine; Vidal, Richard; Agrofoglio, Luigi A

    2008-10-01

    Normal and modified urinary nucleosides represent potential biomarkers for cancer diagnosis. To selectively extract modified nucleosides, we developed a molecularly imprinted polymer (MIP) of 5-methyluridine as selective material for molecularly imprinted solid-phase extraction (MISPE). The MIPs were obtained from vinyl-phenylboronate ester derivative of the template, acrylamide and pentaerythritol triacrylate co-polymer, and were tested in batch and cartridge experiments with aqueous samples. Our results indicated that the imprinted polymer was selective for pyrimidine nucleosides with a K(d) and a B(max) of 46 microM and 18 micromol/g, respectively. Finally, a MISPE of the most common pyrimidine nucleoside cancer markers in urine sample was realized.

  19. A 2-stage phase II design with direct assignment option in stage II for initial marker validation.

    PubMed

    An, Ming-Wen; Mandrekar, Sumithra J; Sargent, Daniel J

    2012-08-15

    Biomarkers are critical to targeted therapies, as they may identify patients more likely to benefit from a treatment. Several prospective designs for biomarker-directed therapy have been previously proposed, differing primarily in the study population, randomization scheme, or both. Recognizing the need for randomization, yet acknowledging the possibility of promising but inconclusive results after a stage I cohort of randomized patients, we propose a 2-stage phase II design on marker-positive patients that allows for direct assignment in a stage II cohort. In stage I, marker-positive patients are equally randomized to receive experimental treatment or control. Stage II has the option to adopt "direct assignment" whereby all patients receive experimental treatment. Through simulation, we studied the power and type I error rate of our design compared with a balanced randomized two-stage design, and conducted sensitivity analyses to study the effect of timing of stage I analysis, population shift effects, and unbalanced randomization. Our proposed design has minimal loss in power (<1.8%) and increased type I error rate (<2.1%) compared with a balanced randomized design. The maximum increase in type I error rate in the presence of a population shift was between 3.1% and 5%, and the loss in power across possible timings of stage I analysis was less than 1.2%. Our proposed design has desirable statistical properties with potential appeal in practice. The direct assignment option, if adopted, provides for an "extended confirmation phase" as an alternative to stopping the trial early for evidence of efficacy in stage I.

  20. Acute effects of calcium carbonate, calcium citrate and potassium citrate on markers of calcium and bone metabolism in young women.

    PubMed

    Karp, Heini J; Ketola, Maarit E; Lamberg-Allardt, Christel J E

    2009-11-01

    Both K and Ca supplementation may have beneficial effects on bone through separate mechanisms. K in the form of citrate or bicarbonate affects bone by neutralising the acid load caused by a high protein intake or a low intake of alkalising foods, i.e. fruits and vegetables. Ca is known to decrease serum parathyroid hormone (S-PTH) concentration and bone resorption. We compared the effects of calcium carbonate, calcium citrate and potassium citrate on markers of Ca and bone metabolism in young women. Twelve healthy women aged 22-30 years were randomised into four controlled 24 h study sessions, each subject serving as her own control. At the beginning of each session, subjects received a single dose of calcium carbonate, calcium citrate, potassium citrate or a placebo in randomised order. The diet during each session was identical, containing 300 mg Ca. Both the calcium carbonate and calcium citrate supplement contained 1000 mg Ca; the potassium citrate supplement contained 2250 mg K. Markers of Ca and bone metabolism were followed. Potassium citrate decreased the bone resorption marker (N-terminal telopeptide of type I collagen) and increased Ca retention relative to the control session. Both Ca supplements decreased S-PTH concentration. Ca supplements also decreased bone resorption relative to the control session, but this was significant only for calcium carbonate. No differences in bone formation marker (bone-specific alkaline phosphatase) were seen among the study sessions. The results suggest that potassium citrate has a positive effect on the resorption marker despite low Ca intake. Both Ca supplements were absorbed well and decreased S-PTH efficiently.

  1. Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain

    EPA Science Inventory

    The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute an...

  2. The Expression and Prognostic Impact of CD95 Death Receptor and CD20, CD34 and CD44 Differentiation Markers in Pediatric Acute Lymphoblastic Leukemia

    PubMed Central

    M. Kamazani, Fatemeh; Bahoush-Mehdiabadi, Gholamreza; Aghaeipour, Mahnaz; Vaeli, Shahram; Amirghofran, Zahra

    2014-01-01

    Objective: This study investigated the expression and prognostic significance of the CD95 death receptor and CD20, a B cell-lineage associated marker, along with CD34 and CD44 non-lineage associated molecules in Iranian children with acute lymphoblastic leukemia (ALL). Methods: We performed immunophenotyping for expressions of the molecules in blood samples from children diagnosed with ALL by using a panel of monoclonal antibodies for flow cytometry analysis. The expression of markers was evaluated in relation to clinical and paraclinical features as well as response to treatment in the patients. Findings : CD95 showed a higher expression in T-ALL compared to B-ALL (P<0.001). Analysis of the clinical and laboratory findings at diagnosis in the group of B-ALL patients revealed an association between CD95 expression with lower white blood cell (WBC) numbers and bone marrow blasts (P<0.05). We detected a positive correlation between the expressions of CD95 and CD44 (r=0.445, P<0.01) in B-ALL patients. There was an association between CD20 expression and several poor prognostic factors that included increased extramedullary involvement (EMI) and decreased platelet numbers (P<0.008). The mean expression of CD34 in B-ALL was higher than T-ALL (P=0.004). At follow-up, complete remission duration (CRD) and survival duration did not significantly differ between patients who were positive or negative for each marker. Conclusion: Association of the studied molecules with several prognostic factors implies the significance of CD95 molecule as favorable and CD20 as unfavorable prognostic markers for childhood ALL. PMID:25755857

  3. Serodiagnostic markers for the prediction of the outcome of intensive phase tuberculosis therapy.

    PubMed

    Baumann, Ralf; Kaempfer, Susanne; Chegou, Novel N; Nene, Nonhlanhla F; Veenstra, Hanne; Spallek, Ralf; Bolliger, Chris T; Lukey, Pauline T; van Helden, Paul D; Singh, Mahavir; Walzl, Gerhard

    2013-03-01

    Treatment failure and relapse may affect many tuberculosis (TB) patients who undergo standard anti-TB therapy. Several independent studies suggested unsuccessful sputum culture conversion at month 2 of treatment (slow response) as risk factor for treatment failure and relapse. However, earlier than month 2 identification of patients with a high risk for poor treatment outcome would offer significant clinical trial and individual patient care benefits. The sensitivity and specificity of serological IgG and IgA responses against four recombinant mycobacterial antigens (ABC transporter PstS3, secreted l-alanine dehydrogenase, culture filtrate protein Tpx and 6 kDa early secretory antigenic target esxa (ESAT-6)) were evaluated separately in a blinded fashion in 21 smear-positive pulmonary TB patient sera taken at diagnosis before commencement of directly observed anti-TB treatment short course comprising 13 slow responder and eight fast responder subjects. We observed a general pattern of higher antibody levels in sera of slow responders. Most pronounced were high levels of anti-alanine dehydrogenase IgG, anti-Tpx IgG, anti-ESAT-6 IgG and anti-ESAT-6 IgA antibodies at diagnosis being associated with slow response with 100% specificity each and 46.2, 53.8, 53.8 or 53.8% sensitivity, respectively, when compared to fast response (P = 0.020, 0.021, 0.040 and 0.011, respectively). Discriminant analysis showed that the combined use of anti-Tpx IgG and anti-ESAT-6 IgA antibody titers before treatment predicted slow responders with 90.5% accuracy. These preliminary results suggest that combinations of serodiagnostic markers measured prior to initiation of treatment may be suitable for the prediction of early treatment response. This approach holds promise and requires further evaluation for its utility in the prediction of treatment failure and relapse, the evaluation of new TB therapeutics, as well as in the care of individual patients.

  4. Serum procalcitonin is a marker for prediction of readmission from an intermediate care to an acute care hospital in neurosurgical patients

    PubMed Central

    Lim, Jia Xu; King, Nicolas; Low, Sharon; Ng, Wai Hoe

    2015-01-01

    Background: Readmission of patients to acute hospitals contributes significantly toward inefficient utilization of healthcare resources, with studies quoting up to 90% being preventable. We aim to report and analyze the factors involved in the readmission of neurosurgical patients who had been previously transferred to an intermediate step-down care facility, and explore possible predictive markers for such readmissions. Methods: We conducted a retrospective analysis of all 129 neurosurgical patients who were transferred from out acute tertiary hospital to an intermediate care facility. The cases were segregated into those who were readmitted and those who were not readmitted back to our acute center. The demographic data, clinical features, diagnoses, treatment modalities, pretransfer laboratory findings, and inpatient complications were compared with readmission rate. Results: There were 23 patients (17.8%) who were readmitted to our acute hospital. The most common causes of readmission was infection (n = 12, 52.2%). We found a statistically significant correlation between the higher pretransfer procalcitonin levels with the readmission of our patients (P = 0.037). There was also a significant difference noted between ethnic groups (P = 0.026) and having no complications of disease or treatment (P = 0.008), with readmission. Conclusion: Procalcitonin is a pro-hormone known to correlate with infection and poor neurological status. We have found that its serum values correlate significantly with the readmission rates of neurosurgical patients in our study. We postulate that by ensuring normality in procalcitonin levels prior to transfer to an intermediate care facility, potentially half of neurosurgical readmissions can be prevented. PMID:26430533

  5. Values of using QTc and N-terminal fragment of B-type natriuretic peptide as markers for early detection of acute antipsychotic drugs-induced cardiotoxicity.

    PubMed

    Khalaf, Mohamed A M; Abdelrahman, Tarek M; Abbas, Mohamed F

    2011-03-01

    We aimed at studying the acute cardiotoxicity of the most commonly used antipsychotics in Egypt using QTc interval and NT-proBNP as markers for the early detection of such cases. Eighty-two admitted patients, at El-Minia PCC (period from 1-7-2005 to 30-6-2010), were classified into 3 groups: I: acute thioridazine overdose (n = 28), II: acute pimozide overdose (n = 23), and III: acute clozapine overdose (n = 31). Patients were investigated for NT-proBNP level and QTc on admission (day 0) and after 24 h (day 1). All the studied drugs had the ability to induce cardiotoxicity in the form of hypotension and dysrhythmias. Thioridazine and pimozide had potentially serious cardiotoxic effects than clozapine. NT-proBNP levels were elevated significantly in all groups on days 0 and 1 when compared with the reference value and a significant decrease in the same parameter on day 1 when compared with that of day 0 within the same group. QTc showed a significant prolongation in all studied groups on days 0 and 1, and there was a significant shortening of QTc on day 1 when compared with that of day 0 within the same group. A significant positive correlation of NT-proBNP level elevation with QTc prolongation was reported in all groups on days 0 and 1. Serious dysrhythmias were associated with QTc prolongation greater than 500 ms. And it was concluded that NT-proBNP, in adjunction with QTc measurement, may be a valuable and sensitive laboratory biomarker to predict cardiotoxicity of antipsychotic overdose. Larger multicenter studies are still needed to verify this possible relationship.

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

    PubMed Central

    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. PMID:28002439

  7. [Acute-phase proteins in the saliva of workers engaged in processing natural gas and condensate high in hydrogen sulfide].

    PubMed

    Boĭko, V I; Dotsenko, Iu I; Boĭko, O V

    2011-06-01

    The paper considers current methods for assessing the workers' health status. It shows it possible to identify increased quantities of acute-phase serum proteins upon exposure to the negative factors characteristic of the Astrakhan gas processing plant. A wider range of tests for acute-phase tissue and serum proteins is proposed to be included in order to gain a fuller insight into the influence of unfavorable industrial factors on man and to make monitoring that enables the existing health risks and the efficiency of preventive measures to be controlled.

  8. Effective factors on linguistic disorder during acute phase following traumatic brain injury in adults.

    PubMed

    Chabok, Shahrokh Yousefzadeh; Kapourchali, Sara Ramezani; Leili, Ehsan Kazemnezhad; Saberi, Alia; Mohtasham-Amiri, Zahra

    2012-06-01

    Traumatic brain injury (TBI) has been known to be the leading cause of breakdown and long-term disability in people under 45 years of age. This study highlights the effective factors on post-traumatic (PT) linguistic disorder and relations between linguistic and cognitive function after trauma in adults with acute TBI. A cross-sectional design was employed to study 60 post-TBI hospitalized adults aged 18-65 years. Post-traumatic (PT) linguistic disorder and cognitive deficit after TBI were respectively diagnosed using the Persian Aphasia Test (PAT) and Persian version of Mini-Mental State Examination (MMSE) at discharge. Primary post-resuscitation consciousness level was determined using the Glasgow Coma Scale (GCS). Paracilinical data was obtained by CT scan technique. Multiple logistic regression analysis illustrated that brain injury severity was the first powerful significant predictor of PT linguistic disorder after TBI and frontotemporal lesion was the second. It was also revealed that cognitive function score was significantly correlated with score of each language skill except repetition. Subsequences of TBI are more commonly language dysfunctions that demand cognitive flexibility. Moderate, severe and fronto-temporal lesion can increase the risk of processing deficit in linguistic macrostructure production and comprehension. The dissociation risk of cortical and subcortical pathways related to cognitive-linguistic processing due to intracranial lesions can augment possibility of lexical-semantic processing deficit in acute phase which probably contributes to later cognitive-communication disorder.

  9. The cerebrovascular CO2 reactivity during the acute phase of brain injury.

    PubMed

    Cold, G E; Jensen, F T; Malmros, R

    1977-01-01

    Using the intra-arterial 133xenon (133Xe) method, the cerebrovascular response to acute Paco2 reduction was studied in 26 unconscious, brain-injured patients subjected to controlled ventilation. The CO2 reactivity was calculated as delta in CBF/delta Paco2. The perfusion pressure was defined as the difference between mean arterial pressure and mean intraventricular pressure. Although the CO2 reactivities did not differ significantly from that in awake, normocapnic subjects, it was low in the acute phase of injury, especially in those patients with severe outcome in whom the brain-stem reflexes were often affected. An increase of the CO2 reactivity with time was observed, indicating normal response after 1-2 weeks. Chronic hypocapnia in six unconscious patients resulted in sustained CSF pH adaptation. The question whether a delay in CSF pH adapation exerts an influence on the CO2 reactivity, and the influence of cerebral lactacidosis on the CO2 response are discussed.

  10. [Acute phase reaction of different macromolecule vascular grafts healing in rat muscle].

    PubMed

    Wang, Weici; Jin, Bi; Ouyang, Chenxi; Li, Yiqing; Xu, Weilin; Yang, Hongjun; Xu, Haiye

    2010-01-01

    To find out which biomaterial had the best biocompatibility, we compared the acute phase reaction of common biomaterials preparing for vascular grafts with the material of polyurethane modified by silk fibroin (SF-PU(1:1)). After transplanted the materials of dacron, polyterafluoroethylene (e-PTFE), polyurethane (PU), SF-PU(1:1) in rat muscle for one week, we studied the influence of different biomaterials on the histocompatibility by using rat acute toxicity test, test of local reaction in muscle, tissue section staining, WBC and PLT count. As a result, dacron had the worst histocompatibility. The other biomaterials had slight local inflammatory reaction. The WBC and PLT was nearly the same with the blank except dacron. e-PTFE, pure PU and SF-PU(1:1) had the better histocompatibility than traditional dacron. Especially SF-PU(1:1) had the best histocompatibility. Because of the better physical properties and histocompatibility of SF-PU( 1:1), the prospect of preparing small-diameter vascular grafts with SF-PU was cheerful.

  11. Telemedicine in Acute-Phase Injury Management: A Review of Practice and Advancements

    PubMed Central

    Lewis, Erin R.; Thomas, Carlos A.; Mbarika, Victor W.A.

    2012-01-01

    Abstract Objectives: To offer a systematic review of the body of literature in the emerging field of telemedicine in the management of acute-phase injuries. Materials and Methods: We conducted a literature review. Results: Telemedicine has only recently been applied to the specialties of trauma, emergency care, and surgery. The potential benefits of telemedicine include a decrease in travel expenses, enhanced continuity of care, and increased access to specialized consultants in medically underserved and rural areas. Conclusions: There still exist barriers to the use of teletechnologies in medicine that limit their wider adoption. Poor infrastructure, limited equipment availability, and insufficient access to training and education for medical personnel have prevented wider use. PMID:22694296

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Acupuncture as a primary and independent treatment in the acute phases of sudden sensorineural hearing loss

    PubMed Central

    Jin, Yuanyuan; Lu, Ming

    2016-01-01

    Abstract Sudden sensorineural hearing loss (SSHL) is an otological emergency defined as a rapid hearing loss, seriously affects patient's social life. To data, no study has reported the treatment by acupuncture alone in the acute phase. In this report, Acupuncture and Moxibustion therapy of excitation-focus transfer is outlined. The patient was a 26-year-old young woman who had an SSHL coupled with ear fullness. The patient had no past medical history, but she had undergone variable emotions and had a history of excessive noise exposure. The patient refused to receive any medicine especially steroids and hyperbaric oxygen therapy. She just only received acupuncture treatment. Her symptoms and outcome measurements were improved every week and completely recovered after the last week. Even though the article presents a single case and is based on self-reports, there are very clear trends on how patients with SSHL responded to acupuncture treatments. PMID:27368045

  14. Dynamics of cellular immune responses in the acute phase of dengue virus infection.

    PubMed

    Yoshida, Tomoyuki; Omatsu, Tsutomu; Saito, Akatsuki; Katakai, Yuko; Iwasaki, Yuki; Kurosawa, Terue; Hamano, Masataka; Higashino, Atsunori; Nakamura, Shinichiro; Takasaki, Tomohiko; Yasutomi, Yasuhiro; Kurane, Ichiro; Akari, Hirofumi

    2013-06-01

    In this study, we examined the dynamics of cellular immune responses in the acute phase of dengue virus (DENV) infection in a marmoset model. Here, we found that DENV infection in marmosets greatly induced responses of CD4/CD8 central memory T and NKT cells. Interestingly, the strength of the immune response was greater in animals infected with a dengue fever strain than in those infected with a dengue hemorrhagic fever strain of DENV. In contrast, when animals were re-challenged with the same DENV strain used for primary infection, the neutralizing antibody induced appeared to play a critical role in sterilizing inhibition against viral replication, resulting in strong but delayed responses of CD4/CD8 central memory T and NKT cells. The results in this study may help to better understand the dynamics of cellular and humoral immune responses in the control of DENV infection.

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

    PubMed Central

    Dalwadi, Pradip P.; Bhagwat, Nikhil M.; Tayde, Parimal S.; Joshi, Ameya S.; Varthakavi, Premlata K.

    2017-01-01

    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 PMID:28217503

  16. Role of Soluble ST2 as a Prognostic Marker in Patients with Acute Heart Failure and Renal Insufficiency.

    PubMed

    Kim, Min-Seok; Jeong, Tae-Dong; Han, Seung-Bong; Min, Won-Ki; Kim, Jae-Joong

    2015-05-01

    This study sought to assess the relationship between serum concentrations of the soluble ST2 (sST2) and B-type natriuretic peptide (BNP) and investigate the role of sST2 as a prognosticator in patients hospitalized with acute heart failure (HF) and renal insufficiency. sST2 was measured at admission and discharge in 66 patients hospitalized with acute decompensated HF and renal insufficiency (estimated glomerular filtration rate [eGFR] < 90 mL/min/1.73 m(2)) using a high sensitivity immunoassay. BNP was sampled at the same time and compared to sST2. Demographical, biochemical, and echocardiographic data were also obtained during hospitalization.There were positive correlations between sST2 and BNP levels at admission (r = 0.330, P = 0.007) and at discharge (r = 0.320, P = 0.009) in overall patients. However, there was no correlation between them at each timepoint in patients with severe renal insufficiency (eGFR < 30 mL/min/1.73 m(2), n = 17). sST2 level was not changed with the degree of renal function, even though BNP level was much higher in patients with severe renal insufficiency. During 3 month follow-up, 9 (13.6%) died and 16 (24.2%) were readmitted due to HF aggravation.On multivariate analysis, sST2 at discharge was independently associated with death or HF readmission during 3 months after discharge (hazard ratio, 1.038; 95% confidence interval, 1.011-1.066, P = 0.006). In conclusion, sST2 is not affected by renal function compared with BNP in acute HF patients. The measurement of predischarge sST2 can be helpful in predicting short-term outcomes in acute decompensated HF patients with renal insufficiency.

  17. Molecular Diagnosis of Chagas Disease in Colombia: Parasitic Loads and Discrete Typing Units in Patients from Acute and Chronic Phases

    PubMed Central

    Hernández, Carolina; Cucunubá, Zulma; Flórez, Carolina; Olivera, Mario; Valencia, Carlos; Zambrano, Pilar; León, Cielo; Ramírez, Juan David

    2016-01-01

    Background The diagnosis of Chagas disease is complex due to the dynamics of parasitemia in the clinical phases of the disease. The molecular tests have been considered promissory because they detect the parasite in all clinical phases. Trypanosoma cruzi presents significant genetic variability and is classified into six Discrete Typing Units TcI-TcVI (DTUs) with the emergence of foreseen genotypes within TcI as TcIDom and TcI Sylvatic. The objective of this study was to determine the operating characteristics of molecular tests (conventional and Real Time PCR) for the detection of T. cruzi DNA, parasitic loads and DTUs in a large cohort of Colombian patients from acute and chronic phases. Methodology/Principal Findings Samples were obtained from 708 patients in all clinical phases. Standard diagnosis (direct and serological tests) and molecular tests (conventional PCR and quantitative PCR) targeting the nuclear satellite DNA region. The genotyping was performed by PCR using the intergenic region of the mini-exon gene, the 24Sa, 18S and A10 regions. The operating capabilities showed that performance of qPCR was higher compared to cPCR. Likewise, the performance of qPCR was significantly higher in acute phase compared with chronic phase. The median parasitic loads detected were 4.69 and 1.33 parasite equivalents/mL for acute and chronic phases. The main DTU identified was TcI (74.2%). TcIDom genotype was significantly more frequent in chronic phase compared to acute phase (82.1% vs 16.6%). The median parasitic load for TcIDom was significantly higher compared with TcI Sylvatic in chronic phase (2.58 vs.0.75 parasite equivalents/ml). Conclusions/Significance The molecular tests are a precise tool to complement the standard diagnosis of Chagas disease, specifically in acute phase showing high discriminative power. However, it is necessary to improve the sensitivity of molecular tests in chronic phase. The frequency and parasitemia of TcIDom genotype in chronic

  18. New compact-type latex photometric immunoassay system for hemoglobin and three acute inflammation markers: neutrophil count, C-reactive protein, and anti-streptolysin O.

    PubMed

    Fukumori, Tatsuo; Ohta, Hironobu; Okubo, Akio; Hino, Masayuki; Ohta, Kensuke; Yamane, Takahisa; Tatsumi, Noriyuki

    2002-01-01

    A new compact-type latex photometric immunoassay system, SPOTCHEM IM SI-3510 (ARKRAY, Inc., Kyoto, Japan), which assays three kinds of inflammatory markers-neutrophil count (NPC), C-reactive protein (CRP), and anti-streptolysin O (ASO)-was evaluated. Hemoglobin (Hb), which is a good marker for anemia, can also be measured with it. NPC and CRP are measured using antibodies against neutrophilic elastase and CRP, purified streptolysin O was used for ASO determination, and Hb was measured by an azide-methemoglobin method. Whole blood, serum, and plasma specimens can be used as samples with this system. In this study, whole blood treated with dipotassium ethylenediamine tetraacetic acid was used for evaluation. Linearity and reproducibility were good for all of the items studied. Good correlations were observed between the results obtained by this system and those obtained by routine methods. Since NPC exhibited a high correlation with the routine white blood cell (WBC) counts, it was judged to be useful as a substitute for WBC counting. Since this system is small and easy to operate, and evaluation revealed reliable results, it was judged to be practical for small laboratories, and satellite testing in hospitals and physicians' office laboratories for patients suspected to have acute inflammation.

  19. Plasma neutrophil gelatinase-associated lipocalin as a marker for the prediction of worsening renal function in children hospitalized for acute heart failure.

    PubMed

    Elsharawy, Sahar; Raslan, Lila; Morsy, Saed; Hassan, Basheir; Khalifa, Naglaa

    2016-01-01

    Acute heart failure (AHF) is frequently associated with worsening renal function in adult patients. Neutrophil gelatinase-associated lipocalin (NGAL) serves as an early marker for acute renal tubular injury. To assess the role of plasma NGAL in predicting worsening renal function (WRF) in children with AHF, we studied 30 children hospitalized for AHF; children with history of chronic renal disease or on nephrotoxic drugs were excluded. Twenty age- and sex-matched healthy children were included in the study as a control group. Echocardiographic examination was performed on admission. Blood urea nitrogen (BUN), serum creatinine, estimated glomerular filtration rate (eGFR) and plasma NGAL levels were measured on admission and 72 h later. Seventeen (56.6%) patients developed WRF within the three-day follow-up period. At presentation, plasma NGAL level was significantly elevated in children who developed WRF. Admission plasma NGAL level correlated with renal parameters (BUN, creatinine and eGFR) as well as with left ventricular systolic parameters (ejection fraction and fractional shortening). For prediction of WRF, admission plasma, NGAL level>27.5 μg/L had sensitivity and specificity of 90% and 68%, respectively. The area under the receiver-operator curve was higher for NGAL (0.869) than for BUN (0.569) or eGFR (0.684). We conclude that admission plasma NGAL level can predict WRF in children hospitalized for AHF.

  20. DO ACUTE PHASE PROTEINS REFLECT SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    EPA Science Inventory

    Title: DO ACUTE PHASE PROTEINS REFLECT THE SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    M. C. Schladweiler, BS 1, P. S. Gilmour, PhD 2, D. L. Andrews, BS 1, D. L. Costa, ScD 1, A. D. Ledbetter, BS 1, K. E. Pinkerton, PhD 3 and U. P. Kodavanti, ...

  1. The acute phase inflammatory response to maximal exercise testing in children and young adults with sickle cell anaemia.

    PubMed

    Liem, Robert I; Onyejekwe, Kasiemobi; Olszewski, Marie; Nchekwube, Chisalu; Zaldivar, Frank P; Radom-Aizik, Shlomit; Rodeghier, Mark J; Thompson, Alexis A

    2015-12-01

    Although individuals with sickle cell anaemia (SCA) have elevated baseline inflammation and endothelial activation, the acute phase response to maximal exercise has not been evaluated among children with SCA. We measured the acute phase response to maximal exercise testing for soluble vascular cell adhesion molecule (sVCAM) as well as interleukin 6 (IL6), total white blood cell (WBC) count, C-reactive protein (CRP) and D-dimer in a cohort of children with SCA and matched controls at baseline, immediately after, and 30, 60 and 120 min following exercise. Despite higher baseline levels of all biomarkers except CRP, the acute phase response from baseline to immediately after exercise was significantly greater in subjects versus controls for CRP (2·1 vs. 0·2 mg/l, P = 0·02) and D-dimer (160 vs. 10 μg/l, P < 0·01) only. Similar between-group trends were observed over time for all biomarkers, including sVCAM, IL6, total WBC, CRP and D-dimer. Lower fitness, defined by peak oxygen consumption (VO2 ), was independently associated with greater acute phase responses to exercise for sVCAM. Our results suggest maximal exercise may not be associated with any greater escalation of endothelial activation or inflammation in SCA and provide preliminary biomarker evidence for the safety of brief, high-intensity physical exertion in children with SCA.

  2. Prenatal transportation alters the acute phase response (APR) of bull calves exposed to a lipopolysaccharide (LPS) challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine if prenatal transportation influences the acute phase response (APR) to a postnatal Lipopolysaccharide (LPS) challenge. Pregnant Brahman cows (n=96) matched by age and parity were separated into transported (TRANS; n=48; transported for 2 hours on gestational day...

  3. Supplementation of Lactobacillus acidophilus fermentation product can attenuate the acute phase response following a lipopolysaccharide challenge in pigs.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine if feeding a Lactobacillus acidophilus fermentation product to weaned pigs would reduce stress and acute phase responses (APR) following a lipopolysaccharide (LPS) challenge. Pigs (n=30; 6.4±0.1 kilograms body weight) were housed individually in pens with ad libi...

  4. Yeast cell wall supplementation alters the physiological and acute phase responses of crossbred heifers to an endotoxin challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study was conducted to determine the effect of feeding yeast cell wall (YCW) products on the physiological and acute phase responses of crossbred newly-received heifers to an endotoxin challenge. Heifers (n = 24; 219 ± 2.4 kg) were separated into treatment groups receiving a Control diet (n = 8), ...

  5. The effect of yeast cell wall supplementation on the physiological and acute phase responses of crossbred heifers to endotoxin challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study was conducted to determine the effect of feeding yeast cell wall (YCW) products on the physiological and acute phase responses of crossbred newly-received heifers to endotoxin (lipopolysaccharide; LPS) challenge. Heifers (n=24; 218.9+/-2.4 kg) were obtained from commercial sale barns and tra...

  6. OmniGen-AF supplementation modulated the physiological and acute phase responses of Brahman heifers to an endotoxin challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the physiological and acute phase responses (APR) of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183±5 kilograms) from the Texas AgriLife Research Center in Overton...

  7. Dried citrus pulp modulates the physiological and acute phase responses of crossbred heifers to an endotoxin challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effect of feeding dried citrus pulp (CP) pellets on the physiological and acute phase responses (APR) of newly-received crossbred heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Heifers (n=24; 218.3±2.4 kg) were obtained from commercial sale barns and transported...

  8. Transcriptional expression levels of cell stress marker genes in the Pacific oyster Crassostrea gigas exposed to acute thermal stress

    PubMed Central

    Farcy, Émilie; Voiseux, Claire; Lebel, Jean-Marc

    2008-01-01

    During the annual cycle, oysters are exposed to seasonal slow changes in temperature, but during emersion at low tide on sunny summer days, their internal temperature may rise rapidly, resulting in acute heat stress. We experimentally exposed oysters to a 1-h acute thermal stress and investigated the transcriptional expression level of some genes involved in cell stress defence mechanisms, including chaperone proteins (heat shock proteins Hsp70, Hsp72 and Hsp90 (HSP)), regulation of oxidative stress (Cu-Zn superoxide dismutase, metallothionein (MT)), cell detoxification (glutathione S-transferase sigma, cytochrome P450 and multidrug resistance (MDR1)) and regulation of the cell cycle (p53). Gene mRNA levels were quantified by reverse transcription-quantitative polymerase chain reaction and expressed as their ratio to actin mRNA, used as a reference. Of the nine genes studied, HSP, MT and MDR1 mRNA levels increased in response to thermal stress. We compared the responses of oysters exposed to acute heat shock in summer and winter and observed differences in terms of magnitude and kinetics. A larger increase was observed in September, with recovery within 48 h, whereas in March, the increase was smaller and lasted more than 2 days. The results were also compared with data obtained from the natural environment. Though the functional molecule is the protein and information at the mRNA level only has limitations, the potential use of mRNAs coding for cell stress defence proteins as early sensitive biomarkers is discussed. PMID:19002605

  9. Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype

    PubMed Central

    Karan-Djurasevic, Teodora; Marjanovic, Irena; Tosic, Natasa; Mitrovic, Mirjana; Djunic, Irena; Colovic, Natasa; Vidovic, Ana; Suvajdzic-Vukovic, Nada; Tomin, Dragica; Pavlovic, Sonja

    2016-01-01

    Abstract Background Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. Patients and methods In our study samples from 110 adult de novo AML-NK were studied for the presence of IDH1 and IDH2 mutations, their associations with other prognostic markers and disease outcome. We also analyzed the stability of these mutations during the course of the disease in complete remission (CR) and relapse. Results IDH mutations were found in 25 (23%) patients. IDH+ patients tend to have lower CR rate compared to IDH-patients (44% vs 62.2%, p = 0.152), and had slightly lower disease free survival (12 months vs 17 months; p = 0.091). On the other hand, the presence of IDH mutations had significant impact on overall survival (2 vs 7 months; p = 0.039). The stability of IDH mutations were studied sequentially in 19 IDH+ patients. All of them lost the mutation in CR, and the same IDH mutations were detected in relapsed samples. Conclusions Our study shows that the presence of IDH mutations confer an adverse effect in AML-NK patients, which in combination with other molecular markers can lead to an improved risk stratification and better treatment. Also, IDH mutations are very stable during the course of the disease and can be potentially used as markers for minimal residual disease detection. PMID:27904446

  10. Acute exposure to 2G phase shifts the rat circadian timing system

    NASA Technical Reports Server (NTRS)

    Hoban-Higgins, T. M.; Murakami, D. M.; Tandon, T.; Fuller, C. A.

    1995-01-01

    The circadian timing system (CTS) provides internal and external temporal coordination of an animal's physiology and behavior. In mammals, the generation and coordination of these circadian rhythms is controlled by a neural pacemaker, the suprachiasmatic nucleus (SCN), located within the hypothalamus. The pacemaker is synchronized to the 24 hour day by time cures (zeitgebers) such as the light/dark cycle. When an animal is exposed to an environment without time cues, the circadian rhythms maintain internal temporal coordination, but exhibit a 'free-running' condition in which the period length is determined by the internal pacemaker. Maintenance of internal and external temporal coordination are critical for normal physiological and psychological function in human and non-human primates. Exposure to altered gravitational environments has been shown to affect the amplitude, mean, and timing of circadian rhythms in species ranging from unicellular organisms to man. However, it has not been determined whether altered gravitational fields have a direct effect on the neural pacemaker, or affect peripheral parameters. In previous studies, the ability of a stimulus to phase shift circadian rhythms was used to determine whether a stimulus has a direct effect on the neural pacemaker. The present experiment was performed in order to determine whether acute exposure to a hyperdynamic field could phase shift circadian rhythms.

  11. Soluble urokinase plasminogen activator receptor (suPAR) in acute care: a strong marker of disease presence and severity, readmission and mortality. A retrospective cohort study

    PubMed Central

    Rasmussen, Line Jee Hartmann; Ladelund, Steen; Haupt, Thomas Huneck; Ellekilde, Gertrude; Poulsen, Jørgen Hjelm; Iversen, Kasper; Eugen-Olsen, Jesper; Andersen, Ove

    2016-01-01

    Objective Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker associated with presence and progression of disease and with increased risk of mortality. We aimed to evaluate the unspecific biomarker suPAR as a prognostic marker in patients admitted to acute care. Methods This registry-based retrospective cohort study included 4343 consecutively admitted patients from the Acute Medical Unit at a large Danish university hospital. Time to readmission and death were analysed by multiple Cox regression. Results were reported as HRs for 30-day and 90-day follow-up. Results During 30-day follow-up, 782 patients (18.0%) were readmitted and 224 patients (5.2%) died. Comparing 30-day readmission and mortality between patients in the highest and lowest suPAR quartiles yielded HRs of 2.11 (95% CI 1.70 to 2.62) and 4.11 (95% CI 2.46 to 6.85), respectively, when adjusting for age, sex, Charlson score and C reactive protein. Area under the curve for receiver operating characteristics curve analysis of suPAR for 30-day mortality was 0.84 (95% CI 0.81 to 0.86). Furthermore, in the entire cohort, women had slightly higher suPAR compared with men, and suPAR was associated with age, admission time, admission to intensive care unit and Charlson score. Conclusions In this large unselected population of acute medical patients, suPAR is strongly associated with disease severity, readmission and mortality after adjusting for all other risk factors, indicating that suPAR adds information to established prognostic indicators. While patients with low suPAR levels have low risk of readmission and mortality, patients with high suPAR levels have a high risk of adverse events. PMID:27590986

  12. Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women.

    PubMed

    Bristow, Sarah M; Gamble, Greg D; Stewart, Angela; Horne, Lauren; House, Meaghan E; Aati, Opetaia; Mihov, Borislav; Horne, Anne M; Reid, Ian R

    2014-11-28

    Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate-carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate-carbonate dose; however, it raised the concentrations of phosphate and the Ca-phosphate product. The citrate-carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.

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

    NASA Astrophysics Data System (ADS)

    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

  14. Increases in the serum acute phase proteins after ozone exposure are associated with induction of genes in the lung but not liver

    EPA Science Inventory

    Acute Phase Response (APR), a systemic reaction to infection, trauma, and inflammation, is characterized by increases and decreases in plasma levels of positive and negative acute phase proteins (APP), respectively. Although the liver has been shown to contribute to APR in variou...

  15. Mimicking acute and chronic stress exposure in naive beef steers alters the acute phase response (APR) associated with vaccination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine the effect of an acute versus chronic stress model on the APR associated with vaccination in naïve beef steers. Steers (n=32; 209 +/- 8 kg) were blocked by body weight and assigned to 1 of 3 treatments: 1) Chronic stress (CHR), 0.5 mg/kg body weight dexamethasone...

  16. Preventive effect of the microalga Chlamydomonas debaryana on the acute phase of experimental colitis in rats.

    PubMed

    Avila-Román, Javier; Talero, Elena; Alcaide, Antonio; Reyes, Carolina de Los; Zubía, Eva; García-Mauriño, Sofía; Motilva, Virginia

    2014-10-14

    Inflammatory bowel diseases (IBD) are characterised by chronic uncontrolled inflammation of intestinal mucosa. Diet and nutritional factors have emerged as possible interventions for IBD. Microalgae are rich sources of n-3 PUFA and derived oxylipins. Oxylipins are lipid mediators involved in the resolution of many inflammatory disorders. The aim of the present study was to investigate the effects of the oxylipin-containing biomass of the microalga Chlamydomonas debaryana and its major oxylipin constituent, (9Z,11E,13S,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid ((13S)-HOTE), on acute 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. Lyophilised microalgal biomass and (13S)-HOTE were administered by oral route 48, 24 and 1 h before the induction of colitis and 24 h later, and the rats were killed after 48 h. The treatment with the lyophilised microalga and (13S)-HOTE improved body-weight loss and colon shortening, as well as attenuated the extent of colonic damage and increased mucus production. Cellular neutrophil infiltration, with the subsequent increase in myeloperoxidase levels induced by TNBS, were also reduced after the administration of the lyophilised microalga or (13S)-HOTE. The anti-inflammatory effects of these treatments were confirmed by the inhibition of colonic TNF-α production. Moreover, lyophilised microalga or (13S)-HOTE down-regulated cyclo-oxygenase-2 and inducible nitric oxide synthase expression. The present study was the first to show the prophylactic effects of a lyophilised biomass sample of the microalga C. debaryana and the oxylipin (13S)-HOTE on TNBS-induced acute colitis in rats. Our findings suggest that the microalga C. debaryana or derived oxylipins could be used as nutraceuticals in the treatment of the active phase of IBD.

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

    PubMed Central

    Askari, Alireza; Zakeri, Habib; Farjam, Mojtaba; Dehghan, Azizallah; Zendehdel, Kazem

    2016-01-01

    Background 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. Methods 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. Results 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. Discussion 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. Conclusion Execution of FaRMI in the form presented is feasible and it will build up a comprehensive population-based registry for MI in the region. PMID:27907128

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

    PubMed Central

    Palac, Hannah L.; Yogev, Ram; Ernst, Linda M.; Mestan, Karen K.

    2017-01-01

    Background 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. Methods 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. 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. Conclusion 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

  19. Prolonged QT interval at onset of acute myocardial infarction in predicting early phase ventricular tachycardia

    SciTech Connect

    Taylor, G.J.; Crampton, R.S.; Gibson, R.S.; Stebbins, P.T.; Waldman, M.T.; Beller, G.A.

    1981-07-01

    The prospectively assessed time course of changes in ventricular repolarization during acute myocardial infarction (AMI) is reported in 32 patients admitted 2.0 +/- 1.8 (SD) hours after AMI onset. The initial corrected QT interval (QTc) upon hospitalization was longer in the 14 patients developing ventricular tachycardia (VT) within the first 48 hours as compared to QTc in the eight patients with frequent ventricular premature beats (VPBs) and to QTc in the 10 patients with infrequent VPBs. By the fifth day after AMI onset, the QTc shortened significantly only in the VT group, suggesting a greater initial abnormality of repolarization in these patients. All 32 patients had coronary angiography, radionuclide ventriculography, and myocardial perfusion scintigraphy before hospital discharge. Significant discriminating factors related to early phase VT in AMI included initially longer QT and QTc intervals, faster heart rate, higher peak serum levels of creatine kinase, acute anterior infarction, angiographically documented proximal stenosis of the left anterior descending coronary artery, and scintigraphic evidence of hypoperfusion of the interventricular septum. Prior infarction, angina pectoris, hypertension, multivessel coronary artery disease, and depressed left ventricular ejection fraction did not provide discrimination among the three different ventricular arrhythmia AMI groups. Researchers conclude that (1) the QT interval is frequently prolonged early in AMI, (2) the initial transiently prolonged ventricular repolarization facilitates and predicts complex ventricular tachyarrhythmias within the first 48 hours of AMI, (3) jeopardized blood supply to the interventricular septum frequently coexists, and (4) therapeutic enhancement of rapid recovery of the ventricular repolarization process merits investigation for prevention of VT in AMI.

  20. Multivariate analysis of apoptotic markers versus cell cycle phase in living human cancer cells by microfluidic cytometry

    NASA Astrophysics Data System (ADS)

    Akagi, Jin; Skommer, Joanna; Matuszek, Anna; Takeda, Kazuo; Fujimura, Yuu; Khoshmanesh, Khashayar; Kalantar-Zadeh, Kourosh; Mitchell, Arnan; Errington, Rachel; Smith, Paul J.; Darzynkiewicz, Zbigniew; Wlodkowic, Donald

    2013-03-01

    Measurement of apoptotic markers in tumors can be directly correlated with the cell cycle phase using flow cytometry (FCM). The conventional DNA content analysis requires cell permeabilization to stain nuclei with fluorescent probes such as propidium iodide or use of a costly UV-excitation line for Hoechst 33342 probe. The access to FCM is also still limited to centralized core facilities due to its inherent high costs and complex operation. This work describes development and proof-of-concept validation of a portable and user-friendly microfluidic flow cytometer (μFCM) that can perform multivariate real time analysis on live cells using sampling volumes as small as 10 microliters. The μFCM system employs disposable microfluidic cartridges fabricated using injection molding in poly(methylmethacrylate) transparent thermoplastic. Furthermore, the dedicated and miniaturized electronic hardware interface enables up to six parameter detection using a combination of spatially separated solid-state 473 (10 mW) and 640 nm (20 mW) lasers and x-y stage for rapid laser alignment adjustment. We provide new evidence that a simple 2D flow focusing on a chip is sufficient to measure cellular DNA content in live tumor cells using a far-red DNA probe DRAQ5. The feasibility of using the μFCM system for a dose-response profiling of investigational anti-cancer agents on human hematopoietic cancer cells is also demonstrated. The data show that μFCM can provide a viable novel alternative to conventional FCM for multiparameter detection of caspase activation and dissipation of mitochondrial inner membrane potential (ΔΨm) in relation to DNA content (cell cycle phase) in live tumor cells.

  1. The novel marker LTBP2 predicts all-cause and pulmonary death in patients with acute dyspnoea.

    PubMed

    Breidthardt, Tobias; Vanpoucke, Griet; Potocki, Mihael; Mosimann, Tamina; Ziller, Ronny; Thomas, Gregoire; Laroy, Wouter; Moerman, Piet; Socrates, Thenral; Drexler, Beatrice; Mebazaa, Alexandre; Kas, Koen; Mueller, Christian

    2012-11-01

    The risk stratification in patients presenting with acute dyspnoea remains a challenge. We therefore conducted a prospective, observational cohort study enrolling 292 patients presenting to the emergency department with acute dyspnoea. A proteomic approach for antibody-free targeted protein quantification based on high-end MS was used to measure LTBP2 [latent TGF (transforming growth factor)-binding protein 2] levels. Final diagnosis and death during follow-up were adjudicated blinded to LTBP2 levels. AHF (acute heart failure) was the final diagnosis in 54% of patients. In both AHF (P<0.001) and non-AHF (P=0.015) patients, LTBP2 levels at presentation were significantly higher in non-survivors compared with survivors with differences on median levels being 2.2- and 1.5-fold respectively. When assessing the cause of death, LTBP2 levels were significantly higher in patients dying from pulmonary causes (P=0.0005). Overall, LTBP2 powerfully predicted early pulmonary death {AUC (area under the curve), 0.95 [95% CI (confidence interval), 0.91-0.98]}. In ROC (receiver operating characteristic) curve analyses for the prediction of 1-year mortality LTBP2 achieved an AUC of 0.77 (95% CI, 0.71-0.84); comparable with the predictive potential of NT-proBNP [N-terminal pro-B-type natriuruetic peptide; 0.77 (95% CI, 0.72-0.82)]. Importantly, the predictive potential of LTBP2 persisted in patients with AHF as the cause of dypnea (AUC 0.78) and was independent of renal dysfunction (AUC 0.77). In a multivariate Cox regression analysis, LTBP2 was the strongest independent predictor of death [HR (hazard ratio), 3.76 (95% CI, 2.13-6.64); P<0.0001]. In conclusion, plasma levels of LTBP2 present a novel and powerful predictor of all-cause mortality, and particularly pulmonary death. Cause-specific prediction of death would enable targeted prevention, e.g. with pre-emptive antibiotic therapy.

  2. Prognostic relations between inflammatory markers and mortality in diabetic patients with non-ST elevation acute coronary syndrome

    PubMed Central

    Sanchez, P L; Morinigo, J L; Pabon, P; Martin, F; Piedra, I; Palacios, I F; Martin-Luengo, C

    2004-01-01

    Objective: To determine the differences in the inflammatory status between diabetic and non-diabetic patients and to evaluate the usefulness of C reactive protein, fibrinogen, and leucocyte count as predictors of death in diabetic patients with unstable coronary disease. Design: Nested case-control comparisons of the inflammatory status between diabetic and non-diabetic patients. Prospective cohort analysis of C reactive protein concentration, fibrinogen concentration, and leucocyte count as predictors of cardiovascular death in diabetic patients. Setting: Coronary care unit in Spain. Participants: 83 diabetic patients with non-ST elevation acute coronary syndrome and 83 sex and aged matched patients selected from 361 non-diabetic patients with non-ST elevation acute coronary syndrome. Main outcome measures: Plasma concentrations of C reactive protein and fibrinogen, and leucocyte count. Investigators contacted patients to assess clinical events. Results: Concentrations of C reactive protein and fibrinogen, and leucocyte count on admission were higher in diabetic than in non-diabetic patients (7 mg/l v 5 mg/l, p  =  0.020; 3.34 g/l v 2.90 g/l, p  =  0.013; and 8.8 × 109/l v 7.8 × 109/l, p  =  0.040). Among diabetic patients, these values were also higher in those who died during the 22 month follow up (13 mg/l v 6 mg/l, p  =  0.001; 3.95 g/l v 3.05 g/l, p < 0.001; and 11.4 × 109/l v 8.4 × 109/l, p  =  0.005). After adjustment for confounding factors, diabetic patients in the highest tertile of C reactive protein had a hazard ratio for cardiovascular death of 4.51 (95% confidence interval (CI) 1.62 to 12.55). Similar hazard ratios were for fibrinogen 3.74 (95% CI 1.32 to 10.62) and for leucocyte count 3.64 (95% CI 1.37 to 9.68). Conclusions: Inflammation appears more evident in diabetic than in non-diabetic patients with acute coronary syndrome. C reactive protein concentration, fibrinogen concentration, and leucocyte count constitute

  3. [Indices of tissue necrosis markers in acute pyo-destructive diseases of organs of the abdominal cavity].

    PubMed

    Ostrovskiĭ, V K; Makarov, S V; Rodionov, P N; Kochetkov, L N

    2011-01-01

    Investigation of indices of lactate dehydrogenase (LDG) and creatine phosphokinase (CPK) in a group of patients with extensive necrotic alterations in organs of the abdominal cavity and in a group of patients without extensive necroses has shown that in the first group there were higher levels of LDG and CPK. It shows that the LDG and CPK indices may be used as markers of tissue necrosis of the abdominal organs. In addition, in patients who died against the background of growing polyorganic insufficiency the LDG and CPK level by the end of treatment was statistically reliably higher than on admission of the same patients that may be an indicator of growing phenomena of dystrophy and micronecroses in vitals, so the indices of LDG and CPK may show the degree of severity of polyorganic insufficiency and determine its prognosis.

  4. Identification of Coupling and Repulsion Phase DNA Marker Associated With an Allele of a Gene Conferring Host Plant Resistance to Pigeonpea sterility mosaic virus (PPSMV) in Pigeonpea (Cajanus cajan L. Millsp.)

    PubMed Central

    Daspute, Abhijit; Fakrudin, B.

    2015-01-01

    Pigeonpea Sterility Mosaic Disease (PSMD) is an important foliar disease caused by Pigeonpea sterility mosaic virus (PPSMV) which is transmitted by eriophyid mites (Aceria cajani Channabasavanna). In present study, a F2 mapping population comprising 325 individuals was developed by crossing PSMD susceptible genotype (Gullyal white) and PSMD resistant genotype (BSMR 736). We identified a set of 32 out of 300 short decamer random DNA markers that showed polymorphism between Gullyal white and BSMR 736 parents. Among them, eleven DNA markers showed polymorphism including coupling and repulsion phase type of polymorphism across the parents. Bulked Segregant Analysis (BSA), revealed that the DNA marker, IABTPPN7, produced a single coupling phase marker (IABTPPN7414) and a repulsion phase marker (IABTPPN7983) co-segregating with PSMD reaction. Screening of 325 F2 population using IABTPPN7 revealed that the repulsion phase marker, IABTPPN7983, was co-segregating with the PSMD responsive SV1 at a distance of 23.9 cM for Bidar PPSMV isolate. On the other hand, the coupling phase marker IABTPPN7414 did not show any linkage with PSMD resistance. Additionally, single marker analysis both IABTPPN7983 (P<0.0001) and IABTPPN 7414 (P<0.0001) recorded a significant association with the PSMD resistance and explained a phenotypic variance of 31 and 36% respectively in F2 population. The repulsion phase marker, IABTPPN7983, could be of use in Marker-Assisted Selection (MAS) in the PPSMV resistance breeding programmes of pigeonpea. PMID:25774108

  5. High mobility group box protein-1 (HMGB-1) as a new diagnostic marker in patients with acute appendicitis

    PubMed Central

    2011-01-01

    Background The aim of this prospective study was therefore to evaluate the diagnostic value of preoperative serum High Mobility Group Box Protein-1 (HMGB-1) levels in patients with Acute Appendicitis (AA) who show normal white blood cell count (WBC) counts. Method Our study was carried out from October 2010 through November 2010 and included 20 healthy control group participants and 60 patients who presented at the emergency department of Erzurum Training and Research Hospital in Turkey with acute abdominal pain complaints, who were pathologically diagnosed with AA after laparotomy, and who agreed to participate in the study. Results Of the 60 patients who underwent appendectomies, 36 were male and 24 were female, and of the healthy group, 12 were male and 8 female. The age averages of the patients in Groups 1, 2 and 3 were, respectively, 31.3+15.4, 34.0+16.3 and 31.0+13.1 years. The WBC averages of Groups 1, 2 and 3 were, respectively, 7.41+2.02 (x109/L), 15.71+2.85 (x109/L) and 8.51+1.84 (x109/L). The HMGB-1 levels for Groups 1 (healthy persons), 2 (AA patients with high WBC counts ) and 3 (AA patients with normal WBC counts) were, respectively, 21.71 ± 11.36, 37.28+13.37 and 36.5 ± 17.73 ng/ml. The average HMGB-1 level of the patients with AA was 36.92 ± 15.43 ng/ml while the average HMGB-1 value of the healthy group was 21.71 ± 11.36 ng/ml. Conclusion The significantly higher levels of HMGB-1 in AA patients compared to healthy persons infer that HMGB-1 might be useful in the diagnosis of AA. Use of HMGB-1, especially in patients with normal WBC counts, will reduce the number of unnecessary explorations. PMID:21507210

  6. Acute effects of ingesting a commercial thermogenic drink on changes in energy expenditure and markers of lipolysis

    PubMed Central

    Dalbo, Vincent J; Roberts, Michael D; Stout, Jeffrey R; Kerksick, Chad M

    2008-01-01

    Background To determine the acute effects of ingesting a thermogenic drink (Celsius, Delray Beach, FL) (TD) on changes in metabolism and lipolysis. Methods Healthy college-aged male (23.2 ± 4.0 y, 177.2 ± 6.1 cm, 81.7 ± 11.3 kg, 22.8 ± 7.3 % fat; n = 30) and female (23.4 ± 3.1 y, 165.6 ± 8.7 cm, 62.1 ± 9.9 kg, 28.3 ± 7.4 % fat; n = 30) participants were matched according to height and weight to consume 336 ml of the TD or a non-caloric, non-caffeinated placebo (PLA). After a 12 h fast, participants reported for pre-consumption measures of height, weight, heart rate, blood pressure, resting energy expenditure (REE), respiratory exchange ratio (RER), glycerol and free-fatty acid (FFA) concentrations. REE and RER were determined at 60, 120, and 180 min post-consumption. Serum glycerol and FFA concentrations were determined at 30, 60, 120 and 180 min post-consumption. Results When compared to PLA, TD significantly increased REE at 60, 120 and 180 min (p < 0.05). FFA concentrations were significantly greater in TD compared to PLA at 30, 60, 120 and 180 min post-consumption (p < 0.05). No between-group differences were found in RER. Conclusion Acute TD ingestion significantly increased REE, FFA and glycerol appearance. If sustained, these changes may help to promote weight loss and improve body composition; however, these findings are currently unknown as are the general safety and efficacy of prolonged consumption. PMID:18289388

  7. Anterior ST segment depression in acute inferior myocardial infarction as a marker of greater inferior, apical, and posterolateral damage

    SciTech Connect

    Ruddy, T.D.; Yasuda, T.; Gold, H.K.; Leinbach, R.C.; Newell, J.B.; McKusick, K.A.; Boucher, C.A.; Strauss, H.W.

    1986-12-01

    The clinical significance of anterior precordial ST segment depression during acute inferior myocardial infarction was evaluated in 67 consecutive patients early after onset of symptoms with gated blood pool scans, thallium-201 perfusion images, and 12-lead ECGs. Patients with anterior ST depression (n = 33) had depressed mean values for left ventricular ejection fraction (54 +/- 2% (mean +/- S.E.M.) vs 59 +/- 2%; p = 0.02), cardiac index (3.1 +/- 0.2 vs 3.6 +/- 0.2 L/m2; p = 0.03), and ratio of systolic blood pressure to end-systolic volume (2.0 +/- 0.1 vs 2.5 +/- 0.3 mm Hg/ml; p = 0.04) compared to patients with no anterior ST depression (n = 34). Patients with anterior ST depression had (1) lower mean wall motion values for the inferior, apical, and inferior posterolateral segments (p less than 0.05) and (2) greater reductions in thallium-201 uptake in the inferior and posterolateral regions (p less than 0.05). However, anterior and septal (1) wall motion and (2) thallium-201 uptake were similar in patients with and without ST depression. Thus, anterior precordial ST segment depression in patients with acute inferior wall myocardial infarction represents more than a reciprocal electrical phenomenon. It identifies patients with more severe wall motion impairment and greater hypoperfusion of the inferior and adjacent segments. The poorer global left ventricular function in these patients is a result of more extensive inferior infarction and not of remote septal or anterior injury.

  8. Adjusting for the acute phase response is essential to interpret iron status indicators among young Zanzibari children prone to chronic malaria and helminth infections.

    PubMed

    Kung'u, Jacqueline K; Wright, Victoria J; Haji, Hamad J; Ramsan, Mahdi; Goodman, David; Tielsch, James M; Bickle, Quentin D; Raynes, John G; Stoltzfus, Rebecca J

    2009-11-01

    The extent to which the acute phase response (APR) influences iron status indicators in chronic infections is not well documented. We investigated this relationship using reported recent fever and 2 acute phase proteins (APP), C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP). In a sample of 690 children matched on age and helminth infection status at baseline, we measured plasma for AGP, CRP, ferritin, transferrin receptor (TfR), and erythropoietin (EPO) and whole blood for hemoglobin (Hb) concentration, zinc protoporphyrin (ZPP), and malaria parasite density, and we obtained maternal reports of recent fever. We then examined the influence of the APR on each iron status indicator using regression analysis with Hb as the outcome variable. Ferritin was inversely related to Hb in the APR-unadjusted model. Adjusting for the APR using reported recent fever alone was not sufficient to reverse the inverse Hb-ferritin relationship. However, using CRP and/or AGP resulted in the expected positive relationship. The best fit model included reported recent fever, AGP and CRP (R(2) = 0.241; P < 0.001). The best fit Hb-ZPP, Hb-TfR, and Hb-EPO models included reported recent fever and AGP but not CRP (R(2) = 0.253, 0.310, and 0.292, respectively; P < 0.001). ZPP, TfR, and EPO were minimally influenced by the APR, whereas ferritin was immensely affected. Reported recent fever alone cannot be used as a marker for the APR. Either AGP or CRP is useful for adjusting if only 1 APP can be measured. However, AGP best predicted the APR in this population.

  9. Acute-Phase Serum Amyloid A: An Inflammatory Adipokine and Potential Link between Obesity and Its Metabolic Complications

    PubMed Central

    Yang, Rong-Ze; Lee, Mi-Jeong; Hu, Hong; Pollin, Toni I; Ryan, Alice S; Nicklas, Barbara J; Snitker, Soren; Horenstein, Richard B; Hull, Kristen; Goldberg, Nelson H; Goldberg, Andrew P; Shuldiner, Alan R; Fried, Susan K; Gong, Da-Wei

    2006-01-01

    Background Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD). However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood. Methods and Findings Acute-phase serum amyloid A (A-SAA) mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index ( r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively). Serum A-SAA levels decreased significantly after weight loss in obese participants ( p = 0.006), as well as in those treated with rosiglitazone ( p = 0.033). The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA ( r = −0.74; p = 0.034). SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL)-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%. Conclusions A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements in

  10. Effect of Acute Gamma Irradiation on Curcuma alismatifolia Varieties and Detection of DNA Polymorphism through SSR Marker

    PubMed Central

    Taheri, Sima; Abdullah, Thohirah Lee; Ahmad, Zaiton; Abdullah, Nur Ashikin Psyquay

    2014-01-01

    The effects of eight different doses (0, 10, 20, 25, 35, 40, 60, and 100 Gy) of acute gamma irradiation on 44 (three varieties of Curcuma alismatifolia: Chiang Mai Red, Sweet Pink, Kimono Pink, and one Curcuma hybrid (Doi Tung 554) individual plants were investigated. Radiation sensitivity tests revealed that the LD50 values of the varieties were achieved at 21 Gy for Chiang Mai Red, 23 Gy for Sweet Pink, 25 Gy for Kimono Pink, and 28 Gy for Doi Tung 554. From the analysis of variance (ANOVA), significant variations were observed for vegetative traits, flowering development, and rhizome characteristics among the four varieties of Curcuma alismatifolia and dose levels as well as the dose × variety interaction. In irradiated plants, the leaf length, leaf width, inflorescence length, the number of true flowers, the number of pink bracts, number of shoots, plant height, rhizome size, number of storage roots, and number of new rhizomes decreased significantly (P < 0.05) as the radiation dose increased. The cophenetic correlation coefficient (CCC) between genetic dissimilarity matrix estimated from the morphological characters and the UPGMA clustering method was r = 0.93, showing a proof fit. In terms of genetic variation among the acutely irradiated samples, the number of presumed alleles revealed by simple sequence repeats ranged from two to seven alleles with a mean value of 3.1, 4.5, and 5.3 alleles per locus for radiation doses of 0, 10, and 20 Gy, respectively. The average values of the effective number of alleles, Nei's gene diversity, and Shannon's information index were 2.5–3.2, 0.51–0.66, and 0.9–1.3, respectively. The constructed dendrogram grouped the entities into seven clusters. Principal component analysis (PCA) supported the clustering results. Consequently, it was concluded that irradiation with optimum doses of gamma rays efficiently induces mutations in Curcuma alismatifolia varieties. PMID:24719878

  11. Influence of transportation on serum concentrations of acute phase proteins in horse.

    PubMed

    Casella, S; Fazio, F; Giannetto, C; Giudice, E; Piccione, G

    2012-10-01

    The modifications of Haptoglobin (Hp), Serum Amyloid A (SAA), Fibrinogen (Fbg) and White Blood Cells (WBCs) were evaluated in 15 Saddle Italian horses. Ten horses were transported covering a distance of about 320 km within 4 h with an average speed of 80 km/h (experimental group) and five horses were not subject to transportation (control group). Blood was collected via jugular venipuncture before the transportation (T0), immediately after the transportation (T1), 12 (T12), 24 (T24) and 48 (T48)hours after the transportation in experimental group and at the same time point in control group. For each parameter statistical analysis of different groups and sampling time was performed using a two-way analysis of covariance, with the data before the transportation (T0) as the covariate, by the GLM procedure of SAS. For all parameters the interaction (Group × Time) was tested and it was resulted no significant. The application of statistical analysis showed significant differences between the control group and horses subjected to transportation (P<0.01), and the influence of sampling time (P<0.05) on Hp, SAA and WBCs. These modifications appeared to be innovative showing that equine Hp, generally considered as moderate acute phase protein, increases more rapidly than the SAA after transportation-induced stress.

  12. Swimming Exercise in the Acute or Late Phase after Sciatic Nerve Crush Accelerates Nerve Regeneration

    PubMed Central

    Teodori, Rosana Macher; Betini, Joice; de Oliveira, Larissa Salgado; Sobral, Luciane Lobato; Takeda, Sibele Yoko Mattozo; Montebelo, Maria Imaculada de Lima

    2011-01-01

    There is no consensus about the best time to start exercise after peripheral nerve injury. We evaluated the morphological and functional characteristics of the sciatic nerves of rats that began to swim immediately after crush nerve injury (CS1), those that began to swim 14 days after injury (CS14), injured rats not submitted to swimming (C), and uninjured rats submitted to swimming (S). After 30 days the number of axons in CS1 and CS14 was lower than in C (P < 0.01). The diameter of axons and nerve fibers was larger in CS1 (P < 0.01) and CS14 (P < 0.05) than in C, and myelin sheath thickness was lower in all crushed groups (P < 0.05). There was no functional difference between CS1 and CS14 (P > 0.05). Swimming exercise applied during the acute or late phase of nerve injury accelerated nerve regeneration and synaptic elimination after axonotmesis, suggesting that exercise may be initiated immediately after injury. PMID:21876821

  13. NRF2 and the Phase II Response in Acute Stress Resistance Induced by Dietary Restriction

    PubMed Central

    Hine, Christopher M.; Mitchell, James R.

    2013-01-01

    Dietary restriction (DR) as a means to increase longevity is well-established in a number of model organisms from yeast to primates. DR also improves metabolic fitness and increases resistance to acute oxidative, carcinogenic and toxicological stressors - benefits with more immediate potential for clinical translation than increased lifespan. While the detailed mechanism of DR action remains unclear, a conceptual framework involving an adaptive, or hormetic response to the stress of nutrient/energy deprivation has been proposed. A key prediction of the hormesis hypothesis of DR is that beneficial adaptations occur in response to an increase in reactive oxygen/nitrogen species (ROS). These ROS may be derived either from increased mitochondrial respiration or increased xenobiotic metabolism in the case of some DR mimetics. This review will focus on the potential role of the redox-sensing transcription factor NF-E2-related factor 2 (NRF2) and its control of the evolutionarily conserved antioxidant/redox cycling and detoxification systems, collectively known as the Phase II response, in the adaptive response to DR. PMID:23505614

  14. [The measurement of CoQ10 in the acute phase of a myocardial infarct].

    PubMed

    Puletti, M; Trappolini, M; Di Palma, A; Curione, M; Schiavone, R A; Matteoli, S; Borgia, C

    1991-05-01

    The authors have studied the behaviour of ubidecorenone (Co Q10) in the acute phase of myocardial infarction in 24 patients, 19 male and 5 female, mean age 56.8 +/- 3.3. Ubidecorenone level was determined on admittance, after 48 hours and on the 7th and 30th days. A significant decrease was observed from the first to the 3rd day (mean values 0.90 +/- 0.18 microgram/ml vs 0.72 +/- 0.22, p less than 0.01). Thereafter a progressive rise was observed, but at the 30th day mean values were still below the basal ones. No significant differences were observed between patients treated with fibrinolytic agents and those not so treated, nor between those in whom reperfusion was obtained and the others. Nor was there a proven correlation with changes in creatinkinase. The behaviour of ubidecorenone may be associated with increased consumption for metabolic needs and increased destruction in scavenger action, and also to a lesser extent to decreased production due to lower food intake.

  15. Intestinal pathogens, diarrhoea and acute phase proteins in naturally infected dairy calves.

    PubMed

    Seppä-Lassila, Leena; Orro, Toomas; Lassen, Brian; Lasonen, Riikka; Autio, Tiina; Pelkonen, Sinikka; Soveri, Timo

    2015-08-01

    In this study, the association between Eimeria spp. related signs and innate immune response in dairy calves was examined. Calves (n=100) aged 15-60 days were clinically examined and faecal samples, blood samples and deep nasopharyngeal swabs obtained. The samples were analysed for intestinal pathogens, acute phase proteins and WBC count, and respiratory tract pathogens, respectively. Diarrhoea was diagnosed in 32.6% (23.3-43.0%, 95% CI) of calves. An association between the pathogenic Eimeria spp. and diarrhoea was detected by multiple correspondence analysis. Eimeria related signs (diarrhoea, presence of pathogenic species and total oocyst count) were combined resulting a four level variable. Calves with weak signs of eimeriosis had decreased haptoglobin concentrations (p=0.02) and increased fibrinogen concentrations (p=0.048) compared to no signs. Increased haptoglobin and fibrinogen concentrations were associated with respiratory tract infection and umbilical infection. Serum amyloid A and WBC counts showed no association with signs of eimeriosis or clinical diagnoses.

  16. Transport proteins and acute phase reactant proteins in children with sickle cell anemia.

    PubMed Central

    Warrier, R. P.; Kuvibidila, S.; Gordon, L.; Humbert, J.

    1994-01-01

    Transport proteins, acute-phase reactant proteins (APRP), hematology, and anthropometry were studied in 34 sickle cell disease (SCD) children (20 boys, 14 girls) and 27 controls without growth deficits (13 boys, 14 girls) [corrected]. The age range was 1/2 to 16 1/2 years. Weight deficits (< 80%) by Waterlow's classification were observed in 41% of SCD boys and 25% of SCD girls, and height deficits (< 90%) were observed in 25% SCD boys and 25% girls. Mean white blood cell counts were significantly higher (P < .001) and hematocrit and hemoglobin (Hb) lower (P < .005) in SCD children than in controls. Although both groups had similar mean levels of albumin, transferrin, and APRP, SCD children had significantly lower mean levels of retinol-binding protein (RBP) (P < .001) and retinol-prealbumin (P < .001). Retinol-binding protein levels were abnormal in 18 (53%) SCD children and in only 23% controls (chi 2 = 14.06; P < 0.005); transferrin levels were abnormal in 20% of SCD children and in none of the controls. Children with SC and SF Hb phenotype had normal mean levels of RBP, whereas those with S beta thal and SS phenotype had levels below normal. Growth-retarded children by weight and height had reduced mean levels of RBP and prealbumin compared with growth-normal SCD children. The implication of primary protein-energy malnutrition on growth retardation in SCD children is under study. PMID:7512147

  17. Acute-phase protein behavior in dairy cattle herd naturally infected with Trypanosoma vivax.

    PubMed

    Sampaio, Paulo Henrique; Fidelis Junior, Otavio Luiz; Marques, Luiz Carlos; Machado, Rosangela Zacarias; Barnabé, Patrícia de Athayde; André, Marcos Rogério; Balbuena, Tiago Santana; Cadioli, Fabiano Antonio

    2015-07-30

    Trypanosoma vivax is a hemoprotozoon that causes disease in cattle and is difficult to diagnose. The host-parasite relationship in cattle that are infected by T. vivax has only been poorly studied. In the present study, a total of 429 serum proteinograms were produced from naturally infected animals (NIF) and were compared with 50 samples from control animals (C). The total protein, IgA band, complement C3 β chain band, albumin band, antitrypsin band, IgG band, haptoglobin band, complement C3c α chain band and protein HP-20 band presented higher levels in the serum proteinograms of the NIF group. Inter-alpha-trypsin inhibitor heavy chain H4, α2-macroglobulin, complement C6, ceruloplasmin, transferrin band and apolipoprotein A1 band presented lower levels in this group. There was no significant difference (p<0.05) in acid glycoprotein serum concentration between the NIF and C groups. Acute phase proteins may be useful for understanding the host-parasite relationship, since the antitrypsin band was only present in the NIF group. This can be used as an indicator for infection in cattle that are naturally infected by T. vivax.

  18. Determination of ceruloplasmin, some other acute phase proteins, and biochemical parameters in cows with endometritis

    PubMed Central

    Kaya, S.; Merhan, O.; Kacar, C.; Colak, A.; Bozukluhan, K.

    2016-01-01

    Aim: The aim of this study is to determine serum ceruloplasmin levels in cows with endometritis of varying degrees of severity and to establish whether or not there is a correlation between acute phase protein (APP) levels and biochemical parameters. Material and Methods: The study was conducted with 100 Brown Swiss cows (3-8 years of age) on days 28-32 postpartum. Cows were divided into endometritis (mild, moderate, and severe endometriosis) and healthy groups based on ultrasonography, vaginoscopy, and cytological examination. Blood samples were collected from all cows. Levels of haptoglobin (Hp), serum amyloid A (SAA), ceruloplasmin, albumin, and some biochemical parameters were analyzed. Results: Hp, SAA, and ceruloplasmin levels were higher in cows with endometritis than in healthy cows (p=0.001), and the levels of these APPs increased as endometritis became more severe (p=0.001). Some significant correlations were found between APPs and the biochemical parameters that were analyzed. In conclusion, it was determined that ceruloplasmin levels increase significantly in the presence of endometritis and proportionate to the severity of endometritis. A significant correlation was found between ceruloplasmin levels and Hp and SAA levels. Conclusion: It was concluded that ceruloplasmin levels can be used in the diagnosis of endometritis as an alternative to Hp and SAA levels. PMID:27847413

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

    PubMed

    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.

  20. The Acute Effects of Simple Sugar Ingestion on Appetite, Gut-Derived Hormone Response, and Metabolic Markers in Men

    PubMed Central

    Yau, Adora M. W.; McLaughlin, John; Gilmore, William; Maughan, Ronald J.; Evans, Gethin H.

    2017-01-01

    This pilot study aimed to investigate the effect of simple sugar ingestion, in amounts typical of common ingestion, on appetite and the gut-derived hormone response. Seven healthy men ingested water (W) and equicaloric solutions containing 39.6 g glucose monohydrate (G), 36 g fructose (F), 36 g sucrose (S), and 19.8 g glucose monohydrate + 18 g fructose (C), in a randomised order. Serum concentrations of ghrelin, glucose dependent insulinotropic polypeptide (GIP), glucagon like peptide-1 (GLP-1), insulin, lactate, triglycerides, non-esterified fatty acids (NEFA), and d-3 hydroxybutyrate, were measured for 60 min. Appetite was measured using visual analogue scales (VAS). The ingestion of F and S resulted in a lower GIP incremental area under the curve (iAUC) compared to the ingestion of G (p < 0.05). No differences in the iAUC for GLP-1 or ghrelin were present between the trials, nor for insulin between the sugars. No differences in appetite ratings or hepatic metabolism measures were found, except for lactate, which was greater following the ingestion of F, S, and C, when compared to W and G (p < 0.05). The acute ingestion of typical amounts of fructose, in a variety of forms, results in marked differences in circulating GIP and lactate concentration, but no differences in appetite ratings, triglyceride concentration, indicative lipolysis, or NEFA metabolism, when compared to glucose. PMID:28216550

  1. Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

    SciTech Connect

    Marín-Prida, Javier; Riva, Federica; Pentón-Arias, Eduardo

    2013-10-01

    Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24 h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H{sub 2}O{sub 2} and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. - Highlights: • Phycocyanobilin (PCB) prevents H{sub 2}O{sub 2} and glutamate induced PC12 cell viability loss. • Anterior cortex and striatum are highly vulnerable to cerebral hypoperfusion (CH). • PCB modulates 190 genes associated to inflammation in acute CH. • PCB regulates 19 genes mostly related to a detrimental pro-inflammatory environment. • PCB restores redox and immune balances showing promise as potential stroke therapy.

  2. Gene expression changes in the hypothalamus provide evidence for regionally-selective changes in IL-1 and microglial markers after acute stress.

    PubMed

    Blandino, Peter; Barnum, Christopher J; Solomon, Lyvia G; Larish, Yaniv; Lankow, Benjamin S; Deak, Terrence

    2009-10-01

    Recent work from our laboratory and others has shown that certain stressors increase expression of the pro-inflammatory cytokine interleukin-1beta (IL-1) in the hypothalamus. The first goal of the following studies was to assess the impact of acute stress on other key inflammatory factors, including both cytokines and cell surface markers for immune-derived cells resident to the CNS in adult male Sprague Dawley rats exposed to intermittent footshock (80 shocks, 90 s variable ITI, 5 s each). While scattered changes in IL-6 and GFAP were observed in the hippocampus and cortex, we found the hypothalamus to be exquisitely sensitive to the effects of footshock. At the level of the hypothalamus, mRNA for IL-1 and CD14 were significantly increased, while at the same time CD200R mRNA was significantly decreased. A subsequent experiment demonstrated that propranolol (20mg/kg i.p.) blocked the increase in IL-1 and CD14 mRNA observed in the hypothalamus, while the decrease in CD200R was unaffected by propranolol. Interestingly, inhibition of glucocorticoid synthesis via injection of metyrapone (50mg/kg s.c.) plus aminoglutethimide (100mg/kg s.c.) increased basal IL-1 mRNA and augmented IL-1 and CD14 expression provoked by footshock. Injection of minocycline, a putative microglial inhibitor, blocked the IL-1 response to footshock, while CD14 and CD200R were unaffected. Together, these gene expression changes (i) provide compelling evidence that stress may provoke neuroinflammatory changes that extend well beyond isolated changes in a single cytokine; (ii) suggest opposing roles for classic stress-responsive factors (norepinephrine and corticosterone) in the modulation of stress-related neuroinflammation; (iii) indicate microglia within the hypothalamus may be key players in stress-related neuroinflammation; and (iv) provide a potential mechanism (increased CD14) by which acute stress primes reactivity to later immune challenge.

  3. Hypercalcemia during the osteogenic phase after rat marrow ablation coincides with increased bone resorption assessed by the NTx marker.

    PubMed

    Gorski, J P; Apone, S; Shaffer, K A; Batchelder, A; Jean, W; Williams, J A; Shacter, E; Eyre, D R

    2000-07-01

    Marrow ablation is a model of bone turnover in which the excavated tibial intramedullary cavity is rapidly and reproducibly filled by osteoblasts with new woven bone (days 6-8), which is then rapidly resorbed by osteoclasts (days 10-15). We showed previously (Magnuson et al., 1997) that marrow ablation induces a dramatic hypercalcemia and hypercalciuria in rats that unexpectedly peaked at the time of maximal osteogenesis and continued throughout the subsequent resorption phase. Based upon the amount of calcium mobilized and a peak of urinary hydroxyproline, we suggested that the hypercalcemia and hypercalciuria were due to increased systemic osteoclastic bone resorption induced by marrow ablation. We now apply a new enzyme-linked immunosorbent assay for rodent alpha(2)(I) N-telopeptide (NTx), a marker of bone resorption, to the marrow ablation model to demonstrate that excretion of NTx parallels that of calcium release in the operated control group. Specifically, maximal NTx/creatinine excretion coincides with the onset of hypercalcemia on days 7-8. A peak of NTx was also observed in methylprednisolone- and deflazacort-treated ablated animals. Analyses for urinary free deoxypyridinoline crosslink failed to detect a significant ablation-induced change in excretion. Interleukin 6 activity was increased in all operated control and glucocorticoid-treated groups after marrow ablation, whereas serum parathyroid hormone remained at presurgical levels in operated controls throughout the 15-day study period. The NTx results confirm that bilateral tibial marrow ablation induces a burst of extratibial bone resorption and hypercalcemia 7-8 days later. We have estimated that the osteogenic phase of the ablation model deposits 40 mg of calcium as hydroxyapatite crystals within the intramedullary cavity on days 6-8; this represents 33%-50% of the total blood calcium content of a young rat. We hypothesize that the size and rapidity of this demand for ionized calcium is met through

  4. Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

    PubMed

    Klafke, J Z; da Silva, M A; Rossato, M F; de Prá, S Dal Toé; Rigo, F K; Walker, C I B; Bochi, G V; Moresco, R N; Ferreira, J; Trevisan, G

    2016-02-01

    Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain.

  5. Effects of repetitive stress during the acute phase of Trypanosoma cruzi infection on chronic Chagas' disease in rats.

    PubMed

    Caetano, Leony Cristina; Brazão, Vânia; Filipin, Marina Del Vecchio; Santello, Fabricia Helena; Caetano, Luana Naiara; Toldo, Miriam Paula Alonso; Caldeira, Jerri C; do Prado, José Clóvis

    2009-03-01

    The effect of repetitive stress during acute infection with Trypanosoma cruzi (T. cruzi) on the chronic phase of ensuing Chagas' disease was the focus of this investigation. The aim of this study was to evaluate in Wistar rats the influence of repetitive stress during the acute phase of infection (7 days) with the Y strain of T. cruzi on the chronic phase of the infection (at 180 days). Exposure to ether vapor for 1 min twice a day was used as a stressor. Repetitive stress enhanced the number of circulating parasites and cardiac tissue disorganization, from a moderate to a severe diffuse mononuclear inflammatory process and the presence of amastigote burden in the cardiac fibers. Immunological parameters revealed that repetitive stress triggered a reduced concanavalin A induced splenocyte proliferation in vitro with major effects on the late chronic phase. Serum interleukin-12 concentration decreased in both stressed and infected rats in the early phase of infection although it was higher on 180 days post-infection. These results suggest that repetitive stress can markedly impair the host's immune system and enhance the pathological process during the chronic phase of Chagas' disease.

  6. Diminished acute phase response and increased hepatic inflammation of aged rats in response to intraperitoneal injection of lipopolysaccharide.

    PubMed

    Gomez, Christian R; Acuña-Castillo, Claudio; Pérez, Claudio; Leiva-Salcedo, Elías; Riquelme, Denise M; Ordenes, Gamaliel; Oshima, Kiyoko; Aravena, Mauricio; Pérez, Viviana I; Nishimura, Sumiyo; Sabaj, Valeria; Walter, Robin; Sierra, Felipe

    2008-12-01

    Aging is associated with a deterioration of the acute phase response to inflammatory challenges. However, the nature of these defects remains poorly defined. We analyzed the hepatic inflammatory response after intraperitoneal administration of lipopolysaccharide (LPS) given to Fisher 344 rats aged 6, 15, and 22-23 months. Induction of the acute phase proteins (APPs), haptoglobin, alpha-1-acid glycoprotein, and T-kininogen was reduced and/or retarded with aging. Initial induction of interleukin-6 in aged rats was normal, but the later response was increased relative to younger counterparts. An exacerbated hepatic injury was observed in aged rats receiving LPS, as evidenced by the presence of multiple microabscesses in portal tracts, confluent necrosis, higher neutrophil accumulation, and elevated serum levels of alanine aminotransferase, relative to younger animals. Our results suggest that aged rats displayed a reduced expression of APPs and increased hepatic injury in response to the inflammatory insult.

  7. Plasma-exchange as a "rescue therapy" for dermato/polymyositis in acute phase. Experience in three young patients.

    PubMed

    Cozzi, Franco; Marson, Piero; Pigatto, Erika; Tison, Tiziana; Polito, Pamela; Galozzi, Paola; De Silvestro, Giustina; Punzi, Leonardo

    2015-12-01

    There are few data in the literature supporting the efficacy of plasma-exchange in dermato/polymyositis. The authors report three cases of patients with acute disease phase showing severe pharyngo-esophageal muscle weakness unresponsive to conventional therapy (corticosteroids and immunosuppressant agents) who were treated with plasma-exchange. As the patients were at high risk of "aspiration pneumonia", tracheostomy and PEG tubes were placed. The patients underwent a series of plasma-exchange for a mean of 15 weeks, during which time they progressively recovered muscle strength, their serum muscle enzyme values returned to normal levels, and MRI showed resolution of muscle edema. The tracheostomy and PEG tubes could be removed. Our findings suggest that plasma-exchange in association with immunosuppressant agents could play a relevant role in the management of dermato/polymyositis in acute phase.

  8. HO-1, RET and PML as possible markers for risk stratification of acute myelocytic leukemia and prognostic evaluation.

    PubMed

    Yu, Meisheng; Wang, Jishi; Ma, Dan; Chen, Shuya; Lin, Xiaojing; Fang, Qin; Zhe, Nana

    2015-11-01

    Heme oxygenase-1 (HO-1) is an inducible isoform of HO that is activated in response to oxidative stress and has anti-apoptotic and pro-proliferative effects on leukemia cells. RET, a tyrosine kinase receptor; its expression levels are associated with the differentiation degree of acute myelocytic leukemia (AML) cells. The promyelocytic leukemia (PML) gene inhibits cell proliferation and tumor growth, participates in the differentiation of hematopoietic progenitor cells and induces cell apoptosis. However, the association between the expression levels of HO-1, RET and PML genes and the risk stratification of AML and prognosis have not previously been reported. In the present study, HO-1 was expressed in the human AML Kasumi-1, HL-60 and THP-1 cell lines, and HO-1 expression was regulated by Hemin (20 µmol/l) and ZnPPIX (10 µmol/l). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that expression of RET and PML were positively and negatively correlated with HO-1 expression, respectively. Bone marrow samples (18 favorable, 55 intermediate, 15 adverse and 2 unknown karyotype AML cases and 20 healthy donors) were collected from 90 randomly selected AML patients upon their first visit. The mRNA and protein expression of HO-1, RET and PML in samples was detected by RT-qPCR and western blot analysis. At the mRNA level, the adverse group expressed significantly higher levels of HO-1 and RET compared with the levels in the favorable and normal groups. The PML mRNA expression levels in adverse patient samples was lower compared with those of the intermediate group and favorable group. Western blot analysis demonstrated that the expression levels of HO-1, RET and PML proteins in all risk groups exhibited the same pattern of expression as was observed for the mRNA levels. The overall survival and relapse-free survival rates were shortest in AML patients with high HO-1 expression (Kaplan-Meier; log-rank, P<0.01). The results of the

  9. Paediatric Dengue Fever diagnosed through parents' epidemiologic report and preventive strategy during the acute phase of infection.

    PubMed

    Poddighe, Dimitri; Bonomelli, Irene; Giardinetti, Silvia; Nedbal, Marco; Bruni, Paola

    2016-01-01

    In Europe, Dengue Fever is one of the most frequent imported diseases and also autochthonous cases occurred in areas where the insect vector is present. Here, we describe a child returning from Philippines and diagnosed with Dengue Fever, through the information provided by parents about an ongoing outbreak in their municipality. An appropriate clinical management in the hospital was established to monitor the occurrence of complications and to cancel the risk of dengue virus transmission in the acute phase of infection.

  10. Induction of several acute-phase protein genes by heavy metals: A new class of metal-responsive genes

    SciTech Connect

    Yiangou, Minas; Ge, Xin; Carter, K.C.; Papaconstantinou, J. Shriners Burns Institute, Galveston, TX )

    1991-04-16

    Acute-phase reactants, metallothioneins, and heat-shock proteins are the products of three families of genes that respond to glucocorticoids and cytokines. Metallothioneins and heat-shock proteins, however, are also stimulated by heavy metals whereas very little is known about the effect of heavy metals on acute-phase-reactant genes. The authors have studied the effect of heavy metals (Hg, Cd, Pb, Cu, Ni, and Zn) and Mg on the acute-phase reactants {alpha}{sub 1}-acid glycoprotein, C-reactive protein, {alpha}{sub 1}-antitrypsin and {alpha}{sub 1}-antichymotrypsin. {alpha}{sub 1}-Acid glycoprotein and C-reactive protein mRNA levels were increased severalfold in livers of heavy-metal-treated Balb/c mice. The strongest induction was mediated by Hg, followed in order of response by Cd > Pb > Cu > Ni > Zn > Mg. None of the metals affected the mRNA levels of albumin, {alpha}{sub 1}-antitrypsin, and {alpha}{sub 1}-antichymotrypsin. Furthermore, failure to repress albumin, a negative acute-phase reactant, indicated that the induction of these genes was not due to a metal-mediated inflammatory response. The metals also induced {alpha}{sub 1}-acid glycoprotein and C-reactive protein in adrenalectomized animals, indicating that induction by the heavy metals is not mediated by the glucocorticoid induction pathway. Sequence analysis has revealed a region of homology to metal-responsive elements in the {alpha}{sub 1}-acid glycoprotein and C-reactive protein promoters. The studies indicate that the induction of {alpha}{sub 1}-acid glycoprotein and C-reactive protein by heavy metals may be regulated by these metal-responsive elements at the level of transcription.

  11. The Concentration of Apolipoprotein A-I Decreases during Experimentally Induced Acute-Phase Processes in Pigs

    PubMed Central

    Carpintero, R.; Piñeiro, M.; Andrés, M.; Iturralde, M.; Alava, M. A.; Heegaard, P. M. H.; Jobert, J. L.; Madec, F.; Lampreave, F.

    2005-01-01

    In this work, apolipoprotein A-I (ApoA-I) was purified from pig sera. The responses of this protein after sterile inflammation and in animals infected with Actinobacillus pleuropneumoniae or Streptococcus suis were investigated. Decreases in the concentrations of ApoA-I, two to five times lower than the initial values, were observed at 2 to 4 days. It is concluded that ApoA-I is a negative acute-phase protein in pigs. PMID:15845530

  12. CXCL12 and TP53 genetic polymorphisms as markers of susceptibility in a Brazilian children population with acute lymphoblastic leukemia (ALL).

    PubMed

    de Lourdes Perim, Aparecida; Guembarovski, Roberta Losi; Oda, Julie Massayo Maeda; Lopes, Leandra Fiori; Ariza, Carolina Batista; Amarante, Marla Karine; Fungaro, Maria Helena Pelegrinelli; de Oliveira, Karen Brajão; Watanabe, Maria Angelica Ehara

    2013-07-01

    Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Genetic polymorphisms in the 3'UTR region of the CXCL12 (rs1801157) and TP53 codon 72 (rs1042522) genes may contribute to susceptibility to childhood ALL because they affect some important processes, such as metastasis regulation and tumor suppression. Thus the objective of the present study was to detect the frequency of two genetic polymorphisms in ALL patients and controls and to add information their impact on genetic susceptibility and prognosis. The CXCL12 and TP53 polymorphisms were tested in 54 ALL child patients and in 58 controls by restriction fragment length polymerase chain reaction and allelic specific chain reaction techniques, respectively. The frequencies of both allelic variants were higher in ALL patients than in the controls and indicated a positive association: OR = 2.44; 95 % CI 1.05-5.64 for CXCL12 and OR = 2.20; 95 % CI 1.03-4.70 for TP53. Furthermore, when the two genetic variants were analyzed together, they increased significantly more than fivefold the risk of this neoplasia development (OR = 5.24; 95 % CI 1.39-19.75), indicating their potential as susceptibility markers for ALL disease and the relevance of the allelic variant combination to increased risk of developing malignant tumors. Future studies may indicate a larger panel of genes involved in susceptibility of childhood ALL and other hematological neoplasias.

  13. Modulation of C4b-binding protein isoforms during the acute phase response caused by orthopedic surgery.

    PubMed

    Criado-García, O; González-Rubio, C; López-Trascasa, M; Pascual-Salcedo, D; Munuera, L; Rodríguez de Córdoba, S

    1997-01-01

    Orthopedic surgery is described as an event with a high risk of thromboembolic diseases. This is probably a consequence of a synergistic combination of different risk factors in the patients subjected to this type of surgery, including age, immobilization, anesthesia and different hypercoagulable states. After surgery patients develop an acute-phase response that leads to changes in several plasma proteins. One of these proteins is the complement regulator C4b-binding protein (C4BP). We have recently shown that in some acute-phase patients C4BP is incorrectly controlled (with elevation of the C4BP beta-containing isoforms), leading to a potential hypercoagulable state by decreasing the plasma levels of free (active) protein S. Here we have studied whether patients subjected to orthopedic surgery have an appropriate modulation of the C4BP isoforms during their postoperative acute-phase responses. We have analyzed the evolution of the C4BP isoforms in serial samples from 11 patients who have undergone knee (or hip) prosthesis surgery (mean age 70 years), or scoliosis surgery (mean age 18 years). Our data suggest a similar evolution of C4BP isoforms in all these patients, with an almost exclusive increase of C4BP isoforms lacking C4BP beta polypeptides and steady levels of free protein S.

  14. PLASMA PROTEIN ELECTROPHORESIS AND SELECT ACUTE PHASE PROTEINS IN HEALTHY BONNETHEAD SHARKS (SPHYRNA TIBURO) UNDER MANAGED CARE.

    PubMed

    Hyatt, Michael W; Field, Cara L; Clauss, Tonya M; Arheart, Kristopher L; Cray, Carolyn

    2016-12-01

    Preventative health care of elasmobranchs is an important but understudied field of aquatic veterinary medicine. Evaluation of inflammation through the acute phase response is a valuable tool in health assessments. To better assess the health of bonnethead sharks ( Sphyrna tiburo ) under managed care, normal reference intervals of protein electrophoresis (EPH) and the acute phase proteins, C-reactive protein (CRP) and haptoglobin (HP), were established. Blood was collected from wild caught, captive raised bonnethead sharks housed at public aquaria. Lithium heparinized plasma was either submitted fresh or stored at -80°C prior to submission. Electrophoresis identified protein fractions with migration characteristics similar to other animals with albumin, α-1 globulin, α-2 globulin, β globulin, and γ globulin. These fractions were classified as fractions 1-5 as fractional contents are unknown in this species. Commercial reagents for CRP and HP were validated for use in bonnethead sharks. Reference intervals were established using the robust method recommended by the American Society for Veterinary Clinical Pathology for the calculation of 90% reference intervals. Once established, the diagnostic and clinical applicability of these reference intervals was used to assess blood from individuals with known infectious diseases that resulted in systemic inflammation and eventual death. Unhealthy bonnethead sharks had significantly decreased fraction 2, fraction 3, and fraction 3:4 ratio and significantly increased fraction 5, CRP, and HP. These findings advance our understanding of elasmobranch acute phase inflammatory response and health and aid clinicians in the diagnosis of inflammatory disease in bonnethead sharks.

  15. Metabolizable protein supply modulated the acute-phase response following vaccination of beef steers.

    PubMed

    Moriel, P; Arthington, J D

    2013-12-01

    Our objective was to evaluate the effects of MP supply, through RUP supplementation, on the acute-phase response of beef steers following vaccination. On d 0, Brangus-crossbred steers (n = 24; 173 ± 31 kg; 175 ± 16 d of age) were randomly assigned to receive 1 of 3 isocaloric diets formulated to provide 85, 100, and 115% of the daily MP requirements of a beef steer gaining 0.66 kg of BW daily. Diets were limit-fed at 1.8% of BW (DM basis) and individually provided to steers once daily (0800 h) from d 0 to 29. Steers were weighed on d 0 and 29, following a 12-h period of feed and water withdrawal. On d 7, steers were vaccinated against Mannheimia haemolytica (OneShot, Pfizer), and blood samples were collected on d 0, 7, 8, 10, 14, 21, and 30. Plasma metabolites were analyzed as repeated measures using the MIXED procedure of SAS. Final BW and ADG were similar (P ≥ 0.50) among treatments (mean = 184 ± 9 kg and 0.5 ± 0.08 kg/d, respectively). Effects of time were detected (P < 0.01) for plasma concentrations of all acute-phase proteins, which peaked between d 7 to 14, returning to baseline concentrations by d 29. Treatment effects were not detected (P ≥ 0.19) for plasma concentrations of acid-soluble protein, albumin, fibrinogen, IGF-1 and serum amyloid-A. Plasma concentrations of total protein (TP) and plasma urea nitrogen (PUN) increased (P ≤ 0.05) with increasing supply of MP (87.1, 89.6, and 90.1 ± 1.09 mg TP/mL and 6.1, 8.3, and 10.3 ± 0.41 mg PUN/dL for 85, 100, and 115% MP steers, respectively). From d 10 to 29, steers provided 115% MP had less (P < 0.001) plasma concentrations of ceruloplasmin than steers fed 85 and 100% MP, which had similar plasma ceruloplasmin concentrations. On d 14, plasma concentrations of haptoglobin were greatest (P ≤ 0.06) for steers fed 115% MP, intermediate for 100% MP, and least for 85% MP (0.98, 0.71 and 0.44 ± 0.099 mg/mL, respectively). On d 10, plasma concentrations of creatinine were greater (P = 0.01) for steers

  16. Urinary neutrophil gelatinase-associated lipocalin (NGAL) might be an independent marker for anticipating scar formation in children with acute pyelonephritis

    PubMed Central

    Rafiei, Alireza; Mohammadjafari, Hamid; Bazi, Sara; Mirabi, Araz Mohammad

    2015-01-01

    Introduction: Urinary tract infections (UTIs) are the most serious common bacterial infections among young children. It may affect kidneys that classified as acute pyelonephritis (APN) and may lead to renal parenchymal involvement and scarring with high prevalence rate (15%-60%) among children. This study aimed to assess the urinary concentration of neutrophil gelatinase-associated lipocalin (NGAL) in patients with APN to diagnose those with potency to scar formation. Patients and Methods: Children who were admitted with a diagnosis of APN were enrolled and divided into two groups; APN with scar and APN without scar. Urinary levels of NGAL and its ratio to creatinine (Cr) levels were measured in the acute phase of infection. A receiver operating characteristic (ROC) curve was generated to allow calculation of cut-off values. Results: Fifty-four children were enrolled across the 2 groups: group 1 consisted of 16 patients (all female); group 2 consisted of 38 children (36 female and 2 male). Urinary levels of NGAL were significantly higher in APN with scar than in APN without scar (P = 0.037). For comparison of groups 1 and 2, the cut-off values were measured as 7.32 ng/ml, sensitivity; 81.3% and specificity; 66%. Conclusion: Evaluation of urinary NGAL levels may help us to identify children with APN who are at risk of developing renal scarring. PMID:26060836

  17. The Fusarium toxin deoxynivalenol (DON) modulates the LPS induced acute phase reaction in pigs.

    PubMed

    Dänicke, Sven; Brosig, Bianca; Kersten, Susanne; Kluess, Jeannette; Kahlert, Stefan; Panther, Patricia; Diesing, Anne-Kathrin; Rothkötter, Hermann-Josef

    2013-07-04

    The systemic effects of the Fusarium toxin deoxynivalenol (DON) and of bacterial lipopolysaccharides (LPS) were studied in male castrated pigs (40.4 ± 3.7 kg) infused intravenously with either DON or LPS alone (100 μg DON/kg/h, 7.5 μg/LPS/kg/h), or together (100 μg DON plus 7.5 μg/LPS/kg/h). The Control group received a saline infusion (n=6/treatment, 24h observation period). An additional DON infusion did not exacerbate the clinical signs observed in LPS-infused pigs. For example, rectal temperature climaxed after 4h (40.4 ± 0.2°C) and 5h (40.1 ± 0.3°C), in the LPS and LPS+DON group, respectively. Saline and DON alone did not induce an acute phase reaction as indicated by unaltered plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) while LPS caused a significant rise of both cytokines. TNF-alpha plasma peak concentrations were significantly higher in the LPS compared to the DON+LPS group (94.3 ± 17.2 ng/mL vs. 79.2 ± 15.7 ng/mL) while IL-6 climaxed earlier in the latter group (3h p.i. vs. 2h p.i.). From the tested clinical-chemical plasma characteristics the total bilirubin concentration and the ASAT activity were strongly elevated by the LPS infusion and additionally increased and decreased by DON, respectively. In conclusion, the LPS-induced effects were only marginally modified by DON.

  18. Influence of induction of parturition on the neonatal acute phase response in foals.

    PubMed

    Duggan, Vivienne E; Holyoak, G Reed; MaCallister, Charles G; Confer, Anthony W

    2007-01-15

    The objectives of the present study were to determine whether induction of parturition in mares at term with low doses of oxytocin (2.5 i.u. i.v. every 20 min) affected the incidence of peri-partum complications or inflammatory responses in the neonatal foal. Parturition was induced in 11 of 26 mares and the remainder foaled spontaneously. Serum concentrations of amyloid A (AA; an acute phase protein) were measured (with a commercial ELISA) from 0 to 72 h postpartum in 18 of the neonatal foals. The incidence of dystocia and premature placental separation was higher in induced mares (2 of 11 and 1 of 11 versus 0 of 15 and 0 of 15, respectively), whereas retained fetal membranes were more common in spontaneous foalings (2 of 15 versus 0 of 11). When abnormal foals were excluded (to decrease the influence of endogenous serum AA elevations), serum concentrations of AA increased to the same extent over time in foals with induced versus spontaneous parturition; foals with spontaneous parturition had a mean serum AA concentration of 7.8 microg/mL at birth that increased to a maximum of 58.9 microg/mL at 36 h; foals with induced parturition had a mean serum AA concentration of 5.4 microg/mL at birth that increased to a maximum of 41.4 microg/mL at 48 h. Baseline serum AA concentrations were lower in induced foals. We concluded that inducing parturition with low doses of oxytocin in mares at term did not affect (relative to spontaneous parturition) the temporal dynamics of serum AA concentrations in the normal foal in the first 72 h of life. However, the induction procedure may lead to complications during parturition that, if not detected early, could result in the development of an inflammatory response in the neonate.

  19. Estimating mortality risk in preoperative patients using immunologic, nutritional, and acute-phase response variables.

    PubMed Central

    Christou, N V; Tellado-Rodriguez, J; Chartrand, L; Giannas, B; Kapadia, B; Meakins, J; Rode, H; Gordon, J

    1989-01-01

    We measured the delayed type hypersensitivity (DTH) skin test response, along with additional variables of host immunocompetence in 245 preoperative patients to determine which variables are associated with septic-related deaths following operation. Of the 14 deaths (5.7%), 12 were related to sepsis and in 2 sepsis was contributory. The DTH response (p less than 0.00001), age (p less than 0.0002), serum albumin (p less than 0.003), hemoglobin (p less than 0.02), and total hemolytic complement (p less than 0.03), were significantly different between those who died and those who lived. By logistic regression analysis, only the DTH skin test response (log likelihood = 41.7, improvement X2 = 6.24, p less than 0.012) and the serum albumin (log likelihood = 44.8, improvement X2 = 17.7, p less than 0.001) were significantly and independently associated with the deaths. The resultant probability of mortality calculation equation was tested in a separate validation group of 519 patients (mortality = 5%) and yielded a good predictive capability as assessed by (1) X2 = 0.08 between observed and expected deaths, NS; (2) Goodman-Kruskall G statistic = 0.673) Receiver-Operating-Characteristic (ROC) curve analysis with an area under the ROC curve, Az = 0.79 +/- 0.05. We conclude that a reduced immune response (DTH skin test anergy) plus a nutritional deficit and/or acute-phase response change are both associated with increased septic-related deaths in elective surgical patients. PMID:2472781

  20. Telemedicine Approaches to Evaluating Acute-phase Retinopathy of Prematurity: Study Design

    PubMed Central

    2016-01-01

    Purpose Detecting sight-threatening retinopathy of prematurity (ROP) relies on a diagnostic examination (DE) performed by an experienced ophthalmologist. An alternative may be a telemedicine system where retinal images of at-risk infants are graded by readers to determine features of ROP indicating the need for a DE. Methods The multicenter “Telemedicine Approaches to Evaluating Acute-phase ROP” (e-ROP) Study is a cohort study of 2,000 infants with birth weights <1251g. At each visit, ophthalmologists perform DEs and non-physician imagers obtain iris and five retinal images with the disc positioned in the center, right, left, up anddown. Images are uploaded to a secure server for grading by non-physician readers for the detection of plus disease, stage 3 ROP and/or zone I disease, any of which indicates “referral-warranted ROP (RW-ROP).” Images from all infants with RW-ROP and a random sample of infants without RW-ROP (based on DEs) are selected for grading. Gradings are compared to DEs to determine the validity and evaluate reliability, feasibility, safety, and cost-effectiveness of the telemedicine system. Results e-ROP is conducted in 12 Clinical Centers in the US and Canada with Study Headquarters, the Data Coordinating Center and the Image Reading Center in Philadelphia and the ROP Data Center in Oklahoma City. 27 Study Center Coordinators, 34 ophthalmologists; 26 imagers, and 4 readers have been certified. All study data are submitted using a secure web-based system. Conclusion The design and findings of this study will be useful to conduct other ROP studies or evaluate telemedicine for other diseases. PMID:24955738

  1. The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity.

    PubMed

    de Laat, M A; Kyaw-Tanner, M T; Nourian, A R; McGowan, C M; Sillence, M N; Pollitt, C C

    2011-04-15

    Metalloproteinases have been implicated in the pathogenesis of equine laminitis and other inflammatory conditions, through their role in the degradation and remodelling of the extracellular matrix environment. Matrix metalloproteinases (MMPs) and their inhibitors are present in normal equine lamellae, with increased secretion and activation of some metalloproteinases reported in horses with laminitis associated with systemic inflammation. It is unknown whether these enzymes are involved in insulin-induced laminitis, which occurs without overt systemic inflammation. In this study, gene expression of MMP-2, MMP-9, MT1-MMP, ADAMTS-4 and TIMP-3 was determined in the lamellar tissue of normal control horses (n=4) and horses that developed laminitis after 48 h of induced hyperinsulinaemia (n=4), using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Protein concentrations of MMP-2 and MMP-9 were also examined using gelatin zymography in horses subject to prolonged hyperinsulinaemia for 6h (n=4), 12h (n=4), 24h (n=4) and 48 h (n=4), and in normal control horses (n=4). The only change in gene expression observed was an upregulation of MMP-9 (p<0.05) in horses that developed insulin-induced laminitis (48 h). Zymographical analysis showed an increase (p<0.05) in pro MMP-9 during the acute phase of laminitis (48 h), whereas pro MMP-2 was present in similar concentration in the tissue of all horses. Thus, MMP-2, MT1-MMP, TIMP-3 and ADAMTS-4 do not appear to play a significant role in the pathogenesis of insulin-induced laminitis. The increased expression of MMP-9 may be associated with the infiltration of inflammatory leukocytes, or may be a direct result of hyperinsulinaemia. The exact role of MMP-9 in basement membrane degradation in laminitis is uncertain as it appears to be present largely in the inactive form.

  2. Synthesis and Characterization of 8-O-Carboxymethylpyranine (CM-Pyranine) as a Bright, Violet-Emitting, Fluid-Phase Fluorescent Marker in Cell Biology

    PubMed Central

    Legenzov, Eric A.; Dirda, Nathaniel D. A.; Hagen, Brian M.; Kao, Joseph P. Y.

    2015-01-01

    To avoid spectral interference with common fluorophores in multicolor fluorescence microscopy, a fluid-phase tracer with excitation and emission in the violet end of the visible spectrum is desirable. CM-pyranine is easily synthesized and purified. Its excitation and emission maxima at 401.5 nm and 428.5 nm, respectively, are well suited for excitation by 405-nm diode lasers now commonly available on laser-scanning microscopes. High fluorescence quantum efficiency (Q = 0.96) and strong light absorption (ε405 > 25,000 M-1cm-1) together make CM-pyranine the brightest violet aqueous tracer. The fluorescence spectrum of CM-pyranine is invariant above pH 4, which makes it a good fluid-phase marker in all cellular compartments. CM-pyranine is very photostable, is retained for long periods by cells, does not self-quench, and has negligible excimer emission. The sum of its properties make CM-pyranine an ideal fluorescent tracer. The use of CM-pyranine as a fluid-phase marker is demonstrated by multicolor confocal microscopy of cells that are also labeled with lipid and nuclear markers that have green and red fluorescence emission, respectively. PMID:26186650

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine if feeding a Saccharomyces 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 body weight) were obtained and transported to an ...

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

    PubMed

    Poulsen, Sarah S; Knudsen, Kristina B; Jackson, Petra; Weydahl, Ingrid E K; Saber, Anne T; Wallin, Håkan; Vogel, Ulla

    2017-01-01

    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 towards designing

  5. Thrombin induces ischemic LTP (iLTP): implications for synaptic plasticity in the acute phase of ischemic stroke

    PubMed Central

    Stein, Efrat Shavit; Itsekson-Hayosh, Zeev; Aronovich, Anna; Reisner, Yair; Bushi, Doron; Pick, Chaim G.; Tanne, David; Chapman, Joab; Vlachos, Andreas; Maggio, Nicola

    2015-01-01

    Acute brain ischemia modifies synaptic plasticity by inducing ischemic long-term potentiation (iLTP) of synaptic transmission through the activation of N-Methyl-D-aspartate receptors (NMDAR). Thrombin, a blood coagulation factor, affects synaptic plasticity in an NMDAR dependent manner. Since its activity and concentration is increased in brain tissue upon acute stroke, we sought to clarify whether thrombin could mediate iLTP through the activation of its receptor Protease-Activated receptor 1 (PAR1). Extracellular recordings were obtained in CA1 region of hippocampal slices from C57BL/6 mice. In vitro ischemia was induced by acute (3 minutes) oxygen and glucose deprivation (OGD). A specific ex vivo enzymatic assay was employed to assess thrombin activity in hippocampal slices, while OGD-induced changes in prothrombin mRNA levels were assessed by (RT)qPCR. Upon OGD, thrombin activity increased in hippocampal slices. A robust potentiation of excitatory synaptic strength was detected, which occluded the ability to induce further LTP. Inhibition of either thrombin or its receptor PAR1 blocked iLTP and restored the physiological, stimulus induced LTP. Our study provides important insights on the early changes occurring at excitatory synapses after ischemia and indicates the thrombin/PAR1 pathway as a novel target for developing therapeutic strategies to restore synaptic function in the acute phase of ischemic stroke. PMID:25604482

  6. Hepatic acute phase proteins--regulation by IL-6- and IL-1-type cytokines involving STAT3 and its crosstalk with NF-κB-dependent signaling.

    PubMed

    Bode, Johannes G; Albrecht, Ute; Häussinger, Dieter; Heinrich, Peter C; Schaper, Fred

    2012-01-01

    The function of the liver as an important constituent of the immune system involved in innate as well as adaptive immunity is warranted by different highly specialized cell populations. As the major source of acute phase proteins, including secreted pathogen recognition receptors (PRRs), short pentraxins, components of the complement system or regulators of iron metabolism, hepatocytes are essential constituents of innate immunity and largely contribute to the control of a systemic inflammatory response. The production of acute phase proteins in hepatocytes is controlled by a variety of different cytokines released during the inflammatory process with IL-1- and IL-6-type cytokines as the leading regulators operating both as a cascade and as a network having additive, inhibitory, or synergistic regulatory effects on acute phase protein expression. Hence, IL-1β substantially modifies IL-6-induced acute phase protein production as it almost completely abrogates production of acute phase proteins such as γ-fibrinogen, α(2)-macroglobulin or α(1)-antichymotrypsin, whereas production of for example hepcidin, C-reactive protein and serum amyloid A is strongly up-regulated. This switch-like regulation of IL-6-induced acute phase protein production by IL-1β is due to a complex processing of the intracellular signaling events activated in response to IL-6 and/or IL-1β, with the crosstalk between STAT3- and NF-κB-mediated signal transduction being of particular importance. Recent data suggest that in this context complex formation between STAT3 and the p65 subunit of NF-κB might be of key importance. The present review summarizes the regulation of acute phase protein production focusing on the role of the crosstalk of STAT3- and NF-κB-driven pathways for transcriptional control of acute phase gene expression.

  7. Ratio of Systolic Blood Pressure to Right Atrial Pressure, a Novel Marker to Predict Morbidity and Mortality in Acute Systolic Heart Failure.

    PubMed

    Omar, Hesham R; Charnigo, Richard; Guglin, Maya

    2017-04-01

    Congestion is the main contributor to heart failure (HF) morbidity and mortality. We assessed the combined role of congestion and decreased forward flow in predicting morbidity and mortality in acute systolic HF. The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial data set was used to determine if the ratio of simultaneously measured systolic blood pressure (SBP)/right atrial pressure (RAP) on admission predicted HF rehospitalization and 6-month mortality. One hundred ninety-five patients (mean age 56.5 years, 75% men) who received pulmonary artery catheterization were studied. The RAP, SBP, and SBP/RAP had an area under the curve (AUC) of 0.593 (p = 0.0205), 0.585 (p = 0.0359), and 0.621 (p = 0.0026), respectively, in predicting HF rehospitalization. The SBP/RAP was a superior marker of HF rehospitalization compared with RAP alone (difference in AUC 0.0289, p = 0.0385). The optimal criterion of SBP/RAP <11 provided the highest combined sensitivity (77.1%) and specificity (50.9%) in predicting HF rehospitalization. The SBP/RAP had an AUC 0.622, p = 0.0108, and a cut-off value of SBP/RAP <8 had a sensitivity of 61.9% and specificity 64.1% in predicting mortality. Multivariate analysis showed that an SBP/RAP <11 independently predicted rehospitalization for HF (estimated odds ratio 3.318, 95% confidence interval 1.692 to 6.506, p = 0.0005) and an SBP/RAP <8 independently predicted mortality (estimated hazard ratio 2.025, 95% confidence interval 1.069 to 3.833, p = 0.030). In conclusion, SBP/RAP ratio is a marker that identifies a spectrum of complications after hospitalization of patients with decompensated systolic HF, starting with increased incidence of HF rehospitalization at SBP/RAP <11 to increased mortality with SBP/RAP <8.

  8. Short Duration Small Sided Football and to a Lesser Extent Whole Body Vibration Exercise Induce Acute Changes in Markers of Bone Turnover.

    PubMed

    Bowtell, J L; Jackman, S R; Scott, S; Connolly, L J; Mohr, M; Ermidis, G; Julian, R; Yousefian, F; Helge, E W; Jørgensen, N R; Fulford, J; Knapp, K M; Krustrup, P

    2016-01-01

    We aimed to study whether short-duration vibration exercise or football sessions of two different durations acutely changed plasma markers of bone turnover and muscle strain. Inactive premenopausal women (n = 56) were randomized to complete a single bout of short (FG15) or long duration (FG60) small sided football or low magnitude whole body vibration training (VIB). Procollagen type 1 amino-terminal propeptide (P1NP) was increased during exercise for FG15 (51.6 ± 23.0 to 56.5 ± 22.5 μg·L(-1), mean ± SD, P < 0.05) and FG60 (42.6 ± 11.8 to 50.2 ± 12.8 μg·L(-1), P < 0.05) but not for VIB (38.8 ± 15.1 to 36.6 ± 14.7 μg·L(-1), P > 0.05). An increase in osteocalcin was observed 48 h after exercise (P < 0.05), which did not differ between exercise groups. C-terminal telopeptide of type 1 collagen was not affected by exercise. Blood lactate concentration increased during exercise for FG15 (0.6 ± 0.2 to 3.4 ± 1.2 mM) and FG60 (0.6 ± 0.2 to 3.3 ± 2.0 mM), but not for VIB (0.6 ± 0.2 to 0.8 ± 0.4 mM) (P < 0.05). Plasma creatine kinase increased by 55 ± 63% and 137 ± 119% 48 h after FG15 and FG60 (P < 0.05), but not after VIB (26 ± 54%, NS). In contrast to the minor elevation in osteocalcin in response to a single session of vibration exercise, both short and longer durations of small sided football acutely increased plasma P1NP, osteocalcin, and creatine kinase. This may contribute to favorable effects of chronic training on musculoskeletal health.

  9. Short Duration Small Sided Football and to a Lesser Extent Whole Body Vibration Exercise Induce Acute Changes in Markers of Bone Turnover

    PubMed Central

    Bowtell, J. L.; Jackman, S. R.; Scott, S.; Connolly, L. J.; Ermidis, G.; Julian, R.; Yousefian, F.; Helge, E. W.; Jørgensen, N. R.; Fulford, J.; Knapp, K. M.

    2016-01-01

    We aimed to study whether short-duration vibration exercise or football sessions of two different durations acutely changed plasma markers of bone turnover and muscle strain. Inactive premenopausal women (n = 56) were randomized to complete a single bout of short (FG15) or long duration (FG60) small sided football or low magnitude whole body vibration training (VIB). Procollagen type 1 amino-terminal propeptide (P1NP) was increased during exercise for FG15 (51.6 ± 23.0 to 56.5 ± 22.5 μg·L−1, mean ± SD, P < 0.05) and FG60 (42.6 ± 11.8 to 50.2 ± 12.8 μg·L−1, P < 0.05) but not for VIB (38.8 ± 15.1 to 36.6 ± 14.7 μg·L−1, P > 0.05). An increase in osteocalcin was observed 48 h after exercise (P < 0.05), which did not differ between exercise groups. C-terminal telopeptide of type 1 collagen was not affected by exercise. Blood lactate concentration increased during exercise for FG15 (0.6 ± 0.2 to 3.4 ± 1.2 mM) and FG60 (0.6 ± 0.2 to 3.3 ± 2.0 mM), but not for VIB (0.6 ± 0.2 to 0.8 ± 0.4 mM) (P < 0.05). Plasma creatine kinase increased by 55 ± 63% and 137 ± 119% 48 h after FG15 and FG60 (P < 0.05), but not after VIB (26 ± 54%, NS). In contrast to the minor elevation in osteocalcin in response to a single session of vibration exercise, both short and longer durations of small sided football acutely increased plasma P1NP, osteocalcin, and creatine kinase. This may contribute to favorable effects of chronic training on musculoskeletal health. PMID:28025642

  10. Effects of Combined Phase III and Phase II Cardiac Exercise Therapy for Middle-aged Male Patients with Acute Myocardial Infarction.

    PubMed

    Lee, Chih-Wei; Wang, Ji-Hung; Hsieh, Jen-Che; Hsieh, Tsung-Cheng; Huang, Chien-Hui

    2013-11-01

    [Purpose] To investigate the effects of cardiac exercise therapy (CET) on exercise capacity and coronary risk factors (CRFs) of patients with acute myocardial infarction (AMI). [Methods] Patients who participated in an 8-week supervised, hospital-based phase II and 6-month home-based phase III CET with monthly telephone and/or home visits were defined as the exercise group (EG) (n=20), while those who did not receive phase II or phase III CET were defined as the no-exercise group (NEG) (n=10). CRFs were evaluated pre- and post-phase II and eight months after discharge. One and two-way repeated measures ANOVA were used to perform intra- and inter-group comparisons. [Results] Thirty men with AMI aged 49.3 ± 8.3 years were studied. EG increased their exercise capacity (METs) (6.8 ± 1.6 vs.10.0 ± 1.9) after phase II CET and was able to maintain it at 8-month follow-up. Both groups had significantly fewer persons who kept on smoking compared to the first examination. High density lipoprotein cholesterol (HDL-C) increased from 38.1 ± 11.0 to 43.7 ± 8.7 mg/dl at follow-up in EG while no significant difference was noted in NEG. [Conclusion] After phase III CET subjects had maintained the therapeutic effects of smoking cessation, and increasing exercise capacity obtained in phase II CET. HDL-C in EG continued to improve during phase III CET.

  11. Evidence for a protective role of tumor necrosis factor in the acute phase of Trypanosoma cruzi infection in mice.

    PubMed Central

    Lima, E C; Garcia, I; Vicentelli, M H; Vassalli, P; Minoprio, P

    1997-01-01

    A possible role for tumor necrosis factor (TNF) alpha during Trypanosoma cruzi infection was explored by using transgenic mice expressing in blood high levels of a soluble TNFR1-FcIgG3 fusion protein, which neutralizes the effects of TNF in vivo. Nontransgenic littermates were used as controls. The transgenic mice showed high susceptibility to T. cruzi infection. Inocula sublethal for control mice resulted in over 80% mortality associated with higher levels of parasites in the blood. In histological sections of the hearts of transgenic mice, large parasitic clusters without inflammatory cell infiltrates around the parasites were seen, while smaller parasitic clusters associated with leukocytes were seen in control mice. No difference in specific antibody response or lymphocyte composition of the spleen was found between transgenic and control mice, although the unresponsiveness of spleen cells to concanavalin A stimulation in vitro, typical of the acute phase of T. cruzi infection, was less pronounced in transgenic mice. Infected transgenic mice produced higher levels of gamma interferon than did control mice. These results confirm that TNF is involved in mechanisms leading to parasite clearance and protection from death in the acute phase of T. cruzi infection. More importantly, the data reveal that TNF is necessary for the establishment of effective tissue inflammation and parasite load control in acute experimental Chagas' disease myocarditis. PMID:9009297

  12. Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection

    PubMed Central

    Kramer, Holger B.; Lavender, Kerry J.; Qin, Li; Stacey, Andrea R.; Liu, Michael K. P.; di Gleria, Katalin; Simmons, Alison; Gasper-Smith, Nancy; Haynes, Barton F.; McMichael, Andrew J.; Borrow, Persephone; Kessler, Benedikt M.

    2010-01-01

    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, β-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. PMID:20463814

  13. Effects of Statin versus the Combination of Ezetimibe plus Statin on Serum Lipid Absorption Markers in Patients with Acute Coronary Syndrome

    PubMed Central

    Watanabe, Erisa; Yamaguchi, Junichi; Arashi, Hiroyuki; Ogawa, Hiroshi; Hagiwara, Nobuhisa

    2015-01-01

    Background. The use of statins is essential for aggressive lipid-lowering treatment in acute coronary syndrome (ACS) patients with dyslipidemia. Recently, elevation of sitosterol, a lipid absorption marker, was reported to be associated with premature atherosclerosis. The purpose of the present study was to examine the impact of ezetimibe, a selective intestinal cholesterol transporter inhibitor, in ACS patients. Methods. A total of 197 ACS patients were randomized to pitavastatin + ezetimibe (n = 100) or pitavastatin (n = 97). Low-density lipoprotein cholesterol (LDL-C) and sitosterol levels were evaluated on admission and after 12 weeks. Results. After 12 weeks, the pitavastatin + ezetimibe group showed a significantly greater decrease of sitosterol (baseline versus after 12 weeks; 2.9 ± 2.5 versus 1.7 ± 1.0 ng/mL, P < 0.001) than the pitavastatin group (2.7 ± 1.5 versus 3.0 ± 1.4 ng/mL). The baseline sitosterol level was significantly higher in patients with achieved LDL-C levels ≥ 70 mg/dL than in patients with levels < 70 mg/dL (3.2 ± 2.5 versus 2.4 ± 1.3 ng/mL, P = 0.006). Conclusions. Ezetimibe plus statin therapy in ACS patients with dyslipidemia decreased LDL-C and sitosterol levels more than statin therapy solo. Sitosterol Elevation was a predictor of poor response to aggressive lipid-lowering treatment in ACS patients. PMID:25815213

  14. Smac mimetic induces cell death in a large proportion of primary acute myeloid leukemia samples, which correlates with defined molecular markers

    PubMed Central

    Lueck, Sonja C.; Russ, Annika C.; Botzenhardt, Ursula; Schlenk, Richard F.; Zobel, Kerry; Deshayes, Kurt; Vucic, Domagoj; Döhner, Hartmut; Döhner, Konstanze

    2016-01-01

    Apoptosis is deregulated in most, if not all, cancers, including hematological malignancies. Smac mimetics that antagonize Inhibitor of Apoptosis (IAP) proteins have so far largely been investigated in acute myeloid leukemia (AML) cell lines; however, little is yet known on the therapeutic potential of Smac mimetics in primary AML samples. In this study, we therefore investigated the antileukemic activity of the Smac mimetic BV6 in diagnostic samples of 67 adult AML patients and correlated the response to clinical, cytogenetic and molecular markers and gene expression profiles. Treatment with cytarabine (ara-C) was used as a standard chemotherapeutic agent. Interestingly, about half (51%) of primary AML samples are sensitive to BV6 and 21% intermediate responsive, while 28% are resistant. Notably, 69% of ara-C-resistant samples show a good to fair response to BV6. Furthermore, combination treatment with ara-C and BV6 exerts additive effects in most samples. Whole-genome gene expression profiling identifies cell death, TNFR1 and NF-κB signaling among the top pathways that are activated by BV6 in BV6-sensitive, but not in BV6-resistant cases. Furthermore, sensitivity of primary AML blasts to BV6 correlates with significantly elevated expression levels of TNF and lower levels of XIAP in diagnostic samples, as well as with NPM1 mutation. In a large set of primary AML samples, these data provide novel insights into factors regulating Smac mimetic response in AML and have important implications for the development of Smac mimetic-based therapies and related diagnostics in AML. PMID:27385100

  15. Acute stress disorder and the transition to post-traumatic stress disorder in children and adolescents: prevalence, course, prognosis, diagnostic suitability and risk markers

    PubMed Central

    Meiser-Stedman, Richard; McKinnon, Anna; Dixon, Clare; Boyle, Adrian; Smith, Patrick; Dalgleish, Tim

    2017-01-01

    Background Early recovery from trauma exposure in youth is poorly understood. This prospective longitudinal study examined the early course of traumatic stress responses in recently trauma-exposed youth; evaluated the revised DSM-5 acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) diagnoses and alternative diagnoses; and identifed risk factors for persistent traumatic stress. Method Participants were 8-17 year old Emergency Departments attendees exposed to single incident traumas. Structured clinical interviews were undertaken at two (n=226) and nine weeks (n=208) post-trauma. Results Using the revised criteria in DSM-5, 14.2% met criteria for ASD at week 2 and 9.6% met criteria for PTSD at 9 weeks. These prevalences were similar to the corresponding DSM-IV diagnoses (18.6% ASD at week two; 8.7% PTSD at week nine). Using the same diagnostic criteria (DSM-IV or DSM-5) across assessments (i.e. ‘2 week PTSD’) suggested that caseness declined in prevalence by approximately half. Overlap between DSM-IV and DSM-5 ASD and DSM-5 preschool child PTSD diagnoses was considerable. Two diagnoses were strongly predictive of corresponding week nine diagnoses. Youth with ASD who subsequently had PTSD reported more negative alterations in cognition and mood at two-weeks than those youth who did not develop PTSD. Conclusions Youth exposed to single-event traumas experience considerable natural recovery in the first months post-trauma. Using DSM-5 criteria, ASD may not capture all clinically significant traumatic stress in the acute phase and is only moderately sensitive for later PTSD. Future research needs to address the role and etiology of negative alterations in cognition and mood symptoms. PMID:28135019

  16. The role and importance of glycosylation of acute phase proteins with focus on alpha-1 antitrypsin in acute and chronic inflammatory conditions.

    PubMed

    McCarthy, Cormac; Saldova, Radka; Wormald, Mark R; Rudd, Pauline M; McElvaney, Noel G; Reeves, Emer P

    2014-07-03

    Acute phase proteins (APPs) are a group of circulating plasma proteins which undergo changes quantitatively or qualitatively at the time of inflammation. Many of these APPs are glycosylated, and it has been shown that alterations in glycosylation may occur in inflammatory and malignant conditions. Changes in glycosylation have been studied as potential biomarkers in cancer and also in chronic inflammatory conditions and have been shown to correlate with disease severity in certain conditions. Serine protease inhibitors (serpins), many of which are also APPs, are proteins involved in the control of proteases in numerous pathways. Alpha-1 Antitrypsin (AAT) is the most abundant serpin within the circulation and is an APP which has been shown to increase in response to inflammation. The primary role of AAT is maintaining the protease/antiprotease balance in the lung, but it also possesses important anti-inflammatory and immune-modulating properties. Several glycoforms of AAT exist, and they possess differing properties in regard to plasma half-life and stability. Glycosylation may also be important in determining the immune modulatory properties of AAT. The review will focus on the role and importance of glycosylation in acute phase proteins with particular attention to AAT and its use as a biomarker of disease. The review describes the processes involved in glycosylation, how glycosylation changes in differing disease states, and the alterations that occur to glycans of APPs with disease and inflammation. Finally, the review explores the importance of changes in glycosylation of AAT at times of inflammation and in malignant conditions and how this may impact upon the functions of AAT.

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

    PubMed Central

    Lucinda, Luciane Boreki; Prosdócimo, Ana Claudia Merchan Giaxa; de Carvalho, Katherine Athayde Teixeira; Francisco, Julio Cesar; Baena, Cristina Pellegrino; Olandoski, Marcia; do Amaral, Vivian Ferreira; Faria, José Rocha; Guarita-Souza, Luiz César

    2015-01-01

    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. PMID:25859863

  18. Acute-phase protein α1-antitrypsin--a novel regulator of angiopoietin-like protein 4 transcription and secretion.

    PubMed

    Frenzel, Eileen; Wrenger, Sabine; Immenschuh, Stephan; Koczulla, Rembert; Mahadeva, Ravi; Deeg, H Joachim; Dinarello, Charles A; Welte, Tobias; Marcondes, A Mario Q; Janciauskiene, Sabina

    2014-06-01

    The angiopoietin-like protein 4 (angptl4, also known as peroxisome proliferator-activated receptor [PPAR]γ-induced angiopoietin-related protein) is a multifunctional protein associated with acute-phase response. The mechanisms accounting for the increase in angptl4 expression are largely unknown. This study shows that human α1-antitrypsin (A1AT) upregulates expression and release of angplt4 in human blood adherent mononuclear cells and in primary human lung microvascular endothelial cells in a concentration- and time-dependent manner. Mononuclear cells treated for 1 h with A1AT (from 0.1 to 4 mg/ml) increased mRNA of angptl4 from 2- to 174-fold, respectively, relative to controls. In endothelial cells, the maximal effect on angptl4 expression was achieved at 8 h with 2 mg/ml A1AT (11-fold induction versus controls). In 10 emphysema patients receiving A1AT therapy (Prolastin), plasma angptl4 levels were higher relative to patients without therapy (nanograms per milliliter, mean [95% confidence interval] 127.1 [99.5-154.6] versus 76.8 [54.8-98.8], respectively, p = 0.045) and correlated with A1AT levels. The effect of A1AT on angptl4 expression was significantly diminished in cells pretreated with a specific inhibitor of ERK1/2 activation (UO126), irreversible and selective PPARγ antagonist (GW9662), or genistein, a ligand for PPARγ. GW9662 did not alter the ability of A1AT to induce ERK1/2 phosphorylation, suggesting that PPARγ is a critical mediator in the A1AT-driven angptl4 expression. In contrast, the forced accumulation of HIF-1α, an upregulator of angptl4 expression, enhanced the effect of A1AT. Thus, acute-phase protein A1AT is a physiological regulator of angptl4, another acute-phase protein.

  19. Complement-dependent acute-phase expression of C-reactive protein and serum amyloid P-component.

    PubMed

    Szalai, A J; van Ginkel, F W; Wang, Y; McGhee, J R; Volanakis, J E

    2000-07-15

    The acute-phase response (APR) is regulated by TNF-alpha, IL-1beta, and IL-6 acting alone, in combination, or in concert with hormones. The anaphylotoxin C5a, generated during complement activation, induces in vitro the synthesis of these cytokines by leukocytes and of acute-phase proteins by HepG2 cells. However, there is no clear evidence for a role of C5a or any other complement activation product in regulation of the APR in vivo. In this study, using human C-reactive protein (CRP) transgenic mice deficient in C3 or C5, we investigated whether complement activation contributes to induction of the acute-phase proteins CRP and serum amyloid P-component (SAP). Absence of C3 or C5 resulted in decreased LPS-induced up-regulation of the CRP transgene and the mouse SAP gene. Also, LPS induced both the IL-1beta and IL-6 genes in normocomplementemic mice, but in complement-deficient mice it significantly induced only IL-6. Like LPS injection, activation of complement by cobra venom factor led to significant elevation of serum CRP and SAP in normocomplementemic mice but not in complement-deficient mice. Injection of recombinant human C5a into human CRP transgenic mice induced the IL-1beta gene and caused significant elevation of both serum CRP and SAP. However, in human CRP transgenic IL-6-deficient mice, recombinant human C5a did not induce the CRP nor the SAP gene. Based on these data, we conclude that during the APR, C5a generated as a consequence of complement activation acts in concert with IL-6 and/or IL-1beta to promote up-regulation of the CRP and SAP genes.

  20. Pulmonary Response to Surface-Coated Nanotitanium Dioxide Particles Includes Induction of Acute Phase Response Genes, Inflammatory Cascades, and Changes in MicroRNAs: A Toxicogenomic Study

    PubMed Central

    Halappanavar, Sabina; Jackson, Petra; Williams, Andrew; Jensen, Keld A; Hougaard, Karin S; Vogel, Ulla; Yauk, Carole L; Wallin, Håkan

    2011-01-01

    Titanium dioxide nanoparticles (nanoTiO2) are used in various applications including in paints. NanoTiO2 inhalation may induce pulmonary toxicity and systemic effects. However, the underlying molecular mechanisms are poorly understood. In this study, the effects of inhaled surface-coated nanoTiO2 on pulmonary global messenger RNA (mRNA) and microRNA (miRNA) expression in mouse were characterized to provide insight into the molecular response. Female C57BL/6BomTac mice were exposed for 1 hr daily to 42.4 ± 2.9 (SEM) mg surface-coated nanoTiO2/m3 for 11 consecutive days by inhalation and were sacrificed 5 days following the last exposure. Physicochemical properties of the particles were determined. Pulmonary response to nanoTiO2 was characterized using DNA microarrays and pathway-specific PCR arrays and related to data on pulmonary inflammation from bronchial lavages. NanoTiO2 exposure resulted 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 < 0.05) following exposure. Real time polymerase chain reaction confirmed the upregulation of miR-1, miR-449a and revealed dramatic induction of miR-135b (60-fold). Thus, inhalation of surface-coated nanoTiO2 results in changes in the expression of genes associated 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.† PMID:21259345

  1. Blood pressure lowering in acute phase of stroke: latest evidence and clinical implications

    PubMed Central

    Patarroyo, Sully Xiomara Fuentes

    2012-01-01

    Persistent controversy exists as to whether there are worthwhile beneficial effects of early, rapid lowering of elevated blood pressure (BP) in acute stroke. Elevated BP or ‘hypertension’ (i.e. systolic >140 mmHg) is common in stroke, especially in patients with pre-existing hypertension and large strokes, due to variable ‘autonomic stress’ and raised intracranial pressure. While positive associations between BP levels and poor outcomes are evident across a range of studies, very low BP levels and large reductions in BP have also been shown to predict death and dependence, more so for ischaemic stroke (IS) than intracerebral haemorrhage (ICH). Accumulating evidence indicates that early BP lowering can reduce haematoma expansion in ICH, but there is uncertainty over whether this translates into improved clinical outcomes, particularly since such an effect was not evident from haemostatic therapy in clinical trials. Guidelines generally recommend control of high systolic BP (>180 mmHg), but recent evidence indicates that even more modest elevation (>140 mmHg) increases risks of cerebral oedema and haemorrhagic transformation following thrombolysis in IS. Thus, any potential benefits of rapid BP lowering in acute stroke, particularly in IS, must be balanced against the potential risks of worsening cerebral ischaemia from altered autoregulation/perfusion. This paper explores current knowledge regarding the management of hypertension in acute stroke and introduces ongoing clinical trials aimed at resolving such a critical issue in the care of patients with acute stroke. PMID:23342232

  2. Serum acute phase proteins in control and Theileria annulata infected water buffaloes (Bubalus bubalis).

    PubMed

    El-Deeb, Wael M; Iacob, Olimpia C

    2012-11-23

    This study was carried out to ascertain the changes in acute phase proteins (APPs) and pro-inflammatory cytokines in Theileria annulata infected water buffalo. Thirty infected water buffaloes and 20 parasitologically free were used. In the present study there was significant (P ≤ 0.05) increase in haptoglobin (Hp), serum amyloid A (SAA), ceruloplasmin, α1-acid glycoprotein (AGP) and fibrinogen levels (2.18 ± 0.29 g/l, 156.58 ± 3.48 mg/l, 31.23 ± 1.25mg/dl, 370.23 ± 33.21 mg/l and 16.17 ± 1.18 g/l, respectively) in T. annulata infected water buffaloes when compared to healthy ones (0.13 ± 0.01 g/l, 23.9 ± 0.56 mg/l, 21.23 ± 1.21 mg/dl, 240.53 ± 22.45 mg/l and 4.2 ± 0.1 6g/l, respectively). Moreover, there was significant (P ≤ 0.05) increase in the levels of TNF-α, IL-1α, IL-6, IL-12, IL-1β and IFN-γ (2.55 ± 0.12 ng/ml, 98.32 ± 4.21 pg/ml, 152.32 ± 5.62 pg/ml, 26.44 ± 1.43 ng/ml, 240.33 ± 20.45 pg/ml and 123.65 ± 5.67 pg/ml, respectively) in T. annulata infected water buffaloes when compared to healthy ones (0.42 ± 0.04 ng/ml, 55.32 ± 3.21 pg/ml, 88.23 ± 3.21 pg/ml, 7.45 ± 0.67 ng/ml, 98.33 ± 3.45 pg/ml and 34.76 ± 1.56 pg/ml, respectively). There was also significant decrease (P ≤ 0.05) in the Hb content, PCV%, RBCs and WBCs counts in the diseased water buffaloes compared to the control ones. Neutropenia, eosinopenia, lymphopenia, monocytopenia and thrombocytopenia were also recorded. The biochemical changes revealed significant (P ≤ 0.05) elevation in the levels of AST, ALT, ALP, LDL-c, VLDL-c, BHBA and NEFA, with significant (P ≤ 0.05) decrease in the levels of total proteins, albumin, globulins, cholesterol, triglyceride, glucose, G6PD, calcium and phosphorus in T. annulata infected water buffaloes when compared to healthy ones. It could be concluded that APPs and pro-inflammatory cytokines could be used as a valuable biomarkers in T. annulata infected water buffaloes (Bubalus bubalis).

  3. An observational study on electrolyte disorders in the acute phase of ischemic stroke and their prognostic value.

    PubMed

    Fofi, Luisa; Dall'armi, Valentina; Durastanti, Laura; Valenza, Alessandro; Lorenzano, Svetlana; Prencipe, Massimiliano; Toni, Danilo

    2012-04-01

    Data on electrolyte disorders in neurological conditions and in acute stroke are somewhat scanty and not easily compared. In our Stroke Unit we studied patients hospitalized within six hours of the onset of an acute ischemic stroke and recorded their demographic and clinical data. Blood test results were recorded before any pharmacological therapy. A total of 475 individuals (256 M, 219 F; range: 14-96 years) treated over a period of 18 consecutive months, were selected. According to multiple logistic regression analysis, the baseline National Institute of Health Stroke Scale (NIHSS) score (odds ratio [OR]=1.33; 95% confidence interval [CI]: 1.22-1.44) and natremia alterations (OR=6.89; 95% CI=1.94-24.40) were associated with higher odds of death. Based on the ordinal logistic regression analysis, the baseline NIHSS score (OR=1.07; 95% CI=1.03-1.10) and baseline hypernatremia (OR=9.69; 95% CI=1.55-60.69) were related to early neurological worsening. Our work suggests an association between serum sodium alterations and mortality, and between high sodium levels and neurological clinical impairment, in the acute phase of an ischemic stroke.

  4. Modifying the acute phase response of Jersey calves by supplementing milk replacer with omega-3 fatty acids from fish oil.

    PubMed

    Ballou, M A; Cruz, G D; Pittroff, W; Keisler, D H; DePeters, E J

    2008-09-01

    Fifty-one Jersey bull calves (5 +/- 1 d old) were assigned to 1 of 3 milk replacers to determine the effects of increasing doses of n-3 fatty acids from fish oil on the acute phase response after an endotoxin challenge. All calves were fed a 22.5% crude protein and 18% lipid milk replacer (Calva Products, Acampo, CA) supplemented with an additional 2% fatty acids. Treatments differed only in the supplemental lipid source and included a 3:1 mix of corn and canola oils, a 1:1 blend of fish oil (Omega Proteins, Houston, TX) and the 3:1 mix of corn and canola oils, and fish oil only. On d 23, each calf was injected subcutaneously with 4 microg/kg of body weight of Salmonella Typhimurium endotoxin. Clinical, hematological, and biochemical parameters were measured at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 18, 24, and 72 h post endotoxin challenge. Endotoxin caused a dramatic rise in respiratory rate; feeding fish oil significantly attenuated the increase. Heart rate and rectal temperature were not affected by treatment. Feeding fish oil attenuated the change in serum iron concentration over time. Endotoxin caused severe hypoglycemia, reaching a nadir at 4 h. Calves supplemented with fish oil had reduced concentrations of serum glucose for 8 to 24 h. Furthermore, calves supplemented with fish oil alone had reduced serum insulin at 12, 28, and 24 h. In contrast, endotoxin caused an acute increase in blood urea nitrogen and nonesterified fatty acids; there were significant linear effects of fish oil on both blood urea nitrogen and nonesterified fatty acids. Serum triglycerides were elevated beginning at 12 h after the endotoxin challenge and returned to baseline values within 72 h. Fish oil suppressed the rise in triglycerides during this period, and the effect was linear with increasing fish oil. Serum concentrations of leptin decreased after the endotoxin challenge; however, the treatment did not influence the response. There was no treatment effect on serum aspartate

  5. Phase I and Pharmacologic Trial of Cytosine Arabinoside with the Selective Checkpoint 1 Inhibitor Sch 900776 in Refractory Acute Leukemias

    PubMed Central

    Karp, Judith E.; Thomas, Brian M.; Greer, Jacqueline M.; Sorge, Christopher; Gore, Steven D.; Pratz, Keith W.; Smith, B. Douglas; Flatten, Karen S.; Peterson, Kevin; Schneider, Paula; Mackey, Karen; Freshwater, Tomoko; Levis, Mark J.; McDevitt, Michael A.; Carraway, Hetty E.; Gladstone, Douglas E.; Showel, Margaret M.; Loechner, Sabine; Parry, David A.; Horowitz, Jo Ann; Isaacs, Randi; Kaufmann, Scott H.

    2013-01-01

    Purpose Incorporation of cytarabine into DNA activates checkpoint kinase 1 (Chk1), which stabilizes stalled replication forks, induces S-phase slowing, and diminishes cytarabine cytotoxicity. The selective Chk1 inhibitor SCH 900776 abrogates cytarabine-induced S-phase arrest and enhances cytarabine cytotoxicity in acute leukemia cell lines and leukemic blasts in vitro. To extend these findings to the clinical setting, we have conducted a phase I study of cytarabine and SCH 900776. Experimental Design Twenty-four adults with relapsed and refractory acute leukemias received timed sequential, continuous infusion cytarabine 2 g/m2 over 72 hours (667 mg/m2/24 hours) beginning on day 1 and again on day 10. SCH 900776 was administered as a 15- to 30-minute infusion on days 2, 3, 11, and 12. The starting dose of SCH 900776 was 10 mg/m2/dose. Results Dose-limiting toxicities consisting of corrected QT interval prolongation and grade 3 palmar-plantar erythrodysesthesia occurred at 140 mg flat dosing (dose level 5, equivalent to 80 mg/m2). Complete remissions occurred in 8 of 24 (33%) patients, with 7 of 8 at 40 mg/m2 or higher. SCH 900776 did not accumulate at any dose level. Marrow blasts obtained pretreatment and during therapy showed increased phosphorylation of H2Ax after SCH 900776 beginning at 40 mg/m2, consistent with unrepaired DNA damage. Conclusions These data support a randomized phase II trial of cytarabine +/− SCH 900776 at a recommended flat dose of 100 mg (equivalent to 56 mg/m2) for adults with poor-risk leukemias. The trial (SP P05247) was registered at www.clinicaltrials.gov as NCT #00907517. PMID:23092873

  6. Triglycerides as a biological marker of repeated re-hospitalization resulting from deliberate self-harm in acute psychiatry patients: a prospective observational study

    PubMed Central

    2014-01-01

    Background Biological factors have been associated with deliberate self-harm (DSH) but have not been integrated with clinical factors in routine risk assessments. This study aimed to examine the incremental validity of lipid levels and platelet serotonin when combined with psychosocial factors in risk assessments for repeated admissions due to DSH. Methods In this prospective observational study of 196 acutely admitted patients, results of blood tests performed upon admission and the MINI Suicidal Scale and psychosocial DSH risk factor assessments performed at discharge were compared with the incidence of DSH recorded during the first 3 and 12 months after discharge. Results High triglyceride levels were found to be a significant marker for patients admitted 3 or more times due to DSH (repeated DSH, DSH-R) when tested against other significant risk factors. When all (9) significant univariate factors associated with 12-month post-discharge DSH-R were analyzed in a multivariate logistic regression, the MINI Suicidal Scale (p = 0.043), a lack of insight (p = 0.040), and triglyceride level (p = 0.020) remained significant. The estimated 12-month area under the curve of the receiver operator characteristic (ROC-AUC) for DSH-R was 0.74 for triglycerides, 0.81 for the MINI, 0.89 for the MINI + psychosocial factors, and 0.91 for the MINI + psychosocial factors + triglycerides. The applied multifaceted approach also significantly discriminated between 12-month post-discharge DSH-R patients and other DSH patients, and a lack of insight (p = 0.047) and triglycerides (p = 0.046) remained significant for DSH-R patients in a multivariate analysis in which other DSH patients served as the reference group (rather than non-DSH patients). Conclusion The triglyceride values provided incremental validity to the MINI Suicidal Scale and psychosocial risk factors in the assessment of the risk of repeated DSH. Therefore, a bio-psychosocial approach appears promising, but further

  7. Is the serum amyloid A protein in acute phase plasma high density lipoprotein the precursor of AA amyloid fibrils?

    PubMed Central

    Baltz, M L; Rowe, I F; Caspi, D; Turnell, W G; Pepys, M B

    1986-01-01

    Serum amyloid A protein (SAA), an apolipoprotein of high density lipoprotein (HDL), is generally considered to be the precursor of AA protein, which forms the fibrils in reactive systemic amyloidosis in man and animals. This view is based on amino acid sequence identity between AA and the amino-terminal portion of SAA. However, in extensive and well-controlled studies of experimentally induced murine AA amyloidosis, we were unable to demonstrate a direct precursor-product relationship between SAA, in SAA-rich HDL preparations from acute phase or amyloidotic mouse or human serum, and AA protein in the amyloid deposits. This raises the possibility that SAA in its usual form, as an apolipoprotein of HDL synthesized during the acute phase response, may not be the major precursor of AA fibrils. The amyloidogenic forms of circulating SAA molecules may not be isolated during the preparation of HDL. Alternatively, particularly in the light of recent evidence that SAA mRNA is expressed in many different tissues throughout the body of appropriately stimulated animals, amyloidogenic SAA may be derived from sources other than the liver cells in which SAA-rich HDL is synthesized. PMID:3105937

  8. Latex-protein complexes from an acute phase recombinant antigen of Toxoplasma gondii for the diagnosis of recently acquired toxoplasmosis.

    PubMed

    Peretti, Leandro E; Gonzalez, Verónica D G; Marcipar, Iván S; Gugliotta, Luis M

    2014-08-01

    The synthesis and characterization of latex-protein complexes (LPC), from the acute phase recombinant antigen P35 (P35Ag) of Toxoplasma gondii and "core-shell" carboxylated or polystyrene (PS) latexes (of different sizes and charge densities) are considered, with the aim of producing immunoagglutination reagents able to detect recently acquired toxoplasmosis. Physical adsorption (PA) and chemical coupling (CC) of P35Ag onto latex particles at different pH were investigated. Greater amounts of adsorbed protein were obtained on PS latexes than on carboxylated latexes, indicating that hydrophobic forces govern the interactions between the protein and the particle surface. In the CC experiments, the highest amount of bound protein was obtained at pH 6, near the isoelectric point of the protein (IP=6.27). At this pH, it decreased both the repulsion between particle surface and protein, and the repulsion between neighboring molecules. The LPC were characterized and the antigenicity of the P35Ag protein coupled on the particles surface was evaluated by Enzyme-Linked ImmunoSorbent Assay (ELISA). Results from ELISA showed that the P35Ag coupled to the latex particles surface was not affected during the particles sensitization by PA and CC and the produced LPC were able to recognize specific anti-P35Ag antibodies present in the acute phase of the disease.

  9. Acute phase protein response during subclinical infection of pigs with H1N1 swine influenza virus.

    PubMed

    Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona; Pejsak, Zygmunt

    2012-10-12

    In the present study acute phase proteins (APPs) responses in pigs after subclinical infection with H1N1 swine influenza virus (SwH1N1) were evaluated. Fourteen 5 weeks old, seronegative piglets, both sexes were used. Ten of them were infected intranasally with SwH1N1. C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA) and pig major acute phase protein (Pig-MAP) concentrations in serum were measured using commercial ELISAs. No significant clinical signs were observed in any of the infected pigs, however, all infected animals developed specific antibodies against SwH1N1 and viral shedding was observed from 2 to 5 dpi. Only concentrations of Hp and SAA were significantly induced after infection, with mean maximum levels from days 1 to 2 post infection (dpi). The concentrations of CRP and Pig-MAP remained generally unchanged, however in half of infected pigs the concentration of CRP tended to increase at 1 dpi (but without statistical significance). The results of our study confirmed that monitoring of APPs may be useful for detection of subclinically infected pigs. The use of SAA or Hp and Pig-MAP may be a valuable in combination [i.e. Hp (increased concentration) and Pig-MAP (unchanged concentration)] to detect subclinically SIV infected pigs, or to identify pigs actually producing a large amount of virus. Additional studies need to be done in order to confirm these findings.

  10. Effect of the consumption of ethanol on the microcirculation of the human optic nerve head in the acute phase

    PubMed

    Kojima; Sugiyama; Kojima; Azuma; Ito

    2000-05-01

    Purpose: The effect of the consumption of ethanol on the circulation of the optic nerve head (ONH) in the human eye in the acute phase and its mechanism were studied.Methods: Eleven volunteers drank a bottle of beer (633 mL) with or without ethanol (29.5 g). Normalized blur (NB), a quantitative index of blood flow velocity, was measured in the temporal site of the ONH. NB, blood pressure (BP) and pulse rate (PR) were measured before, immediately after, and every 15 minutes for 90 minutes after consumption. Intraocular pressure (IOP) and plasma ethanol concentration were measured before, and 30 and 90 minutes after consumption. Genotyping of the aldehyde dehydrogenase (ALDH) 2 gene was also performed.Results: NB in the ONH increased significantly from 15 to 45 minutes after consumption of ethanol and the maximum increase was 14% at 15 minutes. IOP was lowered at 90 minutes after consumption, but it was not significant. Mean BP was lowered significantly after 60 minutes. PR and ocular perfusion pressure did not change. A significant correlation was found between plasma ethanol concentration at 30 minutes and maximum NB. NB in the ALDH 2-deficient group was significantly larger from 15 to 45 minutes after consumption than in the proficient group.Conclusions: It appeared that the consumption of ethanol can increase the blood flow in the human ONH in the acute phase through decreased resistance in blood vessels induced by acetaldehyde, a metabolite of ethanol.

  11. [Cerebroprotective effect of 3-oxypyridine and succinic acid derivatives in acute phase of alloxan-induced diabetes mellitus in rats].

    PubMed

    Volchegorskiĭ, I A; Rassokhina, L M; Miroshnichenko, I Iu

    2011-01-01

    The effects of original domestic derivatives of 3-oxypyridine and succinic acid (emoxipine, reamberin, and mexidol) on cellular composition of cortical and diencephalic structures in rat brain were studied in parallel with monitoring of behavioral, conditional learning, and metabolic disorders in acute phase of alloxan-induced diabetes in rats. The efficiency of 3-oxypyridine derivatives was compared to the results of alpha-lipoic acid administration. Single administration of emoxipine, reamberin, and mexidol in optimal doses prevented lipofuscin deposition in CA1 field neurocytes in hippocampus and/or increased the amount of terminally differentiated cells ofneuroectodermal lineage (oligodendrocytes, pyramid and basket cells) in this zone ofpaleocortex. Concurrently conditional learning capacity in morbid animals was restored. The cerebroprotective and nootropic effects of emoxipine and reamberin were associated with increased exploration motivation in the open field and were independent of their effects on carbohydrate and lipid metabolism dysfunction. On the contrary, the neuroprotective and nootropic effects of mexidol were associated with additional inhibition of morbid rat activity in the open field and a decrease in the level of circulating products of lipid peroxidation. It is established that 3-oxypyridine and succinic acid derivatives significantly exceed alpha-lipoic acid in terms of neuroprotective effects but exhibit significantly lower hypolipdemic activity in acute phase of alloxan diabetes.

  12. Effects of glutamine supplementation on gut barrier, glutathione content and acute phase response in malnourished rats during inflammatory shock

    PubMed Central

    Belmonte, Liliana; Coëffier, Moïse; Pessot, Florence Le; Miralles-Barrachina, Olga; Hiron, Martine; Leplingard, Antony; Lemeland, Jean-François; Hecketsweiler, Bernadette; Daveau, Maryvonne; Ducrotté, Philippe; Déchelotte, Pierre

    2007-01-01

    AIM: To evaluate the effect of glutamine on intestinal mucosa integrity, glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock. METHODS: Plasma acute phase proteins (APP), jejunal APP mRNA levels, liver and jejunal glutathione concentrations were measured before and one, three and seven days after turpentine injection in 4 groups of control, protein-restricted, protein-restricted rats supplemented with glutamine or protein powder. Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed. RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height, and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil, glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ± 0.46 μmol/g tissue, P < 0.05) in the jejunum, whereas in the liver glutathione remained low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation. CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model. PMID:17569119

  13. The acute phase of mild traumatic brain injury is characterized by a distance-dependent neuronal hypoactivity.

    PubMed

    Johnstone, Victoria P A; Shultz, Sandy R; Yan, Edwin B; O'Brien, Terence J; Rajan, Ramesh

    2014-11-15

    The consequences of mild traumatic brain injury (TBI) on neuronal functionality are only now being elucidated. We have now examined the changes in sensory encoding in the whisker-recipient barrel cortex and the brain tissue damage in the acute phase (24 h) after induction of TBI (n=9), with sham controls receiving surgery only (n=5). Injury was induced using the lateral fluid percussion injury method, which causes a mixture of focal and diffuse brain injury. Both population and single cell neuronal responses evoked by both simple and complex whisker stimuli revealed a suppression of activity that decreased with distance from the locus of injury both within a hemisphere and across hemispheres, with a greater extent of hypoactivity in ipsilateral barrel cortex compared with contralateral cortex. This was coupled with an increase in spontaneous output in Layer 5a, but only ipsilateral to the injury site. There was also disruption of axonal integrity in various regions in the ipsilateral but not contralateral hemisphere. These results complement our previous findings after mild diffuse-only TBI induced by the weight-drop impact acceleration method where, in the same acute post-injury phase, we found a similar depth-dependent hypoactivity in sensory cortex. This suggests a common sequelae of events in both diffuse TBI and mixed focal/diffuse TBI in the immediate post-injury period that then evolve over time to produce different long-term functional outcomes.

  14. The Acute Phase of Mild Traumatic Brain Injury Is Characterized by a Distance-Dependent Neuronal Hypoactivity

    PubMed Central

    Johnstone, Victoria P.A.; Shultz, Sandy R.; Yan, Edwin B.; O'Brien, Terence J.

    2014-01-01

    Abstract The consequences of mild traumatic brain injury (TBI) on neuronal functionality are only now being elucidated. We have now examined the changes in sensory encoding in the whisker-recipient barrel cortex and the brain tissue damage in the acute phase (24 h) after induction of TBI (n=9), with sham controls receiving surgery only (n=5). Injury was induced using the lateral fluid percussion injury method, which causes a mixture of focal and diffuse brain injury. Both population and single cell neuronal responses evoked by both simple and complex whisker stimuli revealed a suppression of activity that decreased with distance from the locus of injury both within a hemisphere and across hemispheres, with a greater extent of hypoactivity in ipsilateral barrel cortex compared with contralateral cortex. This was coupled with an increase in spontaneous output in Layer 5a, but only ipsilateral to the injury site. There was also disruption of axonal integrity in various regions in the ipsilateral but not contralateral hemisphere. These results complement our previous findings after mild diffuse-only TBI induced by the weight-drop impact acceleration method where, in the same acute post-injury phase, we found a similar depth-dependent hypoactivity in sensory cortex. This suggests a common sequelae of events in both diffuse TBI and mixed focal/diffuse TBI in the immediate post-injury period that then evolve over time to produce different long-term functional outcomes. PMID:24927383

  15. Role of Occult and Post-acute Phase Replication in Protective Immunity Induced with a Novel Live Attenuated SIV Vaccine

    PubMed Central

    Ham, Claire; Ferguson, Deborah; Tudor, Hannah; Mattiuzzo, Giada; Klaver, Bep; Page, Mark; Stebbings, Richard; Das, Atze T.; Berkhout, Ben; Almond, Neil; Cranage, Martin P.

    2016-01-01

    In order to evaluate the role of persisting virus replication during occult phase immunisation in the live attenuated SIV vaccine model, a novel SIVmac239Δnef variant (SIVrtTA) genetically engineered to replicate in the presence of doxycycline was evaluated for its ability to protect against wild-type SIVmac239. Indian rhesus macaques were vaccinated either with SIVrtTA or with SIVmac239Δnef. Doxycycline was withdrawn from 4 of 8 SIVrtTA vaccinates before challenge with wild-type virus. Unvaccinated challenge controls exhibited ~107 peak plasma viral RNA copies/ml persisting beyond the acute phase. Six vaccinates, four SIVmac239Δnef and two SIVrtTA vaccinates exhibited complete protection, defined by lack of wild-type viraemia post-challenge and virus-specific PCR analysis of tissues recovered post-mortem, whereas six SIVrtTA vaccinates were protected from high levels of viraemia. Critically, the complete protection in two SIVrtTA vaccinates was associated with enhanced SIVrtTA replication in the immediate post-acute vaccination period but was independent of doxycycline status at the time of challenge. Mutations were identified in the LTR promoter region and rtTA gene that do not affect doxycycline-control but were associated with enhanced post-acute phase replication in protected vaccinates. High frequencies of total circulating CD8+T effector memory cells and a higher total frequency of SIV-specific CD8+ mono and polyfunctional T cells on the day of wild-type challenge were associated with complete protection but these parameters were not predictive of outcome when assessed 130 days after challenge. Moreover, challenge virus-specific Nef CD8+ polyfunctional T cell responses and antigen were detected in tissues post mortem in completely-protected macaques indicating post-challenge control of infection. Within the parameters of the study design, on-going occult-phase replication may not be absolutely required for protective immunity. PMID:28002473

  16. Supervised Phase II Cardiac Exercise Therapy Shortens the Recovery of Exercise Capacity in Patients with Acute Myocardial Infarction

    PubMed Central

    Lee, Chih-Wei; Wang, Ji-Hung; Hsieh, Jen-Che; Hsieh, Tsung-Cheng; Wu, Yu-Zu; Chen, Tung-Wei; Huang, Chien-Hui

    2014-01-01

    [Purpose] To investigate the effects of Phase II cardiac exercise therapy (CET) on exercise capacity and changes in coronary risk factors (CRFs) of patients with acute myocardial infarction (AMI). [Subjects] Thirty male subjects with AMI were divided into an experimental group (EG) and a control group (CG). Another 30 age-matched subjects with patent coronary arteries served as a normal-control group (NCG). [Methods] Subjects in EG (n=20) trained using a stationary bicycle for 30 min at their target heart rate twice a week for 8 weeks. Exercise capacity was defined as the maximal metabolic equivalents (METs) that subjects reached during the symptom-limited maximal exercise test. HR, BP and RPP were recorded. Subjects in EG and CG received exercise tests and screening for CRFs at the beginning of, end of, and 3 months after Phase II CET, while subjects in NCG participated only in the 1st test. [Results] METs of CG did not improve until the 3rd test, while RPP at the 2nd test showed a significant increase. However, EG showed increased METs at the 2nd test without increase of RPP, and increased their high density lipoprotein cholesterol (HDL-C) during the follow-up period between the 2nd and 3rd tests. [Conclusion] Phase II CET shortens the recovery time of exercise capacity, helps to maintain the gained exercise capacity and increases HDL-C in phase III. PMID:25276046

  17. Marker development

    SciTech Connect

    Adams, M.R.

    1987-05-01

    This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

  18. Significance and mechanism of CYP7a1 gene regulation during the acute phase of liver regeneration.

    PubMed

    Zhang, Lisheng; Huang, Xiongfei; Meng, Zhipeng; Dong, Bingning; Shiah, Steven; Moore, David D; Huang, Wendong

    2009-02-01

    Cholesterol 7alpha-hydroxylase (CYP7a1) is the rate-limiting enzyme in the classic pathway of bile acid synthesis. Expression of CYP7a1 is regulated by a negative feedback pathway of bile acid signaling. Previous studies have suggested that bile acid signaling is also required for normal liver regeneration, and CYP7a1 expression is strongly repressed after 70% partial hepatectomy (PH). Both the effect of CYP7a1 suppression on liver regrowth and the mechanism by which 70% PH suppresses CYP7a1 expression are unknown. Here we show that liver-specific overexpression of an exogenous CYP7a1 gene impaired liver regeneration after 70% PH, which was accompanied by increased hepatocyte apoptosis and liver injury. CYP7a1 expression was initially suppressed after 70% PH in an farnesoid X receptor/ small heterodimer partner-independent manner; however, both farnesoid X receptor and small heterodimer partner were required to regulate CYP7a1 expression at the later stage of liver regeneration. c-Jun N-terminus kinase and hepatocyte growth factor signaling pathways are activated during the acute phase of liver regeneration. We determined that hepatocyte growth factor and c-Jun N-terminus kinase pathways were involved in the suppressing of the CYP7a1 expression in the acute phase of live regeneration. Taken together, our results provide the significance that CYP7a1 suppression is required for liver protection after 70% PH and there are two distinct phases of CYP7a1 gene regulation during liver regeneration.

  19. Lack of association of the CEP72 rs924607 TT genotype with vincristine-related peripheral neuropathy during the early phase of pediatric acute lymphoblastic leukemia treatment in a Spanish population.

    PubMed

    Gutierrez-Camino, Angela; Martin-Guerrero, Idoia; Lopez-Lopez, Elixabet; Echebarria-Barona, Aizpea; Zabalza, Iñaki; Ruiz, Irune; Guerra-Merino, Isabel; Garcia-Orad, Africa

    2016-02-01

    Vincristine is a component of acute lymphoblastic leukemia (ALL) treatment with the potential to induce peripheral neuropathy. Recently, the CEP72 rs924607 TT genotype was found to be associated with vincristine-induced toxicity during the continuation phase in pediatric ALL patients treated on the Total XIIIB and COG AALL0433 protocols at St Jude Children's Research Hospital and Children's Oncology Group. This finding could provide a base for safer dosing of vincristine. Nevertheless, there are variations in vincristine regimens among ALL treatment protocols and phases in different populations. Therefore, the aim of this study was to determine whether the CEP72 rs924607 TT genotype is a useful marker of vincristine neuropathy during induction therapy among Spanish children with B-ALL treated on the LAL-SHOP protocols. No association was found between neurotoxicity during the induction phase and the rs924607 TT genotype. This lack of association could be because of population differences and/or differences in neurotoxicity etiology between induction and continuation phases of treatment.

  20. Predicting value of cerebrospinal fluid proinflammatory factors in acute phase of ischemic stroke.

    PubMed

    Beridze, M; Shakarishvili, R

    2006-03-01

    Study purposed to establish the correlation between proinflammatory cytokines' initial CSF levels and neurological outcome on 7th day of acute ischemic stroke. 58 patients with acute ischemic stroke have been investigated. Neurological impairment assessed in 48 hours and on 7th day of stroke applying the international scales NIHSS and GCS. Patients divided into two groups: with severe stroke (GCS>9, NIHSS>15) and stroke with moderate severity (GCS=14,15; NIHSS=10-15). On 7th day increase of NIHSS score and decrease of GCS score at least 1 point was considered as deterioration and decrease of NIHSS score and increase of GCS score at least 1 point was considered as amelioration. CSF levels of proinflamatory cytokines determined using the enzyme-linked immunosorbent assay (ELISA). Control consisted with 15 patients, which were taken CSF in relation with vertebral discopathies. Means calculated by t-paired test. Pearson correlation and multivariate logistic regression were used. In 48 hours of stroke onset the CSF levels of interleukine-1beta (IL-1beta), interleukine-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were elevated compared to control. Statistical differences were not found between groups regarding the initial CSF levels of IL-1beta and TNF-alpha (p<0,5), while the significant statistical differences were found in regard with IL-6 CSF levels (p<0,05) between groups and against control. Significant positive correlation was found between initial CSF IL-6 levels and ischemic lesion size and neurological outcome at 1 week as well (r=+0,48 p<0,05 and r=+0,54 p<0,01 respectively). Thus, the IL-6 CSF levels in acute stage of ischemic stroke might be considered as the relatively stable prognostic indicator of clinical course of the disease.

  1. Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hepatoma cells in vitro

    PubMed Central

    1986-01-01

    Human hepatoma cells mimic the acute phase response after treatment with monocyte-conditioned medium. Levels of secreted fibrinogen, alpha- 1 acid glycoprotein, C-reactive protein, haptoglobin, and the third component of complement were elevated compared with control levels after 48 h of incubation with conditioned supernatant medium from an enriched fraction of normal peripheral monocytes. Albumin levels declined and alpha-1 antitrypsin remained unchanged. Levels of specific mRNA were measured by hybridization to slot blots and Northern blots and changed in correspondence with protein alterations. Interleukin-1 and tumor necrosis factor stimulated the third component of complement, but did not elevate any other member of the acute phase group and were therefore only partially active in this system. The identification of an in vitro model of the human acute phase response will permit analysis of the molecular basis for coordinate regulation of this group of facultative genes. PMID:3017995

  2. Cellular and molecular mechanisms regulating the hepatic erythropoietin expression during acute-phase response: a role for IL-6.

    PubMed

    Ramadori, Pierluigi; Ahmad, Ghayyor; Ramadori, Giuliano

    2010-09-01

    The source of circulating erythropoietin (EPO), the mediators and the mechanisms involved in the upregulation of EPO gene expression during acute-phase reaction are still poorly understood. Acute-phase reaction was induced by either intramuscular turpentine oil (TO) or intraperitoneal lipopolysaccharide (LPS) administration into wild-type and interleukin (IL)-6 knockout (KO) mice. Animals were killed at different time points and blood, liver and muscle tissue were collected. Serum levels of EPO were measured by enzyme-linked immunoadsorbent assay; liver and injured muscle samples were processed for RNA isolation and for protein analysis. EPO, hypoxia-inducible factors 1alpha and 2alpha (HIF-1alpha and HIF-2alpha) mRNA were analyzed by RT-PCR and the protein levels were analyzed by western blot and electrophoretic mobility shift assay. HIF-1alpha and HIF-2alpha localization was performed through immunofluorescence staining. EPO, HIF-1 and HIF-2 gene and protein expression levels were also analyzed in isolated mouse hepatocytes after stimulation with IL-6. In the wild-type animals, EPO serum levels increased dramatically at 12 h after the insults together with the hepatic gene expression. In TO-treated animals, the EPO gene expression reached an 8.2-fold increase at 12 h, and in LPS-treated mice a similar induction was recorded at 6 h (about 4.5-fold increase). In the IL-6KO strain, the upregulation after the inflammatory stimuli was much lower (only 2.0-fold increase). A progressive upregulation of HIF-1alpha and HIF-2alpha was detectable until 6 h after the insults, but only HIF-1alpha upregulation was reduced in IL-6KO mice. In isolated hepatocytes, stimulation with a single dose of IL-6 induced a nuclear accumulation of HIF-1alpha, in parallel with an increase of EPO mRNA. No effect on HIF-2alpha expression was found. IL-6 appears to be the main regulator of EPO gene expression and a major contributor for HIF-1alpha induction in hepatocytes and Kupffer cells

  3. Immunomodulatory properties of gamithromycin and ketoprofen in lipopolysaccharide-challenged calves with emphasis on the acute-phase response.

    PubMed

    Plessers, Elke; Wyns, Heidi; Watteyn, Anneleen; Pardon, Bart; De Baere, Siegrid; Sys, Stanislas U; De Backer, Patrick; Croubels, Siska

    2016-03-01

    Macrolide antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to be modulators of the innate immune response, irrespectively of their antimicrobial and anti-inflammatory actions. Therefore, it was our objective to evaluate whether the macrolide gamithromycin (GAM) and the NSAID ketoprofen (KETO) attenuate the acute-phase response in calves, and whether their combined administration is beneficial due to synergistic and/or additive effects. To this end, both drugs, as well as their combination, were studied in a previously developed inflammation model, i.e., the induction of an acute-phase response by an intravenous lipopolysaccharide (LPS) challenge (0.5 μg/kg body weight). Sixteen 4-week-old Holstein-Friesian calves were randomized into 4 groups: a positive control (+CONTR) group, receiving LPS but no pharmacological treatment (n=4) and a GAM (n=4), a KETO (n=4) and a GAM-KETO (n=4) group, receiving the respective drugs 1h prior to LPS administration. Clinical scoring and blood collection were performed at regular time points until 72 h post LPS challenge. Plasma concentrations of the selected cytokines (tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6)), acute-phase protein (serum amyloid A (SAA)) and prostaglandin E2 (PGE2) were subsequently quantified. Pre-treatment with GAM had no effect in the inflammation model compared to the +CONTR group. KETO, on the other hand, completely inhibited depression, anorexia and fever. This remarkable influence was associated with a significant reduction of PGE2 synthesis by KETO, while the effect on TNF-α, IL-6 and SAA was not straightforward. The combined administration of GAM and KETO provided no synergistic or additive effects in this model, neither clinically nor regarding the studied inflammatory mediators. In conclusion, KETO entirely inhibited PGE2 synthesis, fever development and depression, while GAM did not exert any effect in this model. These results promote the concomitant

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

    PubMed Central

    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

  5. [Asystolias in the acute phase of brain stroke. Report of a case].

    PubMed

    Belvis, R; Marti-Fàbregas, J; Franquet, E; Cocho, D; Valencia, C; Martí-Vilalta, J L

    2003-04-01

    Brain areas involved in heart autonomic control are not well characterized. Insulae have been proposed as control centers. A lesion in these areas may induce a cardiac autonomic dysfunction (arrhythmias, atrioventricular conduction abnormalities). Asystolia has not been previously reported. A 65-year-old man suffered an acute ischemia of the right middle cerebral artery (MCA) territory. NIHSS score was 19 points. Brain CT scan was normal. Transcranial Doppler (TCD) showed occlusion of the right MCA. Fibrinolysis was initiated 135 minutes after stroke onset with TCD monitoring. Twenty minutes later he suffered cardiac arrest with asystolia trace in the ECG monitor. Fibrinolysis was stopped during resuscitation. Four minutes later, he recovered with the same NIHSS score. Aggressive resuscitation maneuvers were not necessary. A repeated brain CT scan showed infarct signs in the whole MCA territory and a new TCD did not show any change. Serial blood analyses including cardiac nzymes were normal. The patient experienced four brief cardiac arrests in the next nine hours, so a temporary cardiac pacemaker was placed for four days. He was treated with aspirin and was discharged 14 days after admission. He has not experienced recurrences during a 6-month follow-up. We could not diagnose the etiology of the cardiac arrests. All the episodes occurred in the acute stroke stage and arrhythmia, atrioventricular block, myocardial ischemia or structural lesions were not found in the cardiac study. We propose that ischemia in the right insula induced sudden and transitory interruptions of the sympathetic cardiac tone.

  6. Biphasic CD8+ T-Cell Defense in Simian Immunodeficiency Virus Control by Acute-Phase Passive Neutralizing Antibody Immunization

    PubMed Central

    Iseda, Sumire; Takahashi, Naofumi; Poplimont, Hugo; Nomura, Takushi; Seki, Sayuri; Nakane, Taku; Nakamura, Midori; Shi, Shoi; Ishii, Hiroshi; Furukawa, Shota; Harada, Shigeyoshi; Naruse, Taeko K.; Kimura, Akinori; Matano, Tetsuro

    2016-01-01

    ABSTRACT Identifying human immunodeficiency virus type 1 (HIV-1) control mechanisms by neutralizing antibodies (NAbs) is critical for anti-HIV-1 strategies. Recent in vivo studies on animals infected with simian immunodeficiency virus (SIV) and related viruses have shown the efficacy of postinfection NAb passive immunization for viremia reduction, and one suggested mechanism is its occurrence through modulation of cellular immune responses. Here, we describe SIV control in macaques showing biphasic CD8+ cytotoxic T lymphocyte (CTL) responses following acute-phase NAb passive immunization. Analysis of four SIVmac239-infected rhesus macaque pairs matched with major histocompatibility complex class I haplotypes found that counterparts receiving day 7 anti-SIV polyclonal NAb infusion all suppressed viremia for up to 2 years without accumulating viral CTL escape mutations. In the first phase of primary viremia control attainment, CD8+ cells had high capacities to suppress SIVs carrying CTL escape mutations. Conversely, in the second, sustained phase of SIV control, CTL responses converged on a pattern of immunodominant CTL preservation. During this sustained phase of viral control, SIV epitope-specific CTLs showed retention of phosphorylated extracellular signal-related kinase (ERK)hi/phosphorylated AMP-activated protein kinase (AMPK)lo subpopulations, implying their correlation with SIV control. The results suggest that virus-specific CTLs functionally boosted by acute-phase NAbs may drive robust AIDS virus control. IMPORTANCE In early HIV infection, NAb responses are lacking and CTL responses are insufficient, which leads to viral persistence. Hence, it is important to identify immune responses that can successfully control such HIV replication. Here, we show that monkeys receiving NAb passive immunization in early SIV infection strictly control viral replication for years. Passive infusion of NAbs with CTL cross-priming capacity resulted in induction of functionally

  7. Proteins involved on TGF-β pathway are up-regulated during the acute phase of experimental Chagas disease.

    PubMed

    Ferreira, Roberto Rodrigues; de Souza, Elen Mello; de Oliveira, Fabiane Loiola; Ferrão, Patrícia Mello; Gomes, Leonardo Henrique Ferreira; Mendonça-Lima, Leila; Meuser-Batista, Marcelo; Bailly, Sabine; Feige, Jean Jacques; de Araujo-Jorge, Tania Cremonini; Waghabi, Mariana Caldas

    2016-05-01

    Studies developed by our group in the last years have shown the involvement of TGF-β in acute and chronic Chagas heart disease, with elevated plasma levels and activated TGF-β cell signaling pathway as remarkable features of patients in the advanced stages of this disease, when high levels of cardiac fibrosis is present. Imbalance in synthesis and degradation of extracellular matrix components is the basis of pathological fibrosis and TGF-β is considered as one of the key regulators of this process. In the present study, we investigated the activity of the TGF-β signaling pathway, including receptors and signaling proteins activation in the heart of animals experimentally infected with Trypanosoma cruzi during the period that mimics the acute phase of Chagas disease. We observed that T. cruzi-infected animals presented increased expression of TGF-β receptors. Overexpression of receptors was followed by an increased phosphorylation of Smad2/3, p38 and ERK. Furthermore, we correlated these activities with cellular factors involved in the fibrotic process induced by TGF-β. We observed that the expression of collagen I, fibronectin and CTGF were increased in the heart of infected animals on day 15 post-infection. Correlated with the increased TGF-β activity in the heart, we found that serum levels of total TGF-β were significantly higher during acute infection. Taken together, our data suggest that the commitment of the heart associates with increased activity of TGF-β pathway and expression of its main components. Our results, confirm the importance of this cytokine in the development and maintenance of cardiac damage caused by T. cruzi infection.

  8. Phase I Trial of Total Marrow and Lymphoid Irradiation Transplantation Conditioning in Patients with Relapsed/Refractory Acute Leukemia.

    PubMed

    Stein, Anthony; Palmer, Joycelynne; Tsai, Ni-Chun; Al Malki, Monzr M; Aldoss, Ibrahim; Ali, Haris; Aribi, Ahmed; Farol, Len; Karanes, Chatchada; Khaled, Samer; Liu, An; O'Donnell, Margaret; Parker, Pablo; Pawlowska, Anna; Pullarkat, Vinod; Radany, Eric; Rosenthal, Joseph; Sahebi, Firoozeh; Salhotra, Amandeep; Sanchez, James F; Schultheiss, Tim; Spielberger, Ricardo; Thomas, Sandra H; Snyder, David; Nakamura, Ryotaro; Marcucci, Guido; Forman, Stephen J; Wong, Jeffrey

    2017-04-01

    Current conditioning regimens provide insufficient disease control in relapsed/refractory acute leukemia patients undergoing hematopoietic stem cell transplantation (HSCT) with active disease. Intensification of chemotherapy and/or total body irradiation (TBI) is not feasible because of excessive toxicity. Total marrow and lymphoid irradiation (TMLI) allows for precise delivery and increased intensity treatment via sculpting radiation to sites with high disease burden or high risk for disease involvement, while sparing normal tissue. We conducted a phase I trial in 51 patients (age range, 16 to 57 years) with relapsed/refractory acute leukemia undergoing HSCT (matched related, matched unrelated, or 1-allele mismatched unrelated) with active disease, combining escalating doses of TMLI (range, 1200 to 2000 cGy) with cyclophosphamide (CY) and etoposide (VP16). The maximum tolerated dose was declared at 2000 cGy, as TMLI simulation studies indicated that >2000 cGy might deliver doses toxic for normal organs at or exceeding those delivered by standard TBI. The post-transplantation nonrelapse mortality (NRM) rate was only 3.9% (95% confidence interval [CI], .7 to 12.0) at day +100 and 8.1% (95% CI, 2.5 to 18.0) at 1 year. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 43.1% (95% CI, 29.2 to 56.3) and for grade III and IV, it was 13.7% (95% CI, 6.9 to 27.3). The day +30 complete remission rate for all patients was 88% and was 100% for those treated at 2000 cGy. The overall 1-year survival was 55.5% (95% CI, 40.7 to 68.1). The TMLI/CY/VP16 conditioning regimen is well tolerated at TMLI doses up to 2000 cGy with a low 100-day and 1-year NRM rate and no increased risk of GVHD with higher doses of radiation.

  9. Zoledronic acid exerts antitumor effects in NB4 acute promyelocytic leukemia cells by inducing apoptosis and S phase arrest.

    PubMed

    Liu, Shou-Sheng; Wang, Xiao-Pai; Li, Xiu-Bo; Liang, Jia-Yi; Liu, Ling-Ling; Lu, Ying; Zhong, Xue-Yun; Chen, Yun-Xian

    2014-10-01

    The aim of this study was to investigate the antitumor effect of zoledronic acid (ZOL) in the NB4 human acute promyelocytic leukemia (APL) cell line and explore the potential mechanism of action of this compound. NB4 cells were exposed to various concentrations (0-200μM) of ZOL. Cell viability was measured by MTS assay. The extent of cell apoptosis and distribution of cells in the different phases of the cell cycle were analyzed with flow cytometry. The expression of apoptosis- and cell cycle-related proteins was assayed by Western blot. The combined effect of ZOL and arsenic trioxide (ATO) on the proliferation of NB4 cells was also determined. The results of this study indicate that ZOL inhibits cell proliferation in a time- and dose-dependent fashion and also induces apoptosis and S phase arrest in a dose-dependent manner. The Western blot analysis confirmed the induction of apoptosis and S phase arrest, revealing that the pro-apoptosis proteins Bax, Puma and activated caspase-9 were upregulated and the anti-apoptosis proteins Bcl-2 and Bcl-xL were downregulated. ZOL at a concentration of 50μM synergized with 0.5μM ATO on the growth inhibition of NB4 cells. Taken together, our data indicate that ZOL exerts a potent antitumor effect on NB4 cells by inducing apoptosis and cell cycle arrest, and that ZOL can synergize with the traditional chemotherapy drug ATO.

  10. [Anaemia, iron index status and acute phase proteins in malaria (Abidjan, Côte d'Ivoire)].

    PubMed

    Ahiboh, H; Oga, A S; Yapi, H F; Kouakou, G; Boua, K D; Edjeme, N; Monnet, D

    2008-02-01

    Clinical signs of malaria are the combined expression of several biological mechanisms. During this parasite infection, anaemia can be the consequence of several different pathogenic mechanisms. It can be an acute haemolytic anaemia due to a mechanical and immune action of the parasite or an inflammation. Besides, in Africa malaria matches with iron deficiency area. So, malarial anaemia in tropical area can be a characteristic of iron deficiency The purpose of this survey was to define the features of malarial anaemia and elucidate the link of all biological processes involved. A black population living in tropical urban areas, with fever and diagnosed Plasmodium-infection was assessed. Parasitaemia, haemoglobin, hematocrit, average corpuscular volume and average corpuscular haemoglobin were determined. For each patient, iron index status and acute phase protein were assessed with the plasmatic iron, ferritin, haptoglobin, transferrin and C-reactive protein. Regardless of gender and age, the characteristics of malarial anaemia are microcythaemia and hypochromia. Anaemia occurs as frequently as parasitaemia is high. When parasitaemia is low anaemia gets a haemolytic feature. When parasitaemia is high, anaemia gets haemolytic and inflammatory features. Anaemia occurs more often with a good iron index status.

  11. Individuals with hematological malignancies before undergoing chemotherapy present oxidative stress parameters and acute phase proteins correlated with nutritional status.

    PubMed

    Camargo, Carolina de Quadros; Borges, Dayanne da Silva; de Oliveira, Paula Fernanda; Chagas, Thayz Rodrigues; Del Moral, Joanita Angela Gonzaga; Durigon, Giovanna Steffanello; Dias, Bruno Vieira; Vieira, André Guedes; Gaspareto, Patrick; Trindade, Erasmo Benício Santos de Moraes; Nunes, Everson Araújo

    2015-01-01

    Hematological malignancies present abnormal blood cells that may have altered functions. This study aimed to evaluate nutritional status, acute phase proteins, parameters of cell's functionality, and oxidative stress of patients with hematological malignancies, providing a representation of these variables at diagnosis, comparisons between leukemias and lymphomas and establishing correlations. Nutritional status, C-reactive protein (CRP), albumin, phagocytic capacity and superoxide anion production of mononuclear cells, lipid peroxidation and catalase activity in plasma were evaluated in 16 untreated subjects. Main diagnosis was acute leukemia (n = 9) and median body mass index (BMI) indicated overweight (25.6 kg/m(2)). Median albumin was below (3.2 g/dL) and CRP above (37.45 mg/L) the reference values. Albumin was inversely correlated with BMI (r = -0.53). Most patients were overweight before the beginning of treatment and had a high CRP/albumin ratio, which may indicate a nutrition inflammatory risk. BMI values correlated positively with lipid peroxidation and catalase activity. A strong correlation between catalase activity and lipid peroxidation was found (r = 0.75). Besides the elevated BMI, these patients also have elevated CRP values and unexpected relations between nutritional status and albumin, reinforcing the need for nutritional counseling during the course of chemotherapy, especially considering the correlations between oxidative stress parameters and nutritional status evidenced here.

  12. SHARED, NOT UNIQUE, COMPONENTS OF PERSONALITY AND PSYCHOSOCIAL FUNCTIONING PREDICT DEPRESSION SEVERITY AFTER ACUTE-PHASE COGNITIVE THERAPY

    PubMed Central

    Clark, Lee Anna; Vittengl, Jeffrey R.; Kraft, Dolores; Jarrett, Robin B.

    2005-01-01

    In a sample of 100 patients with recurrent major depression, we collected depression severity data early and late in acute-phase cognitive therapy, plus a wide range of psychosocial variables that have been studied extensively in depression research, including measures of interpersonal, cognitive, and social functioning, and personality traits using an inventory that is linked with the Big-Three tradition in personality assessment theory. By assessing this broad range of variables in a single study, we could examine the extent to which relations of these variables with depression were due to (a) a common factor shared across this diverse set of constructs, (b) factors shared among each type of construct (personality vs. psychosocial measures), or (c) specific aspects of the individual measures. Only the most general factor shared across the personality and psychosocial variables predicted later depression. PMID:14632375

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

    PubMed Central

    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

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

    PubMed Central

    Guo, Xiaoli; He, Yongzhi; Lu, Hongyang; Li, Yao; Su, Xin; Jiang, Ying; Tong, Shanbao

    2016-01-01

    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. PMID:27144032

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

    PubMed Central

    Barrios, M. N.; Martín, T.; Sánchez, M. L.; Buitrago, J. M. González; Jiménez, A.

    1995-01-01

    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. PMID:18475615

  16. Phase sensitive detection of light reflected from a Fabry{endash}P{acute e}rot interferometer

    SciTech Connect

    Bava, E.; Massari, F.

    1996-05-01

    We present an analysis of the Fabry{endash}P{acute e}rot response to a phase-modulated light in the reflection mode, by considering the general problem of the lock-in detection at the {ital p}th harmonics of the rf modulating frequency. Suitable frequency modulation conditions for servo-locking purposes are obtained and the values of modulation index which maximize the sensitivity for the first, third, and fifth harmonics are found. Moreover, we investigate the effects of the residual amplitude modulation introduced by the electro-optic frequency modulator, the presence of laser amplitude and frequency noise, and the dependence of the achievable closed-loop frequency fluctuation spectrum on the modulation index and detection noise. {copyright} {ital 1996 American Institute of Physics.}

  17. Early diagnosis of congenital Trypanosoma cruzi infection, using shed acute phase antigen, in Ushuaia, Tierra del Fuego, Argentina.

    PubMed

    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.

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

    PubMed

    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.

  19. Complement Factor H Binds at Two Independent Sites to C-reactive Protein in Acute Phase Concentrations*♦

    PubMed Central

    Okemefuna, Azubuike I.; Nan, Ruodan; Miller, Ami; Gor, Jayesh; Perkins, Stephen J.

    2010-01-01

    Factor H (FH) regulates the activation of C3b in the alternative complement pathway, both in serum and at host cell surfaces. It is composed of 20 short complement regulator (SCR) domains. The Y402H polymorphism in FH is a risk factor for age-related macular degeneration. C-reactive protein (CRP) is an acute phase protein that binds Ca2+. We established the FH-CRP interaction using improved analytical ultracentrifugation (AUC), surface plasmon resonance (SPR), and synchrotron x-ray scattering methods. Physiological FH and CRP concentrations were used in 137 mm NaCl and 2 mm Ca2+, in which the occurrence of denatured CRP was avoided. In solution, AUC revealed FH-CRP binding. The FH-CRP interaction inhibited the formation of higher FH oligomers, indicating that CRP blocked FH dimerization sites at both SCR-6/8 and SCR-16/20. SPR confirmed the FH-CRP interaction and its NaCl concentration dependence upon using either immobilized FH or CRP. The SCR-1/5 fragment of FH did not bind to CRP. In order of increasing affinity, SCR-16/20, SCR-6/8 (His-402), and SCR-6/8 (Tyr-402) fragments bound to CRP. X-ray scattering showed that FH became more compact when binding to CRP, which is consistent with CRP binding at two different FH sites. We concluded that FH and CRP bind at elevated acute phase concentrations of CRP in physiological buffer. The SCR-16/20 site is novel and indicates the importance of the FH-CRP interaction for both age-related macular degeneration and atypical hemolytic uremic syndrome. PMID:19850925

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

    PubMed Central

    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. PMID:26587339

  1. Single-scan measurement of conductance of a quartz crystal microbalance array coupled with resonant markers for biosensing in liquid phase

    SciTech Connect

    Hsiao, Hsien-Yi; Chen, Richie L. C.; Cheng, Tzong-Jih

    2009-04-15

    This work presents a method for sensing the viscoelastic property of liquid/solid interface using a quartz crystal microbalance (QCM) array. Each sensor in a QCM array has a unique resonant frequency and can be identified by a single-scan measurement of admittance (or impedance). The resonant frequency encoding at each sensor in an array was realized by connecting a capacitor with a known capacitance, called a resonant marker, to the sensor in series. Changes in the resonant frequency of all sensors in an array can be determined using an impedance analyzer and a program that determines the frequencies at which the conductance is at a local maximum. The sensing method allows every sensor output (resonant frequency) to be obtained without the use of time-consuming multiplexed hardware and software. Adsorptions of biomolecules by multiple sensor are monitored in the liquid phase to demonstrate the feasibility of frequency encoding using resonant markers and the single-scan measurement of conductance of a QCM array.

  2. Linguistic Markers of Processing Trauma Experience in Women’s Written Narratives During Different Breast Cancer Phases: Implications for Clinical Interventions

    PubMed Central

    Martino, Maria Luisa; Onorato, Raffaella; Freda, Maria Francesca

    2015-01-01

    Research into the change processes underlying the benefits of expressive writing is still incomplete. To fill this gap, we investigated the linguistic markers of change in cognitive and emotional processing among women with breast cancer, highlighting the differences and peculiarities during different treatment phases. A total of 60 writings were collected from 20 women: 10 receiving chemotherapy and 10 receiving biological therapy. We performed a series of repeated measures ANOVA for the most meaningful LIWC linguistic categories, including positive/negative emotions and cognitive processes, to assess change over three sessions. Results demonstrated a significant increase in the positive emotions category for the entire group of women, with particular relevance for the biological therapy group of women, and a marginally significant (p = .07) greater use of words indicating cognitive processes for women receiving biological therapy. For the negative emotions category time was significant for the whole group of women, showing a peak of use in the second session of writing. Peculiar differences in the linguistic markers of processing trauma were observed between the two groups. Although the writing intervention is a support for both groups of women, it seems to be beneficial when there is a large time gap since the administration of chemotherapy and, thus, when the patient can revisit the experience. The relationship of the illness with life can be rearticulated, and the writing becomes a space for resignifying the traumatic cancer experience. PMID:27247683

  3. SURVIVIN as a marker for quiescent-breast cancer stem cells-An intermediate, adherent, pre-requisite phase of breast cancer metastasis.

    PubMed

    Siddharth, Sumit; Das, Sarita; Nayak, Anmada; Kundu, Chanakya Nath

    2016-10-01

    Cancer stem cells drive the metastatic cascade by undergoing epithelial to mesenchymal transition (EMT) and again mesenchymal to epithelial transition (MET). Using multiple breast cancer cell lines including cigarette smoke induced breast cancer cells and tumor derived primary cells from patient sample; we developed a breast cancer metastasis model and reported the existence of an adherent, distinct pre-metastatic phase, quiescent-breast cancer stem cells (Q-BCSCs) prior to attaining an EMT. SURVIVIN was found to be expressed in Q-BCSCs. Time dependant biphasic expression of SURVIVIN in Q-BCSCs reveals that Q-BCSCs is a pre-metastatic phase distinct from both epithelial and mesenchymal counterparts. SURVIVIN favours metastasis and up-regulates WNT/β-CATENIN pathway in a PI3 K/AKT-dependant manner for self-renewal. Knockdown of SURVIVIN in Q-BCSCs lost the metastatic property of cells by inhibiting invasion, EMT-MET, PI3 K/AKT/WNT cascade, and induced apoptosis. Thus, our data suggest the existence of a novel pre-metastatic phase (Q-BCSCs) before EMT and SURVIVIN acts as a marker for Quiescent-BCSCs.

  4. Marker chromosomes.

    PubMed

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  5. DNA double strand breaks in the acute phase after synchrotron pencilbeam irradiation

    NASA Astrophysics Data System (ADS)

    Fernandez-Palomo, C.; Bräuer-Krisch, E.; Trippel, M.; Schroll, C.; Requardt, H.; Bartzsch, S.; Nikkhah, G.; Schültke, E.

    2013-07-01

    Introduction. At the biomedical beamline of the European Synchrotron Radiation Facility (ESRF), we have established a method to study pencilbeam irradiation in-vivoin small animal models. The pencilbeam irradiation technique is based on the principle of microbeam irradiation, a concept of spatially fractionated high-dose irradiation. Using γH2AX as marker, we followed the development of DNA double strand breaks over 48 hrs after whole brain irradiation with the pencilbeam technique. Method. Almost square pencilbeams with an individual size of 51 × 50 μm were produced with an MSC collimator using a step and shoot approach, while the animals were moved vertically through the beam. The center-to-center distance (ctc) was 400 μm, with a peak-to-valley dose ratio (PVDR) of about 400. Five groups of healthy adult mice received peak irradiation doses of either 330 Gy or 2,460 Gy and valley doses of 0.82 Gy and 6.15 Gy, respectively. Animals were sacrificed at 2, 12 and 48 hrs after irradiation. Results. DNA double strand breaks are observed in the path of the pencilbeam. The size of the damaged volume undergoes changes within the first 48 hours after irradiation. Conclusions. The extent of DNA damage caused by pencilbeam irradiation, as assessed by H2AX antibody staining, is dose- dependent.

  6. [Auriculoventricular blocks in the acute phase of myocardial infarction. Course and prognosis. Apropos of 90 cases].

    PubMed

    Hannachi, N; Derbel, F; Ben Ismail, M

    1988-03-01

    The objective is to study the clinical and electrocardiographic characteristics as well as the course of myocardial infarction complicated by atrio-ventricular block (AVB), and to propose a management to acute myocardial infarction with A-V block. This study concerns 90 patients (78 men and 12 women), with a mean age of 58 years. The overall frequency of AVB is 7.6 p. cent. The infarction is most of the time found posteriorly (51 p. cent of the cases). Syncopes are essentially seen in complete AVB (81 p. cent) and with deep antero-septal necrosis (73 p. cent). Heart failure is especially the complication of anterior (73 p. cent) and deep septal (78 p. cent) necrosis. The mortality of myocardial infarction complicated by A-V block (41 p. cent) is higher than that of uncomplicated necroses (15 p. cent). The prognosis is usually favorable in posteriorly located infarctions where the A-V block is usually regressive and benign while it is much more severe in other locations where the conduction disorders associated with severe myocardial lesions. Temporary and/or permanent electrosystolic stimulation must be well codified in its indications which should be broadened, especially in case of anterior or deep septal necrosis.

  7. Variable but consistent pattern of Meningioma 1 gene (MN1) expression in different genetic subsets of acute myelogenous leukaemia and its potential use as a marker for minimal residual disease detection

    PubMed Central

    Rosso, Valentina; Calabrese, Chiara; Signorino, Elisabetta; Bot-Sartor, Giada; Nicoli, Paolo; Gallo, Daniela; Bracco, Enrico; Morotti, Alessandro; Panuzzo, Cristina; Gottardi, Enrico; Cilloni, Daniela

    2016-01-01

    Meningioma 1 (MN1) gene overexpression has been reported in acute myeloid leukaemia (AML) patients and identified as a negative prognostic factor. In order to characterize patients presenting gene overexpression and to verify if MN1 transcript could be a useful marker for minimal residual disease detection, MN1 was quantified in 136 AML patients with different cytogenetic risk and in 50 normal controls. In 20 patients bearing a fusion gene transcript suitable for minimal residual disease quantitative assessment and in 8 patients with NPM1 mutation, we performed a simultaneous analysis of MN1 and the fusion-gene transcript or NPM1 mutation during follow-up. Sequential MN1 and WT1 analysis was also performed in 13 AML patients lacking other molecular markers. The data obtained show that normal cells consistently express low levels of MN1 transcript. In contrast, high levels of MN1 expression are present in 47% of patients with normal karyotype and in all cases with inv(16). MN1 levels during follow-up were found to follow the pattern of other molecular markers (fusion gene transcripts, NPM1 and WT1). Increased MN1 expression in the BM during follow up was always found to be predictive of an impending hematological relapse. PMID:27765915

  8. Factors associated with acute-phase response of bisphosphonate-naïve or pretreated women with osteoporosis receiving an intravenous first dose of zoledronate or ibandronate.

    PubMed

    Popp, A W; Senn, R; Curkovic, I; Senn, C; Buffat, H; Popp, P F; Lippuner, K

    2017-03-15

    A first intravenous dose of bisphosphonates may be associated with an acute-phase response (APR). In bisphosphonate-naïve women with postmenopausal osteoporosis, the characteristics and frequency of APR may differ by compound. Prior bisphosphonate exposure was predictive of APR risk and severity.

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

    EPA Science Inventory

    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...

  10. Guidelines on selection of laboratory tests for monitoring the acute phase response. International Committee for Standardization in Haematology (expert panel on blood rheology).

    PubMed Central

    1988-01-01

    These guidelines refer to laboratory tests for monitoring changes in acute phase proteins in patients with an inflammatory response to tissue damage. Quantitative measurements of acute phase proteins are a valuable indicator of the presence, extent, and response of inflammation to treatment. When short term (less than 24 hours) changes in the inflammatory response are expected, quantitative assay of C reactive protein is the test of choice. The hyperproteinaemia that develops in response to a longer term (more than 24 hours) inflammatory response is complex and may vary from one disease to another. A test that is sensitive to the combined effect of several plasma proteins is therefore indicated, and appropriate tests include the erythrocyte sedimentation rate and plasma viscosity--the latter having several advantages. Tests for monitoring short term and long term changes in acute phase proteins are complementary and should be used for different clinical purposes; no one test is ideal for all clinical situations. A quality control programme is an essential component of laboratory tests for monitoring the acute phase response. PMID:2463272

  11. A phase I study of intermediate dose cytarabine in combination with lenalidomide in relapsed/refractory acute myeloid leukemia.

    PubMed

    Griffiths, Elizabeth A; Brady, William E; Tan, Wei; Vigil, Carlos E; Thompson, James E; Ford, Laurie A; Dickey, Noelle M; L Bashaw, Heather; Sperrazza, Jill; Wetzler, Meir; Wang, Eunice S

    2016-04-01

    Relapsed/refractory (r/r) Acute Myeloid Leukemia (AML) remains a therapeutic challenge. Cytarabine arabinoside (AraC) forms the backbone of most regimens, with complete responses (CR) ranging from 17 to 20%. Lenalidomide (Len) is approved by the FDA for multiple myeloma and myelodysplasia and has demonstrated activity in AML. We developed a phase I study to evaluate the safety and tolerability of Len in combination with intermediate dose AraC (1.5 g/m(2)/day given on days 1-5) in adults with r/r AML. The maximally tolerated dose for this combination was 10mg daily on days 6-26 of a 28 day cycle. Dose de-escalation from 25mg was required due to rash, liver function abnormalities, and hypokalemia. Of 32 evaluable patients, five achieved CR (16%), 5CRi (16%) and 3 had hematological improvements for an overall response rate of 41% (13/32). Median overall survival (95% confidence interval) for patients treated on study was 5.8 (2.5-10.6) months and disease free survival was 3.4 (2.3-6.2) months. This single institute phase I trial of Len and intermediate dose AraC was associated with marked skin and other toxicities. At the dose and schedule tested, this combination did not appear to result in improved CR over single agent AraC for r/r AML.

  12. The Diagnostic Usefulness of Serum Total Bile Acid Concentrations in the Early Phase of Acute Pancreatitis of Varied Etiologies

    PubMed Central

    Maleszka, Aleksandra; Dumnicka, Paulina; Matuszyk, Aleksandra; Pędziwiatr, Michał; Mazur-Laskowska, Małgorzata; Sporek, Mateusz; Ceranowicz, Piotr; Olszanecki, Rafał; Kuźniewski, Marek; Kuśnierz-Cabala, Beata

    2017-01-01

    The most common causes of acute pancreatitis (AP) are biliary tract diseases with cholestasis and alcohol consumption. In 10%–15% of patients, etiology determination is difficult. Identification of the etiology allows for the implementation of adequate treatment. The aim of this study was to assess the utility of the serum concentrations of total bile acids (TBA) to diagnose AP etiology in the early phase of the disease. We included 66 patients with AP, admitted within the first 24 h from the onset of symptoms. TBA were measured in serum at 24, 48, and 72 h from the onset of AP, using an automated fifth generation assay. The bilirubin-to-TBA ratio (B/TBA) was calculated. TBA was highest on the first day of AP and decreased subsequently. In patients with biliary etiology, serum TBA was significantly higher compared to those with alcoholic and other etiologies. B/TBA was significantly higher in patients with alcoholic etiology. At admission, the cut-off values of 4.7 µmol/L for TBA and 4.22 for the B/TBA ratio allowed for a differentiation between biliary and other etiologies of AP with a diagnostic accuracy of 85 and 83%. Both TBA and B/TBA may help in the diagnosis of AP etiology in the early phase of AP. PMID:28067818

  13. ACUTE PHASE DEATHS FROM MURINE POLYMICROBIAL SEPSIS ARE CHARACTERIZED BY INNATE IMMUNE SUPPRESSION RATHER THAN EXHAUSTION1

    PubMed Central

    Chiswick, Evan L.; Mella, Juan R.; Bernardo, John; Remick, Daniel

    2015-01-01

    Sepsis, a leading cause of death in the U.S., has poorly understood mechanisms of mortality. To address this, our model of Cecal Ligation and Puncture (CLP) induced sepsis stratifies mice as predicted to Live (Live-P) or Die (Die-P) based on plasma IL-6. Six hours post-CLP, both Live-P and Die-P groups have equivalent peritoneal bacterial colony forming units and recruitment of phagocytes. By 24hr, however, Die-P mice have increased bacterial burden, despite increased neutrophil recruitment, suggesting Die-P phagocytes have impaired bacterial killing. Peritoneal cells were used to study multiple bactericidal processes: bacterial killing, Reactive Oxygen Species (ROS) generation, and phagocytosis. Total phagocytosis and intra-phagosomal processes were determined with triple-labeled E.coli, covalently labeled with ROS and pH sensitive probes, and an ROS/pH insensitive probe for normalization. While similar proportions of Live-P and Die-P phagocytes responded to exogenous stimuli, Die-P phagocytes showed marked deficits in all parameters measured, thus suggesting immunosuppression rather than exhaustion. This contradicts the prevailing sepsis paradigm that acute phase sepsis deaths (<5 days) result from excessive inflammation, whereas chronic phase deaths (>5 days) are characterized by insufficient inflammation and immunosuppression. These data suggest that suppression of cellular innate immunity in sepsis occurs within the first six hours. PMID:26371253

  14. Insights on Sources, Growth, and Phase Partitioning of Atmospheric Particles from Hourly Measurements of Organic Marker Compounds

    NASA Astrophysics Data System (ADS)

    Williams, B.; Goldstein, A.; Kreisberg, N.; Hering, S.; Docherty, K.; Jimenez, J.; Shields, L.; Qin, X.; Prather, K.; Ziemann, P.

    2007-12-01

    Atmospheric aerosols have adverse affects on human health and have direct and indirect affects on the global radiation balance. In order to implement particle concentration control strategies, we must first understand particle origins. Atmospheric aerosols have both primary sources such as combustion processes and secondary sources such as photochemically driven gas to particle phase partitioning. By monitoring changes in the molecular composition of the organic fraction of atmospheric aerosols, these various sources can be differentiated. Thermal desorption Aerosol Gas chromatography (TAG) is a new in-situ instrument capable of identifying and quantifying organic aerosol chemical composition with one hour time resolution. TAG is fully automated, offering around the clock measurements to determine diurnal, weekly, and seasonal patterns in organic aerosol composition, hence, determining aerosol sources and transformation processes. We report results from ambient measurements made in Southern California during the summer and fall of 2005 as part of the Study of Organic Aerosol at Riverside (SOAR). We use hourly measurements of over 300 individual organic compounds to define both primary and secondary particle sources. The particle sources defined include primary anthropogenic sources such as vehicle emissions, meat cooking, biomass burning, pesticide use, herbicide use, along with primary biogenic sources such as plant emissions and plant waxes. We also explore secondary particle sources (i.e. SOA) formed as a result of the oxidation of biogenic and anthropogenic precursor gases. Comparisons are made between TAG-defined sources and aerosol sources defined using Aerosol Time-Of-Flight Mass Spectrometer (ATOFMS) and Aerosol Mass Spectrometer (AMS) data. In addition to source apportionment results, we present seasonal changes in ambient phase partitioning of organic compounds as a function of carbon number for multiple compound classes.

  15. Ischemia-Modified Albumin as a Marker of Acute Coronary Syndrome: The Case for Revising the Concept of “N-Terminal Modification” to “Fatty Acid Occupation” of Albumin

    PubMed Central

    Oran, Bulent

    2017-01-01

    Ischemia-modified albumin (IMA) is assumed “N-terminal modified” albumin which is generated immediately following myocardial ischemia. The diagnosis of IMA is based on reduced cobalt binding affinity to albumin which is attributed mainly to incapability of cobalt to bind at albumin's modified N-terminus. Although the albumin cobalt binding test was accepted as a potentially powerful marker for discriminating acute coronary syndrome from nonischemic chest pain, its usefulness has been brought into question in recent years. Patients with acutely ischemic myocardium exhibit a rapid increase in serum levels of fatty acids (FAs). Almost all released FAs are strongly bound to albumin which create conformational changes in the protein with resultant reduced cobalt binding affinity. There is a clear metabolic and temporal relationship between IMA measured via albumin cobalt binding testing and serum levels of FAs. In line with what has been suggested recently in the literature, we conclude that a shift from the concept of “N-terminal modified” to “FA-occupied” albumin is required, as this better describes IMA in patients with acute coronary syndrome. We also offer “oxidation modified albumin, OMA,” which is conceptually different from the “FA-occupied” IMA, to describe modification of albumin in chronic disease associated with increased oxidative stress. PMID:28356609

  16. Mild sensory stimulation re-establishes cortical function during the acute phase of ischemia

    PubMed Central

    Lay, Christopher C.; Davis, Melissa F.; Chen-Bee, Cynthia H.; Frostig, Ron D.

    2011-01-01

    When delivered within 1 and in most cases 2 hours of permanent middle cerebral artery occlusion (pMCAO), mild sensory stimulation (intermittent single whisker stimulation) was shown to be completely neuroprotective according to assessment with multiple techniques 24 hours after pMCAO in a rodent model of ischemic stroke (Lay et al., 2010). The acute effect of stimulation treatment on the ischemic cortex however, had yet to be reported. Here we characterize cortical function and perfusion during the 120 minute whisker stimulation period in four experimental groups with treatment initiated 0, 1, 2 hours (protected groups) or 3 hours post-pMCAO (unprotected group) using multiple techniques. According to functional imaging, a gradual return of evoked whisker functional representation to baseline levels was initiated with treatment onset and completed within the treatment period. Evoked neuronal activity and reperfusion to the ischemic area also showed a gradual recovery in protected animals. Surprisingly, a similar recovery profile was observed in response to treatment in all protected animals, irrespective of treatment onset time. Non-stimulated pMCAO control group data demonstrate that reperfusion is not spontaneous. This makes the complete protection observed in the majority of animals stimulated at 2 hours post-pMCAO even more surprising as these animals recovered despite having been in this severely ischemic state for two full hours. In summary, when delivered within a 2 hour window post- pMCAO, whisker stimulation treatment initiated reperfusion and a gradual recovery of cortical function that was completed or nearly completed within the treatment period. PMID:21832179

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

    SciTech Connect

    Ganusov, Vitaly V; Korber, Bette M; Perelson, Alan S

    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.

  18. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response.

    PubMed

    Yang, Yang; Zhang, Yan; Wang, Zhaotao; Wang, Shanshan; Gao, Mou; Xu, Ruxiang; Liang, Chunyang; Zhang, Hongtian

    2016-04-01

    The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability.

  19. Randomised phase 2 trial of intra-coronary nitrite during acute myocardial infarction

    PubMed Central

    Jones, Daniel A; Pellaton, Cyril; Velmurugan, Shanti; Rathod, Krishnaraj Sinha; Andiapen, Mervyn; Antoniou, Sotiris; van Eijl, Sven; Webb, Andrew J; Westwood, Mark A; Parmar, Mahesh K; Mathur, Anthony; Ahluwalia, Amrita

    2015-01-01

    Rationale Pre-clinical evidence demonstrates that inorganic nitrite, following its in situ conversion to nitric oxide, attenuates consequent myocardial reperfusion injury. Objective We investigated whether intra-coronary injection of nitrite during primary percutaneous coronary intervention (PCI) might improve infarct size in ST-elevated myocardial infarction (STEMI). Methods and Results Patients undergoing primary PCI (n=80) were randomised to receive intracoronary (10mL) sodium nitrite (1.8μmol) or NaCl (placebo) before balloon inflation. The primary endpoint was infarct size assessed by measuring creatine kinase (CK) release. Secondary outcomes included infarct size assessed by troponin T release and by cardiac magnetic resonance imaging (CMR) on day 2. Baseline characteristics were similar between the groups. No evidence of differences in CK release (p=0.92), troponin T (p=0.85) or CMR-assessed infarct size (p=0.254) were evident. In contrast there was an improvement in myocardial salvage index (p=0.05) and reduction in MACE at 1 year (2.6% vs 15.8%, p=0.04) in the nitrite group. In a 66-patient sub-group with TIMI≤1 flow there was reduced serum CK (p=0.030) and a 19% reduction in CMR-determined infarct size (p=0.034) with nitrite. No adverse effects of nitrite were detected. Conclusions In this phase II study intra-coronary nitrite infusion did not alter infarct size although a trend to improved myocardial salvage index and a significant reduction in MACE was evident. In a sub-group of patients with TIMI flow≤1 nitrite reduced infarct size and MACE and improved myocardial salvage index indicating that a phase III clinical trial assessing intra-coronary nitrite administration as an adjunct to PCI in STEMI patients is warranted. Clinical Trial Registration URL: http://clinicaltrials.gov NCT01584453. PMID:25512434

  20. Acute-phase response to benzo[a]pyrene and induction of rat ALDH3A1.

    PubMed

    Pappas, Periklis; Sotiropoulou, Marianthi; Karamanakos, Petros; Kostoula, Aggeliki; Levidiotou, Stamatia; Marselos, Marios

    2003-02-01

    The aldehyde dehydrogenase-3A1 (ALDH3A1) enzyme, encoded by a member of the [Ah]-gene family, is dramatically increased (more than 100-fold) by benzo[a]pyrene (BaP) and other polycyclic hydrocarbons. Although much is known regarding the mechanism for the drug-metabolizing enzymes up-regulated by the Ah receptor, the physiological role of that tremendously increased ALDH3A1 enzyme activity is not yet fully clarified. The aim of this study was to identify a possible acute-phase response to different classes of xenobiotics affecting the metabolic capacity of the hepatocyte, by studying possible changes of serum acute-phase proteins (APPs) of hepatic origin, before and after BaP administration. Male Wistar rats were used in different series of experiments. The effects of BaP were estimated in terms of dose-response and time-response, with regard to the serum level of several APPs such as alpha-1-acid-glycoprotein (AAG), alpha-1-antitrypsin (AAT), C-reactive protein (CRP), and haptoglobin (HPT). In parallel experiments, levels of the same proteins have been determined after a time-dependent treatment with lipopolysaccharide (LPS). The changes in serum proteins were compared with the results of BaP or LPS administration on both hepatic ALDH3A1 and total ALDH enzyme activities. The results showed that BaP induced CRP and HPT in a time-dependent way, proportional to that caused by LPS. Additionally, ALDH3A1, CRP, and HPT were induced by BaP subacute treatment, whereas another type of ALDH inducer, phenobarbital, did not affect the levels of APPs or ALDH3A1, but did increase ALDH1A3 activity. Former studies of our group have shown that the inhibitory effects of different non-steroidal anti-inflammatory drugs (NSAIDs) on the ALDH3A1 induction were most possibly due to a decreased formation of arachidonic products like prostaglandins. Considering the changes of APPs caused by BaP, this study further supports the suggestion that the induction of ALDH3A1 is related to an

  1. C-reactive protein, haptoglobin and Pig-Major acute phase protein profiles of pigs infected experimentally by different isolates of porcine reproductive and respiratory syndrome virus.

    PubMed

    Saco, Y; Martínez-Lobo, F; Cortey, M; Pato, R; Peña, R; Segalés, J; Prieto, C; Bassols, A

    2016-02-01

    Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) is the etiologic agent of PRRS, one of the most important diseases in swine worldwide. In the present work, the effects of different PRRSV strains were tested on a piglet experimental model to study the induced acute phase response. For this purpose, pigs (n=15 for each group) were intranasally inoculated with one of five PRRSV strains (isolates EU10, 12, 17, 18 from genotype 1 and isolate JA-142 from genotype 2). The acute phase response was monitored by measuring acute phase proteins (APPs). Specifically, the serum concentration of haptoglobin (Hp), C-reactive protein (CRP) and Pig-Major Acute Protein (Pig-MAP) was determined at 0, 3, 6, 9, 12, 15, 18 and 21 days p.i. Clinical signs and growth performance were also monitored during the experiment. All animals became viremic after inoculation during the study period. The APP response was heterogeneous and dependent on the strain, being strains EU10, EU 18 and JA-142 those that induced the highest response and the strongest clinical signs. In general, Hp was the most sensitive biomarker for PRRSV infection, CRP behaved as moderate and Pig-MAP was the less responsive during the course of PRRSV experimental infection. Hp and CRP were significantly discriminatory between infected and control pigs, but not Pig-MAP.

  2. Stress-dependent changes in neuroinflammatory markers observed after common laboratory stressors are not seen following acute social defeat of the Sprague Dawley rat.

    PubMed

    Hueston, Cara M; Barnum, Christopher J; Eberle, Jaime A; Ferraioli, Frank J; Buck, Hollin M; Deak, Terrence

    2011-08-03

    Exposure to acute stress has been shown to increase the expression of pro-inflammatory cytokines in brain, blood and peripheral organs. However, the nature of the inflammatory response evoked by acute stress varies depending on the stressor used and species examined. The goal of the following series of studies was to characterize the consequences of social defeat in the Sprague Dawley (SD) rat using three different social defeat paradigms. In Experiments 1 and 2, adult male SD rats were exposed to a typical acute resident-intruder paradigm of social defeat (60 min) by placement into the home cage of a larger, aggressive Long Evans rat and brain tissue was collected at multiple time points for analysis of IL-1β protein and gene expression changes in the PVN, BNST and adrenal glands. In subsequent experiments, rats were exposed to once daily social defeat for 7 or 21 days (Experiment 3) or housed continuously with an aggressive partner (separated by a partition) for 7 days (Experiment 4) to assess the impact of chronic social stress on inflammatory measures. Despite the fact that social defeat produced a comparable corticosterone response as other stressors (restraint, forced swim and footshock; Experiment 5), acute social defeat did not affect inflammatory measures. A small but reliable increase in IL-1 gene expression was observed immediately after the 7th exposure to social defeat, while other inflammatory measures were unaffected. In contrast, restraint, forced swim and footshock all significantly increased IL-1 gene expression in the PVN; other inflammatory factors (IL-6, cox-2) were unaffected in this structure. These findings provide a comprehensive evaluation of stress-dependent inflammatory changes in the SD rat, raising intriguing questions regarding the features of the stress challenge that may be predictive of stress-dependent neuroinflammation.

  3. Phase 1 Multicenter Study of Vincristine Sulfate Liposomes Injection and Dexamethasone in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia

    PubMed Central

    Thomas, Deborah A.; Kantarjian, Hagop M.; Stock, Wendy; Heffner, Leonard T.; Faderl, Stefan; Garcia-Manero, Guillermo; Ferrajoli, Alessandra; Wierda, William; Pierce, Sherry; Lu, Biao; Deitcher, Steven R.; O’Brien, Susan

    2015-01-01

    BACKGROUND Dose intensification of chemotherapy has improved outcome for younger adults with de novo acute lymphoblastic leukemia (ALL). Novel formulations of standard chemotherapy agents may further reduce the incidence of disease recurrence after frontline chemotherapy. Vincristine (VCR) sulfate liposomes injection (VSLI) is a sphingomyelin/cholesterol nanoparticle encapsulated VCR formulation that improves the pharmacokinetic profile of VCR without augmenting neurotoxicity. METHODS A phase 1 trial of weekly, intravenous VSLI at 1.5 mg/m2, 1.825 mg/m2, 2.0 mg/m2, 2.25 mg/m2, or 2.4 mg/m2 was conducted to determine the maximum tolerated dose (MTD) using a standard, 3 + 3 dose-escalation design. Dexamethasone (40 mg) was given on Days 1 through 4 and on Days 11 through 14 of each 4-week cycle. RESULTS Thirty-six adults with relapsed/refractory ALL, all previously treated with conventional VCR, received at least 1 dose of VSLI. The MTD of VSLI was 2.25 mg/m2 based on dose-limiting toxicities of grade 3 motor neuropathy, grade 4 seizure, and grade 4 hepatotoxicity in 1 patient each at the 2.4 mg/m2 dose level. The most common toxicities attributed to VSLI included peripheral neuropathy (55%) and constipation (53%). A complete response (CR) was achieved in 7 of 36 patients (19%) based on an intent-to-treat analysis; the CR rate was 29% for the 14 patients who underwent therapy as their first salvage attempt. Four of 7 patients who achieved a CR underwent subsequent allogeneic stem cell transplantation in remission. CONCLUSIONS In this study, VSLI plus dexamethasone appeared to be an effective salvage therapy option for relapsed/refractory ALL. A phase 2, international, multicenter clinical trial assessing the efficacy of single-agent VSLI as second salvage therapy for patients with previously treated ALL is underway. PMID:19708032

  4. Exacerbated skeletal muscle inflammation and calcification in the acute phase of infection by Mexican Trypanosoma cruzi DTUI strain.

    PubMed

    Vizcaíno-Castillo, Andrea; Jiménez-Marín, Andrea; Espinoza, Bertha

    2014-01-01

    A murine model was used to study the histopathological aspects and cytokine expression levels in skeletal muscle provoked by the infection with Mexican TcI strains. BALB/c mice were inoculated with the virulent Querétaro strain and the nonvirulent Ninoa strain. Parasite numbers were counted in blood and skeletal muscle at different times post-infection, and real time-PCR expression levels of the cytokines IL-12, IL-4, IL-10, IFN- γ , and TNF- α were evaluated. In the acute phase of infection, a high parasitic load, both in blood and skeletal muscle, was detected. The histopathological analyses showed an exacerbated inflammation and granulomatous-like infiltrate with the Querétaro strain. Interestingly, extensive calcification areas were observed in the skeletal muscle surrounded by inflammatory infiltrates. TNF- α and IL-10 expression exhibited a significant increase at the peak of infection. In summary, Querétaro strain, a Mexican TcI strain, is virulent enough to induce high inflammation and calcification in skeletal muscle of the hind limbs, which could be related to high expression levels of TNF- α .

  5. A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia.

    PubMed

    Fehniger, Todd A; Uy, Geoffrey L; Trinkaus, Kathryn; Nelson, Alissa D; Demland, Jeffery; Abboud, Camille N; Cashen, Amanda F; Stockerl-Goldstein, Keith E; Westervelt, Peter; DiPersio, John F; Vij, Ravi

    2011-02-10

    Older patients with acute myeloid leukemia (AML) have limited treatment options and a poor prognosis, thereby warranting novel therapeutic strategies. We evaluated the efficacy of lenalidomide as front-line therapy for older AML patients. In this phase 2 study, patients 60 years of age or older with untreated AML received high-dose (HD) lenalidomide at 50 mg daily for up to 2 28-day cycles. If patients achieved a complete remission (CR)/CR with incomplete blood count recovery (CRi) or did not progress after 2 cycles of HD lenalidomide, they received low-dose lenalidomide (10 mg daily) until disease progression, an unacceptable adverse event, or completion of 12 cycles. Thirty-three AML patients (median age, 71 years) were enrolled with intermediate (55%), unfavorable (39%), or unknown (6%) cytogenetic risk. Overall CR/CRi rate was 30%, and 53% in patients completing HD lenalidomide. The CR/CRi rate was significantly higher in patients presenting with a low (< 1000/μL) circulating blast count (50%, P = .01). The median time to CR/CRi was 30 days, and duration of CR/CRi was 10 months (range, 1- ≥ 17 months). The most common grades ≥ 3 toxicities were thrombocytopenia, anemia, infection, and neutropenia. HD lenalidomide has evidence of clinical activity as initial therapy for older AML patients, and further study of lenalidomide in AML and MDS is warranted. This study is registered at www.clinicaltrials.gov as #NCT00546897.

  6. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia

    PubMed Central

    Eghtedar, Alireza; Verstovsek, Srdan; Estrov, Zeev; Burger, Jan; Cortes, Jorge; Bivins, Carol; Faderl, Stefan; Ferrajoli, Alessandra; Borthakur, Gautam; George, Solly; Scherle, Peggy A.; Newton, Robert C.; Kantarjian, Hagop M.

    2012-01-01

    We conducted a phase 2 study of ruxolitinib in patients with relapsed/refractory leukemias. Patients with acceptable performance status (0-2), adequate organ function, and no active infection, received ruxolitinib 25 mg orally twice a day for 4 weeks (1 cycle). Response was assessed after every 2 cycles of treatment, and patients who completed 2 cycles were allowed to continue treatment until disease progression. Dose escalation to 50 mg twice daily was permitted in patients demonstrating a benefit. Thirty-eight patients, with a median age of 69 years (range, 45-88), were treated. The median number of prior therapies was 2 (range, 1-6). Twelve patients had JAK2V617F mutation. Patients received a median of 2 cycles of therapy (range, 1-22). Three of 18 patients with postmyeloproliferative neoplasm (MPN) acute myeloid leukemia (AML) showed a significant response; 2 achieved complete remission (CR) and one achieved a CR with insufficient recovery of blood counts (CRi). The responding patients with palpable spleens also had significant reductions in spleen size. Overall, ruxolitinib was very well tolerated with only 4 patients having grade 3 or higher toxicity. Ruxolitinib has modest antileukemic activity as a single agent, particularly in patients with post-MPN AML. The study was registered at www.clinicaltrials.gov as NCT00674479. PMID:22422826

  7. A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia

    PubMed Central

    Fehniger, Todd A.; Uy, Geoffrey L.; Trinkaus, Kathryn; Nelson, Alissa D.; Demland, Jeffery; Abboud, Camille N.; Cashen, Amanda F.; Stockerl-Goldstein, Keith E.; Westervelt, Peter; DiPersio, John F.

    2011-01-01

    Older patients with acute myeloid leukemia (AML) have limited treatment options and a poor prognosis, thereby warranting novel therapeutic strategies. We evaluated the efficacy of lenalidomide as front-line therapy for older AML patients. In this phase 2 study, patients 60 years of age or older with untreated AML received high-dose (HD) lenalidomide at 50 mg daily for up to 2 28-day cycles. If patients achieved a complete remission (CR)/CR with incomplete blood count recovery (CRi) or did not progress after 2 cycles of HD lenalidomide, they received low-dose lenalidomide (10 mg daily) until disease progression, an unacceptable adverse event, or completion of 12 cycles. Thirty-three AML patients (median age, 71 years) were enrolled with intermediate (55%), unfavorable (39%), or unknown (6%) cytogenetic risk. Overall CR/CRi rate was 30%, and 53% in patients completing HD lenalidomide. The CR/CRi rate was significantly higher in patients presenting with a low (< 1000/μL) circulating blast count (50%, P = .01). The median time to CR/CRi was 30 days, and duration of CR/CRi was 10 months (range, 1- ≥ 17 months). The most common grades ≥ 3 toxicities were thrombocytopenia, anemia, infection, and neutropenia. HD lenalidomide has evidence of clinical activity as initial therapy for older AML patients, and further study of lenalidomide in AML and MDS is warranted. This study is registered at www.clinicaltrials.gov as #NCT00546897. PMID:21051557

  8. A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib in patients with refractory or relapsed acute myeloid leukemia.

    PubMed

    Harousseau, Jean-Luc; Lancet, Jeffrey E; Reiffers, Josy; Lowenberg, Bob; Thomas, Xavier; Huguet, Francoise; Fenaux, Pierre; Zhang, Steven; Rackoff, Wayne; De Porre, Peter; Stone, Richard

    2007-06-15

    This phase 2 study evaluated the efficacy and safety of the oral farnesyltransferase inhibitor tipifarnib in adults with refractory or relapsed acute myeloid leukemia (AML). Patients (n=252) received tipifarnib 600 mg twice a day for 21 days in 28-day cycles. Median age was 62 years; 99 (39%) patients were 65 years or older. Eleven (4%) of 252 patients achieved complete remission (CR) or complete remission with incomplete platelet recovery (CRp; 9 CR and 2 CRp). Nineteen patients (8%), including those who achieved CR/CRp, achieved a reduction in bone marrow blasts to less than 5% blasts. Bone marrow blasts were reduced more than 50% in an additional 8 patients (total = 27; 11%). Median survival was 369 days for patients who achieved CR/CRp. Myelosuppression was the most common adverse event. The most common nonhematologic toxicities were fever, nausea, and hypokalemia. Single-agent treatment with tipifarnib induced durable CR/CRp, which was associated with prolonged survival, in some patients with refractory or relapsed AML. The response rate observed in this heavily pretreated group of patients suggests the requirement to enhance the response rate either by combining tipifarnib with other active agents or determining factors that are predictive of response.

  9. Phase I clinical study of RG7356, an anti-CD44 humanized antibody, in patients with acute myeloid leukemia

    PubMed Central

    Vey, Norbert; Delaunay, Jacques; Martinelli, Giovanni; Fiedler, Walter; Raffoux, Emmanuel; Prebet, Thomas; Gomez-Roca, Carlos; Papayannidis, Cristina; Kebenko, Maxim; Paschka, Peter; Christen, Randolph; Guarin, Ernesto; Bröske, Ann-Marie; Baehner, Monika; Brewster, Michael; Walz, Antje-Christine; Michielin, Francesca; Runza, Valeria; Meresse, Valerie; Recher, Christian

    2016-01-01

    RG7356, a recombinant anti-CD44 immunoglobulin G1 humanized monoclonal antibody, inhibits cell adhesion and has been associated with macrophage activation in preclinical models. We report results of a phase I dose-escalation study of RG7356 in relapsed/refractory acute myeloid leukemia (AML). Eligible patients with refractory AML, relapsed AML after induction chemotherapy, or previously untreated AML not eligible for intensive chemotherapy were enrolled and received intravenous RG7356 at dosages ≤ 2400 mg every other week or ≤ 1200 mg weekly or twice weekly; dose escalation started at 300 mg. Forty-four patients (median age, 69 years) were enrolled. One dose-limiting toxicity occurred (grade 3 hemolysis exacerbation) after one 1200 mg dose (twice-weekly cohort). The majority of adverse events were mild/moderate. Infusion-related reactions occurred in 64% of patients mainly during cycle 1. Two patients experienced grade 3 drug-induced aseptic meningitis. Pharmacokinetics increased supraproportionally, suggesting a target-mediated drug disposition (TMDD) at ≥ 1200 mg. Two patients achieved complete response with incomplete platelet recovery or partial response, respectively. One patient had stable disease with hematologic improvement. RG7356 was generally safe and well tolerated. Maximum tolerated dose was not reached, but saturation of TMDD was achieved. The recommended dose for future AML evaluations is 2400 mg every other week. PMID:27081038

  10. Acute-phase proteins, oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin in Arabian mares affected with pyometra.

    PubMed

    El-Bahr, S M; El-Deeb, W M

    2016-09-01

    New biomarkers are essential for diagnosis of pyometra in mares. In this context, 12 subfertile Arabian mares suffered from pyometra were admitted to the Veterinary Teaching Hospital. The basis for diagnosis of pyometra was positive findings of clinical examination and rectal palpation. Blood samples were collected from diseased animals and from five Arabian healthy mares, which were considered as control group. Acute-phase proteins (APP), oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin I were estimated in the harvested sera of both groups. Clinical examination revealed purulent yellowish fluid discharged from vagina of affected animals and rectal palpation of the reproductive tract revealed uterine distention. The biochemical analysis of the serum revealed significant increase in cardiac troponin I, creatin kinase, alkaline phosphatase, malondialdehyde, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin, and serum amyloid A and significant decrease in reduced glutathione, superoxide dismutase (SOD), total antioxidant capacity, and nitric oxide (NO) of mares affected with pyometra compare to control. Cardiac troponin I was positively correlated with aspartate aminotransferase, creatin kinase, malondialdehyde, alkaline phosphatase, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin and serum amyloid A and negatively correlated with glutathione, superoxide dismutase, total antioxidant capacity and nitric oxide in serum of mares affected with pyometra. Moreover, there was high positive correlation between proinflammatory cytokines and APP in serum of mares affected with pyometra. The present study suggests cardiac troponin I together with APP, proinflammatory cytokines, and oxidative stress parameters as biomarkers for pyometra in Arabian mares.

  11. Antibiotics Increase Gut Metabolism and Antioxidant Proteins and Decrease Acute Phase Response and Necrotizing Enterocolitis in Preterm Neonates

    PubMed Central

    Jiang, Pingping; Jensen, Michael Ladegaard; Cilieborg, Malene Skovsted; Thymann, Thomas; Wan, Jennifer Man-Fan; Sit, Wai-Hung; Tipoe, George L.; Sangild, Per Torp

    2012-01-01

    Background The appropriate use of antibiotics for preterm infants, which are highly susceptible to develop necrotizing enterocolitis (NEC), is not clear. While antibiotic therapy is commonly used in neonates with NEC symptoms and sepsis, it remains unknown how antibiotics may affect the intestine and NEC sensitivity. We hypothesized that broad-spectrum antibiotics, given immediately after preterm birth, would reduce NEC sensitivity and support intestinal protective mechanisms. Methodology/Principal Findings Preterm pigs were treated with antibiotics for 5 d (oral and systemic doses of gentamycin, ampicillin and metrodinazole; AB group) and compared with untreated pigs. Only the untreated pigs showed evidence of NEC lesions and reduced digestive function, as indicated by lowered villus height and activity of brush border enzymes. In addition, 53 intestinal and 22 plasma proteins differed in expression between AB and untreated pigs. AB treatment increased the abundance of intestinal proteins related to carbohydrate and protein metabolism, actin filaments, iron homeostasis and antioxidants. Further, heat shock proteins and the complement system were affected suggesting that all these proteins were involved in the colonization-dependent early onset of NEC. In plasma, acute phase proteins (haptoglobin, complement proteins) decreased, while albumin, cleaved C3, ficolin and transferrin increased. Conclusions/Significance Depressed bacterial colonization following AB treatment increases mucosal integrity and reduces bacteria-associated inflammatory responses in preterm neonates. The plasma proteins C3, ficolin, and transferrin are potential biomarkers of the colonization-dependent NEC progression in preterm neonates. PMID:23028687

  12. In vitro culture and drug sensitivity assay of Plasmodium falciparum with nonserum substitute and acute-phase sera.

    PubMed

    Ringwald, P; Meche, F S; Bickii, J; Basco, L K

    1999-03-01

    The short-term in vitro growth of Plasmodium falciparum parasites in the asexual erythrocytic stage and the in vitro activities of eight standard antimalarial drugs were assessed and compared by using RPMI 1640 medium supplemented with 10% nonimmune human serum, 10% autologous or homologous acute-phase serum, or 0.5% Albumax I (lipid-enriched bovine serum albumin). In general, parasite growth was maximal with autologous (or homologous) serum, followed by Albumax I and nonimmune serum. The 50% inhibitory concentrations (IC50s) varied widely, depending on the serum or serum substitute. The comparison of IC50s between assays with autologous and nonimmune sera showed that monodesethylamodiaquine, halofantrine, pyrimethamine, and cycloguanil had similar IC50s. Although the IC50s of chloroquine, monodesethylamodiaquine, and dihydroartemisinin were similar with Albumax I and autologous sera, the IC50s of all test compounds obtained with Albumax I differed considerably from the corresponding values obtained with nonimmune serum. Our results suggest that Albumax I and autologous and homologous sera from symptomatic, malaria-infected patients may be useful alternative sources of serum for in vitro culture of P. falciparum isolates in the field. However, autologous sera and Albumax I do not seem to be suitable for the standardization of isotopic in vitro assays for all antimalarial drugs.

  13. Acute phase proteins increase with sarcoptic mange status and severity in Iberian ibex (Capra pyrenaica, Schinz 1838).

    PubMed

    Ráez-Bravo, Arián; Granados, José Enrique; Cerón, José Joaquín; Cano-Manuel, Francisco Javier; Fandos, Paulino; Pérez, Jesús María; Espinosa, José; Soriguer, Ramón Casimiro; López-Olvera, Jorge Ramón

    2015-11-01

    Sarcoptic mange is a contagious skin disease caused by Sarcoptes scabiei, affecting both domestic and wild mammals, including the Iberian ibex (Capra pyrenaica), a medium-sized mountain ungulate almost endemic to the Iberian Peninsula. Acute phase proteins (APPs) could be an indicator of sarcoptic mange disease and severity in Iberian ibex. Serum samples from 131 healthy and sarcoptic mange-affected Iberian ibexes were collected from 2005 to 2012 in Sierra Nevada Natural Space in southern Spain. Serum alpha-1-acid glycoprotein (AGP), serum amyloid A (SAA) and haptoglobin (Hp) concentrations were quantified, and statistically significant differences according to sarcoptic mange disease and severity were assessed. Both AGP and SAA were significantly higher in the sarcoptic mange-affected ibexes than in the healthy ones as well as in the severely affected ibexes as compared to those with less than 50 % of the body surface affected. For the first time, changes in APP are reported in relation to sarcoptic mange in Iberian ibex. It is also reported for the first time that the intensity of APP increase depends on the severity of sarcoptic mange, which could be related with the pathological secondary amyloidosis, leading to organ dysfunction in severely mange-affected animals. Species and population differences in the increase of APP in response to sarcoptic mange could indicate individual and population differences in the immune capability of each population to deal with mange, population prevalence and mortality being the last indicators of such sensitivity.

  14. Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia.

    PubMed

    Konopleva, Marina; Pollyea, Daniel A; Potluri, Jalaja; Chyla, Brenda; Hogdal, Leah; Busman, Todd; McKeegan, Evelyn; Salem, Ahmed Hamed; Zhu, Ming; Ricker, Justin L; Blum, William; DiNardo, Courtney D; Kadia, Tapan; Dunbar, Martin; Kirby, Rachel; Falotico, Nancy; Leverson, Joel; Humerickhouse, Rod; Mabry, Mack; Stone, Richard; Kantarjian, Hagop; Letai, Anthony

    2016-10-01

    We present a phase II, single-arm study evaluating 800 mg daily venetoclax, a highly selective, oral small-molecule B-cell leukemia/lymphoma-2 (BCL2) inhibitor in patients with high-risk relapsed/refractory acute myelogenous leukemia (AML) or unfit for intensive chemotherapy. Responses were evaluated following revised International Working Group (IWG) criteria. The overall response rate was 19%; an additional 19% of patients demonstrated antileukemic activity not meeting IWG criteria (partial bone marrow response and incomplete hematologic recovery). Twelve (38%) patients had isocitrate dehydrogenase 1/2 mutations, of whom 4 (33%) achieved complete response or complete response with incomplete blood count recovery. Six (19%) patients had BCL2-sensitive protein index at screening, which correlated with time on study. BH3 profiling was consistent with on-target BCL2 inhibition and identified potential resistance mechanisms. Common adverse events included nausea, diarrhea and vomiting (all grades), and febrile neutropenia and hypokalemia (grade 3/4). Venetoclax demonstrated activity and acceptable tolerability in patients with AML and adverse features.

  15. A phase I/II trial of Erlotinib in higher risk myelodysplastic syndromes and acute myeloid leukemia after azacitidine failure.

    PubMed

    Thepot, Sylvain; Boehrer, Simone; Seegers, Valérie; Prebet, Thomas; Beyne-Rauzy, Odile; Wattel, Eric; Delaunay, Jacques; Raffoux, Emmanuel; Hunault, Mathilde; Jourdan, Eric; Chermat, Fatiha; Sebert, Marie; Kroemer, Guido; Fenaux, Pierre; Adès, Lionel

    2014-12-01

    Survival after azacitidine (AZA) failure in higher-risk myelodysplastic syndromes (MDS) is poor and new treatment options are needed. Erlotinib, an oral inhibitor of the epidermal-growth-factor-receptor (EGFR), has shown in preclinical models some efficacy in higher risk MDS and acute myeloid leukemia (AML). In this phase I/II trial, 30 patients received 100mg/day (n=5) or 150mg/day (n=25) of Erlotinib orally after primary or secondary resistance to AZA treatment. Eighteen MDS and 12 AML patients were treated. This outpatient treatment was well tolerated with limited grade III-IV extra hematological toxicities (skin (n=1), and diarrhea (n=3). Response was observed in 6 patients (20%) including 1 complete remission (CR), 1 marrow CR and 4 hematological improvement (2 erythroid and 2 on platelets). Median duration of response was 5 months. Erlotinib appears to induce a significant number of responses in higher risk MDS/AML having failed AZA treatment. Given the good safety profile of Erlotinib, its combination with other drugs could be tested in the future in MDS and AML.

  16. Challenge with lipopolysaccharides or Freund's adjuvant? What is the best option to trigger acute phase protein production in broilers?

    PubMed

    Koppenol, A; Everaert, N; Buyse, J; Delezie, E

    2015-04-01

    Broilers were injected at 10 days of age with either Escherichia coli lipopolysaccharides (LPS) or with Freund's adjuvants (FA) to investigate its triggering effect on the acute phase reaction (APR). First the kinetics of certain APP was studied by sampling blood 4 h, 8 h, 12 h and 24 h post injection with LPS. Ovotransferrin (OVT) and α-1 acid glycoprotein (AGP) concentration increased with time post injection (PI) with LPS to reach a plateau at 12 and 24 h PI. Caeruloplasmin (CP) did not increase with time PI. Compared to injection with phosphate buffered saline, OVT concentrations were higher when injecting chicks with LPS at all time points PI. At 24 h PI, LPS injection resulted in higher OVT and AGP concentration compared to injection with FA. It is recommended to use LPS instead of FA to trigger the APR. The best time point to sample blood for APP determination is 24 h PI.

  17. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia.

    PubMed

    Eghtedar, Alireza; Verstovsek, Srdan; Estrov, Zeev; Burger, Jan; Cortes, Jorge; Bivins, Carol; Faderl, Stefan; Ferrajoli, Alessandra; Borthakur, Gautam; George, Solly; Scherle, Peggy A; Newton, Robert C; Kantarjian, Hagop M; Ravandi, Farhad

    2012-05-17

    We conducted a phase 2 study of ruxolitinib in patients with relapsed/refractory leukemias. Patients with acceptable performance status (0-2), adequate organ function, and no active infection, received ruxolitinib 25 mg orally twice a day for 4 weeks (1 cycle). Response was assessed after every 2 cycles of treatment, and patients who completed 2 cycles were allowed to continue treatment until disease progression. Dose escalation to 50 mg twice daily was permitted in patients demonstrating a benefit. Thirty-eight patients, with a median age of 69 years (range, 45-88), were treated. The median number of prior therapies was 2 (range, 1-6). Twelve patients had JAK2V617F mutation. Patients received a median of 2 cycles of therapy (range, 1-22). Three of 18 patients with postmyeloproliferative neoplasm (MPN) acute myeloid leukemia (AML) showed a significant response; 2 achieved complete remission (CR) and one achieved a CR with insufficient recovery of blood counts (CRi). The responding patients with palpable spleens also had significant reductions in spleen size. Overall, ruxolitinib was very well tolerated with only 4 patients having grade 3 or higher toxicity. Ruxolitinib has modest antileukemic activity as a single agent, particularly in patients with post-MPN AML. The study was registered at www.clinicaltrials.gov as NCT00674479.

  18. RNA-Seq Characterization of Spinal Cord Injury Transcriptome in Acute/Subacute Phases: A Resource for Understanding the Pathology at the Systems Level

    PubMed Central

    Chen, Kenian; Deng, Shuyun; Lu, Hezuo; Zheng, Yiyan; Yang, Guodong; Kim, Dong; Cao, Qilin; Wu, Jia Qian

    2013-01-01

    Spinal cord injury (SCI) is a devastating neurological disease without effective treatment. To generate a comprehensive view of the mechanisms involved in SCI pathology, we applied RNA-Sequencing (RNA-Seq) technology to characterize the temporal changes in global gene expression after contusive SCI in mice. We sequenced tissue samples from acute and subacute phases (2 days and 7 days after injury) and systematically characterized the transcriptomes with the goal of identifying pathways and genes critical in SCI pathology. The top enriched functional categories include “inflammation response,” “neurological disease,” “cell death and survival” and “nervous system development.” The top enriched pathways include LXR/RXR Activation and Atherosclerosis Signaling, etc. Furthermore, we developed a systems-based analysis framework in order to identify key determinants in the global gene networks of the acute and sub-acute phases. Some candidate genes that we identified have been shown to play important roles in SCI, which demonstrates the validity of our approach. There are also many genes whose functions in SCI have not been well studied and can be further investigated by future experiments. We have also incorporated pharmacogenomic information into our analyses. Among the genes identified, the ones with existing drug information can be readily tested in SCI animal models. Therefore, in this study we have described an example of how global gene profiling can be translated to identifying genes of interest for functional tests in the future and generating new hypotheses. Additionally, the RNA-Seq enables splicing isoform identification and the estimation of expression levels, thus providing useful information for increasing the specificity of drug design and reducing potential side effect. In summary, these results provide a valuable reference data resource for a better understanding of the SCI process in the acute and sub-acute phases. PMID:23951329

  19. Markers of inflammation.

    PubMed

    Germolec, Dori R; Frawley, Rachel P; Evans, Ellen

    2010-01-01

    Inflammation is a complex and necessary component of an organism's response to biological, chemical or physical stimuli. In the acute phase, cells of the immune system migrate to the site of injury in a carefully orchestrated sequence of events that is mediated by cytokines and acute phase proteins. Depending upon the degree of injury, this acute phase may be sufficient to resolve the damage and initiate healing. Persistent inflammation as a result of prolonged exposure to stimulus or an inappropriate reaction to self molecules can lead to the chronic phase, in which tissue damage and fibrosis can occur. Chronic inflammation is reported to contribute to numerous diseases including allergy, arthritis, asthma, atherosclerosis, autoimmune diseases, diabetes, and cancer, and to conditions of aging. Hematology and clinical chemistry data from standard toxicology studies can provide an initial indication of the presence and sometimes location of inflammation in the absence of specific data on the immune tissues. These data may suggest more specific immune function assays are necessary to determine the existence or mechanism(s) of -immunomodulation. Although changes in hematology dynamics, acute phase proteins, complement factors and cytokines are common to virtually all inflammatory conditions and can be measured by a variety of techniques, individual biomarkers have yet to be strongly associated with specific pathologic events. The specific profile in a given inflammatory condition is dependent upon species, mechanisms, severity, chronicity, and capacity of the immune system to respond and adapt.

  20. Indomethacin submicron particle capsules provide effective pain relief in patients with acute pain: a phase 3 study.

    PubMed

    Altman, Roy; Daniels, Stephen; Young, Clarence L

    2013-11-01

    Although frequently prescribed to relieve acute pain in patients, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with dose-related gastrointestinal, cardiovascular, and renal complications. Investigational, submicron particle NSAIDs are being developed that could provide effective pain relief at lower doses than currently available oral NSAIDs. This is the first phase 3 study evaluating the analgesic efficacy and safety of lower-dose indomethacin submicron particle capsules in patients following elective surgery. This multicenter, double-blind study enrolled patients aged 18 to 68 years who underwent bunionectomy under regional anesthesia. Patients with a pain intensity rating of ≥40 mm on a 100-mm Visual Analog Scale were randomized to receive indomethacin submicron particle capsules (40 mg 3 times daily [TID], 40 mg twice daily [BID], or 20 mg TID), celecoxib (400 mg loading dose, then 200 mg BID), or placebo. The primary efficacy parameter was the overall (summed) pain intensity difference measured by a Visual Analog Scale during a period of 48 hours. Scheduled assessments measured secondary efficacy parameters such as patient pain intensity differences. Indomethacin submicron particle capsules 40 mg 3 times daily (509.6 ± 91.9 overall [summed] pain intensity difference), 40 mg twice daily (328.0 ± 92.9 overall [summed] pain intensity difference), and 20 mg 3 times daily (380.5 ± 92.9 overall [summed] pain intensity difference) reduced pain intensity from 0 to 48 hours (P ≤ 0.046 for all 3 groups) compared with placebo (67.8 ± 91.4 overall [summed] pain intensity difference). There was some evidence of patient analgesia for celecoxib (279.4 ± 91.9 overall [summed] pain intensity difference; P = 0.103). Some evidence of pain control was observed in patients as early as 2 hours following administration of indomethacin submicron particle capsules and was sustained throughout the treatment period. Indomethacin submicron particle capsules were

  1. Analysis of Phase 3 telavancin nosocomial pneumonia data excluding patients with severe renal impairment and acute renal failure

    PubMed Central

    Torres, A.; Rubinstein, E.; Corey, G. R.; Stryjewski, M. E.; Barriere, S. L.

    2014-01-01

    Objectives Telavancin is approved in Europe for the treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus when other alternatives are not suitable. The approved European prescribing information contraindicates the use of telavancin in patients with severe renal impairment (creatinine clearance <30 mL/min, including patients on haemodialysis) and pre-existing acute renal failure owing to the higher observed mortality in these patients. Data from the ATTAIN studies were reanalysed, excluding patients with these contraindicating conditions at baseline. (At the time of submission of this article, the European marketing authorization of telavancin for the treatment of nosocomial pneumonia was suspended pending evidence of a new European Medicines Agency-approved supplier. Clinigen Healthcare Ltd, Theravance's commercialization partner for telavancin in Europe, is in the process of seeking approval of a new manufacturing source.) Methods A post hoc analysis of data from two Phase 3 ATTAIN trials of telavancin for the treatment of Gram-positive nosocomial pneumonia assessing clinical outcomes and safety. Results The all-treated population for this analysis represented 84.2% (1266/1503) of the ATTAIN all-treated population. The cure rates in the clinically evaluable population were similar in the telavancin (82.5%, 231/280) and vancomycin (81.3%, 243/299) groups [treatment difference (95% CI): 1.3% (−5.0% to 7.6%)], and were consistent with the overall ATTAIN study results. The cure rate was higher in the telavancin than the vancomycin treatment group in microbiologically evaluable patients with only Gram-positive pathogens isolated at baseline [85.0% (130/153) versus 75.2% (109/145), respectively; treatment difference (95% CI): 9.7% (0.6%–18.8%)]. The incidences of adverse events were similar between treatment groups and consistent with the overall findings of the ATTAIN study. Conclusions This analysis demonstrated that in the subset

  2. 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

    SciTech Connect

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

    2012-02-01

    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.

  3. [Complex network analysis on dynamic change regularity of combining use of Chinese and western medicine in 27,678 cases with ischemic stroke in acute phase].

    PubMed

    Yang, Wei; Li, Yang; Sun, Lei-lei; Xie, Yan-ming; Guo, Chong-hui; Zhuang, Yan

    2015-12-01

    The acute phase of ischemic stroke patients are often treated with both Chinese patent medicine:and western medicine therapies in clinical practice. This research included 27,678 cases of the acute phase of ischemic stroke came from 14 3A level hospitals. We collected data from patients with ischemic stroke who used both Chinese patent medicine and western medicine and were hopitalized within 14 days from hospital information system (HIS). Constructing complex network of Chinese patent medicine and western medicine were found to show scale-free network. Hierarchical structure of the core algorithm was used to analyze the characteristics of combined core Chinese patent medicine and western medicine in admission condition of "acute", "critically", and "general" of ischemic stroke acute phase patient within one day, 2-3 days, 4-7 days and 8-14 days. We found that the core Chinese patent medicine mainly used for activate blood and resolve stasis medicine, and phlegm eliminating brain refreshing medicine in all kinds of patients, but the phlegm eliminating brain refreshing medicine were used to reduce with time elapsing. The core western medicine mainly used for anti-platelet medicine, improve circulation medicine, neuroprotective medicine, anticoagulants medicine and dehydration medicine. The dehydration medicine as the core western medicine for critically patients within 14 days, but the patients for general admission as core western medicine within 3 days. The neuroprotective medicine was used to decreases after 7 days in hospital. Combination of Chinese patent medicine and western medicine were mainly for neuroprotective medicine + activate blood and resolve stasis medicine, and anti-platelet medicine + activate blood and resolve stasis medicine, and improve circulation medicine + activate blood and resolve stasis medicine. The phlegm eliminating brain refreshing medicine was mainly combined with neuroprotective medicine by urgent and general admission condition

  4. Phase angle and handgrip strength are sensitive early markers of energy intake in hypophagic, non-surgical patients at nutritional risk, with contraindications to enteral nutrition.

    PubMed

    Caccialanza, Riccardo; Cereda, Emanuele; Klersy, Catherine; Bonardi, Chiara; Cappello, Silvia; Quarleri, Lara; Turri, Annalisa; Montagna, Elisabetta; Iacona, Isabella; Valentino, Francesco; Pedrazzoli, Paolo

    2015-03-11

    The assessment of nutritional intakes during hospitalization is crucial, as it is known that nutritional status tends to worsen during the hospital stay, and this can lead to the negative consequences of malnutrition. International guidelines recommend the use of parenteral nutrition (PN) in hypophagic, non-surgical patients at nutritional risk, with contraindications to enteral nutrition. However, to date, there are no published data regarding either energy intake or objective measurements associated with it in this patient population. The aim of the present exploratory methodological study was to evaluate whether phase angle (PhA) and handgrip strength normalized for skeletal muscle mass (HG/SMM) are sensitive early markers of energy intake in hypophagic, non-surgical patients at nutritional risk, with contraindications to enteral nutrition. We evaluated 30 eligible patients, who were treated with personalized dietary modifications and supplemental PN for at least one week during hospitalization. In a liner regression model adjusted for age, gender, basal protein intake and the basal value of each variable, a trend toward improvement of PhA and preservation of HG/SMM was observed in patients satisfying the estimated calorie requirements (N = 20), while a significant deterioration of these parameters occurred in those who were not able to reach the target (N = 10). The mean adjusted difference and 95% CI were +1.4° (0.5-2.3) (p = 0.005) for PhA and +0.23 (0.20-0.43) (p = 0.033) for HG/SMM. A significant correlation between PhA and HG/SMM variations was also observed (r = 0.56 (95% CI, 0.23-0.77); p = 0.0023). PhA and HG/SMM were able to distinguish between hypophagic, non-surgical patients at nutritional risk who satisfied their estimated caloric requirements and those who did not after a one-week personalized nutritional support. Clinical studies are warranted, in order to verify these preliminary observations and to validate the role of PhA variations as early

  5. Significance of Foxp3+CD4+ regulatory T cells in the peripheral blood of Uygur patients in the acute and chronic phases of pigeon breeder’s lung

    PubMed Central

    Yu, Biqing; Yang, Xiaohong; Li, Fengsen; Wu, Chao; Wang, Wenyi; Ding, Wei

    2017-01-01

    Pigeon breeder’s lung (PBL) is a type of lung inflammatory disease associated with the immune response to repeated pigeon-derived antigen exposure. The pathogenesis of PBL remains unclear. In this study, peripheral blood samples were collected from Uygur acute - and chronic-phase PBL patients and healthy subjects with pigeon contact. Foxp3+CD4+ regulatory T cell (Treg) activity in different phases of PBL was characterized by changes in Foxp3+CD4+ Treg, CD4+CD25+ T cell, and T lymphocyte subsets. Based on hypersensitivity pneumonitis (HP) diagnosis criteria, 32 PBL cases from January 2012 to December 2013 in the People’s Hospital of Xinjiang Uygur Autonomous Region Respiratory Department were included. Lung high-resolution computed tomography was performed, and the cases were classified based on the HP phase into 15 acute-phase and 17 chronic-phase cases. The control group included 30 healthy subjects with Uygur pigeon contact. Blood samples were collected, and the T cell subsets were analyzed via flow cytometry. In both PBL groups, the Foxp3+CD4+ Treg and CD4+CD25+ and CD4+CD3+ T cell percentages and CD4+/CD8+ ratios were significantly lower than in the control group (p < 0.01). In the PBL groups, particularly the acute-phase group, the CD8+CD3+ T lymphocyte percentage was significantly higher than in the control group (p < 0.01). There were no significant differences in CD4+CD25+ cells between the PBL groups. In peripheral blood from the PBL groups, the CD4+/CD8+ ratio was positively correlated with the Foxp3+CD4+ Treg (r = 0.864, p < 0.05) and CD4+/CD25+ cell (r = 0.34, p < 0.05) percentages. Low Foxp3+CD4+ Treg expression or overconsumption may be a pathogenic factor in PBL. PMID:27448583

  6. Thermal transitions in serum amyloid A in solution and on the lipid: implications for structure and stability of acute-phase HDL.

    PubMed

    Jayaraman, Shobini; Haupt, Christian; Gursky, Olga

    2015-08-01

    Serum amyloid A (SAA) is an acute-phase protein that circulates mainly on plasma HDL. SAA interactions with its functional ligands and its pathogenic deposition in reactive amyloidosis depend, in part, on the structural disorder of this protein and its propensity to oligomerize. In vivo, SAA can displace a substantial fraction of the major HDL protein, apoA-I, and thereby influence the structural remodeling and functions of acute-phase HDL in ways that are incompletely understood. We use murine SAA1.1 to report the first structural stability study of human plasma HDL that has been enriched with SAA. Calorimetric and spectroscopic analyses of these and other SAA-lipid systems reveal two surprising findings. First, progressive displacement of the exchangeable fraction of apoA-I by SAA has little effect on the structural stability of HDL and its fusion and release of core lipids. Consequently, the major determinant for HDL stability is the nonexchangeable apoA-I. A structural model explaining this observation is proposed, which is consistent with functional studies in acute-phase HDL. Second, we report an α-helix folding/unfolding transition in SAA in the presence of lipid at near-physiological temperatures. This new transition may have potentially important implications for normal functions of SAA and its pathogenic misfolding.

  7. Kinetic modeling and mathematical analysis indicate that acute phase gene expression in Hep 3B cells is regulated by both transcriptional and posttranscriptional mechanisms.

    PubMed Central

    Jiang, S L; Samols, D; Rzewnicki, D; Macintyre, S S; Greber, I; Sipe, J; Kushner, I

    1995-01-01

    To evaluate the possible role of posttranscriptional mechanisms in the acute phase response, we determined the kinetics of transcription (by nuclear run-on assay) and mRNA accumulation of five human acute phase genes in Hep 3B cells incubated with conditioned medium from LPS-stimulated monocytes. Increase in mRNA accumulation was comparable to increase in transcription rate for fibrinogen-alpha and alpha-1 protease inhibitor, suggesting largely transcriptional regulation. In contrast, mRNA accumulation was about 10-20-fold greater than transcriptional increase for serum amyloid A, C3, and factor B, suggesting participation of posttranscriptional mechanisms. Since finding a disparity between the magnitudes of increase in mRNA and transcription does not definitively establish involvement of posttranscriptional mechanisms, we subjected our data to modeling studies and dynamic mathematical analysis to evaluate this possibility more rigorously. In modeling studies, accumulation curves resembling those observed for these three mRNAs could be generated from the nuclear run-on results only if posttranscriptional regulation was assumed. Dynamic mathematical analysis of relative transcription rates and relative mRNA abundance also strongly supported participation of posttranscriptional mechanisms. These observations suggest that posttranscriptional regulation plays a substantial role in induction of some, but not all acute phase proteins. Images PMID:7883974

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

    SciTech Connect

    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.

    2013-03-01

    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. Selected acute phase proteins and interleukin-6 in systemic lupus erythematosus patients treated with low doses of quinagolide.

    PubMed

    Hrycek, Antoni; Pochopień-Kenig, Grazyna; Scieszka, Joanna

    2007-05-01

    The relationship between endocrine regulation and immune system has recently become the subject of intense investigations. The objective of this study was to determine the extent of selected serum acute phase proteins (APP), IL-6 and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) involvement in systemic lupus erythematosus (SLE) patients during quinagolide therapy. A further aim of this study was to evaluate the relationships between the above mentioned parameters. In 25 SLE patients treated with a low dose of quinagolide (12.5-50 microg per day) and in 25 healthy persons who constituted the control group, serum concentration of C-creative protein (CRP), alpha-1-antitripsin (AAT), ceruloplasmin (CER), IL-6 and prolactin (PRL) were estimated at entry and in patients after 3 months of treatment. Moreover, SLEDAI score was calculated at entry and after 3 months of therapy with quinagolide. IL-6 and PRL levels were significantly higher in SLE group whereas the concentrations of CRP, AAT and CER were higher than in the controls, but without statistical significance. After 3 month therapy statistically significant decrease of serum level of IL-6 and PRL was revealed. Statistically significant lower serum concentration of CER was also obtained after 3 months of therapy whereas serum CRP and AAT concentration was lower compared with the mean pretreatment level but the results did not reach statistical significance. A raised SLEDAI score at entry was significantly reduced after 3 month therapy and positive correlation with PRL level in examined group of patients with SLE was noted at entry. The decreased serum concentration of IL-6, APP and SLEDAI score observed during applied therapy with small dose of quinagolide confirms the hypothesis that quinagolide may become a valuable and safe drug in the therapy of patients with mild SLE.

  10. Strong associations among rumen endotoxin and acute phase proteins with plasma minerals in lactating cows fed graded amounts of concentrate.

    PubMed

    Zebeli, Q; Dunn, S M; Ametaj, B N

    2010-04-01

    The objective of this investigation was to determine associations among rumen endotoxin, plasma serum amyloid A (SAA), and C-reactive protein (CRP) with plasma Ca, Fe, Zn, and Cu in lactating cows challenged with graded amounts of rolled barley grain in the diet (i.e., 0, 15, 30, and 45% of DMI). Correlative relationships among variables were determined by linear and nonlinear regression procedures adjusted for the effects of day, animal, and experimental period. Increasing the amount of grain in the diet was successful in inducing an acute phase response, as assessed by augmentation of rumen endotoxin and plasma CRP and SAA (P < 0.01). The correlative analysis revealed inverse, nonlinear relationships of rumen endotoxin and plasma SAA with circulating Ca. Interestingly, plasma Ca reached the asymptotic plateau at 10.6 mg/dL. The increase in rumen endotoxin was associated with an abrupt decrease in plasma Fe (R(2) = 0.91; P < 0.001). A similar relationship, although at a reduced estimation accuracy (R(2) = 0.21; P < 0.01), was observed between rumen endotoxin and plasma Zn. Augmentation of rumen endotoxin and plasma CRP resulted in a positive, biphasic response of plasma Cu. In conclusion, the increase in rumen endotoxin in response to high-grain diets, and the resulting increases in plasma SAA and CRP, were strongly correlated with fluctuations of plasma minerals. Results suggest that new feeding strategies should be developed to curb the release of endotoxin in the rumen fluid to prevent perturbing minerals in the plasma.

  11. Rapid Sequential Changeover of Expressed p44 Genes during the Acute Phase of Anaplasma phagocytophilum Infection in Horses

    PubMed Central

    Wang, Xueqi; Rikihisa, Yasuko; Lai, Tzung-Hui; Kumagai, Yumi; Zhi, Ning; Reed, Stephen M.

    2004-01-01

    Anaplasma phagocytophilum immunodominant polymorphic major surface protein P44s have been hypothesized to go through antigenic variation, but the within-host dynamics of p44 expression has not been demonstrated. In the present study we investigated the composition and changes of p44 transcripts in the blood during the acute phase of well-defined laboratory A. phagocytophilum infections in naïve equine hosts. Three traveling waves of sequential population changeovers of the p44 transcript species were observed within a single peak of rickettsemia of less than 1 month. During the logarithmic increase, the rapid switch-off of the initial dominant transcript p44-18 occurred regardless of whether the bacterium was transmitted by ticks or by intravenous inoculation. Each of the subsequently dominant p44 transcript species was phylogenetically dissimilar from p44-18. Development of antibody to the hypervariable region of P44-18 during the rickettsemia suggests the suppression of dominance of immuno-cross-reactive p44 populations. When A. phagocytophilum was preincubated with plasma from the infected horse and then coincubated with HL-60 cells, the dominance of the p44-18 transcript was rapidly suppressed in vitro and most of the newly emerged p44 transcript species were previously undetected in this horse. This work provides experimental evidence of within-host p44 antigenic variation. Results suggest that the rapid and synchronized switch of expression is an intrinsic property of p44s reinitiated after transmission to naïve mammalian hosts and shaped upon exposure to immune plasma. PMID:15557606

  12. The rat acute-phase protein α2-macroglobulin plays a central role in amifostine-mediated radioprotection.

    PubMed

    Mirjana, Mihailović; Goran, Poznanović; Nevena, Grdović; Melita, Vidaković; Svetlana, Dinić; Ilijana, Grigorov; Desanka, Bogojević

    2010-09-01

    Previously we reported that elevated circulating concentrations of the acute-phase (AP) protein α(2)-macroglobulin (α(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(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 α(2)M in the circulation led us to hypothesise that α(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 α(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 α(2)M gene in amifostine-pretreated animals. In both α(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 α(2)M plays a central role in amifostine-provided radioprotection.

  13. [Insulin-like growth factor 1 and the key markers of proteolysis during the acute period of readaptation of the muscle atrophied as a result of unloading].

    PubMed

    Kachaeva, E V; Turtikova, O V; Leĭnsoo, T A; Shenkman, B S

    2010-01-01

    It has been shown that, after prolonged disuse, the accumulation of muscle mass and the recovery of soleus fibers volume are caused by water accumulation rather than protein synthesis intensification. At the same time, expression rate of the main markers of the activity of ubiquitin-proteasome system remained increased on the 3rd day of reloading and decreased to the control by the 7th day. Both the quantity of the insulin-like growth factor 1 and the number of satellite cells fused with muscle fibers and of myonuclei began to increase only on the 7th day of reloading. The data obtained evidenced a significant inertness of the postural muscle during its adaptation to the load (normal gravity) after prolonged disuse.

  14. CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia

    PubMed Central

    Palmi, Chiara; Savino, Angela M.; Silvestri, Daniela; Bronzini, Ilaria; Cario, Gunnar; Paganin, Maddalena; Buldini, Barbara; Galbiati, Marta; Muckenthaler, Martina U.; Bugarin, Cristina; Mina, Pamela Della; Nagel, Stefan; Barisone, Elena; Casale, Fiorina; Locatelli, Franco; Nigro, Luca Lo; Micalizzi, Concetta; Parasole, Rosanna; Pession, Andrea; Putti, Maria C.; Santoro, Nicola; Testi, Anna M.; Ziino, Ottavio; Kulozik, Andreas E.; Zimmermann, Martin; Schrappe, Martin; Villa, Antonello; Gaipa, Giuseppe; Basso, Giuseppe; Biondi, Andrea; Valsecchi, Maria G.; Stanulla, Martin; Conter, Valentino; te Kronnie, Geertruy; Cazzaniga, Giovanni

    2016-01-01

    Pediatric T-ALL patients have a worse outcome compared to BCP-ALL patients and they could benefit from new prognostic marker identification. Alteration of CRLF2 gene, a hallmark correlated with poor outcome in BCP-ALL, has not been reported in T-ALL. We analyzed CRLF2 expression in 212 T-ALL pediatric patients enrolled in AIEOP-BFM ALL2000 study in Italian and German centers. Seventeen out of 120 (14.2%) Italian patients presented CRLF2 mRNA expression 5 times higher than the median (CRLF2-high); they had a significantly inferior event-free survival (41.2%±11.9 vs. 68.9%±4.6, p=0.006) and overall survival (47.1%±12.1 vs. 73.8%±4.3, p=0.009) and an increased cumulative incidence of relapse/resistance (52.9%±12.1 vs. 26.2%±4.3, p=0.007) compared to CRLF2-low patients. The prognostic value of CRLF2 over-expression was validated in the German cohort. Of note, CRLF2 over-expression was associated with poor prognosis in the high risk (HR) subgroup where CRLF2-high patients were more frequently allocated. Interestingly, although in T-ALL CRLF2 protein was localized mainly in the cytoplasm, in CRLF2-high blasts we found a trend towards a stronger TSLP-induced pSTAT5 response, sensitive to the JAK inhibitor Ruxolitinib. In conclusion, CRLF2 over-expression is a poor prognostic marker identifying a subset of HR T-ALL patients that could benefit from alternative therapy, potentially targeting the CRLF2 pathway. PMID:27449287

  15. Evaluation of volatile metabolites as markers in Lycopersicon esculentum L. cultivars discrimination by multivariate analysis of headspace solid phase microextraction and mass spectrometry data.

    PubMed

    Figueira, José; Câmara, Hugo; Pereira, Jorge; Câmara, José S

    2014-02-15

    To gain insights on the effects of cultivar on the volatile metabolomic expression of different tomato (Lycopersicon esculentum L.) cultivars--Plum, Campari, Grape, Cherry and Regional, cultivated under similar edafoclimatic conditions, and to identify the most discriminate volatile marker metabolites related to the cultivar, the chromatographic profiles resulting from headspace solid phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-qMS) analysis, combined with multivariate analysis were investigated. The data set composed by the 77 volatile metabolites identified in the target tomato cultivars, 5 of which (2,2,6-trimethylcyclohexanone, 2-methyl-6-methyleneoctan-2-ol, 4-octadecyl-morpholine, (Z)-methyl-3-hexenoate and 3-octanone) are reported for the first time in tomato volatile metabolomic composition, was evaluated by chemometrics. Firstly, principal component analysis was carried out in order to visualise data trends and clusters, and then, linear discriminant analysis in order to detect the set of volatile metabolites able to differentiate groups according to tomato cultivars. The results obtained revealed a perfect discrimination between the different Lycopersicon esculentum L. cultivars considered. The assignment success rate was 100% in classification and 80% in prediction ability by using "leave-one-out" cross-validation procedure. The volatile profile was able to differentiate all five cultivars and revealed complex interactions between them including the participation in the same biosynthetic pathway. The volatile metabolomic platform for tomato samples obtained by HS-SPME/GC-qMS here described, and the interrelationship detected among the volatile metabolites can be used as a roadmap for biotechnological applications, namely to improve tomato aroma and their acceptance in the final consumer, and for traceability studies.

  16. Quasispecies tropism and compartmentalization in gut and peripheral blood during early and chronic phases of HIV-1 infection: possible correlation with immune activation markers.

    PubMed

    Rozera, G; Abbate, I; Vlassi, C; Giombini, E; Lionetti, R; Selleri, M; Zaccaro, P; Bartolini, B; Corpolongo, A; D'Offizi, G; Baiocchini, A; Del Nonno, F; Ippolito, G; Capobianchi, M R

    2014-03-01

    HIV quasispecies was analysed in plasma and proviral genomes hosted by duodenal mucosa and peripheral blood cells (PBMC) from patients with early or chronic infection, with respect to viral heterogeneity, tropism compartmentalization and extent of immune activation. Seventeen HIV-1-infected combined antiretroviral therapy naive patients were enrolled (11 early infection and six chronic infection). V3 and nef genomic regions were analysed by ultra-deep pyrosequencing. Sequences were used to infer co-receptor usage and to construct phylogenetic trees. As markers of immune activation, plasma sCD14 and soluble tumour necrosis factor receptor II (sTNFRII) levels were measured. Median diversity of HIV RNA was lower in patients with early infection versus chronic infection patients. Overall, direct correlation was observed between V3 diversity and X4 frequency; V3 diversity of HIV RNA was inversely correlated with CD4 T-cell count; median sCD14 and sTNFRII values were similar in early and chronic patients, but X4 frequency of HIV RNA was directly correlated with plasma sCD14. The proportion of patients harbouring X4 variants and median intra-patient X4 frequency of proviral genomes tended to be higher in chronic infection than early infection patients. More pronounced compartmentalization of proviral quasispecies in gut compared with PBMC samples was observed in patients with early infection compared with chronic patients. The loss of gut/PBMC compartmentalization in more advanced stages of HIV infection was confirmed by longitudinal observation. More studies are needed to understand the pathogenetic significance of early HIV quasispecies compartmentalization and progressive intermixing of viral variants in subsequent phases of the infection, as well as the role of immune activation in tropism switch.

  17. Increase in Th17 and T-reg lymphocytes and decrease of IL22 correlate with the recovery phase of acute EAE in rat.

    PubMed

    Almolda, Beatriz; Costa, Manuela; Montoya, Maria; González, Berta; Castellano, Bernardo

    2011-01-01

    Experimental autoimmune encephalomyelitis (EAE), a well-established model of multiple sclerosis, is characterised by microglial activation and lymphocyte infiltration. Induction of EAE in Lewis rats produces an acute monophasic disease characterised by a single peak of disability followed by a spontaneous and complete recovery and a subsequent tolerance to further immunizations. In the current study we have performed a detailed analysis of the dynamics of different lymphocyte populations and cytokine profile along the induction, peak, recovery and post-recovery phases in this paradigm. MBP-injected rats were sacrificed attending exclusively to their clinical score, and the different populations of T-lymphocytes as well as the dynamics of different pro- and anti-inflammatory cytokines were analysed in the spinal cord by flow cytometry, immunohistochemistry and ELISA. Our results revealed that, during the induction and peak phases, in parallel to an increase in symptomatology, the number of CD3+ and CD4+ cells increased progressively, showing a Th1 phenotype, but unexpectedly during recovery, although clinical signs progressively decreased, the number and proportion of CD3+ and CD4+ populations remained unaltered. Interestingly, during this recovery phase, we observed a marked decrease of Th1 and an important increase in Th17 and T-reg cells. Moreover, our results indicate a specific cytokine expression profile along the EAE course characterized by no changes of IL10 and IL17 levels, decrease of IL21 on the peak, and high IL22 levels during the induction and peak phases that markedly decrease during recovery. In summary, these results revealed the existence of a specific pattern of lymphocyte infiltration and cytokine secretion along the different phases of the acute EAE model in Lewis rat that differs from those already described in chronic or relapsing-remitting mouse models, where Th17-cells were found mostly during the peak, suggesting a specific role of these

  18. Increase in Th17 and T-reg Lymphocytes and Decrease of IL22 Correlate with the Recovery Phase of Acute EAE IN Rat

    PubMed Central

    Almolda, Beatriz; Costa, Manuela; Montoya, Maria; González, Berta; Castellano, Bernardo

    2011-01-01

    Experimental autoimmune encephalomyelitis (EAE), a well-established model of multiple sclerosis, is characterised by microglial activation and lymphocyte infiltration. Induction of EAE in Lewis rats produces an acute monophasic disease characterised by a single peak of disability followed by a spontaneous and complete recovery and a subsequent tolerance to further immunizations. In the current study we have performed a detailed analysis of the dynamics of different lymphocyte populations and cytokine profile along the induction, peak, recovery and post-recovery phases in this paradigm. MBP-injected rats were sacrificed attending exclusively to their clinical score, and the different populations of T-lymphocytes as well as the dynamics of different pro- and anti-inflammatory cytokines were analysed in the spinal cord by flow cytometry, immunohistochemistry and ELISA. Our results revealed that, during the induction and peak phases, in parallel to an increase in symptomatology, the number of CD3+ and CD4+ cells increased progressively, showing a Th1 phenotype, but unexpectedly during recovery, although clinical signs progressively decreased, the number and proportion of CD3+ and CD4+ populations remained unaltered. Interestingly, during this recovery phase, we observed a marked decrease of Th1 and an important increase in Th17 and T-reg cells. Moreover, our results indicate a specific cytokine expression profile along the EAE course characterized by no changes of IL10 and IL17 levels, decrease of IL21 on the peak, and high IL22 levels during the induction and peak phases that markedly decrease during recovery. In summary, these results revealed the existence of a specific pattern of lymphocyte infiltration and cytokine secretion along the different phases of the acute EAE model in Lewis rat that differs from those already described in chronic or relapsing-remitting mouse models, where Th17-cells were found mostly during the peak, suggesting a specific role of these

  19. Ferroportin-1 is a 'nuclear'-negative acute-phase protein in rat liver: a comparison with other iron-transport proteins.

    PubMed

    Naz, Naila; Malik, Ihtzaz A; Sheikh, Nadeem; Ahmad, Shakil; Khan, Sajjad; Blaschke, Martina; Schultze, Frank; Ramadori, Giuliano

    2012-06-01

    Liver is the central organ of iron metabolism. During acute-phase-response (APR), serum iron concentration rapidly decreases. The current study aimed to compare expression and localization of iron transport protein ferroportin-1 (Fpn-1) and of other iron import proteins after experimental tissue damage induced by injecting turpentine oil in the hind limbs of rats and mice. Serum and spleen iron concentration decreased with an increase in total liver, cytoplasmic and nuclear iron concentration. In liver, mRNA amount of Fpn-1, Fpn-1a, Fpn-1b, HFE, hemojuvelin (HJV) and hephaestin (heph) genes showed a rapid decrease. Hepcidin, divalent metal transporter-1 (DMT-1), transferrin (Tf) and Tf-receptor-1 (TfR1), TfR-2 (TfR2) gene expression was increased. Western blot analysis of liver tissue lysate confirmed the changes observed at mRNA level. In spleen, a rapid decrease in gene expression of Fpn-1, Fpn-1a, Fpn-1b, DMT-1, Tf, TfR1 and TfR2, and an increase in hepcidin was observed. Immunohistochemistry of DMT-1 and TfR2 were mainly detected in the nucleus of rat liver and spleen, whereas TfR1 was clearly localized in the plasma membrane. Fpn-1 was mostly found in the nuclei of liver cells, whereas in spleen, the protein was mainly detected in the cell membrane. Western blot analysis of liver fractions confirmed immunohistochemical results. In livers of wild-type mice, gene expression of Fpn-1, Fpn-1a and Fpn-1b was downregulated, whereas hepcidin gene expression was increased. In contrast, these changes were less pronounced in IL-6ko-mice. Cytokine (IL-6, IL-1b and TNF-a) treatment of rat hepatocytes showed a downregulation of Fpn-1, Fpn-1a and Fpn-1b, and upregulation of hepcidin gene expression. Moreover, western blot analysis of cell lysate of IL-6-treated hepatocytes detected, as expected, an increase of a2-macroglobulin (positive acute-phase protein), whereas albumin (negative acute-phase protein) and Fpn-1 were downregulated. Our results demonstrate that liver

  20. Serum leptin levels in community acquired pneumonia (CAP) are related to nutritional status and not to acute phase reaction.

    PubMed

    Díez, María-Luisa; Santolaria, Francisco; Tejera, Alicia; Alemán, María-Remedios; González-Reimers, Emilio; Milena, Antonio; de la Vega, María-José; Martínez-Riera, Antonio

    2008-05-01

    To determine whether leptin in patients with CAP acts as a nutritional or as an inflammatory marker and whether leptin plays any role regarding survival, we included 222 patients diagnosed of CAP, 142 men and 80 women, median age 74 years. We did not find significant differences in serum leptin levels between CAP patients and healthy controls, even after adjusting by BMI. Serum leptin levels were directly related with BMI, body fat and muscle mass and inversely related with inflammatory markers, including pro- and anti-inflammatory cytokines. Patients with positive blood cultures showed lower serum leptin and raised inflammatory markers. Although patients who died showed lower values of serum leptin, multivariate analysis showed that the prognostic value of low serum leptin levels depends on impaired nutritional status. In conclusion, we suggest that in CAP patients, leptin does not act as an inflammatory reactant but as a nutritional marker.

  1. GFAP-BDP as an Acute Diagnostic Marker in Traumatic Brain Injury: Results from the Prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study

    PubMed Central

    Yue, John K.; Puccio, Ava M.; Panczykowski, David M.; Inoue, Tomoo; McMahon, Paul J.; Sorani, Marco D.; Yuh, Esther L.; Lingsma, Hester F.; Maas, Andrew I.R.; Valadka, Alex B.; Manley, Geoffrey T.; Casey, Scott S.; Cheong, Maxwell; Cooper, Shelly R.; Dams-O'Connor, Kristen; Gordon, Wayne A.; Hricik, Allison J.; Hochberger, Kerri; Menon, David K.; Mukherjee, Pratik; Sinha, Tuhin K.; Schnyer, David M.; Vassar, Mary J.

    2013-01-01

    Abstract Reliable diagnosis of traumatic brain injury (TBI) is a major public health need. Glial fibrillary acidic protein (GFAP) is expressed in the central nervous system, and breakdown products (GFAP-BDP) are released following parenchymal brain injury. Here, we evaluate the diagnostic accuracy of elevated levels of plasma GFAP-BDP in TBI. Participants were identified as part of the prospective Transforming Research And Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study. Acute plasma samples (<24 h post-injury) were collected from patients presenting with brain injury who had CT imaging. The ability of GFAP-BDP level to discriminate patients with demonstrable traumatic lesions on CT, and with failure to return to pre-injury baseline at 6 months, was evaluated by the area under the receiver operating characteristic curve (AUC). Of the 215 patients included for analysis, 83% had mild, 4% had moderate, and 13% had severe TBI; 54% had acute traumatic lesions on CT. The ability of GFAP-BDP level to discriminate patients with traumatic lesions on CT as evaluated by AUC was 0.88 (95% confidence interval [CI], 0.84–0.93). The optimal cutoff of 0.68 ng/mL for plasma GFAP-BDP level was associated with a 21.61 odds ratio for traumatic findings on head CT. Discriminatory ability of unfavorable 6 month outcome was lower, AUC 0.65 (95% CI, 0.55–0.74), with a 2.07 odds ratio. GFAP-BDP levels reliably distinguish the presence and severity of CT scan findings in TBI patients. Although these findings confirm and extend prior studies, a larger prospective trial is still needed to validate the use of GFAP-BDP as a routine diagnostic biomarker for patient care and clinical research. The term “mild” continues to be a misnomer for this patient population, and underscores the need for evolving classification strategies for TBI targeted therapy. (ClinicalTrials.gov number NCT01565551; NIH Grant 1RC2 NS069409) PMID:23489259

  2. Clara Cell Protein (CC16), a Marker of Lung Epithelial Injury, Is Decreased in Plasma and Pulmonary Edema Fluid From Patients With Acute Lung Injury

    PubMed Central

    Kropski, Jonathan A.; Fremont, Richard D.; Calfee, Carolyn S.; Ware, Lorraine B.

    2009-01-01

    Background: Acute lung injury (ALI) and ARDS are common clinical syndromes that are underdiagnosed. Clara cell secretory protein (CC16) is an antiinflammatory protein secreted by the Clara cells of the distal respiratory epithelium that has been proposed as a biomarker of lung epithelial injury. We tested the diagnostic and prognostic utility of CC16 in patients with non–trauma-related ALI/ARDS compared to a control group of patients with acute cardiogenic pulmonary edema (CPE). Methods: Plasma and pulmonary edema fluid samples were obtained from medical and surgical patients with ALI/ARDS or CPE requiring intubation for mechanical ventilation. The etiology of pulmonary edema was determined using consensus clinical criteria for ALI/ARDS and CPE and the edema fluid-to-plasma protein ratio. Plasma and edema fluid CC16 levels were measured by sandwich enzyme-linked immunosorbent assay. CC16 levels were log transformed for analysis, and comparisons were made by the Student t test or χ2 as appropriate. Results: Compared to patients with CPE (n = 9), patients with ALI/ARDS (n = 23) had lower median CC16 levels in plasma (22 ng/mL [interquartile range (IQR), 9 to 44 ng/mL] vs 55 ng/mL [IQR, 18 to 123 ng/mL], respectively; p = 0.053) and pulmonary edema fluid (1,950 ng/mL [IQR, 1,780 to 4,024 ng/mL] vs 4,835 ng/mL [IQR, 2,006 to 6,350 ng/mL], respectively; p = 0.044). Relative to total pulmonary edema fluid protein concentration, the median CC16 level was significantly lower in patients with ALI/ARDS (45 ng CC16/mg total protein [IQR, 4 to 64 ng CC16/mg total protein] vs 120 ng CC16/mg total protein [IQR, 87 to 257 ng CC16/mg total protein], respectively; p = 0.005). Neither plasma nor edema fluid CC16 levels predicted mortality, the number of days of unassisted ventilation, or ICU length of stay. Conclusion: CC16 is a promising diagnostic biomarker for helping to discriminate ALI from CPE. Larger scale validation is warranted to better characterize the utility of CC16

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

    PubMed

    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 (P<0.01), especially in maintenance phase. Contrary to the previous reports, obesity was not associated with L-asparaginase-related hyperglycemia. 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.

  4. [Acute pancreatitis].

    PubMed

    Hecker, M; Mayer, K; Askevold, I; Collet, P; Weigand, M A; Krombach, G A; Padberg, W; Hecker, A

    2014-03-01

    Acute pancreatitis is a potentially fatal disease with individually differing expression of systemic involvement. For this reason early diagnosis with subsequent risk stratification is essential in the clinical management of this frequent gastroenterological disorder. Severe forms of acute pancreatitis occur in approximately 20 % of cases often requiring intensive care monitoring and interdisciplinary therapeutic approaches. In the acute phase adequate fluid replacement and sufficient analgesic therapy is of major therapeutic importance. Concerning the administration of antibiotics and the nutritional support of patients with acute pancreatitis a change in paradigms could be observed in recent years. Furthermore, endoscopic, radiological or surgical interventions can be necessary depending on the severity of the disease and potential complications.

  5. Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction

    PubMed Central

    Teren, A.; Kirsten, H.; Beutner, F.; Scholz, M.; Holdt, L. M.; Teupser, D.; Gutberlet, M.; Thiery, J.; Schuler, G.; Eitel, I.

    2017-01-01

    Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after primary angioplasty within 12 h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20 h (interquartile range: 15–25 h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarct size (IS), area at risk (AAR), myocardial salvage index (MSI) and the extent of late microvascular obstruction (lateMO). We found 398 genes associated with lateMO and two genes with IS. Neither AAR, nor MSI showed significant correlations with gene expression. Genes correlating with lateMO were strongly related to several canonical pathways, including positive regulation of T-cell activation (p = 3.44 × 10−5), and regulation of inflammatory response (p = 1.86 × 10−3). Network analysis of multiple gene expression alterations associated with larger lateMO identified the following functional consequences: facilitated utilisation and decreased concentration of free fatty acid, repressed cell differentiation, enhanced phagocyte movement, increased cell death, vascular disease and compensatory vasculogenesis. In conclusion, the extent of lateMO after acute, reperfused STEMI correlated with altered activation of multiple genes related to fatty acid utilisation, lymphocyte differentiation, phagocyte mobilisation, cell survival, and vascular dysfunction. PMID:28155873

  6. [Acute leukemia with active hemophagocytosis, positive immunologic markers for the megakaryocyte-platelet lineage, and translocation (16; 21) (p11; q22].

    PubMed

    Shimizu, H; Ui, T; Kawai, S; Kaneko, Y; Fujimoto, T

    1990-01-01

    We report a case of infantile acute leukemia with t(16; 21) (p11; q22). The patient was a phenotypically normal one-year-old girl without lymphadenopathy or hepatosplenomegaly. Her peripheral blood at diagnosis showed anemia, thrombocytopenia, and many circulating blasts. Bone marrow blasts were monocytoid with fine reticular nuclear chromatin, abundant grayish-blue cytoplasm with occasional pseudopods or cytoplasmic projections and active hemophagocytosis. Serum levels of lysozyme and ferritin were normal. These blasts were not stained with butyrate esterase and immunologic study showed KOR-P77+ (anti-megakaryocyte monoclonal antibody), MY9+, Ia-. Electron microscopic examination failed to show platelet peroxidase activity. Remission was not induced by mini-COAP or VP-16 and the patient died of measles pneumonitis. The patient's blasts took typical appearance of megakaryoblasts later in the course, although some of them retained the ability of hemophagocytosis observed in the original blasts. This case is considered to be quite atypical since leukemic cells with active hemophagocytosis, megakaryoblastic appearance and t(16; 21) (p11; q22) have not been reported in the literature.

  7. New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B-cell precursor acute lymphoblastic leukaemia.

    PubMed

    van der Velden, Vincent H J; de Launaij, Daphne; de Vries, Jeltje F; de Haas, Valerie; Sonneveld, Edwin; Voerman, Jane S A; de Bie, Maaike; Revesz, Tamas; Avigad, Smadar; Yeoh, Allen E J; Swagemakers, Sigrid M A; Eckert, Cornelia; Pieters, Rob; van Dongen, Jacques J M

    2016-03-01

    In childhood acute lymphoblastic leukaemia (ALL), central nervous system (CNS) involvement is rare at diagnosis (1-4%), but more frequent at relapse (~30%). Because of the significant late sequelae of CNS treatment, early identification of patients at risk of CNS relapse is crucial. Using microarray-analysis, we discovered multiple differentially expressed genes between B-cell precursor (BCP) ALL cells in bone marrow (BM) and BCP-ALL cells in cerebrospinal fluid (CSF) at the time of isolated CNS relapse. After confirmation by real-time quantitative polymerase chain reaction, selected genes (including SCD and SPP1) were validated at the protein level by flowcytometric analysis of BCP-ALL cells in CSF. Further flowcytometric validation showed that a subpopulation of BCP-ALL cells (>1%) with a 'CNS protein profile' (SCD positivity and increased SPP1 expression) was present in the BM at diagnosis in patients who later developed an isolated CNS relapse, whereas this subpopulation was <1% or absent in all other patients. These data indicate that the presence of a (small) subpopulation of BCP-ALL cells with a 'CNS protein profile' at diagnosis (particularly SCD-positivity) is associated with isolated CNS relapse. Such information can be used to design new diagnostic and treatment strategies that aim at prevention of CNS relapse with reduced toxicity.

  8. Factors affecting the blood concentration of ionized magnesium in patients in the acute phase of myocardial infarction.

    PubMed

    Ueshima, Kenji; Tachibana, Hideaki; Suzuki, Tomomi; Hiramori, Katsuhiko

    2004-11-01

    Magnesium is physiologically active in its free state (Mg2+). In the present study, we attempted to clarify factors affecting blood concentrations of Mg2+ in the acute phase of myocardial infarction (AMI). Subjects were 84 consecutive patients with AMI. Blood samples were collected at the time of admission, 24h after admission, and 1 week after admission, to measure blood concentration of Mg2+ and noradrenaline (NA). Furthermore, to assess daily Mg intake the hardness of local drinking water was determined, and a survey was conducted regarding dietary preferences and habits. Based on the results of this survey, the patients were defined as having a low Mg intake (L Group) or not. In addition, based on chronological shifts in blood Mg2+ concentrations, subjects were divided into the following four groups: Normal group, blood concentration of Mg2+ within normal range at all measurement points; Early recovery group, low at time of admission, but normalized on the next day; Delayed recovery group, low at time of admission, but normalized 1 week after admission; and Unrecovered group, below normal range at all measurement points. The mean blood Mg2+ concentration on admission was 0.52 +/- 0.06 mmol/l, significantly lower than the normal range (P < 0.05). A negative correlation between blood Mg2+ and NA concentrations on admission was observed (r = 0.49, P < 0.005). As a result, blood Mg2+ concentrations were normalized in 94% of subjects by 1 week after admission. Mean blood Mg2+ concentration on admission in the L Group was 0.47 +/- 0.05 mmol/l, significantly lower than that found in other subjects (0.52 +/- 0.05 mmol/l, P < 0.01). Eighty percent of the patients classified into the Unrecovered group belonged to the L Group. These findings suggest that lower blood concentrations of Mg2+ and higher plasma NA levels may be a result of serious AMI. However, chronic Mg intake deficiency may play a partial role in patients whose blood concentrations of Mg2+ remain low for

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

    PubMed

    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

  10. Porosity, single-phase permeability, and capillary pressure data from preliminary laboratory experiments on selected samples from Marker Bed 139 at the Waste Isolation Pilot Plant. Volume 3 of 3: Appendices C, D, E, and F

    SciTech Connect

    Howarth, S.M.; Christian-Frear, T.

    1997-08-01

    This volume contains the mineralogy, porosity, and permeability results from the Marker Bed 139 anhydrite specimens evaluated by TerraTek, Inc. for the Waste Isolation Pilot Plant. This volume also documents the brine recipe used by RE/SPEC, Inc., the parameter package submitted to Performance Assessment based on all the data, and a memo on the mixed Brooks and Corey two-phase characteristic curves.

  11. Neutrophil Gelatinase-Associated Lipocalin as a Diagnostic Marker for Acute Kidney Injury in Oliguric Critically Ill Patients: A Post-Hoc Analysis

    PubMed Central

    Egal, Mohamud; de Geus, Hilde R.H.; Groeneveld, A.B. Johan

    2016-01-01

    Background Oliguria occurs frequently in critically ill patients, challenging clinicians to distinguish functional adaptation from serum-creatinine-defined acute kidney injury (AKIsCr). We investigated neutrophil gelatinase-associated lipocalin (NGAL)'s ability to differentiate between these 2 conditions. Methods This is a post-hoc analysis of a prospective cohort of adult critically ill patients. Patients without oliguria within the first 6 h of admission were excluded. Plasma and urinary NGAL were measured at 4 h after admission. AKIsCr was defined using the AKI network criteria with pre-admission serum creatinine or lowest serum creatinine value during the admission as the baseline value. Hazard ratios for AKIsCr occurrence within 72 h were calculated using Cox regression and adjusted for risk factors such as sepsis, pre-admission serum creatinine, and urinary output. Positive predictive values (PPV) and negative predictive values (NPV) were calculated for the optimal cutoffs for NGAL. Results Oliguria occurred in 176 patients, and 61 (35%) patients developed AKIsCr. NGAL was a predictor for AKIsCr in univariate and multivariate analysis. When NGAL was added to a multivariate model including sepsis, pre-admission serum creatinine and lowest hourly urine output, it outperformed the latter model (plasma p = 0.001; urinary p = 0.048). Cutoff values for AKIsCr were 280 ng/ml for plasma (PPV 80%; NPV 79%), and 250 ng/ml for urinary NGAL (PPV 58%; NPV 78%). Conclusions NGAL can be used to distinguish oliguria due to the functional adaptation from AKIsCr, directing resources to patients more likely to develop AKIsCr. PMID:27505067

  12. Acute Effects of Dietary Fat on Inflammatory Markers and Gene Expression in First-Degree Relatives of Type 2 Diabetes Patients

    PubMed Central

    Pietraszek, Anna; Gregersen, Søren; Hermansen, Kjeld

    2011-01-01

    BACKGROUND: Subjects with type 2 diabetes (T2D) and their relatives (REL) carry an increased risk of cardiovascular disease (CVD). Low-grade inflammation, an independent risk factor for CVD, is modifiable by diet. Subjects with T2D show elevated postprandial inflammatory responses to fat-rich meals, while information on postprandial inflammation in REL is sparse. AIM: To clarify whether medium-chain saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) have differential acute effects on low-grade inflammation in REL compared to controls (CON). METHODS: In randomized order, 17 REL and 17 CON ingested two fat-rich meals, with 72 energy percent from MUFA and 79 energy percent from mainly medium-chain SFA, respectively. Plasma high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), adiponectin, and leptin were measured at baseline, 15 min, 60 min, and 240 min postprandially. Muscle and adipose tissue biopsies were taken at baseline and 210 min after the test meal, and expression of selected genes was analyzed. RESULTS: Plasma IL-6 increased (p < 0.001) without difference between REL and CON and between the meals, whereas plasma adiponectin and plasma hs-CRP were unchanged during the 240 min observation period. Plasma leptin decreased slightly in response to medium-chain SFA in both groups, and to MUFA in REL. Several genes were differentially regulated in muscle and adipose tissue of REL and CON. CONCLUSIONS: MUFA and medium-chain SFA elicit similar postprandial circulating inflammatory responses in REL and CON. Medium-chain SFA seems more proinflammatory than MUFA, judged by the gene expression in muscle and adipose tissue of REL and CON. PMID:22580729

  13. Phase III trials of new oral anticoagulants in the acute treatment and secondary prevention of VTE: comparison and critique of study methodology and results.

    PubMed

    Cohen, Alexander T; Imfeld, Stephan; Rider, Thomas

    2014-05-01

    The traditional treatment of venous thromboembolism (VTE) has been use of heparin and vitamin K antagonists (VKA), and although shown to be effective, they have numerous limitations. New oral anticoagulants (NOACs) including direct thrombin (factor IIa) inhibitors (dabigatran) and selective factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) have emerged as promising alternatives with the potential to overcome the limitations of traditional treatments. Clinical trials have been performed with a view to making significant changes to the acute, long-term and extended treatment of VTE. Data are now available on the efficacy and safety, including bleeding rates, of the NOACs in comparison with VKA in the acute treatment and secondary prevention of VTE as well as in comparison with placebo extended VTE treatment. This review compares and contrasts the design and results of the Phase III trials of NOACs in VTE and discusses the implications of the NOACs in terms of treatment strategies in VTE patients.

  14. Myeloperoxidase and serum amyloid A contribute to impaired in vivo reverse cholesterol transport during the acute phase response but not group IIA secretory phospholipase A2[S

    PubMed Central

    Annema, Wijtske; Nijstad, Niels; Tölle, Markus; de Boer, Jan Freark; Buijs, Ruben V. C.; Heeringa, Peter; van der Giet, Markus; Tietge, Uwe J. F.

    2010-01-01

    Atherosclerosis is linked to inflammation. HDL protects against atherosclerotic cardiovascular disease, mainly by mediating cholesterol efflux and reverse cholesterol transport (RCT). The present study aimed to test the impact of acute inflammation as well as selected acute phase proteins on RCT with a macrophage-to-feces in vivo RCT assay using intraperitoneal administration of [3H]cholesterol-labeled macrophage foam cells. In patients with acute sepsis, cholesterol efflux toward plasma and HDL were significantly decreased (P < 0.001). In mice, acute inflammation (75 µg/mouse lipopolysaccharide) decreased [3H]cholesterol appearance in plasma (P < 0.05) and tracer excretion into feces both within bile acids (−84%) and neutral sterols (−79%, each P < 0.001). In the absence of systemic inflammation, overexpression of serum amyloid A (SAA, adenovirus) reduced overall RCT (P < 0.05), whereas secretory phospholipase A2 (sPLA2, transgenic mice) had no effect. Myeloperoxidase injection reduced tracer appearance in plasma (P < 0.05) as well as RCT (−36%, P < 0.05). Hepatic expression of bile acid synthesis genes (P < 0.01) and transporters mediating biliary sterol excretion (P < 0.01) was decreased by inflammation. In conclusion, our data demonstrate that acute inflammation impairs cholesterol efflux in patients and macrophage-to-feces RCT in vivo in mice. Myeloperoxidase and SAA contribute to a certain extent to reduced RCT during inflammation but not sPLA2. However, reduced bile acid formation and decreased biliary sterol excretion might represent major contributing factors to decreased RCT in inflammation. PMID:20061576

  15. Relationship between Barthel Index scores during the acute phase of rehabilitation and subsequent ADL in stroke patients.

    PubMed

    Nakao, Shigetaka; Takata, Shinjiro; Uemura, Hirokazu; Kashihara, Michiharu; Osawa, Toshifumi; Komatsu, Koji; Masuda, Yuki; Okahisa, Tetsuya; Nishikawa, Koji; Kondo, Shin; Yamada, Megumi; Takahara, Risa; Ogata, Yoshimi; Nakamura, Yuka; Nagahiro, Shinji; Kaji, Ryuji; Yasui, Natsuo

    2010-02-01

    The Barthel Index (BI) cannot be used to measure initial stroke severity or by extension, to stratify patients by severity in acute stroke trials because most patients are bedbound in the first few hours after stroke, either by their deficit or by medical directive. Our objectives were to clarify the threshold of acute BI for use in the prediction of subsequent independence in activities of daily living (ADL) and to assist in the definition of acute stroke rehabilitation goals. Subjects comprised 78 patients out of 191 inpatients admitted with acute stroke at our hospital during 2006-2007. The BI ADL score was divided into 2 ranges (BI> or =60 and < or =40), in a process similar to previous studies. During the acute period (from onset to approximately 3 weeks), all patients with a BI> or =40 could improve their ADL in 6 months. Patients with a BI< or =40 exhibited two ADL recovery outcomes (improved and no change) at 6 months. We also found that the skill level of basic activities related to standing was significant indicator of BI improvement (P<0.001). BI scores determined at approximately 3 weeks were reliable predictors of ADL disabilities at 6 months.

  16. The Neuroprotection with Statin Therapy for Acute Recovery Trial (NeuSTART): an adaptive design phase I dose-escalation study of high-dose lovastatin in acute ischemic stroke

    PubMed Central

    Elkind, Mitchell S. V.; Sacco, Ralph L.; MacArthur, Robert B.; Fink, Daniel J.; Peerschke, Ellinor; Andrews, Howard; Neils, Greg; Stillman, Josh; Corporan, Tania; Leifer, Dana; Cheung, Ken

    2014-01-01

    There is growing experimental and clinical evidence that by reducing downstream products of the mevalonate pathway other than cholesterol, HMG-CoA reductase inhibitors (‘statins’) have beneficial effects on endothelial function, coronary and cerebral blood flow, inflammation, and hemostasis. Statins have been shown in rodent models of acute ischemic stroke to reduce neuronal injury and infarct size in a dose-dependent fashion. The objective of this early phase trial will be to determine the maximal-tolerated dose of lovastatin for short-term acute stroke therapy. In this multicenter phase 1B dose-escalation and dose-finding study, 33 patients with acute ischemic stroke will be administered lovastatin in increasing doses from one to 10 mg/kg daily for 3 days beginning within 24 hours after symptom onset. The primary safety outcomewill be occurrence of myotoxicity or hepatotoxicity, defined by clinical and laboratory criteria, and the study is designed to determine the highest dose of lovastatin that can be administered with <10% risk of myotoxicity or hepatotoxicity. The statistical design of the study utilizes an adaptive design, the Continual Reassessment Method, which is novel to stroke trials, to find the optimal dosage. The dose–toxicity model is calibrated such that the method will eventually select a dose that causes 7–13% dose-limiting toxicity (within 3% of target). A sample size of 33 will ensure that estimates of any binary variables will have a 95% confidence interval of width ≤0·34, and enable us to detect any unexpected toxicity that occurs at 5% rate (in a non-dose-dependent fashion) with probability 0·82. The probability of choosing a dose for further trials with 25% or higher likelihood of toxicity is no more than 23%. The presently described trial represents a new approach for treatment of acute ischemic stroke, as well as a novel way of conducting a phase I trial, evaluating safety and determining an optimal dose of a potential

  17. Effects of Valproic Acid and Dexamethasone Administration on Early Bio-Markers and Gene Expression Profile in