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Sample records for human acute myelocytic

  1. Acquired dyschromatopsia in acute myelocytic leukaemia.

    Science.gov (United States)

    Ziaei, Mohammed; Holder, Graham E; Elgohary, Mostafa A; Bremner, Fion D

    2013-12-01

    Patients with haematological malignancy are referred to the ophthalmologist either with visual symptoms or to exclude orbital or intraocular involvement after the diagnosis has been established. This report describes a patient with acute myelocytic leukaemia (AML) whose presenting symptom was dyschromatopsia. A 52-year-old female, previously in good health, presented with a disturbance of colour vision. On examination, there was bilateral reduction in visual acuity, impaired colour vision and severely constricted visual fields. Electrophysiological testing and colour contrast sensitivity (CCS) assessment were performed. CCS showed bilateral threshold elevation in the tritan axis of both eyes, right worse than left. Pattern ERG showed marked macular dysfunction in the right eye, but was normal in the left eye. Full-field ERGs fell within the normal range. Pattern VEPs were reduced in the right eye, without peak time shift; flash VEPs showed bilateral delay. Investigation showed severe anaemia, and a bone marrow biopsy confirmed a diagnosis of acute AML. There was symptomatic improvement in visual acuity and colour vision following blood transfusion and initiation of chemotherapy. This appears to be the first case report of dyschromatopsia in AML with symptomatic improvement following treatment. The case lends support to previously suggested hypotheses of chromatic visual disturbance in association with presumed hypoxia.

  2. [Mixed myelocytic and lymphocytic acute leukemia. Case report].

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    Casanova, E R; Cabrera, M E; Klaasen, R; Tapia, P; Yáñez, V

    1992-09-01

    A patient with acute mixed myelocytic and lymphocytic leukemia is reported. The patient showed two populations of malignant myeloid and lymphoid cells with predominance of myeloid lineage. According to the present knowledge, it is hypothesized that its origin is at a pluripotent transformed stem cell which has the capability of differentiating through myeloid and lymphoid lineages. Its maturation is arrested at certain level, thus raising two monoclonal populations simultaneously in the same patient. The treatment should be combined with drugs used in acute myeloblastic and lymphoblastic leukemia. The response to chemotherapy is generally poor.

  3. "Time sequential high dose of Cytarabine in acute myelocytic leukemia "

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    Ghavamzadeh A

    2003-05-01

    Full Text Available Given preliminary evidence of timed, sequential chemotherapy of high dose cytosine arabinoside the current study was initiated to assess the side effects and efficacy of this regimen in patients with newly acute myelocytic leukemia (AML. Nineteen adults who referred to Hematology-Oncology and Bone Marrow Transplantation (BMT research center of Tehran University of Medical Sciences were enrolled in a trial from Aug 1999 to Nov 2000. All patients had a Karnofski classification above 60%. At this time induction therapy consisted of daunorubicin or idarubicin given at a dose of 60 mg/m² and 12 mg/m² IV respectively on days 1-3, and cytarabine (Ara-C 100 mg/m² intravenously by continuous infusion on days 1-7, followed by Ara-C 1000 mg/m² given on day 8-10 every 12 hours by IV infusion. Consolidation therapy started after 35th day. Of 19 fully evaluable patients, 10 patients achieved a complete remission, whereas 36.6% patients succumbed to death due to regeneration failure. The clinical data show that the overall survival rate from diagnosis 55.5% (95% CI, 30.8-78.5 at 6 months for the entire cohort of the patients. Disease free survival is also 50% (95% CI, 26-74. Mean duration of death due to treatment was 20 days (range 17-29 after beginning the regimen. Presenting WBC counts, French-American-British (FAB classification, sex and age were not useful prognostic variables. Fever, diarrhea, nausea and vomiting and GI hemorrhage were seen in 19, 6, 4, 7 patients respectively. It seems the 3+7+3 regimen is a promising approach for the AML patients regarding to high complete remission rate, but more supportive care should be considered. Furthermore any, benefit in long-term outcome can’t be determined regardless to the choice of post remission therapy (e.g., GCSF, appropriate antibiotics and etc.

  4. Orbital granulocytic sarcoma: an unusual presentation of acute myelocytic leukemia

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    Stein-Wexler, Rebecca; Wootton-Gorges, Sandra L. [University of California, Davis Medical Center, Davis Children' s Hospital, Sacramento, CA 95817 (United States); West, Daniel C. [Department of Pediatrics, University of California, Davis Medical Center, Davis Children' s Hospital, Sacramento, CA 95817 (United States)

    2003-02-01

    Granulocytic sarcoma is an unusual manifestation of acute myelogenous leukemia in children and presents a diagnostic dilemma when it precedes the development of systemic disease. We present CT and MRI findings of an extraconal mass proven to be granulocytic sarcoma in a 6-year-old otherwise healthy boy with several months' history of worsening unilateral proptosis. This case is unique in providing exquisite CT and MRI correlation and in demonstrating rapid response to therapy. Further, as cytogenetics were positive for the t(8,21) translocation, this case provides opportunity for discussion of the associated incidence of this translocation and concomitant better prognosis. (orig.)

  5. Advances in understanding the biology and genetics of acute myelocytic leukemia.

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    McKenzie, Shirlyn B

    2005-01-01

    Acute myelocytic leukemia (AML) is a malignant neoplasm of hematopoietic cells characterized by an abnormal proliferation of myeloid precursor cells, decreased rate of self-destruction and an arrest in cellular differentiation. The leukemic cells have an abnormal survival advantage. Thus, the bone marrow and peripheral blood are characterized by leukocytosis with a predominance of immature cells, primarily blasts. As the immature cells accumulate in the bone marrow, they replace the normal myelocytic cells, megakaryocytes, and erythrocytic cells. This leads to a loss of normal bone marrow function and associated complications of bleeding, anemia, and infection. The incidence of AML increases with age, peaking in the sixth decade of life. In the United States, there are about 10,000 new cases of AML and 7,000 deaths in those with an AML diagnosis per year. Current molecular studies of AML demonstrate that it is a heterogeneous disorder of the myeloid cell lineage. This paper will discuss the most recent understanding and research of the cellular origin of AML and associated common genetic mutations that fuel the neoplastic process. Also discussed are how these advances have impacted the classification, selection of therapy, and definition of complete remission in AML. Promyelocytic leukemia will be discussed in detail as this AML subtype reveals how our understanding of the biology and genetics of the disease has led to targeted therapy that results in a cure in up to 80% of patients.

  6. [Prognosis improvements in children with acute myelocytic leucemia after more intensive induction therapy (author's transl)].

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    Scheer, U; Schellong, G; Riehm, H

    1979-03-01

    Between October 1974 and October 1978 23 children with acute myelocytic leucemia (AML) received intensive therapy in the Univ.-Kinderklinik Münster: 4 children were treated according to the ALGB-protocol consisting of 5-7 day courses of ARA-C-infusion and 3 DNR-injections. 19 patients received the West-Berlin-protocol: The first 7 the original ALL protocol, 11 the modified form of AML, which will be presented here as AML-therapy-study BFM 78. 4 of the 23 patients died with early acute cerebral bleeding. 2 patients were nonresponders. 17 children went into remission. One girl died in remission of septicemic aspergillosis. 4 children had a relapse. In November 1978 there were still 12 patients in continuous complete remission, 3 of them already without therapy. 13 of the 19 patients, who were treated with the West-Berlin-protocol went into remission. 1 had a relapse. At present there are 11 patients in continuous complete remission. The above results and those found in the literature could signify that the long term prognosis of children with AML will be improved. To coordinate efforts toward this goal a cooperative AML-therapy-study in the "Deutsche Arbeitsgemeinschaft für Leukämieforschung" (BFM-group) using the here presented therapy protocol was formed in November 1978.

  7. C. zeylanicum aqueous extract induced apoptosis in the human myelocytic leukemia cell line (THP-1).

    Science.gov (United States)

    Assadollahi, V; Gholami, M; Zendedel, A

    2015-01-01

    The aim of this study was to evaluate the effect of C. zeylanicum aqueous extract on cell growth in the human myelocytic leukemia cell line (THP-1). Today, application of Cinnamon for treatment of cancer investigates extensively. Cinnamon has antioxidant, anti-apoptotic and anti-inflammatory properties. In this experimental study, THP-1 was incubated in 2, 1, 0.1 and 0.01 mg/ml C. zeylanicum solutions for 24, 48 and 72 hours. Cell cycle was assessed with flow cytometry. Apoptotic cells were identified by Hoechst 33342 staining. Cell proliferation was assessed by the MTT assay. The data were analyzed using descriptive statistics and analytical tests. Samples that supplemented with 0.1 mg/ml C. zeylanicum aqueous extract enhanced induction of apoptosis in THP-1 cell line compared to samples that supplemented with 2, 1 and 0.01 mg/ml. According to flow cytometry analysis, after 24 and 72 hours of incubation in 0.1 and 2 mg/ml C. zeylanicum aqueous extract, respectively, the amount of cells in apoptosis phase was higher than that in the control sample. Supplemented C. zeylanicum aqueous extract induced apoptosis in the human myelocytic leukemia cell line (Fig. 4, Ref. 20).

  8. Granulocyte Colony-stimulating Factor-primed Bone Marrow: An Excellent Stem-cell Source for Transplantation in Acute Myelocytic Leukemia and Chronic Myelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Yuhang Li

    2015-01-01

    Full Text Available Background: Steady-state bone marrow (SS-BM and granulocyte colony-stimulating growth factor-primed BM/peripheral blood stem-cell (G-BM/G-PBSC are the main stem-cell sources used in allogeneic hematopoietic stem-cell transplantation. Here, we evaluated the treatment effects of SS-BM and G-BM/G-PBSC in human leucocyte antigen (HLA-identical sibling transplantation. Methods: A total of 226 patients (acute myelogenous leukemia-complete remission 1, chronic myelogenous leukemia-chronic phase 1 received SS-BM, G-BM, or G-PBSC from an HLA-identical sibling. Clinical outcomes (graft-versus-host disease [GVHD], overall survival, transplant-related mortality [TRM], and leukemia-free survival [LFS] were analyzed. Results: When compared to SS-BM, G-BM gave faster recovery time to neutrophil or platelet (P 0.05. Conclusions: G-CSF-primed bone marrow shared the advantages of G-PBSC and SS-BM. We conclude that G-BM is an excellent stem-cell source that may be preferable to G-PBSC or SS-BM in patients receiving HLA-identical sibling hematopoietic stem-cell transplantation.

  9. [CD13- and CD33-negative acute myelocytic leukemia (FAB classification; M2) with morphological changes and CD13 expression on recurrence].

    Science.gov (United States)

    Aoyama, Y; Yamane, T; Kanashima, H; Takeoka, Y; Koh, K; Nakao, Y; Yamamura, R; Nakamae, H; Ohta, K; Inoue, T; Hino, M; Tatsumi, N

    2001-04-01

    A 42-year-old man was diagnosed as having acute myelocytic leukemia in July 1998. The leukemic cells tended to be differentiated, and on the basis of positive peroxidase staining, this case was considered to be AML (M2) according to the FAB classification. t(8;21)(q22;q22) chromosomal abnormality was observed, but surface antigen analysis revealed no expression of either CD13 or CD33, a finding characteristic of myelocytic leukemia. Combination chemotherapy resulted in complete remission, and allogeneic bone marrow transplantation was performed with donor cells from the patient's sister. Unfortunately, however, the patient died about 18 months after the onset of leukemia. Comparison of the findings at recurrence with those at initial diagnosis revealed morphological changes in non-differentiated immature cells (AML-M1) and CD13 surface antigen expression. This was considered to be a rare case of AML with neither CD13 nor CD33 expression at onset, but with CD13 expression at recurrence.

  10. Systematic screening at diagnosis of -5/del(5)(q31), -7, or chromosome 8 aneuploidy by interphase fluorescence in situ hybridization in 110 acute myelocytic leukemia and high-risk myelodysplastic syndrome patients: concordances and discrepancies with conventional cytogenetics.

    NARCIS (Netherlands)

    Beyer, V.; Castagne, C.; Muhlematter, D.; Parlier, V.; Gmur, J.; Hess, U.; Kovacsovics, T.; Meyer-Monard, S.; Tichelli, A.; Tobler, A.; Jacky, E.; Schanz, U.; Bargetzi, M.; Hagemeijer, A.; Witte, T.J.M. de; Melle, G. van; Jotterand-Bellomo, M.

    2004-01-01

    To assess the contribution of interphase fluorescence in situ hybridization (I-FISH) toward the detection of recurring unbalanced chromosomal anomalies at diagnosis, a systematic screening of -5/del(5)(q31), -7, and chromosome 8 aneuploidy was performed on 110 patients with acute myelocytic leukemia

  11. Importance of No. 21 chromosome in translocation t(8:21) in acute myelocytic leukemia (AML) to the genesis of the disease

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    Ishihara, T.; Minamihisamatsu, M.

    1986-05-01

    The results are reported of the chromosome analysis of 17 cases of acute myelocytic leukemia (AML), mostly belonging to M2 of the FAB classification, especially on the translocation t(8:21) and its variant translocations. The presence of two cases with simple variant translocation not involving No. 8 chromosome seems to suggest that No. 21 chromosome is more important to the genesis of AML than the No. 8 chromosome. This assumption appears to be supported by findings on cases with complex translocation: In two cases with complex translocation, the portion translocated from No. 21 chromosome onto No. 8 was firmly maintained in the specific site (q21) on No. 8 whereas the portion translocated from No. 8 chromosome onto No. 21 was involved in further translocation with another chromosome, onto which it was re-translocated. The results of the present cytogenetic study indicate that the analysis of variant translocations in various specific chromosome translocations in leukemia and other malignant disorders is very useful to elucidate the problem as to whether the genesis of such disorders lies in either one or both of the pair of chromosomes involved in the specific translocations of the respective diseases.

  12. Homologous lactoferrin triggers mobilization of the myelocytic lineage of bone marrow in experimental mice.

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    Zimecki, Michał; Artym, Jolanta; Kocięba, Maja; Kaleta-Kuratewicz, Katarzyna; Kuropka, Piotr; Kuryszko, Jan; Kruzel, Marian

    2013-12-15

    The effects of lactoferrin (LF), an iron binding protein, on myelopoiesis have been studied extensively in vitro and in vivo in human and murine models over the past three decades. Due to the lack of high-quality homologous LFs, however, the conclusions are still unequivocal. Recently, both human and murine LFs have become available as recombinant products expressed in Chinese hamster ovary (CHO) cell lines showing mammalian type of glycosylation, thus apparently species compatible. In this study, we present the effects of homologous recombinant mouse LF (rmLF) on myelopoiesis in CBA mice. The myelocytic lineage has been assessed by their appearance in circulating blood and bone marrow, and induction of relevant mediators of inflammation. Intravenous injection of rmLF (100 μg/mouse) resulted in a significantly increased number of myelocytic cells in the circulating blood after 24 h. Mouse serum transferrin, used as a control protein, showed no stimulatory effect. The increase in output of neutrophil precursors, neutrophils, and eosinophils was correlated with a twofold increase of leukocyte concentrations. The analysis of the bone marrow sections confirmed increased myelopoiesis. The alterations in the bone marrow cell composition were statistically significant regarding mature neutrophils (10.8% vs. 27.7%), metamyelocytes (11.4% vs. 16.0%), and myelocytes (2.4% vs. 4.0%). The mobilization of the myelocytic cells in the bone marrow and the increased output of these cells into circulation were accompanied by elevated serum concentrations of interleukin-6 at 6 h and haptoglobin at 24 h following administration of rmLF. In conclusion, the homologous LF elicits significant and transient myelopoiesis in experimental mice.

  13. Highly glycosylated alpha1-acid glycoprotein is synthesized in myelocytes, stored in secondary granules, and released by activated neutrophils

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, Kim; Jacobsen, Lars C; Rasmussen, Thomas

    2005-01-01

    enriched in promyelocytes, myelocytes/metamyelocytes (MYs), and BM neutrophils. These analyses demonstrated a transient, high mRNA expression of genuine secondary/tertiary granule proteins and AGP in MYs. In agreement with this, immunocytochemistry revealed the presence of AGP protein and the secondary...... granule protein lactoferrin in cells from the MY stage and throughout granulocytic differentiation. Immunoelectron microscopy demonstrated the colocalization of AGP and lactoferrin in secondary granules of neutrophils. This finding was substantiated by the failure to detect AGP and lactoferrin in blood......Alpha-1-acid glycoprotein (AGP) is an acute-phase protein produced by hepatocytes and secreted into plasma in response to infection/injury. We recently assessed the transcriptional program of terminal granulocytic differentiation by microarray analysis of bone marrow (BM) populations highly...

  14. Thrombotic microangiopathy associated with alpha-interferon therapy for chronic myelocytic leukemia.

    Science.gov (United States)

    Honda, K; Ando, A; Endo, M; Shimizu, K; Higashihara, M; Nitta, K; Nihei, H

    1997-07-01

    A 31-year-old man diagnosed as having chronic myelocytic leukemia (CML) developed renal insufficiency with nephrotic-range proteinuria during alpha-interferon (IFN) therapy for CML. A renal biopsy specimen showed remarkable thrombotic microangiopathic lesions resembling those of hemolytic-uremic syndrome. The patient had papules on both lower legs, and a cutaneous biopsy showed similar microangiopathic lesions in dermal and subcutaneous vessels. Although discontinuation of IFN and initiation of prednisolone therapy resulted in resolution of proteinuria, renal insufficiency persisted. These findings suggest that long-term IFN therapy can induce late-onset thrombotic microangiopathy in systemic microvessels.

  15. Human bocavirus and acute wheezing in children

    NARCIS (Netherlands)

    Allander, Tobias; Jartti, Tuomas; Gupta, Shawon; Niesters, Hubert G M; Lehtinen, Pasi; Osterback, Riikka; Vuorinen, Tytti; Waris, Matti; Bjerkner, Annelie; Tiveljung-Lindell, Annika; van den Hoogen, Bernadette G; Hyypiä, Timo; Ruuskanen, Olli

    2007-01-01

    BACKGROUND: Human bocavirus is a newly discovered parvovirus. It has been detected primarily in children with acute lower respiratory tract infection, but its occurrence, clinical profile, and role as a causative agent of respiratory tract disease are not clear. METHODS: We investigated the presence

  16. Human urinary amylolytic enzymes in acute hepatitis

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    Franzini, C.; Moda, S.

    1965-01-01

    Using paper eletrophoresis two amylolytic enzymes in human urine were demonstrated. A main peak was shown in the gamma globulin zone in normal urine and a second minor peak, in contrast to earlier findings, in the beta globulin zone. The organic source of the minor peak is probably in the liver. Urines from cases of acute hepatitis were studied in the same way and showed that the electrophoretic beta peak was raised in acute hepatitis, also pointing to a possible origin in the liver. Further studies are required to confirm this hypothesis. PMID:5844206

  17. Zebrafish Models for Human Acute Organophosphorus Poisoning.

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    Faria, Melissa; Garcia-Reyero, Natàlia; Padrós, Francesc; Babin, Patrick J; Sebastián, David; Cachot, Jérôme; Prats, Eva; Arick Ii, Mark; Rial, Eduardo; Knoll-Gellida, Anja; Mathieu, Guilaine; Le Bihanic, Florane; Escalon, B Lynn; Zorzano, Antonio; Soares, Amadeu M V M; Raldúa, Demetrio

    2015-10-22

    Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning.

  18. The chilblain-like eruption as a diagnostic clue to the blast crisis of chronic myelocytic leukemia.

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    Yazawa, Hitoshi; Saga, Kenji; Omori, Fusayuki; Jimbow, Kowichi; Sasagawa, Yutaka

    2004-02-01

    A 70-year-old Japanese man visited our clinic with the chief complaint of chilblain-like eruptions on the toes of both feet. His toes were bluish, erythematous, and swollen. Neither oral administration of vitamin E for 2 weeks nor wearing insulated socks improved the clinical manifestations. Peripheral blood examination revealed the presence of a large number of monocytic atypical cells and myeloblasts, anemia, and thrombocytopenia. In the bone marrow, monocytic cells were elevated, and myelocytic atypical cells were observed. Chromosomal analysis demonstrated Philadelphia chromosome. We diagnosed him as having a blast crisis of chronic myelocytic leukemia (CML). A biopsy specimen of the skin from the chilblain-like eruption showed infiltration of large, atypical, mononuclear cells; most of them were positive for CD68, and some of them were positive for CD14. Therefore, we concluded that the chilblain-like eruptions on his toes were specific skin lesions of a blast crisis in CML.

  19. STUDIES ON THE MATURATION OF MYELOBLASTS INTO MYELOCYTES AND ON AMITOTIC CELL DIVISION IN THE PERIPHERAL BLOOD IN SUBACUTE MYELOBLASTIC LEUCEMIA.

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    Sabin, F R; Austrian, C R; Cunningham, R S; Doan, C A

    1924-11-30

    1. Myeloblasts can be discriminated in the supravital technique by the great numbers of tiny mitochondria in the cytoplasm and the absence of any other vitally stainable substance. 2. There are three stages in the maturation of myelocytes. 3. These three phases can be correlated with three types of the oxidase reaction. 4. One case of myeloblastic leucemia showed such an amount of an abnormal type of amitosis as to suggest the disordered cell division of neoplasms. 5. In this case transfusions were correlated with a maturation of myeloblasts into myelocytes, with an increase of the oxidase reaction, and with an increase in amitosis.

  20. Ph sup 1 chromosomes and bcr gene rearrangements in chronic myelocytic leukemia patients developed from atomic bomb survivors

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    Tanaka, Kimio; Takechi, Miho; Shigeta, Chiharu; Sakatani, Keiko; Oguma, Nobuo; Kamada, Nanao; Takimoto, Yasuo; Kuramoto, Atsushi (Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology)

    1989-01-01

    This study compared findings of chronic myelocytic leukemia (CML) in A-bomb survivors (n=8) developing CML within 10 years after the bombing and in non-exposed CML patients (n=14). Both Ph{sup 1} chromosomes and bcr rearrangement were observed in all patients in both exposed and non-exposed groups. There was no significant difference in distribution sites of bcr rearrangement between the groups. These results suggest that bcr-abl chimera mRNA and chimera protein associated with Ph{sup 1} chromosomes have an important role in the development of CML among A-bomb survivors, as well as among non-exposed patients. (N.K.).

  1. Acute psychophysiological stress impairs human associative learning.

    Science.gov (United States)

    Ehlers, M R; Todd, R M

    2017-11-01

    Addiction is increasingly discussed asa disorder of associative learning processes, with both operant and classical conditioning contributing to the development of maladaptive habits. Stress has long been known to promote drug taking and relapse and has further been shown to shift behavior from goal-directed actions towards more habitual ones. However, it remains to be investigated how acute stress may influence simple associative learning processes that occur before a habit can be established. In the present study, healthy young adults were exposed to either acute stress or a control condition half an hour before performing simple classical and operant conditioning tasks. Psychophysiological measures confirmed successful stress induction. Results of the operant conditioning task revealed reduced instrumental responding under delayed acute stress that resembled behavioral responses to lower levels of reward. The classical conditioning experiment revealed successful conditioning in both experimental groups; however, explicit knowledge of conditioning as indicated by stimulus ratings differentiated the stress and control groups. These findings suggest that operant and classical conditioning are differentially influenced by the delayed effects of acute stress with important implications for the understanding of how new habitual behaviors are initially established. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Effect of riluzole on acute pain and hyperalgesia in humans

    DEFF Research Database (Denmark)

    Hammer, N A; Lillesø, J; Pedersen, J L

    1999-01-01

    Riluzole modulates several transmitter systems which may be involved in nociception. Antinociceptive effects have been shown in animal studies, but there are no human data. Therefore, we have examined the acute analgesic effect of riluzole in a human model of inflammatory pain induced by a thermal...

  3. Acute Disseminated Encephalomyelitis After Human Parechovirus Infection.

    Science.gov (United States)

    Obermeier, Patrick E; Karsch, Katharina; Hoppe, Christian; Seeber, Lea; Schneider, Joanna; Mühlhans, Susann; Chen, Xi; Tief, Franziska; Kaindl, Angela M; Weschke, Bernhard; Böttcher, Sindy; Diedrich, Sabine; Rath, Barbara

    2016-01-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory, demyelinating disease occurring several weeks after viral infection. Enteroviruses have been described as potential triggers of ADEM, but the closely related parechoviruses have not. The objective of the study is to assess the prevalence and disease presentation of ADEM after parechovirus infection in a syndromic surveillance program for pediatric infection/inflammation of the central nervous system (CNS). The surveillance was conducted at the Charité Department of Pediatrics in Berlin, Germany, from November 2010 to November 2014. All hospitalized children meeting predefined case criteria underwent highly standardized prospective clinical assessments based on the published case definitions, including for ADEM. Stool samples were independently analyzed by enterovirus and parechovirus real-time polymerase chain reaction at the Robert Koch Institute. Of 105,557 patients screened, 774 (0.7%) fulfilled entry criteria for CNS infection/inflammation, with 114 cases ascertained as ADEM. Parechoviruses were detected in 2.5% of patients with CNS infection/inflammation, including 1 case fulfilling ADEM case criteria with the highest level of diagnostic certainty. We report a first case of ADEM after parechovirus infection in a 5-year-old female presenting with acute hemiparesis 2 weeks after a respiratory illness. Parechovirus disease should be included in the differential diagnosis of ADEM.

  4. Prevalence of Human Rhinovirus Infection in Children with Acute ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    Prevalence of Human Rhinovirus Infection in Children with. Acute Respiratory Symptoms in Ilorin, Nigeria. Olatunji Matthew Kolawole\\ Busayo Joseph Adeyemf1 and Aishat Abdulrahman. Gobir2. 1lnfectious Diseases and Environmental Health Research Group, Department of Microbiology,. Faculty of Life Sciences ...

  5. Human solvent exposure. Factors influencing the pharmacokinetics and acute toxicity

    DEFF Research Database (Denmark)

    Bælum, Jesper

    1991-01-01

    The purpose of this review has been to discuss human and environmental factors which may influence the acute irritative and neurotoxic effects of organic solvents. The review is based on a field study and on four human experimental studies. Several studies have shown that printers and other workers...... exposed to mixtures of solvents experience an increased frequency of work related irritative and neurological symptoms although the exposure has been far below the occupational exposure limits. A series of controlled human exposure studies was carried out. Different groups of persons were exposed...

  6. Human Hendra virus infection causes acute and relapsing encephalitis.

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    Wong, K T; Robertson, T; Ong, B B; Chong, J W; Yaiw, K C; Wang, L F; Ansford, A J; Tannenberg, A

    2009-06-01

    To study the pathology of two cases of human Hendra virus infection, one with no clinical encephalitis and one with relapsing encephalitis. Autopsy tissues were investigated by light microscopy, immunohistochemistry and in situ hybridization. In the patient with acute pulmonary syndrome but not clinical acute encephalitis, vasculitis was found in the brain, lung, heart and kidney. Occasionally, viral antigens were demonstrated in vascular walls but multinucleated endothelial syncytia were absent. In the lung, there was severe inflammation, necrosis and viral antigens in type II pneumocytes and macrophages. The rare kidney glomerulus showed inflammation and viral antigens in capillary walls and podocytes. Discrete necrotic/vacuolar plaques in the brain parenchyma were associated with antigens and viral RNA. Brain inflammation was mild although CD68(+) microglia/macrophages were significantly increased. Cytoplasmic viral inclusions and antigens and viral RNA in neurones and ependyma suggested viral replication. In the case of relapsing encephalitis, there was severe widespread meningoencephalitis characterized by neuronal loss, macrophages and other inflammatory cells, reactive blood vessels and perivascular cuffing. Antigens and viral RNA were mainly found in neurones. Vasculitis was absent in all the tissues examined. The case of acute Hendra virus infection demonstrated evidence of systemic infection and acute encephalitis. The case of relapsing Hendra virus encephalitis showed no signs of extraneural infection but in the brain, extensive inflammation and infected neurones were observed. Hendra virus can cause acute and relapsing encephalitis and the findings suggest that the pathology and pathogenesis are similar to Nipah virus infection.

  7. Rhabdomyolysis among acute human poisoning cases.

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    Talaie, H; Pajouhmand, A; Abdollahi, M; Panahandeh, R; Emami, H; Hajinasrolah, S; Tghaddosinezhad, M

    2007-07-01

    Rhabdomyolysis is a clinical and biochemical syndrome occurring when skeletal muscle cells erupt and result in release of creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and myoglobin into the interstitial space and plasma. Mechanical trauma, compression, excessive muscle activity and ischemia are frequent causes, but non-traumatic rhabdomyolysis is usually caused by a toxic reaction to drugs. In this study, 181 patients suspected of rhabdomyolysis were admitted to the poisoning center of Loghman-Hakim Hospital in Tehran during one year (September 2004 to September 2005) were studied. Patients were included on the basis of physical examination and blood analysis for CPK and LDH. Rhabdomyolysis was confirmed if CPK level has been greater than 975 U/L. Out of 181 patients, 64 were female and 117 were male with an age range between 13-78 years. One-hundred and forty-three (79%) patients had CPK greater than 975 U/L. In 6% of the cases, multiple drug poisoning were observed. Two patients (1.1%) had muscle pain, five patients (2.8%) had rigidity and five patients (2.8%) had muscle inflammation. One-hundred and nineteen patients (65.7%) were febrile. The most common cause of rhabdomyolysis was opium. Blood ALT showed an increase in 109 patients (60.9%), AST in 80 patients (44.7%), and LDH in 144 patients (79.6%). Fifty patients (28.2%) had higher blood direct bilirubin and 64 patients (36.4%) showed higher total bilirubin. Six percent of patients had been diagnosed as ARF by indication of creatinine greater than 1.4 mg/dL. Five percent of patients had hypernatremia and 1.1% of patients had hyperkalemia. It is concluded that rhabdomyolysis is a matter of concern in human poisonings and needs special approach to attend.

  8. Human Metapneumovirus Infection and Acute Respiratory Distress Syndrome During Pregnancy.

    Science.gov (United States)

    Fuchs, Alina; McLaren, Rodney; Saunders, Paul; Karakash, Scarlett; Minkoff, Howard

    2017-09-01

    Human metapneumovirus has recently been recognized as an important cause of severe respiratory viral infections and of viral infections in patients admitted to intensive care units. Little is known about the course of this infection in pregnancy. A late-preterm primigravid woman was admitted to the intensive care unit for acute respiratory distress syndrome and subsequently diagnosed with human metapneumovirus. Because of worsening maternal respiratory status, she was intubated and a primary cesarean delivery was performed. The patient's respiratory status continued to decline postpartum, and she ultimately required extracorporeal membrane oxygenation. She was treated supportively until her respiratory status improved, at which time she was extubated and weaned off extracorporeal membrane oxygenation and subsequently discharged home. Human metapneumovirus can lead to severe respiratory illness during pregnancy.

  9. Eliminating acute lymphoblastic leukemia cells from human testicular cell cultures: a pilot study

    NARCIS (Netherlands)

    Sadri-Ardekani, Hooman; Homburg, Christa H.; van Capel, Toni M. M.; van den Berg, Henk; van der Veen, Fulco; van der Schoot, C. Ellen; van Pelt, Ans M. M.; Repping, Sjoerd

    2014-01-01

    To study whether acute lymphoblastic leukemia (ALL) cells survive in a human testicular cell culture system. Experimental laboratory study. Reproductive biology laboratory, academic medical center. Acute lymphoblastic leukemia cells from three patients and testicular cells from three other patients.

  10. Acute human immunodeficiency virus syndrome in an adolescent.

    Science.gov (United States)

    Aggarwal, Mridula; Rein, Jeffrey

    2003-10-01

    Acute human immunodeficiency virus (HIV) seroconversion illness is a difficult diagnosis to make because of its nonspecific and protean manifestations. We present such a case in an adolescent. A 15-year-old boy presented with a 5-day history of fever, sore throat, vomiting, and diarrhea. The patient also reported a nonproductive cough, coryza, and fatigue. The patient's only risk factor for HIV infection was a history of unprotected intercourse with 5 girls. Physical examination was significant for fever, exudative tonsillopharyngitis, shotty cervical lymphadenopathy, and palpable purpura on both feet. Laboratory studies demonstrated lymphopenia and mild thrombocytopenia. Hemoglobin, serum creatinine, and urinalysis were normal. The following day, the patient remained febrile. Physical examination revealed oral ulcerations, conjunctivitis, and erythematous papules on the thorax; the purpura was unchanged. Serologies for hepatitis B, syphilis, HIV, and Epstein-Barr virus were negative. Bacterial cultures of blood and stool and viral cultures of throat and conjunctiva showed no pathogens. Coagulation profile and liver enzymes were normal. Within 1 week, all symptoms had resolved. The platelet count normalized. Repeat HIV serology was positive, as was HIV DNA polymerase chain reaction. Subsequent HIV viral load was 350 000, and the CD4 lymphocyte count was 351/mm3. HIV is the seventh leading cause of death among people aged 15 to 24 in the United States, and up to half of all new infections occur in adolescents. Our patient presented with many of the typical signs and symptoms of acute HIV infection: fever, fatigue, rash, pharyngitis, lymphadenopathy, oral ulcers, emesis, and diarrhea. Other symptoms commonly reported include headache, myalgias, arthralgias, aseptic meningitis, peripheral neuropathy, thrush, weight loss, night sweats, and genital ulcers. Common seroconversion laboratory findings include leukopenia, thrombocytopenia, and elevated transaminases. The

  11. Human bocavirus in children with acute respiratory infections in Vietnam.

    Science.gov (United States)

    Tran, Dinh Nguyen; Nguyen, Tran Quynh Nhu; Nguyen, Tuan Anh; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

    2014-06-01

    Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co-infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12-24 months old were the most affected age group. Infections with HBoV were found year-round, though most cases occurred in the dry season (December-April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P-value infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. © 2013 Wiley Periodicals, Inc.

  12. Biology and relevance of human acute myeloid leukemia stem cells.

    Science.gov (United States)

    Thomas, Daniel; Majeti, Ravindra

    2017-03-23

    Evidence of human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly 2 decades ago through the identification of rare subpopulations of engrafting cells in xenotransplantation assays. These AML LSCs were shown to reside at the apex of a cellular hierarchy that initiates and maintains the disease, exhibiting properties of self-renewal, cell cycle quiescence, and chemoresistance. This cancer stem cell model offers an explanation for chemotherapy resistance and disease relapse and implies that approaches to treatment must eradicate LSCs for cure. More recently, a number of studies have both refined and expanded our understanding of LSCs and intrapatient heterogeneity in AML using improved xenotransplant models, genome-scale analyses, and experimental manipulation of primary patient cells. Here, we review these studies with a focus on the immunophenotype, biological properties, epigenetics, genetics, and clinical associations of human AML LSCs and discuss critical questions that need to be addressed in future research. © 2017 by The American Society of Hematology.

  13. Raman spectroscopy of human saliva for acute myocardial infarction detection

    Science.gov (United States)

    Chen, Maowen; Chen, Yuanxiang; Wu, Shanshan; Huang, Wei; Lin, Jinyong; Weng, Guo-Xing; Chen, Rong

    2014-09-01

    Raman spectroscopy is a rapidly non-invasive technique with great potential for biomedical research. The aim of this study was to evaluate the feasibility of using Raman spectroscopy of human saliva for acute myocardial infarction (AMI) detection. Raman spectroscopy measurements were performed on two groups of saliva samples: one group from patients (n=30) with confirmed AMI and the other group from healthy controls (n=31). The diagnostic performance for differentiating AMI saliva from normal saliva was evaluated by multivariate statistical analysis. The combination of principal component analysis (PCA) and linear discriminate analysis (LDA) of the measured Raman spectra separated the spectral features of the two groups into two distinct clusters with little overlaps, rendering the sensitivity of 80.0% and specificity of 80.6%. The results from this exploratory study demonstrated that Raman spectroscopy of human saliva can serve as a potentially clinical tool for rapid AMI detection and screening.

  14. Human rhinovirus infection in young African children with acute wheezing

    Directory of Open Access Journals (Sweden)

    Zar Heather J

    2011-03-01

    Full Text Available Abstract Background Infections caused by human rhinoviruses (HRVs are important triggers of wheezing in young children. Wheezy illness has increasingly been recognised as an important cause of morbidity in African children, but there is little information on the contribution of HRV to this. The aim of this study was to determine the role of HRV as a cause of acute wheezing in South African children. Methods Two hundred and twenty children presenting consecutively at a tertiary children's hospital with a wheezing illness from May 2004 to November 2005 were prospectively enrolled. A nasal swab was taken and reverse transcription PCR used to screen the samples for HRV. The presence of human metapneumovirus, human bocavirus and human coronavirus-NL63 was assessed in all samples using PCR-based assays. A general shell vial culture using a pool of monoclonal antibodies was used to detect other common respiratory viruses on 26% of samples. Phylogenetic analysis to determine circulating HRV species was performed on a portion of HRV-positive samples. Categorical characteristics were analysed using Fisher's Exact test. Results HRV was detected in 128 (58.2% of children, most (72% of whom were under 2 years of age. Presenting symptoms between the HRV-positive and negative groups were similar. Most illness was managed with ambulatory therapy, but 45 (35% were hospitalized for treatment and 3 (2% were admitted to intensive care. There were no in-hospital deaths. All 3 species of HRV were detected with HRV-C being the most common (52% followed by HRV-A (37% and HRV-B (11%. Infection with other respiratory viruses occurred in 20/128 (16% of HRV-positive children and in 26/92 (28% of HRV-negative samples. Conclusion HRV may be the commonest viral infection in young South African children with acute wheezing. Infection is associated with mild or moderate clinical disease.

  15. Acute activation, desensitization and smoldering activation of human acetylcholine receptors.

    Science.gov (United States)

    Campling, Barbara G; Kuryatov, Alexander; Lindstrom, Jon

    2013-01-01

    The behavioral effects of nicotine and other nicotinic agonists are mediated by AChRs in the brain. The relative contribution of acute activation versus chronic desensitization of AChRs is unknown. Sustained "smoldering activation" occurs over a range of agonist concentrations at which activated and desensitized AChRs are present in equilibrium. We used a fluorescent dye sensitive to changes in membrane potential to examine the effects of acute activation and chronic desensitization by nicotinic AChR agonists on cell lines expressing human α4β2, α3β4 and α7 AChRs. We examined the effects of acute and prolonged application of nicotine and the partial agonists varenicline, cytisine and sazetidine-A on these AChRs. The range of concentrations over which nicotine causes smoldering activation of α4β2 AChRs was centered at 0.13 µM, a level found in smokers. However, nicotine produced smoldering activation of α3β4 and α7 AChRs at concentrations well above levels found in smokers. The α4β2 expressing cell line contains a mixture of two stoichiometries, namely (α4β2)2β2 and (α4β2)2α4. The (α4β2)2β2 stoichiometry is more sensitive to activation by nicotine. Sazetidine-A activates and desensitizes only this stoichiometry. Varenicline, cytisine and sazetidine-A were partial agonists on this mixture of α4β2 AChRs, but full agonists on α3β4 and α7 AChRs. It has been reported that cytisine and varenicline are most efficacious on the (α4β2)2α4 stoichiometry. In this study, we distinguish the dual effects of activation and desensitization of AChRs by these nicotinic agonists and define the range of concentrations over which smoldering activation can be sustained.

  16. Acute activation, desensitization and smoldering activation of human acetylcholine receptors.

    Directory of Open Access Journals (Sweden)

    Barbara G Campling

    Full Text Available The behavioral effects of nicotine and other nicotinic agonists are mediated by AChRs in the brain. The relative contribution of acute activation versus chronic desensitization of AChRs is unknown. Sustained "smoldering activation" occurs over a range of agonist concentrations at which activated and desensitized AChRs are present in equilibrium. We used a fluorescent dye sensitive to changes in membrane potential to examine the effects of acute activation and chronic desensitization by nicotinic AChR agonists on cell lines expressing human α4β2, α3β4 and α7 AChRs. We examined the effects of acute and prolonged application of nicotine and the partial agonists varenicline, cytisine and sazetidine-A on these AChRs. The range of concentrations over which nicotine causes smoldering activation of α4β2 AChRs was centered at 0.13 µM, a level found in smokers. However, nicotine produced smoldering activation of α3β4 and α7 AChRs at concentrations well above levels found in smokers. The α4β2 expressing cell line contains a mixture of two stoichiometries, namely (α4β22β2 and (α4β22α4. The (α4β22β2 stoichiometry is more sensitive to activation by nicotine. Sazetidine-A activates and desensitizes only this stoichiometry. Varenicline, cytisine and sazetidine-A were partial agonists on this mixture of α4β2 AChRs, but full agonists on α3β4 and α7 AChRs. It has been reported that cytisine and varenicline are most efficacious on the (α4β22α4 stoichiometry. In this study, we distinguish the dual effects of activation and desensitization of AChRs by these nicotinic agonists and define the range of concentrations over which smoldering activation can be sustained.

  17. MR-visible brain water content in human acute stroke

    DEFF Research Database (Denmark)

    Gideon, P; Rosenbaum, S; Sperling, B

    1999-01-01

    Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate...... brain water content during the course of cerebral infarction. Measurements were performed serially in the acute, subacute, and chronic phase of infarction. Fourteen patients with acute cerebral infarction were examined as well as 9 healthy controls. To correlate with regional cerebral blood flow (r......CBF from Day 0-3 to Day 4-7 (p = 0.050) and from Day 0-3 to Day 8-21 (p = 0.028). No correlation between rCBF and water content was found. Water content in ischemic brain tissue increased significantly between Day 4-7 after stroke. This should be considered when performing quantitative 1H-MRS using water...

  18. MR-visible brain water content in human acute stroke

    DEFF Research Database (Denmark)

    Gideon, P; Rosenbaum, S; Sperling, B

    1999-01-01

    CBF) SPECT-scanning using 99mTc-HMPAO as flow tracer was performed in the patients. Mean water content (SD) in the infarct area was 37.7 (5.1); 41.8 (4.8); 35.2 (5.4); and 39.3 (5.1) mol x [kg wet weight](-1) at 0-3; 4-7; 8-21; and >180 days after stroke, respectively. Water content increased between Day 0......Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate...... brain water content during the course of cerebral infarction. Measurements were performed serially in the acute, subacute, and chronic phase of infarction. Fourteen patients with acute cerebral infarction were examined as well as 9 healthy controls. To correlate with regional cerebral blood flow (r...

  19. Human bocavirus in children with acute gastroenteritis in Albania.

    Science.gov (United States)

    La Rosa, G; Della Libera, S; Iaconelli, M; Donia, D; Cenko, F; Xhelilaj, G; Cozza, P; Divizia, M

    2016-05-01

    Human Bocavirus (HBoV) has been recently identified in association with acute viral gastroenteritis (AGE). The objective of this work was to investigate the prevalence of HBoV in children with AGE in Albania. Stool specimens collected from 142 children were analyzed by amplification of partial NP1 and Vp1/Vp2 genes. HBoV was detected in 13 samples (9.1%), 12 HBoV-1 and one HBoV-2. All HBoV-positive patients were co-infected with rotavirus and/or adenovirus, a finding which might indicate that there is no clear causal association of this agent with diarrhea. Further investigation is needed to assess the pathogenic role of HBoV in childhood diarrhea. © 2015 Wiley Periodicals, Inc.

  20. Effect of acute hyperinsulinemia on magnesium homeostasis in humans.

    Science.gov (United States)

    Xu, Li Hao Richie; Maalouf, Naim M

    2017-02-01

    Insulin may influence magnesium homeostasis through multiple mechanisms. Acutely, it stimulates the shift of magnesium from plasma into red blood cells and platelets, and in vitro, it stimulates the activity of the TRPM6 channel, a key regulator of renal magnesium reabsorption. We investigated the impact of hyperinsulinemia on magnesium handling in participants with a wide range of insulin sensitivity. Forty-seven participants were recruited, including 34 nondiabetic controls and 13 with type 2 diabetes mellitus. After stabilization under fixed metabolic diet, participants underwent hyperinsulinemic-euglycemic clamp. Serum and urine samples were collected before and during hyperinsulinemia. Change in serum magnesium, urinary magnesium to creatinine (Mg(2)(+) :Cr) ratio, fractional excretion of urinary magnesium (FEMg(2)(+) ), and estimated transcellular shift of magnesium were compared before and during hyperinsulinemia. Hyperinsulinemia led to a small but statistically significant decrease in serum magnesium, and to a shift of magnesium into the intracellular compartment. Hyperinsulinemia did not significantly alter urinary magnesium to creatinine ratio or fractional excretion of urinary magnesium in the overall population, although a small but statistically significant decline in these parameters occurred in participants with diabetes. There was no significant correlation between change in fractional excretion of urinary magnesium and body mass index or insulin sensitivity measured as glucose disposal rate. In human participants, acute hyperinsulinemia stimulates the shift of magnesium into cells with minimal alteration in renal magnesium reabsorption, except in diabetic patients who experienced a small decline in fractional excretion of urinary magnesium. The magnitude of magnesium shift into the intracellular compartment in response to insulin does not correlate with that of insulin-stimulated glucose entry into cells. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Human rotavirus genotypes causing acute watery diarrhea among ...

    African Journals Online (AJOL)

    Background: Diarrhea is a major cause of childhood morbidity and mortality in the developing countries. Rotavirus is a major cause of acute watery diarrhea. Aim: This study aims at characterizing the prevalent rotavirus G-genotypes among under.five children presenting with acute watery diarrhea in Benin City, Nigeria.

  2. Alveolar recruitment of ficolin-3 in response to acute pulmonary inflammation in humans

    DEFF Research Database (Denmark)

    Plovsing, Ronni R; Berg, Ronan M G; Munthe-Fog, Lea

    2016-01-01

    acute lung and systemic inflammation induce recruitment of lectins in humans. METHODS: Fifteen healthy volunteers received LPS intravenously (IV) or in a lung subsegment on two different occasions. Volunteers were evaluated by consecutive blood samples and by bronchoalveolar lavage 2, 4, 6, 8, or 24h...... acute phase response with an increase in CRP (precruitment...

  3. Human coronavirus and severe acute respiratory infection in Southern Brazil.

    Science.gov (United States)

    Trombetta, Hygor; Faggion, Heloisa Z; Leotte, Jaqueline; Nogueira, Meri B; Vidal, Luine R R; Raboni, Sonia M

    2016-05-01

    Human coronaviruses (HCoVs) are an important cause of respiratory tract infection and are responsible for causing the common cold in the general population. Thus, adequate surveillance of HCoV is essential. This study aimed to analyze the impact of HCoV infections and their relation to severe acute respiratory infection (SARI) in a hospitalized population in Southern Brazil. A cross-sectional study was conducted at a tertiary care hospital, and assessed inpatients under investigation for SARI by the hospital epidemiology department, and all patients who had nasopharyngeal aspirates collected from January 2012 to December 2013 to detect respiratory viruses (RVs). Viral infection was detected by multiplex reverse transcriptase polymerase chain reaction (RT-PCR), with primers specific to the subtypes HCoV-229E/NL63 and OC43/HKU1. The overall positivity rate was 58.8% (444/755), and HCoVs were detected in 7.6% (n = 34) of positive samples. Children below two years of age were most frequently affected (62%). Comorbidities were more likely to be associated with HCoVs than with other RVs. Immunosuppression was an independent risk factor for HCoV infection (OR = 3.5, 95% CI 1.6-7.6). Dyspnea was less frequently associated with HCoV infection (p infected with HCoV (9%) died from respiratory infection. HCoVs are important respiratory pathogens, especially in hospitalized children under 2 years of age and in immunosuppressed patients. They may account for a small proportion of SARI diagnoses, increased need for mechanical ventilation, intensive care unit admission, and death.

  4. Tumefactive acute disseminated encephalomyelitis complicating human swine influenza (H1N1).

    Science.gov (United States)

    Chan, Amanda C Y; Ng, S H

    2014-10-01

    This report illustrates an adult patient presenting with tumefactive acute disseminated encephalomyelitis complicating human swine influenza. Its presentation, diagnosis, investigation findings, course, and response to treatment are discussed herein.

  5. Technical advance: immunophenotypical characterization of human neutrophil differentiation

    DEFF Research Database (Denmark)

    Mora-Jensen, Helena Isabel; Jendholm, Johan; Fossum, Anna

    2011-01-01

    The current study reports a flow cytometry-based protocol for the prospective purification of human BM populations representing six successive stages of terminal neutrophil differentiation, including early promyelocytes and late promyelocytes, myelocytes, metamyelocytes, band cells, and PMN...... differentiation in vivo in the human setting and constitutes an important alternative to models that are based on in vitro differentiation of myeloid cell lines and HPCs....

  6. Orbital tumour as initial manifestation of acute myeloid leukemia: granulocytic sarcoma: case report.

    Science.gov (United States)

    Maka, Erika; Lukáts, Olga; Tóth, Jeannette; Fekete, Sándor

    2008-06-01

    We report orbital involvement as an initial manifestation of acute myeloid leukemia in a 57-year-old woman. The patient presented with painful proptosis and limited ocular motility. Orbital computed tomography revealed bilateral homogeneous masses. Orbital biopsy was performed on the right side; and histopathology disclosed a myelocytic tumour. Despite treatment using irradiation and chemotherapy, the patient died eleven months after presentation. There appear to be only a few previous reports of acute myeloid leukemia cases presenting with orbital involvement, and most cases occurred in children. This very rare condition has a poor survival prognosis, even with radiation treatment and chemotherapy.

  7. Effects of gabapentin in acute inflammatory pain in humans

    DEFF Research Database (Denmark)

    Werner, M U; Perkins, F M; Holte, Kathrine

    2001-01-01

    BACKGROUND AND OBJECTIVES: The aim of the study was to examine the analgesic effects of the anticonvulsant, gabapentin, in a validated model of acute inflammatory pain. METHODS: Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Gabapentin 1...... stimuli (visual analog scale [VAS]), assessments of thermal and mechanical detection thresholds, and areas of secondary hyperalgesia. Side effects drowsiness and postural instability were assessed by subjective ratings (VAS). RESULTS: The burn injury induced significant primary and secondary hyperalgesia...... not significantly changed by gabapentin (P effect in normal skin, but may reduce primary mechanical allodynia in acute...

  8. Cerebrovascular response to acute metabolic acidosis in humans.

    NARCIS (Netherlands)

    Ven, M.T.P. van de; Colier, W.N.J.M.; Kersten, B.T.P.; Oeseburg, B.; Folgering, H.T.M.

    2003-01-01

    OBJECTIVES: Evaluation of the cerebrovascular response (delta CBV/delta PaCO2) during baseline metabolic conditions and acute metabolic acidosis. METHODS: 15 healthy subjects, 5 m, 10 f, 56 +/- 10 yrs were investigated. For acidification, NH4Cl was given orally. CBV was measured using Near Infrared

  9. Acute exercise remodels promoter methylation in human skeletal muscle

    DEFF Research Database (Denmark)

    Barrès, Romain; Yan, Jie; Egan, Brendan

    2012-01-01

    DNA methylation is a covalent biochemical modification controlling chromatin structure and gene expression. Exercise elicits gene expression changes that trigger structural and metabolic adaptations in skeletal muscle. We determined whether DNA methylation plays a role in exercise-induced gene...... methylation of PGC-1a, PDK4, and PPAR-d was markedly decreased in mouse soleus muscles 45 min after ex vivo contraction. In L6 myotubes, caffeine exposure induced gene hypomethylation in parallel with an increase in the respective mRNA content. Collectively, our results provide evidence that acute gene...

  10. Random-start IVF treatment: An emergent fertility preservation technique between cytotoxic treatment courses and stem-cell transplantation in acute myelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Ghada Hussein

    2015-12-01

    Conclusions: Although it is still experimental, emergency IVF treatment considered as a novel approach for fertility preservation in cancer patients not only before the start of chemotherapy but even between the treatment courses if the patient’s physical and psychological conditions are stable and acceptable.

  11. Acute and non-acute effects of cannabis on human memory function: a critical review of neuroimaging studies.

    Science.gov (United States)

    Bossong, Matthijs G; Jager, Gerry; Bhattacharyya, Sagnik; Allen, Paul

    2014-01-01

    Smoking cannabis produces a diverse range of effects, including impairments in learning and memory. These effects are exerted through action on the endocannabinoid system, which suggests involvement of this system in human cognition. Learning and memory deficits are core symptoms of psychiatric and neurological disorders such as schizophrenia and Alzheimer's disease, and may also be related to endocannabinoid dysfunction in these disorders. However, before new research can focus on potential treatments that work by manipulating the endocannabinoid system, it needs to be elucidated how this system is involved in symptoms of psychiatric disorders. Here we review neuroimaging studies that investigated acute and non-acute effects of cannabis on human learning and memory function, both in adults and in adolescents. Overall, results of these studies show that cannabis use is associated with a pattern of increased activity and a higher level of deactivation in different memory-related areas. This could reflect either increased neural effort ('neurophysiological inefficiency') or a change in strategy to maintain good task performance. However, the interpretation of these findings is significantly hampered by large differences between study populations in cannabis use in terms of frequency, age of onset, and time that subjects were abstinent from cannabis. Future neuroimaging studies should take these limitations into account, and should focus on the potential of cannabinoid compounds for treatment of cognitive symptoms in psychiatric disorders.

  12. The effect of acute exercise on collagen turnover in human tendons

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Pingel, Jessica; Boesen, Mikael

    2013-01-01

    Mechanical loading of human tendon stimulates collagen synthesis, but the relationship between acute loading responses and training status of the tendon is not clear. We tested the effect of prolonged load deprivation on the acute loading-induced collagen turnover in human tendons, by applying...... the same absolute load to a relative untrained Achilles tendon (2-week immobilization period prior to acute loading) and a habitually loaded contra-lateral Achilles tendon, respectively, within the same individuals. Eight untrained, healthy males had one lower limb totally immobilized for 2 weeks, whereas...... the contra-lateral leg was used habitually. Following the procedure both Achilles tendons and calf muscles were loaded with the same absolute load during a 1-h treadmill run. Tissue collagen turnover was measured by microdialysis performed post-immobilization but pre-exercise around both Achilles tendons...

  13. Inhibitory and Cytotoxic Activities of Salvia Officinalis L. Extract on Human Lymphoma and Leukemia Cells by Induction of Apoptosis

    Directory of Open Access Journals (Sweden)

    Abbas Azadmehr

    2013-02-01

    Full Text Available Purpose: Salvia officinalis L., also known as Maryam Goli, is one of the native plants used to Persian medicinal herbs. Hence, the objective of this study was to examine the in vitro cytotoxic activities of a standardized crude methanol extracts prepared from Salvia officinalis L., on a non-Hodgkin’s B-cell lymphoma (Raji and human leukemic monocyte lymphoma (U937, Human acute myelocytic leukemia (KG-1A and Human Umbilical Vein Endothelial (HUVEC cell lines. Methods: The effect of methanolic extract on the inhibition of cell proliferation and cytotoxic activity was evaluated by Dye exclusion and Micro culture tetrazolium test (MTT cytotoxicity assay. Cell death ELISA was employed to quantify the nucleosome production result from nuclear DNA fragmentation during apoptosis and determined whether the mechanism involves induction of apoptosis or necrosis. Results: The present results demonstrated that methanolic extract at 50 to 800 μg/ml dose and time-dependently suppressed the proliferation of KG-1A, U937 and Raji cells by more than 80% (p800 Ag/ml. Nucleosome productions in KG-1A, Raji and U937 cells were significantly increased respectively upon the treatment of Salvia officinalis L. extract. Conclusion: The Salvia officinalis L. extract was found dose and time-dependently inhibits the proliferation of lymphoma and leukemic cells possibly via an apoptosis-dependent pathway.

  14. Inhibitory and cytotoxic activities of salvia officinalis L. Extract on human lymphoma and leukemia cells by induction of apoptosis.

    Science.gov (United States)

    Zare Shahneh, Fatemeh; Valiyari, Samira; Baradaran, Behzad; Abdolalizadeh, Jalal; Bandehagh, Ali; Azadmehr, Abass; Hajiaghaee, Reza

    2013-01-01

    Salvia officinalis L., also known as Maryam Goli, is one of the native plants used to Persian medicinal herbs. Hence, the objective of this study was to examine the in vitro cytotoxic activities of a standardized crude methanol extracts prepared from Salvia officinalis L., on a non-Hodgkin's B-cell lymphoma (Raji) and human leukemic monocyte lymphoma (U937), Human acute myelocytic leukemia (KG-1A) and Human Umbilical Vein Endothelial (HUVEC) cell lines. The effect of methanolic extract on the inhibition of cell proliferation and cytotoxic activity was evaluated by Dye exclusion and Micro culture tetrazolium test (MTT) cytotoxicity assay. Cell death ELISA was employed to quantify the nucleosome production result from nuclear DNA fragmentation during apoptosis and determined whether the mechanism involves induction of apoptosis or necrosis. The present results demonstrated that methanolic extract at 50 to 800 μg/ml dose and time-dependently suppressed the proliferation of KG-1A, U937 and Raji cells by more than 80% (p800 Ag/ml). Nucleosome productions in KG-1A, Raji and U937 cells were significantly increased respectively upon the treatment of Salvia officinalis L. extract. The Salvia officinalis L. extract was found dose and time-dependently inhibits the proliferation of lymphoma and leukemic cells possibly via an apoptosis-dependent pathway.

  15. Acute cytotoxic effects of marketed ophthalmic formulations on human corneal epithelial cells.

    Science.gov (United States)

    Hakkarainen, Jenni J; Reinisalo, Mika; Ragauskas, Symantas; Seppänen, Aila; Kaja, Simon; Kalesnykas, Giedrius

    2016-09-10

    The purpose of the study was to devise a fast, reliable and sensitive cell viability assay for assessment of acute cytotoxicity on human corneal epithelial cells by using a clinically relevant exposure time. Acute cytotoxic effects of the pharmaceutical excipients benzalkonium chloride (BAC), macrogolglycerol hydroxystearate (MGHS40), polysorbate 80 (PS80) and marketed ophthalmic formulations (Lumigan(®), Monoprost(®), Taflotan(®), Travatan(®), Xalatan(®)) containing these excipients were tested. Human corneal epithelial cell (HCE-T) viability was assessed by measuring the reduction of resazurin to highly fluorescent resorufin. Expression of the tight junction proteins in HCE-T cells were characterized by immunofluorescence staining. Presence of tight junction proteins in HCE-T cells was demonstrated. BAC preserved ophthalmic formulations showed concentration-dependent and time-dependent cytotoxicity to human corneal epithelium. In contrast, no acute cytotoxicity of non-ionic stabilizing/solubilizing excipients (MGSH40 and PS80) or ophthalmic formulation containing these excipients was observed. Marketed ophthalmic formulations used for glaucoma medication show differential toxicity on human corneal epithelial cells. The present study revealed that BAC-preserved ophthalmic formulations were able to induce acute cytotoxic effects even during a clinically relevant exposure time, which was not observed with MGSH40 and PS80 excipients or ophthalmic formulations containing these excipients. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Atrial distension, haemodilution, and acute control of renin release during water immersion in humans

    DEFF Research Database (Denmark)

    Gabrielsen, A; Pump, B; Bie, P

    2002-01-01

    We tested the hypothesis that atrial distension (stimulation of cardiopulmonary baroreceptors) is not the single pivotal stimulus for the acute suppression of renin release during water immersion in humans and that immersion-induced haemodilution constitutes an important additional stimulus. In n...

  17. Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation

    NARCIS (Netherlands)

    Spronk, D.B.; De Bruijn, E.R.; van Wel, J.H.; Ramaekers, J.G.; Verkes, R.J.

    2016-01-01

    Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  19. Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human

    OpenAIRE

    Song, Huai-Dong; Tu, Chang-chun; Zhang, Guo-wei; Wang, Sheng-Yue; Zheng, Kui; Lei, Lian-Cheng; Chen, Qiu-Xia; Gao, Yu-Wei; Zhou, Hui-qiong; Xiang, Hua; Zheng, Hua-Jun; Chern, Shur-Wern Wang; Cheng, Feng; Pan, Chun-Ming; Xuan, Hua

    2005-01-01

    The genomic sequences of severe acute respiratory syndrome coronaviruses from human and palm civet of the 2003/2004 outbreak in the city of Guangzhou, China, were nearly identical. Phylogenetic analysis suggested an independent viral invasion from animal to human in this new episode. Combining all existing data but excluding singletons, we identified 202 single-nucleotide variations. Among them, 17 are polymorphic in palm civets only. The ratio of nonsynonymous/synonymous nucleotide substitut...

  20. Baroreflex Responses to Acute Changes in Blood Volume in Humans

    Science.gov (United States)

    Thompson, Cynthia A.; Tatro, Dana L.; Ludwig, David A.; Convertino, Victor A.

    1990-01-01

    To test the hypothesis that acute changes in plasma volume affect the stimulus-response relations of high- and low- pressure baroreflexes, eight men (27-44 yr old) underwent measurements for carotid-cardiac and cardiopulmonary baro-reflex responses under the following three volemic conditions: hypovolemic, normovolemic, and hypervolemic. The stimulus- response relation of the carotid-cardiac response curve was generated using a neck cuff device, which delivered pressure changes between +40 and -65 mmHg in continuous steps of 15 mmHg. The stimulus-response relationship, of the cardio-pulmonary baroreflex were studied by measurements of Forearm Vascular Resistance (FVR) and Peripheral Venous Pressure (PVP) during low levels of lower body negative pressure (O to -20 mmHg). The results indicate greater demand for vasoconstriction for equal reductions in venous pressure during progressive hypovolemia; this condition may compromise the capacity to provide adequate peripheral resistance during severe orthostatic stress. Fluid loading before reentry after spaceflight may act to restore vasoconstrictive capacity of the cardiopulmonary baroreflex but may not be an effective countermeasure against potential post- flight impairment of the carotid-cardiac baroreflex.

  1. Human immunodeficiency virus seroconversion presenting with acute inflammatory demyelinating polyneuropathy: a case report

    Directory of Open Access Journals (Sweden)

    Sloan Derek J

    2008-12-01

    Full Text Available Abstract Introduction Acute Human Immunodeficiency Virus infection is associated with a range of neurological conditions. Guillain-Barré syndrome is a rare presentation; acute inflammatory demyelinating polyneuropathy is the commonest form of Guillain-Barré syndrome. Acute inflammatory demyelinating polyneuropathy has occasionally been reported in acute Immunodeficiency Virus infection but little data exists on frequency, management and outcome. Case presentation We describe an episode of Guillain-Barré syndrome presenting as acute inflammatory demyelinating polyneuropathy in a 30-year-old man testing positive for Immunodeficiency Virus, probably during acute seroconversion. Clinical suspicion was confirmed by cerebrospinal fluid analysis and nerve conduction studies. Rapid clinical deterioration prompted intravenous immunoglobulin therapy and early commencement of highly active anti-retroviral therapy. All symptoms resolved within nine weeks. Conclusion Unusual neurological presentations in previously fit patients are an appropriate indication for Immunodeficiency-Virus testing. Highly active anti-retroviral therapy with adequate penetration of the central nervous system should be considered as an early intervention, alongside conventional therapies such as intravenous immunoglobulin.

  2. Chronic Myelocytic Leukemia (CML) Patient-Derived Dendritic Cells Transfected with Autologous Total RNA Induces CML-Specific Cytotoxicity.

    Science.gov (United States)

    Yu, Li; Hu, Ting; Zou, Tian; Shi, Qingzhi; Chen, Guoan

    2016-12-01

    The oncogenic bcr/abl1 fusion gene is a chronic myelogenous leukemia (CML)-specific antigen which is absent in normal tissues. This makes bcr/abl1 a perfect target for developing CML vaccines that elicit specific immune responses against minimal residual disease while sparing normal tissue. The aim of this study was to use different methods to induce dendritic cells (DCs) derived from patients with CML (CML-DCs) and analyze them for CML-specific tumor cytotoxicity for immune therapy. Bone marrow-derived mononuclear cells from ten CML patients were studied to induce CML-DC differentiation in the presence of recombinant human interleukin-4, rh-granulocyte-macrophage-colony stimulating factor, and tumor necrosis factor-alpha with either a total RNA-lipofectamine complex, total RNA or CML tumor lysate (freeze-thawed). CML-DC maturation, confirmed by expression of CD1α, CD40, CD80, CD83, CD86 and by real-time polymerase chain reaction, validated the CML-origin of these DC cells. CML-DCs stimulated cytotoxic T-cell (CTL) apoptosis, high levels of IL-12 secretion, and had significant inhibitory effect on K562 tumorigenicity in nude mice. CML-DCs pulsed with total RNA by lipofectamine transfection produced the strongest effect in tumor-specific CTL functions. These results indicate that CML-DCs transfected with total RNA by lipofectamine induce the strongest CTL cytotoxicity and have the greatest potential for CML immune therapy. This study holds promise for a DC-based strategy for inducing anti-leukemia responses and establishes a foundation for developing RNA vaccination against CML.

  3. Effects of acute hypoxia on human cognitive processing: a study using ERPs and SEPs.

    Science.gov (United States)

    Nakata, Hiroki; Miyamoto, Tadayoshi; Ogoh, Shigehiko; Kakigi, Ryusuke; Shibasaki, Manabu

    2017-11-01

    Although hypoxia has the potential to impair the cognitive function, the effects of acute hypoxia on the high-order brain function (executive and/or inhibitory processing) and somatosensory ascending processing remain unknown. We tested the hypothesis that acute hypoxia impairs both motor executive and inhibitory processing and somatosensory ascending processing. Fifteen healthy subjects performed two sessions (sessions 1 and 2), consisting of electroencephalographic event-related potentials with somatosensory Go/No-go paradigms and somatosensory-evoked potentials (SEPs) under two conditions (hypoxia and normoxia) on different days. On 1 day, participants breathed room air in the first and second sessions of the experiment; on the other day, participants breathed room air in the first session, and 12% O2 in the second session. Acute hypoxia reduced the peak amplitudes of Go-P300 and No-go-P300, and delayed the peak latency of Go-P300. However, no significant differences were observed in the peak amplitude or latency of N140, behavioral data, or the amplitudes and latencies of individual SEP components between the two conditions. These results suggest that acute hypoxia impaired neural activity in motor executive and inhibitory processing, and delayed higher cognitive processing for motor execution, whereas neural activity in somatosensory processing was not affected by acute hypoxia.NEW & NOTEWORTHY Hypoxia has the potential to impair the cognitive function, but the effects of acute hypoxia on the cognitive function remain debatable. We investigated the effects of acute hypoxia on human cognitive processing using electroencephalographic event-related potentials and somatosensory-evoked potentials. Acute normobaric hypoxia impaired neural activity in motor executive and inhibitory processing, but no significant differences were observed in neural activity in somatosensory processing. Copyright © 2017 the American Physiological Society.

  4. Human in situ cytokine and leukocyte responses to acute smoking.

    Science.gov (United States)

    Kastelein, Tegan; Duffield, Rob; Marino, Frank

    2017-12-01

    This study examined immune/inflammatory parameters following an acute tobacco smoking episode in smokers with varying smoking histories. Twenty-eight male habitual smokers were categorized according to smoking history, e.g. younger smoker (YSM) or middle-aged smoker (MSM). Participants were matched for fitness and smoking habits and following baseline testing, undertook a smoking protocol involving consumption of two cigarettes within 15 min. Venous blood was collected pre- and immediately, 1 h, and 4 h post-protocol to permit analyses of circulating levels of interleukin (IL)-6, IL-1β, IL-1ra, monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP), and leukocytes. No baseline differences were observed between groups for IL-1ra, IL-1β, or leukocytes. MCP-1 and IL-6 levels were significantly (p < 0.05) elevated at baseline in YSM. Both groups showed an increase in MCP-1 levels from pre- to immediately post-cigarette consumption. The MSM also displayed an increase in IL-6 post-smoking, followed by a decline over the period from 1 to 4 h thereafter. A significant decline in circulating lymphocyte and eosinophil levels from immediately post-cigarette consumption to 1 h later was observed in both groups. Monocyte levels in the YSM followed a similar profile but no significant effects on this cell type were evident in the MSM. From these results, a 10-year difference in smoking history induces mild leukopenia. Altered responses due to smoking were also evident with respect to levels of circulating biomarkers, which may be indicative of an effect of differences in cumulative smoking history.

  5. Histamine is not released in acute thermal injury in human skin in vivo: a microdialysis study

    DEFF Research Database (Denmark)

    Petersen, Lars J; Pedersen, Juri L; Skov, Per S

    2009-01-01

    BACKGROUND: Animal models have shown histamine to be released from the skin during the acute phase of a burn injury. The role of histamine during the early phase of thermal injuries in humans remains unclear. PURPOSE: The objectives of this trial were to study histamine release in human skin during...... the acute phase of a standardized thermal injury in healthy volunteers. METHODS: Histamine concentrations in human skin were measured by skin microdialysis technique. Microdialysis fibers were inserted into the dermis in the lower leg in male healthy volunteers. A standardized superficial thermal injury...... was elicited by a heating thermode (49 degrees C) applied to the skin for 5 min. Histamine in dialysate was analyzed for up to 2 h after the injury using two different analytical methods. RESULTS: Spectrofluorometric assay of histamine showed no histamine release in separate studies using 2-min samples over 20...

  6. No inflammatory gene-expression response to acute exercise in human Achilles tendinopathy

    DEFF Research Database (Denmark)

    Pingel, Jessica; Fredberg, Ulrich; Mikkelsen, Lone Ramer

    2013-01-01

    Although histology data favour the view of a degenerative nature of tendinopathy, indirect support for inflammatory reactions to loading in affected tendons exists. The purpose of the present study was to elucidate whether inflammatory signalling responses after acute mechanical loading were more....... All ultrasonographic outcomes were unchanged in response to acute exercise and not influenced by NSAID. The signalling for collagen and TGF-beta was upregulated after acute loading in tendinopathic tendon. In contrast to the hypothesis, inflammatory signalling was not exaggerated in tendinopathic...... pronounced in tendinopathic versus healthy regions of human tendon and if treatment with non-steroidal anti-inflammatory medications (NSAID's) reduces this response. Twenty-seven tendinopathy patients (>6 months) were randomly assigned to a placebo (n = 14) or NSAID (Ibumetin NYCOMED GmbH Plant Oranienburg...

  7. Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers

    DEFF Research Database (Denmark)

    Øzbay, Aygen; Møller, Niels; Juhl, Claus

    2012-01-01

    of ciclosporin and tacrolimus. We document that both drugs acutely increase insulin sensitivity, while first phase and pulsatile insulin secretion remain unaffected. This study demonstrates that ciclosporin and tacrolimus have similar acute effects on glucose metabolism in healthy humans. AIM The introduction...... and tacrolimus has been attributed to both beta cell dysfunction and impaired insulin sensitivity. WHAT THIS STUDY ADDS: This is the first trial to investigate beta cell function and insulin sensitivity using gold standard methodology in healthy human volunteers treated with clinically relevant doses...... of calcineurin inhibitors (CNIs) ciclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) cause impairment of survival rates. The relative contribution of each CNI to the pathogenesis and development...

  8. Human Parechovirus Infection in Children Hospitalized with Acute Gastroenteritis in Sri Lanka▿

    Science.gov (United States)

    Pham, Ngan Thi Kim; Takanashi, Sayaka; Tran, Dinh Nguyen; Trinh, Quang Duy; Abeysekera, Chandra; Abeygunawardene, Asiri; Khamrin, Pattara; Okitsu, Shoko; Shimizu, Hiroyuki; Mizuguchi, Masashi; Ushijima, Hiroshi

    2011-01-01

    Of 362 fecal specimens collected from infants and children hospitalized with acute gastroenteritis in Sri Lanka from September 2005 to August 2006, 30 (8.3%) were positive for human parechovirus (HPeV). Six different HPeV genotypes, including HPeV1, -3, -4, -5, -10, and -11, were identified, of these, HPeV11 was reported for the first time. PMID:21048003

  9. Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis

    OpenAIRE

    Christos Skouras; Xiaozhong Zheng; Margaret Binnie; Homer, Natalie Z.M.; Murray, Toby B. J.; Darren Robertson; Lesley Briody; Finny Paterson; Heather Spence; Lisa Derr; Hayes, Alastair J; Andreas Tsoumanis; Dawn Lyster; Parks, Rowan W; O. James Garden

    2016-01-01

    Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite conc...

  10. Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions.

    Science.gov (United States)

    Dutta, Sara; Mincholé, Ana; Quinn, T Alexander; Rodriguez, Blanca

    2017-10-01

    Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce. In this study, we assess the ability of four human ventricular action potential models (ten Tusscher and Panfilov, 2006; Grandi et al., 2010; Carro et al., 2011; O'Hara et al., 2011) to simulate key electrophysiological consequences of acute myocardial ischemia in single cell and tissue simulations. We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia. Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model. With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia. However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Angiographic Features and Cardiovascular Risk Factors in Human Immunodeficiency Virus-Infected Patients With First-Time Acute Coronary Syndrome

    DEFF Research Database (Denmark)

    Knudsen, Andreas; Mathiasen, Anders B; Worck, R.H.

    2013-01-01

    A matched cohort study was conducted comparing patients with first-time acute coronary syndromes infected with human immunodeficiency virus (HIV) to non-HIV-infected patients with and without diabetes matched for smoking, gender, and type of acute coronary syndrome who underwent first-time corona...

  12. [Human Bocavirus 1: role in the acute respiratory infection and epidemiology in Cordoba, Argentina].

    Science.gov (United States)

    Adamo, María Pilar

    2017-01-01

    Human bocavirus 1 (HBoV1) is an agent of acute respiratory infection frequent in children. It can cause pneumonia in infants, in the absence of epidemiological risk factors and comorbidities. Well-controlled studies of clinical cases and case series are still useful for the characterization of the clinicoepideiological features of the infection, while research dives on the molecular biology of the virus and the virus-cell relationship allowing to unveil tha natural history of the infection. This article reviews the state of the art and future perspectives on this new human parvovirus and its etiological role in the respiratory pathology.

  13. Peripheral inflammation acutely impairs human spatial memory via actions on medial temporal lobe glucose metabolism.

    Science.gov (United States)

    Harrison, Neil A; Doeller, Christian F; Voon, Valerie; Burgess, Neil; Critchley, Hugo D

    2014-10-01

    Inflammation impairs cognitive performance and is implicated in the progression of neurodegenerative disorders. Rodent studies demonstrated key roles for inflammatory mediators in many processes critical to memory, including long-term potentiation, synaptic plasticity, and neurogenesis. They also demonstrated functional impairment of medial temporal lobe (MTL) structures by systemic inflammation. However, human data to support this position are limited. Sequential fluorodeoxyglucose positron emission tomography together with experimentally induced inflammation was used to investigate effects of a systemic inflammatory challenge on human MTL function. Fluorodeoxyglucose positron emission tomography scanning was performed in 20 healthy participants before and after typhoid vaccination and saline control injection. After each scanning session, participants performed a virtual reality spatial memory task analogous to the Morris water maze and a mirror-tracing procedural memory control task. Fluorodeoxyglucose positron emission tomography data demonstrated an acute reduction in human MTL glucose metabolism after inflammation. The inflammatory challenge also selectively compromised human spatial, but not procedural, memory; this effect that was independent of actions on motivation or psychomotor response. Effects of inflammation on parahippocampal and rhinal glucose metabolism directly mediated actions of inflammation on spatial memory. These data demonstrate acute sensitivity of human MTL to mild peripheral inflammation, giving rise to associated functional impairment in the form of reduced spatial memory performance. Our findings suggest a mechanism for the observed epidemiologic link between inflammation and risk of age-related cognitive decline and progression of neurodegenerative disorders including Alzheimer's disease. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Recombinant human activated protein C in the treatment of acute respiratory distress syndrome : A randomized clinical trial

    NARCIS (Netherlands)

    A.D. Cornet (Alexander); A.B.J. Groeneveld (Johan); J.J. Hofstra (Jorrit Jan); A.P.J. Vlaar (Alexander); S. Tuinman (Sietske); A. van Lingen (Arthur); M. Levi (Michael); A.R.J. Girbes (Armand); M.J. Schultz (Marcus); A. Beishuizen (Auke)

    2014-01-01

    textabstractRationale: Pulmonary coagulopathy may play a pathogenetic role in acute respiratory distress syndrome (ARDS), by contributing to alveolocapillary inflammation and increased permeability. Recombinant human activated protein C (rh-APC) may inhibit this process and thereby improve patient

  15. Dual specificity phosphatase 5 and 6 are oppositely regulated in human skeletal muscle by acute exercise.

    Science.gov (United States)

    Pourteymour, Shirin; Hjorth, Marit; Lee, Sindre; Holen, Torgeir; Langleite, Torgrim M; Jensen, Jørgen; Birkeland, Kåre I; Drevon, Christian A; Eckardt, Kristin

    2017-10-01

    Physical activity promotes specific adaptations in most tissues including skeletal muscle. Acute exercise activates numerous signaling cascades including pathways involving mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK)1/2, which returns to pre-exercise level after exercise. The expression of MAPK phosphatases (MKPs) in human skeletal muscle and their regulation by exercise have not been investigated before. In this study, we used mRNA sequencing to monitor regulation of MKPs in human skeletal muscle after acute cycling. In addition, primary human myotubes were used to gain more insights into the regulation of MKPs. The two ERK1/2-specific MKPs, dual specificity phosphatase 5 (DUSP5) and DUSP6, were the most regulated MKPs in skeletal muscle after acute exercise. DUSP5 expression was ninefold higher immediately after exercise and returned to pre-exercise level within 2 h, whereas DUSP6 expression was reduced by 43% just after exercise and remained below pre-exercise level after 2 h recovery. Cultured myotubes express both MKPs, and incubation with dexamethasone (Dex) mimicked the in vivo expression pattern of DUSP5 and DUSP6 caused by exercise. Using a MAPK kinase inhibitor, we showed that stimulation of ERK1/2 activity by Dex was required for induction of DUSP5 However, maintaining basal ERK1/2 activity was required for basal DUSP6 expression suggesting that the effect of Dex on DUSP6 might involve an ERK1/2-independent mechanism. We conclude that the altered expression of DUSP5 and DUSP6 in skeletal muscle after acute endurance exercise might affect ERK1/2 signaling of importance for adaptations in skeletal muscle during exercise. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  16. Erythropoietin augments the cytokine response to acute endotoxin-induced inflammation in humans

    DEFF Research Database (Denmark)

    Hojman, Pernille; Taudorf, Sarah; Lundby, Carsten

    2009-01-01

    Recent studies have shown that erythropoietin (EPO) offers protection against ischemia, hemorrhagic shock and systemic inflammation in many tissues and it has been suggested that EPO has anti-inflammatory effects. With the aim of investigating the potential acute anti-inflammatory effects of EPO ...... with endotoxin, the levels of TNF-alpha and IL-6 were enhanced by 5- and 40-fold, respectively, whereas the endotoxin-induced increase in IL-10 response was not influenced by EPO. In contrast to our hypothesis, we find that EPO augments the acute inflammatory effect.......Recent studies have shown that erythropoietin (EPO) offers protection against ischemia, hemorrhagic shock and systemic inflammation in many tissues and it has been suggested that EPO has anti-inflammatory effects. With the aim of investigating the potential acute anti-inflammatory effects of EPO...... in a human in vivo model of acute systemic low-grade inflammation, we measured circulating inflammatory mediators after intravenous administration of Escherichia coli endotoxin (LPS) bolus injection (0.1 ng/kg of body weight) in young healthy male subjects. The subjects were divided into three groups...

  17. Human Parechovirus as a Cause of Isolated Pediatric Acute Liver Failure.

    Science.gov (United States)

    Bigelow, Amee M; Scott, John P; Hong, Johnny C; Cronin, David C; Vitola, Bernadette E; Fons, Roger A; Petersen, Tara L

    2016-11-01

    Among infants, almost half of acute liver failure cases are classified as indeterminate, whereas only a small number of cases show a documented viral infection. We present the first reported case of isolated acute hepatic failure in an infant in the setting of a human parechovirus (HPeV) infection. HPeV also may have been contributory to the posttransplant complication of 2 intussusceptions. This is a 10-month-old girl who presented with only symptoms of fussiness and was noted to have progressive decline in synthetic liver function as well as worsening coagulopathy requiring a liver transplant. The acute liver failure was in the setting of a positive serum RNA HPeV, subtype 3 (HPeV-3), after extensive diagnostic testing with genetic, autoimmune, and infectious causes otherwise negative. After liver transplantation, the postoperative course was complicated by both an ileal-ileal intussusception as well as a jejunal intussusception. Viral testing in pediatric acute liver failure is often performed, but the workup is frequently incomplete. This case report would support more extensive viral testing in this population of patients. In the setting of HPeV, clinicians could be alerted to the possibility of delayed gastrointestinal pathology in the posttransplant phase. Wider use of routine HPeV testing may more clearly define the variable clinical presentations and outcomes. Copyright © 2016 by the American Academy of Pediatrics.

  18. Frequency of chromosomally-integrated human herpesvirus 6 in children with acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Annie Gravel

    Full Text Available Human herpesvirus 6 (HHV-6 is a ubiquitous pathogen infecting nearly 100% of the human population. Of these individuals, between 0.2% and 1% of them carry chromosomally-integrated HHV-6 (ciHHV-6. The biological consequences of chromosomal integration by HHV-6 remain unknown.To determine and compare the frequency of ciHHV-6 in children with acute lymphoblastic leukemia to healthy blood donors.A total of 293 DNA samples from children with pre-B (n=255, pre-pre-B (n=4, pre-T (n=26 and undetermined (n=8 leukemia were analyzed for ciHHV-6 by quantitative TaqMan PCR (QPCR using HHV-6 specific primers and probe. As control, DNA samples from 288 healthy individuals were used. Primers and probe specific to the cellular GAPDH gene were used to estimate integrity and DNA content.Out of 293 DNA samples from the leukemic cohort, 287 contained amplifiable DNA. Of these, only 1 (0.35% contained ciHHV-6. Variant typing indicates that the ci-HHV-6 corresponds to variant A. None of the 288 DNA samples from healthy individuals contained ciHHV-6.The frequency of ciHHV-6 in children with acute lymphoblastic leukemia is similar (p=0.5 to that of healthy individuals. These results suggest that acute lymphoblastic leukemia does not originate as a consequence to integration of HHV-6 within the chromosomes.

  19. Candesartan acutely recruits skeletal and cardiac muscle microvasculature in healthy humans.

    Science.gov (United States)

    Sauder, Matthew A; Liu, Jia; Jahn, Linda A; Fowler, Dale E; Chai, Weidong; Liu, Zhenqi

    2012-07-01

    Angiotensin II type 1 receptor (AT(1)R) tone restricts muscle microvascular blood volume (MBV) and decreases muscle insulin delivery and glucose use. The objective of the study was to examine whether acute AT(1)R blockade alters microvascular perfusion in skeletal and cardiac muscle in humans. The study was conducted at the General Clinical Research Center at the University of Virginia. Eight overnight-fasted healthy young adults were studied thrice in random order. In study 1, each subject received candesartan (32 mg) orally at time 0. In study 2, each subject received placebo at time 0 and a 1 mU/min · kg euglycemic insulin clamp from time 240 to 360 min. In study 3, each subject received candesartan (32 mg) orally at time 0 and insulin infusion from 240 to 360 min. Forearm skeletal and cardiac muscle MBV, microvascular flow velocity, and microvascular blood flow (MBF) were determined at baseline and at 240 and 360 min. Candesartan treatment acutely recruited microvasculature in both skeletal and cardiac muscle by significantly increasing MBV (P candesartan ingestion did not further recruit microvasculature. Insulin-mediated whole-body glucose disposal did not differ with or without candesartan pretreatment. Acute AT(1)R blockade with candesartan recruits skeletal as well as cardiac muscle microvasculature in healthy humans without altering insulin-mediated whole-body glucose disposal. This may contribute to the observed improvement in the cardiovascular outcomes in patients receiving prolonged treatment with AT(1)R blockers.

  20. Cerebral water and ion balance remains stable when humans are exposed to acute hypoxic exercise

    DEFF Research Database (Denmark)

    Avnstorp, Magnus B; Rasmussen, Peter; Brassard, Patrice

    2015-01-01

    both circumstances. No cerebral net exchange of Na(+) or K(+) was evident. Likewise, no significant net-exchange of water over the brain was demonstrated and the arterial and jugular venous hemoglobin concentrations were similar. CONCLUSION: Challenging exercise in hypoxia for 30 min affected muscle......Avnstorp, Magnus B., Peter Rasmussen, Patrice Brassard, Thomas Seifert, Morten Overgaard, Peter Krustrup, Niels H. Secher, and Nikolai B. Nordsborg. Cerebral water and ion balance remains stable when humans are exposed to acute hypoxic exercise. High Alt Med Biol 16:000-000, 2015.-Background......: Intense physical activity increases the prevalence of acute mountain sickness (AMS) that can occur within 10 h after ascent to altitudes above 1500 m and is likely related to development of cerebral edema. This study evaluated whether disturbed cerebral water and ion homeostasis can be detected when...

  1. Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

    Directory of Open Access Journals (Sweden)

    Jakubowski Ann A

    2009-12-01

    Full Text Available Abstract We have described a severe combined immunodeficiency (SCID mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL and 66 acute myeloid leukemia (AML in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8% displayed an aggressive growth pattern, 14 (10.5% displayed an indolent growth pattern and 74 (55.6% did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.

  2. The acute effects of cannabinoids on memory in humans: a review.

    Science.gov (United States)

    Ranganathan, Mohini; D'Souza, Deepak Cyril

    2006-11-01

    Cannabis is one of the most frequently used substances. Cannabis and its constituent cannabinoids are known to impair several aspects of cognitive function, with the most robust effects on short-term episodic and working memory in humans. A large body of the work in this area occurred in the 1970s before the discovery of cannabinoid receptors. Recent advances in the knowledge of cannabinoid receptors' function have rekindled interest in examining effects of exogenous cannabinoids on memory and in understanding the mechanism of these effects. The literature about the acute effects of cannabinoids on memory tasks in humans is reviewed. The limitations of the human literature including issues of dose, route of administration, small sample sizes, sample selection, effects of other drug use, tolerance and dependence to cannabinoids, and the timing and sensitivity of psychological tests are discussed. Finally, the human literature is discussed against the backdrop of preclinical findings. Acute administration of Delta-9-THC transiently impairs immediate and delayed free recall of information presented after, but not before, drug administration in a dose- and delay-dependent manner. In particular, cannabinoids increase intrusion errors. These effects are more robust with the inhaled and intravenous route and correspond to peak drug levels. This profile of effects suggests that cannabinoids impair all stages of memory including encoding, consolidation, and retrieval. Several mechanisms, including effects on long-term potentiation and long-term depression and the inhibition of neurotransmitter (GABA, glutamate, acetyl choline, dopamine) release, have been implicated in the amnestic effects of cannabinoids. Future research in humans is necessary to characterize the neuroanatomical and neurochemical basis of the memory impairing effects of cannabinoids, to dissect out their effects on the various stages of memory and to bridge the expanding gap between the humans and

  3. Acute Consumption of Flavan-3-ol-Enriched Dark Chocolate Affects Human Endogenous Metabolism.

    Science.gov (United States)

    Ostertag, Luisa M; Philo, Mark; Colquhoun, Ian J; Tapp, Henri S; Saha, Shikha; Duthie, Garry G; Kemsley, E Kate; de Roos, Baukje; Kroon, Paul A; Le Gall, Gwénaëlle

    2017-07-07

    Flavan-3-ols and methylxanthines have potential beneficial effects on human health including reducing cardiovascular risk. We performed a randomized controlled crossover intervention trial to assess the acute effects of consumption of flavan-3-ol-enriched dark chocolate, compared with standard dark chocolate and white chocolate, on the human metabolome. We assessed the metabolome in urine and blood plasma samples collected before and at 2 and 6 h after consumption of chocolates in 42 healthy volunteers using a nontargeted metabolomics approach. Plasma samples were assessed and showed differentiation between time points with no further separation among the three chocolate treatments. Multivariate statistics applied to urine samples could readily separate the postprandial time points and distinguish between the treatments. Most of the markers responsible for the multivariate discrimination between the chocolates were of dietary origin. Interestingly, small but significant level changes were also observed for a subset of endogenous metabolites. 1 H NMR revealed that flavan-3-ol-enriched dark chocolate and standard dark chocolate reduced urinary levels of creatinine, lactate, some amino acids, and related degradation products and increased the levels of pyruvate and 4-hydroxyphenylacetate, a phenolic compound of bacterial origin. This study demonstrates that an acute chocolate intervention can significantly affect human metabolism.

  4. Exosomes from Human Dental Pulp Stem Cells Suppress Carrageenan-Induced Acute Inflammation in Mice.

    Science.gov (United States)

    Pivoraitė, Ugnė; Jarmalavičiūtė, Akvilė; Tunaitis, Virginijus; Ramanauskaitė, Giedrė; Vaitkuvienė, Aida; Kašėta, Vytautas; Biziulevičienė, Genė; Venalis, Algirdas; Pivoriūnas, Augustas

    2015-10-01

    The primary goal of this study was to examine the effects of human dental pulp stem cell-derived exosomes on the carrageenan-induced acute inflammation in mice. Exosomes were purified by differential ultracentrifugation from the supernatants of stem cells derived from the dental pulp of human exfoliated deciduous teeth (SHEDs) cultivated in serum-free medium. At 1 h post-carrageenan injection, exosomes derived from supernatants of 2 × 10(6) SHEDs were administered by intraplantar injection to BALB/c mice; 30 mg/kg of prednisolone and phosphate-buffered saline (PBS) were used as positive and negative controls, respectively. Edema was measured at 6, 24, and 48 h after carrageenan injection. For the in vivo imaging experiments, AngioSPARK750, Cat B 750 FAST, and MMPSense 750 FAST were administered into the mouse tail vein 2 h post-carrageenan injection. Fluorescence images were acquired at 6, 24, and 48 h after edema induction by IVIS Spectrum in vivo imaging system. Exosomes significantly reduced the carrageenan-induced edema at all the time points studied (by 39.5, 41.6, and 25.6% at 6, 24, and 48 h after injection, respectively), to similar levels seen with the positive control (prednisolone). In vivo imaging experiments revealed that, both exosomes and prednisolone suppress activities of cathepsin B and matrix metalloproteinases (MMPs) at the site of carrageenan-induced acute inflammation, showing more prominent effects of prednisolone at the early stages, while exosomes exerted their suppressive effects gradually and at later time points. Our study demonstrates for the first time that exosomes derived from human dental pulp stem cells suppress carrageenan-induced acute inflammation in mice.

  5. Hyperalgesia in a human model of acute inflammatory pain: a methodological study

    DEFF Research Database (Denmark)

    Pedersen, J L; Kehlet, H

    1998-01-01

    was demonstrated by significantly higher pain thresholds and lower pain responses on the second and third day of the study. The burn model is a sensitive psychophysical model of acute inflammatory pain, when cross-over designs and within-day comparisons are used, and the model is suitable for double-blind, placebo......The aim of the study was to examine reproducibility of primary and secondary hyperalgesia in a psychophysical model of human inflammatory pain. Mild burns were produced on the crura of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Assessments of (i) cold and warm detection...

  6. Two Cases of Acute Disseminated Encephalomyelitis Following Vaccination Against Human Papilloma Virus.

    Science.gov (United States)

    Sekiguchi, Kenji; Yasui, Naoko; Kowa, Hisatomo; Kanda, Fumio; Toda, Tatsushi

    We herein present two cases of acute disseminated encephalomyelitis (ADEM) following vaccination against human papilloma virus (HPV). Case 1 experienced diplopia and developed an unstable gait 14 days after a second vaccination of Cervarix. Brain magnetic resonance imaging (MRI) showed an isolated small, demyelinating lesion in the pontine tegmentum. Case 2 experienced a fever and limb dysesthesia 16 days after a second vaccination of Gardasil. Brain MRI revealed hyperintense lesion in the pons with slight edema on a T2-weighted image. Both cases resolved completely. It is important to accumulate further data on confirmed cases of ADEM temporally associated with HPV vaccination.

  7. Pronounced effects of acute endurance exercise on gene expression in resting and exercising human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Milène Catoire

    Full Text Available Regular physical activity positively influences whole body energy metabolism and substrate handling in exercising muscle. While it is recognized that the effects of exercise extend beyond exercising muscle, it is unclear to what extent exercise impacts non-exercising muscles. Here we investigated the effects of an acute endurance exercise bouts on gene expression in exercising and non-exercising human muscle. To that end, 12 male subjects aged 44-56 performed one hour of one-legged cycling at 50% W(max. Muscle biopsies were taken from the exercising and non-exercising leg before and immediately after exercise and analyzed by microarray. One-legged cycling raised plasma lactate, free fatty acids, cortisol, noradrenalin, and adrenalin levels. Surprisingly, acute endurance exercise not only caused pronounced gene expression changes in exercising muscle but also in non-exercising muscle. In the exercising leg the three most highly induced genes were all part of the NR4A family. Remarkably, many genes induced in non-exercising muscle were PPAR targets or related to PPAR signalling, including PDK4, ANGPTL4 and SLC22A5. Pathway analysis confirmed this finding. In conclusion, our data indicate that acute endurance exercise elicits pronounced changes in gene expression in non-exercising muscle, which are likely mediated by changes in circulating factors such as free fatty acids. The study points to a major influence of exercise beyond the contracting muscle.

  8. Human metapneumovirus and respiratory syncytial virus detection in young children with acute bronchiolitis.

    Science.gov (United States)

    Teeratakulpisarn, Jamaree; Ekalaksananan, Tipaya; Pientong, Chamsai; Limwattananon, Chulaporn

    2007-01-01

    This study was conducted to detect human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) in young children hospitalized with acute bronchiolitis, using reverse transcriptase polymerase chain reaction (RT-PCR). Nasopharyngeal secretions were collected from 170 children between 1 and 24 months of age admitted to two tertiary hospitals in northeastern Thailand, between 2002 and 2004. Acute bronchiolitis was defined as the first episode of wheezing associated with tachypnea, increased respiratory effort and an upper respiratory tract infection. Two-thirds (115/170) were positive for viral etiologies: 64.7% RSV (110/170) and 3.5% hMPV (6/170). One patient had a dual infection. hMPV was detected between August and November, while RSV was prevalent from July through March. The clinical manifestations among the 6 hMPV, RSV and non-RSV-infected children were similar. RSV was the leading cause of acute bronchiolitis in young children and hMPV had a low prevalence in northeastern Thailand.

  9. Prevalence of human coronaviruses in adults with acute respiratory tract infections in Beijing, China.

    Science.gov (United States)

    Ren, Lili; Gonzalez, Richard; Xu, Jin; Xiao, Yan; Li, Yongjun; Zhou, Hongli; Li, Jianguo; Yang, Qingqing; Zhang, Jing; Chen, Lan; Wang, Wei; Vernet, Guy; Paranhos-Baccalà, Gláucia; Wang, Zhong; Wang, Jianwei

    2011-02-01

    Human coronaviruses (HCoVs) are a common etiological agent of acute respiratory tract infections. HCoV infections, especially those caused by the two HCoVs identified most recently, NL63 and HKU-1, have not been characterized fully. To evaluate the prevalence and clinical presentations of HKU1 and NL63 in adults with acute respiratory tract infections, an investigation of HCoV infections in Beijing, China from 2005 to 2009 was performed by using reverse transcriptase PCR assays and sequencing analysis. Among 8,396 respiratory specimens studied, 87 (1%) clinical samples were positive for HCoVs, of which 50 samples (0.6% of the total) were positive for HCoV-OC43, 15 (0.2%) for HCoV-229E, 14 (0.2%) for HCoV-HKU1, and 8 (0.1%) for HCoV-NL63. The prevalence of HCoV infection in adults exhibited distinct seasonal fluctuations during the study period. In addition, patients positive for HCoV-229E infections were more likely to be co-infected with other respiratory viruses. Enterovirus, rhinovirus, and parainfluenza virus type 3 were the most common viruses found in patients with HCoV infections. The demographic and clinical data present in this study of HCoV infections in adults with acute respiratory tract infections should improve our understanding of the pathogenesis of HCoVs. 2010 Wiley-Liss, Inc.

  10. Effect of Human Amnion Epithelial Cells on the Acute Inflammatory Response in Fetal Sheep

    Directory of Open Access Journals (Sweden)

    Alana Westover

    2017-11-01

    Full Text Available Intra-amniotic (IA lipopolysaccharide (LPS injection in sheep induces inflammation in the fetus. Human amnion epithelial cells (hAECs moderate the effect of IA LPS on fetal development, but their influence on the acute inflammatory response to IA LPS is unknown. We aimed to determine the effects of hAECs on the acute fetal inflammatory response to IA LPS. After surgical instrumentation at 116 days' gestation (d ewes were randomized to 1 of 4 groups at 123 d: IA LPS (10 mg and intravenous (IV saline (n = 8, IA LPS and IV hAECs (n = 6, IA saline and IV saline (n = 5 or IA saline and IV hAECs (n = 5. IV injections were administered immediately after IA injections. Serial fetal blood samples were collected. At 125 d, placental, fetal lung and liver samples were collected. IA LPS increased inflammatory cell recruitment in the placenta and lungs, increased IL-1β and IL-8 mRNA levels in the lungs and increased serum amyloid A3 (SAA3 and C-reactive protein (CRP mRNA levels in the liver. IV hAECs reduced fetal lung inflammatory cell recruitment but did not otherwise alter indices of placental, fetal lung or liver inflammation. The acute fetal inflammatory response to IA LPS is not substantially altered by IV hAEC treatment.

  11. Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia.

    Science.gov (United States)

    Hals, I K; Rokstad, A M; Strand, B L; Oberholzer, J; Grill, V

    2013-01-01

    Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1-0.3% O2 for 8 h, followed by reoxygenation) on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8 ± 3.5% in encapsulated and 42.9 ± 5.2% in nonencapsulated islets (P microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation.

  12. Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

    Science.gov (United States)

    Hals, I. K.; Rokstad, A. M.; Strand, B. L.; Oberholzer, J.; Grill, V.

    2013-01-01

    Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1–0.3% O2 for 8 h, followed by reoxygenation) on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8 ± 3.5% in encapsulated and 42.9 ± 5.2% in nonencapsulated islets (P microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation. PMID:24364039

  13. GABAergic modulation of human social interaction in a prisoner's dilemma model by acute administration of alprazolam.

    Science.gov (United States)

    Lane, Scott D; Gowin, Joshua L

    2009-10-01

    Recent work in neuroeconomics has used game theory paradigms to examine neural systems that subserve human social interaction and decision making. Attempts to modify social interaction through pharmacological manipulation have been less common. Here we show dose-dependent modification of human social behavior in a prisoner's dilemma model after acute administration of the γ-aminobutyric acid (GABA)-A modulating benzodiazepine alprazolam. Nine healthy adults received doses of placebo, 0.5, 1.0, and 2.0 mg alprazolam in a counterbalanced within-subject design, while completing multiple test blocks per day on an iterated prisoner's dilemma game. During test blocks in which peak subjective effects of alprazolam were reported, cooperative choices were significantly decreased as a function of dose. Consistent with previous reports showing that high acute doses of GABA-modulating drugs are associated with violence and other antisocial behavior, our data suggest that at sufficiently high doses, alprazolam can decrease cooperation. These behavioral changes may be facilitated by changes in inhibitory control facilitated by GABA. Game theory paradigms may prove useful in behavioral pharmacology studies seeking to measure social interaction, and may help inform the emerging field of neuroeconomics.

  14. Role of inflammation and infection in the pathogenesis of human acute liver failure: Clinical implications for monitoring and therapy.

    Science.gov (United States)

    Donnelly, Mhairi C; Hayes, Peter C; Simpson, Kenneth J

    2016-07-14

    Acute liver failure is a rare and devastating clinical condition. At present, emergency liver transplantation is the only life-saving therapy in advanced cases, yet the feasibility of transplantation is affected by the presence of systemic inflammation, infection and resultant multi-organ failure. The importance of immune dysregulation and acquisition of infection in the pathogenesis of acute liver failure and its associated complications is now recognised. In this review we discuss current thinking regarding the role of infection and inflammation in the pathogenesis of and outcome in human acute liver failure, the implications for the management of such patients and suggest directions for future research.

  15. RNAi mediated acute depletion of Retinoblastoma protein (pRb promotes aneuploidy in human primary cells via micronuclei formation

    Directory of Open Access Journals (Sweden)

    Iovino Flora

    2009-11-01

    Full Text Available Abstract Background Changes in chromosome number or structure as well as supernumerary centrosomes and multipolar mitoses are commonly observed in human tumors. Thus, centrosome amplification and mitotic checkpoint dysfunctions are believed possible causes of chromosomal instability. The Retinoblastoma tumor suppressor (RB participates in the regulation of synchrony between DNA synthesis and centrosome duplication and it is involved in transcription regulation of some mitotic genes. Primary human fibroblasts were transfected transiently with short interfering RNA (siRNA specific for human pRb to investigate the effects of pRb acute loss on chromosomal stability. Results Acutely pRb-depleted fibroblasts showed altered expression of genes necessary for cell cycle progression, centrosome homeostasis, kinetochore and mitotic checkpoint proteins. Despite altered expression of genes involved in the Spindle Assembly Checkpoint (SAC the checkpoint seemed to function properly in pRb-depleted fibroblasts. In particular AURORA-A and PLK1 overexpression suggested that these two genes might have a role in the observed genomic instability. However, when they were post-transcriptionally silenced in pRb-depleted fibroblasts we did not observe reduction in the number of aneuploid cells. This finding suggests that overexpression of these two genes did not contribute to genomic instability triggered by RB acute loss although it affected cell proliferation. Acutely pRb-depleted human fibroblasts showed the presence of micronuclei containing whole chromosomes besides the presence of supernumerary centrosomes and aneuploidy. Conclusion Here we show for the first time that RB acute loss triggers centrosome amplification and aneuploidy in human primary fibroblasts. Altogether, our results suggest that pRb-depleted primary human fibroblasts possess an intact spindle checkpoint and that micronuclei, likely caused by mis-attached kinetochores that in turn trigger

  16. Nicotine Acutely Enhances Reinforcement from Non-Drug Rewards in Humans

    Directory of Open Access Journals (Sweden)

    Kenneth A. Perkins

    2017-05-01

    Full Text Available Preclinical research documents that, aside from the primary and secondary reinforcing effects of nicotine intake itself, nicotine also acutely enhances the reinforcing efficacy of non-drug reinforcers (“rewards”. Study of these effects in humans has largely been overlooked, but very recent findings suggest they may have clinical implications for more fully understanding the persistence of tobacco dependence. This overview first outlines the topic and notes some recent human studies indirectly addressing nicotine effects on related responses (e.g., subjective ratings, explaining why those findings do not directly confirm enhancement of behavioral reinforcement per se due to nicotine. Then, the methodology used in the subsequently presented studies is described, demonstrating how those studies specifically did demonstrate enhancement of reinforced responding for non-drug rewards. The main section focuses on the limited controlled research to date directly assessing nicotine’s acute reinforcement-enhancing effects in humans, particularly as it relates to reinforced behavioral responding for non-drug rewards in non-human animal models. After detailing those few existing human studies, we address potential consequences of these effects for dependence and tobacco cessation efforts and then suggest directions for future research. This research indicates that nicotine per se increases responding in humans that is reinforced by some rewards (auditory stimuli via music, visual stimuli via video, but perhaps not by others (e.g., money. These reinforcement-enhancing effects in smokers are not due to dependence or withdrawal relief and can be restored by a small amount of nicotine (similar to a smoking lapse, including from e-cigarettes, a non-tobacco nicotine product. Future clinical research should examine factors determining which types of rewards are (or are not enhanced by nicotine, consequences of the loss of these nicotine effects after quitting

  17. Acinar injury and early cytokine response in human acute biliary pancreatitis.

    Science.gov (United States)

    Jakkampudi, Aparna; Jangala, Ramaiah; Reddy, Ratnakar; Mitnala, Sasikala; Rao, G Venkat; Pradeep, Rebala; Reddy, D Nageshwar; Talukdar, Rupjyoti

    2017-11-10

    Clinical acute pancreatitis (AP) is marked by an early phase of systemic inflammatory response syndrome (SIRS) with multiorgan dysfunction (MODS), and a late phase characterized by sepsis with MODS. However, the mechanisms of acinar injury in human AP and the associated systemic inflammation are not clearly understood. This study, for the first time, evaluated the early interactions of bile acid induced human pancreatic acinar injury and the resulting cytokine response. We exposed freshly procured resected human pancreata to taurolithocolic acid (TLCS) and evaluated for acinar injury, cytokine release and interaction with peripheral blood mononuclear cells (PBMCs). We observed autophagy in acinar cells in response to TLCS exposure. There was also time-dependent release of IL-6, IL-8 and TNF-α from the injured acini that resulted in activation of PBMCs. We also observed that cytokines secreted by activated PBMCs resulted in acinar cell apoptosis and further cytokine release from them. Our data suggests that the earliest immune response in human AP originates within the acinar cell itself, which subsequently activates circulating PBMCs leading to SIRS. These findings need further detailed evaluation so that specific therapeutic targets to curb SIRS and resulting early adverse outcomes could be identified and tested.

  18. Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans

    Directory of Open Access Journals (Sweden)

    Eaton John W

    2007-07-01

    Full Text Available Abstract Background Medical implants often fail as a result of so-called foreign body reactions during which inflammatory cells are recruited to implant surfaces. Despite the clinical importance of this phenomenon, the mechanisms involved in these reactions to biomedical implants in humans are not well understood. The results from animal studies suggest that both fibrinogen adsorption to the implant surface and histamine release by local mast cells are involved in biomaterial-mediated acute inflammatory responses. The purpose of this study was to test this hypothesis in humans. Methods Thirteen male medical student volunteers (Caucasian, 21–30 years of age were employed for this study. To assess the importance of fibrinogen adsorption, six volunteers were implanted with polyethylene teraphthalate disks pre-coated with their own (fibrinogen-containing plasma or (fibrinogen-free serum. To evaluate the importance of histamine, seven volunteers were implanted with uncoated disks with or without prior oral administration of histamine receptor antagonists. The acute inflammatory response was estimated 24 hours later by measuring the activities of implant-associated phagocyte-specific enzymes. Results Plasma coated implants accumulated significantly more phagocytes than did serum coated implants and the recruited cells were predominantly macrophage/monocytes. Administration of both H1 and H2 histamine receptor antagonists greatly reduced the recruitment of macrophages/monocytes and neutrophils on implant surfaces. Conclusion In humans – as in rodents – biomaterial-mediated inflammatory responses involve at least two crucial events: histamine-mediated phagocyte recruitment and phagocyte accumulation on implant surfaces engendered by spontaneously adsorbed host fibrinogen. Based on these results, we conclude that reducing fibrinogen:surface interactions should enhance biocompatibility and that administration of histamine receptor antagonists prior

  19. Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon.

    Science.gov (United States)

    Couch, Daniel G; Tasker, Chris; Theophilidou, Elena; Lund, Jonathan N; O'Sullivan, Saoirse E

    2017-11-01

    We sought to quantify the anti-inflammatory effects of two cannabinoid drugs, cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue. These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants. Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease (IBD) or acute appendicitis resections, and were treated with the following drug treatments: vehicle, an inflammatory protocol of interferon γ (IFNγ) and tumour necrosis factor α (TNFα; 10 ng/ml), inflammation and PEA (10 µM), inflammation and CBD (10 µM), and PEA or CBD alone, CBD or vehicle were added simultaneously with IFNγ. Nine intracellular signalling phosphoproteins were determined by multiplex. Inflammatory cytokine secretion was determined using ELISA. Receptor mechanisms were investigated using antagonists for CB1, CB2, PPARα, PPARγ, TRPV1 and GPR55. IFNγ and TNFα treatment increased phosphoprotein and cytokine levels in Caco-2 cultures and colonic explants. Phosphoprotein levels were significantly reduced by PEA or CBD in Caco-2 cultures and colonic explants. CBD and PEA prevented increases in cytokine production in explant colon, but not in Caco-2 cells. CBD effects were blocked by the CB2 antagonist AM630 and TRPV1 antagonist SB366791. PEA effects were blocked by the PPARα antagonist GW6471. PEA and CBD were anti-inflammatory in IBD and appendicitis explants. PEA and CBD are anti-inflammatory in the human colon. This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  20. Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans

    Science.gov (United States)

    Zdolsek, Johann; Eaton, John W; Tang, Liping

    2007-01-01

    Background Medical implants often fail as a result of so-called foreign body reactions during which inflammatory cells are recruited to implant surfaces. Despite the clinical importance of this phenomenon, the mechanisms involved in these reactions to biomedical implants in humans are not well understood. The results from animal studies suggest that both fibrinogen adsorption to the implant surface and histamine release by local mast cells are involved in biomaterial-mediated acute inflammatory responses. The purpose of this study was to test this hypothesis in humans. Methods Thirteen male medical student volunteers (Caucasian, 21–30 years of age) were employed for this study. To assess the importance of fibrinogen adsorption, six volunteers were implanted with polyethylene teraphthalate disks pre-coated with their own (fibrinogen-containing) plasma or (fibrinogen-free) serum. To evaluate the importance of histamine, seven volunteers were implanted with uncoated disks with or without prior oral administration of histamine receptor antagonists. The acute inflammatory response was estimated 24 hours later by measuring the activities of implant-associated phagocyte-specific enzymes. Results Plasma coated implants accumulated significantly more phagocytes than did serum coated implants and the recruited cells were predominantly macrophage/monocytes. Administration of both H1 and H2 histamine receptor antagonists greatly reduced the recruitment of macrophages/monocytes and neutrophils on implant surfaces. Conclusion In humans – as in rodents – biomaterial-mediated inflammatory responses involve at least two crucial events: histamine-mediated phagocyte recruitment and phagocyte accumulation on implant surfaces engendered by spontaneously adsorbed host fibrinogen. Based on these results, we conclude that reducing fibrinogen:surface interactions should enhance biocompatibility and that administration of histamine receptor antagonists prior to, and shortly after

  1. Human cardiac-derived adherent proliferating cells reduce murine acute Coxsackievirus B3-induced myocarditis.

    Directory of Open Access Journals (Sweden)

    Kapka Miteva

    Full Text Available BACKGROUND: Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs. They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3-induced myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression. CONCLUSIONS: We conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis.

  2. Human bocavirus isolated from children with acute respiratory tract infections in Korea, 2010-2011.

    Science.gov (United States)

    Ahn, Jong Gyun; Choi, Seong Yeol; Kim, Dong Soo; Kim, Ki Hwan

    2014-12-01

    Human bocavirus (HBoV) was first recognized in respiratory samples in 2005. The clinical importance of HBoV infection remains unclear. This report describes the clinical features and molecular phylogeny of HBoV isolates in children with acute respiratory infections. Nasopharyngeal aspirates were obtained from 1,528 children with acute respiratory infections between 2010 and 2011. Respiratory samples were screened for HBoV by multiplex PCR. A phylogenetic analysis of the HBoV VP1/VP2 gene was also undertaken. HBoV was detected in 187 (12.2%) of the 1,528 patients with a peak incidence of infection observed in patients aged 12-24 months. Coinfection with other respiratory viruses was observed in 107 (57.2%) of the HBoV-positive children. The peak of HBoV activity occurred during the month of June in both 2010 and 2011. A higher previous history of wheezing (P = 0.016), a higher frequency of chest retraction (P respiratory symptom score (P = 0.002), and a longer duration of hospital stay (P = 0.021) were observed in HBoV-positive children compared with the HBoV-negative group. Phylogenetic analysis showed all 187 HBoV-positive isolates were identified as HBoV 1, indicating minimal sequence variations among the isolates. A single lineage of HBoV 1 was found to have circulated in children with acute respiratory infections between 2010 and 2011 and was associated with several clinical characteristics including age, seasonality, and clinical severity with retraction, wheezing, and longer hospitalization. The clinical relevance of the minimal sequence variations of HBoV remains to be determined. © 2014 Wiley Periodicals, Inc.

  3. Impact of Global Fxr Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the FXR Locus in Human Acute Pancreatitis

    NARCIS (Netherlands)

    Nijmeijer, R.M.; Schaap, F.G.; Smits, A.J.A.; Kremer, A.E.; Akkermans, L.M.; Kroese, A.B.A.; Rijkers, G.T.; Schipper, M.E.; Verheem, A.; Wijmenga, C.; Gooszen, H.G.; Erpecum, K.J. van

    2014-01-01

    BACKGROUND: Infectious complications often occur in acute pancreatitis, related to impaired intestinal barrier function, with prolonged disease course and even mortality as a result. The bile salt nuclear receptor farnesoid X receptor (FXR), which is expressed in the ileum, liver and other organs

  4. Impact of Global Fxr Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the FXR Locus in Human Acute Pancreatitis

    NARCIS (Netherlands)

    Nijmeijer, Rian M.; Schaap, Frank G.; Smits, Alexander J. J.; Kremer, Andreas E.; Akkermans, Louis M. A.; Kroese, Alfons B. A.; Rijkers, Ger. T.; Schipper, Marguerite E. I.; Verheem, Andre; Wijmenga, Cisca; Gooszen, Hein G.; van Erpecum, Karel J.

    2014-01-01

    Background: Infectious complications often occur in acute pancreatitis, related to impaired intestinal barrier function, with prolonged disease course and even mortality as a result. The bile salt nuclear receptor farnesoid X receptor (FXR), which is expressed in the ileum, liver and other organs

  5. [Acute liver failure due to human herpesvirus 6 in an infant].

    Science.gov (United States)

    Tronconi, G M; Mariani, B; Pajno, R; Fomasi, M; Cococcioni, L; Biffi, V; Bove, M; Corsin, P; Garbetta, G; Barera, G

    2012-01-01

    We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF) with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus), drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6) genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases' review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus's genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus.

  6. Effects of acute hyperthermia on the carotid baroreflex control of heart rate in humans

    Science.gov (United States)

    Yamazaki, F.; Sagawa, S.; Torii, R.; Endo, Y.; Shiraki, K.

    The purpose of this study was to examine the effect of hyperthermia on the carotid baroreceptor-cardiac reflexes in humans. Nine healthy males underwent acute hyperthermia (esophageal temperature 38.0° C) produced by hot water-perfused suits. Beat-to-beat heart rate (HR) responses were determined during positive and negative R-wave-triggered neck pressure steps from +40 to -65 mm Hg during normothermia and hyperthermia. The carotid baroreceptor-cardiac reflex sensitivity was evaluated from the maximum slope of the HR response to changes in carotid distending pressure. Buffering capacity of the HR response to carotid distending pressure was evaluated in % from a reference point calculated as (HR at 0 mm Hg neck pressure-minimum HR)/HR range ×100. An upward shift of the curve was evident in hyperthermia because HR increased from 57.7+/-2.4 beats/min in normothermia to 88.7+/-4.1 beats/min in hyperthermia (Phypotension is reduced and the capacity for bradycardia response to sudden hypertension is increased during acute hyperthermia.

  7. Acute liver failure due to Human Herpesvirus 6 in an infant

    Directory of Open Access Journals (Sweden)

    G.M. Tronconi

    2012-10-01

    Full Text Available We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus, drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6 genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases’ review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus’s genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus.

  8. Acute mitochondrial and chronic toxicological effects of 1-methyl-4-phenylpyridinium in human neuroblastoma cells.

    Science.gov (United States)

    Stephans, Stacy E; Miller, Gary W; Levey, Allan I; Greenamyre, J Timothy

    2002-10-01

    At low micromolar concentrations, 1-methyl-4-phenylpyridinium (MPP+), the toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) selectively kills nigrostriatal dopaminergic neurons by mechanisms believed to involve impairment of mitochondrial complex I. A human neuroblastoma cell line expressing the dopamine transporter (DAT) was utilized to examine the effects of MPP+ on acute physiologic responses and subsequent cell death. Acute responses were measured by microphysiometry and by monitoring mitochondrial membrane potential with [3H]tetraphenylphosphonium (TPP+) uptake. MPP+ (10 microM) increased extracellular proton excretion in DAT-expressing cells within 2-3 min, but had no effect in untransfected cells. The lipophilic complex I inhibitor, rotenone, increased proton excretion in both cell lines. In DAT-expressing cells, mitochondrial membrane potential was reduced within I h of 10 microM MPP+ exposure. Rotenone reduced mitochondrial membrane potential in both cell lines. MPP+ caused apoptotic death of DAT-transfected cells 2-3 days after drug application, but did not kill untransfected cells. Thus, MPP+ produces immediate mitochondrial impairment only in cells that express DAT, and these changes occur days before overt cellular toxicity. The magnitude, time course and nature of these changes were similar to those produced by rotenone, confirming the site of action of MPP+ as mitochondrial complex I. These immediate mitochondrial effects appear to be an accurate predictor of subsequent cell death.

  9. Two-dimensional electrophoresis protein profiling as an analytical tool for human acute leukemia classification.

    Science.gov (United States)

    Cui, Jiu-Wei; Wang, Jie; He, Kun; Jin, Bao-Feng; Wang, Hong-Xia; Li, Wei; Kang, Li-Hua; Hu, Mei-Ru; Li, Hui-Yan; Yu, Ming; Shen, Bei-Fen; Wang, Guan-Jun; Zhang, Xue-Min

    2005-01-01

    Two-dimensional electrophoresis (2-DE) was used to profile the proteins of leukemic cells from 61 cases of akute leukemia (AL) characterized by the French-American-British (FAB) classification. The differentially expressed protein spots were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and electrospray ionization-tandem MS (ESI-MS/MS). The distinct protein profiles (DPPs) of AL FAB subtypes were explored successfully, including acute myeloid leukemia (AML), its subtypes (M2, M3, and M5), and acute lymphoid leukemia (ALL), which were homogeneous within different samples of the same subgroup but clearly differed from all other subgroups. We also found a group of proteins differentially expressed between AL cells and normal white blood cells. Among the DPPs of AL subtypes, some proteins have been reported, but most of them were first reported here to mark AML differentiation and to discriminate AML from ALL. These data show that 2-DE protein profiling could be used as an analytical tool for facilitating molecular definition of human AL classification and understanding the mechanism of leukemogensis, and the extension of the present analysis to the currently less well-defined AL will identify additional subgroups and may promote the identification of new targets for specific treatment approaches.

  10. Recombinant human soluble thrombomodulin prevents acute lung injury in a rat cardiopulmonary bypass model.

    Science.gov (United States)

    Hirao, Shingo; Minakata, Kenji; Masumoto, Hidetoshi; Yamazaki, Kazuhiro; Ikeda, Tadashi; Minatoya, Kenji; Sakata, Ryuzo

    2017-12-01

    Cardiopulmonary bypass (CPB) may induce systemic inflammatory responses causing acute lung injury. Recombinant human soluble thrombomodulin (rTM) is reported to attenuate the secretion of inflammatory cytokines and the high-mobility group box 1 (HMGB1) protein, which is critical in controlling systemic inflammation and apoptosis. We investigated the protective effects of rTM on CPB-induced lung injury in a rat model. Eighteen male Sprague-Dawley rats were divided into 3 groups: sham, control (CPB alone), and rTM (CPB + rTM). CPB was conducted in the control group and the rTM group. A bolus of rTM (3 mg/kg) was administered to the rTM group rats before CPB establishment. The ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen only dropped markedly from before CPB in the control group (P rTM group. The number of apoptotic cells and the protein of cleaved Caspase-3 were reduced in the rTM group. These results suggest that rTM prevents acute lung injury through attenuating inflammation and apoptosis during and after CPB in a rat model. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  11. Quantitative analysis of human herpesvirus-6 and human cytomegalovirus in blood and saliva from patients with acute leukemia.

    Science.gov (United States)

    Nefzi, Faten; Ben Salem, Nabil Abid; Khelif, Abderrahim; Feki, Salma; Aouni, Mahjoub; Gautheret-Dejean, Agnès

    2015-03-01

    Human herpesvirus-6 (HHV-6) and human cytomegalovirus (HCMV) DNAs were quantified by real-time PCR assays in blood and saliva obtained from 50 patients with acute leukemia at the time of diagnosis (50 of each matrix), aplasia (65 of each matrix), remission (55 of each matrix), and relapse (20 of each matrix) to evaluate which biological matrix was more suitable to identify a viral reactivation, search for a possible link between HHV-6 and HCMV reactivations, and evaluate the relations between viral loads and count of different leukocyte types in blood. The median HHV-6 loads were 136; 219; 226, and 75 copies/million cells in blood at diagnosis, aplasia, remission and relapse, respectively. The HCMV loads were 193 and 317 copies/million cells in blood at diagnosis and remission. In the saliva samples, the HHV-6 loads were 22,165; 15,238; 30,214, and 17,454 copies/million cells at diagnosis, aplasia, remission, and relapse, respectively. The HCMV loads were 8,991; 1,461; 2,980, and 4,283 copies/million cells at diagnosis, aplasia, remission, and relapse, respectively. The HHV-6 load in the blood was correlated to the counts of polymorphonuclear leukocytes (R(2)  = 0.5; P blood in the detection of HHV-6 or HCMV reactivations. The HHV-6 and HCMV reactivations were linked only in saliva. © 2014 Wiley Periodicals, Inc.

  12. Time course of proteolytic, cytokine, and myostatin gene expression after acute exercise in human skeletal muscle.

    Science.gov (United States)

    Louis, Emily; Raue, Ulrika; Yang, Yifan; Jemiolo, Bozena; Trappe, Scott

    2007-11-01

    The aim of this study was to examine the time course induction of select proteolytic [muscle ring finger-1 (MuRF-1), atrogin-1, forkhead box 3A (FOXO3A), calpain-1, calpain-2], myostatin, and cytokine (IL -6, -8, -15, and TNF-alpha) mRNA after an acute bout of resistance (RE) or run (RUN) exercise. Six experienced RE (25 +/- 4 yr, 74 +/- 14 kg, 1.71 +/- 0.11 m) and RUN (25 +/- 4 yr, 72 +/- 5 kg, 1.81 +/- 0.07 m) subjects had muscle biopsies from the vastus lateralis (RE) or gastrocnemius (RUN) before, immediately after, and 1, 2, 4, 8, 12, and 24 h postexercise. RE increased (P suppressed (3.6-fold; P suppression of myostatin. These data provide basic information for the timing of human muscle biopsy samples for gene expression studies involving exercise. Furthermore, this information suggests a greater induction of proteolytic genes following RUN compared with RE.

  13. Caffeine intake increases plasma ketones: an acute metabolic study in humans.

    Science.gov (United States)

    Vandenberghe, Camille; St-Pierre, Valérie; Courchesne-Loyer, Alexandre; Hennebelle, Marie; Castellano, Christian-Alexandre; Cunnane, Stephen C

    2017-04-01

    Brain glucose uptake declines during aging and is significantly impaired in Alzheimer's disease. Ketones are the main alternative brain fuel to glucose so they represent a potential approach to compensate for the brain glucose reduction. Caffeine is of interest as a potential ketogenic agent owing to its actions on lipolysis and lipid oxidation but whether it is ketogenic in humans is unknown. This study aimed to evaluate the acute ketogenic effect of 2 doses of caffeine (2.5; 5.0 mg/kg) in 10 healthy adults. Caffeine given at breakfast significantly stimulated ketone production in a dose-dependent manner (+88%; +116%) and also raised plasma free fatty acids. Whether caffeine has long-term ketogenic effects or could enhance the ketogenic effect of medium chain triglycerides remains to be determined.

  14. Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects

    Science.gov (United States)

    Young, Simon N.

    2013-01-01

    The acute tryptophan depletion (ATD) technique has been used extensively to study the effect of low serotonin in the human brain. This review assesses the validity of a number of published criticisms of the technique and a number of previously unpublished potential criticisms. The conclusion is that ATD can provide useful information when results are assessed in conjunction with results obtained using other techniques. The best-established conclusion is that low serotonin function after tryptophan depletion lowers mood in some people. However, this does not mean that other variables, altered after tryptophan depletion, are necessarily related to low serotonin. Each aspect of brain function has to be assessed separately. Furthermore, a negative tryptophan depletion study does not mean that low serotonin cannot influence the variable studied. This review suggests gaps in knowledge that need to be filled and guidelines for carrying out ATD studies. PMID:23428157

  15. Human herpesvirus 6 encephalitis followed by acute disseminated encephalomyelitis in an immunocompetent adult.

    Science.gov (United States)

    Horie, Junichi; Suzuki, Keisuke; Nakamura, Toshiki; Okamura, Madoka; Iwasaki, Akio; Hirata, Koichi

    2017-04-28

    A 26-year-old, otherwise healthy man presented with visual abnormality followed by loss of consciousness and convulsion. The patient then developed headache and fever 14 days later. Brain MRI showed hyperintensities in the left cingulate cortex. The cerrebrospinal fluid examinations showed mononuclear pleocytosis and positive PCR results for human herpesvirus 6 (HHV-6). A diagnosis of HHV-6 encephalitis and symptomatic epilepsy was made. The patient's clinical symptoms improved promptly following acyclovir treatment. However, 3 months later the patient noticed dysesthesia in the trunk, the left upper limb and the right lower limb. Brain and spine MRI showed multiple brain white matter lesions, the middle cerebellar peduncle and cervical spinal lesions. The symptoms resolved following methylprednisolone pulse therapy only. We report an adult patient with HHV-6 encephalitis followed by acute disseminated encephalomyelitis whose initial presentation was epilepsy. HHV-6 encephalitis should be included in the differential diagnosis of encephalitis of unknown etiology in an immunocompetent adult.

  16. Human metapneumovirus and respiratory syncytial virus in hospitalized danish children with acute respiratory tract infection

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Larsen, Hans Henrik; Eugen-Olsen, Jesper

    2004-01-01

    The newly discovered human metapneumovirus (hMPV) has been shown to be associated with respiratory illness. We determined the frequencies and clinical features of hMPV and respiratory syncytial virus (RSV) infections in 374 Danish children with 383 episodes of acute respiratory tract infection...... children 1-6 months of age. Asthmatic bronchitis was diagnosed in 66.7% of hMPV and 10.6% of RSV-infected children (p infected children required respiratory support. hMPV is present in young.......6%) ARTI episodes by real-time reverse transcription-polymerase chain reaction using primers targeting the hMPV N gene and the RSV L gene. Two children were co-infected with hMPV and RSV. They were excluded from statistical analysis. Hospitalization for ARTI caused by hMPV was restricted to very young...

  17. Effect of Losartan on the Acute Response of Human Elderly Skeletal Muscle to Exercise

    DEFF Research Database (Denmark)

    Heisterberg, Mette Flindt; Andersen, Jesper L; Schjerling, Peter

    2017-01-01

    PURPOSE: To investigate the effect of blocking the angiotensin II type I receptor (AT1R) upon the response to acute heavy resistance exercise in elderly human skeletal muscle. The hypothesis was that AT1R blocking would result in a superior myogenic response accompanied by downregulation of TGF......-β and upregulation of IGF-1 signalling. METHODS: 28 healthy elderly men (+64 years) were randomized into two groups, consuming either AT1R blocker (Losartan, 100mg/day) or Placebo for 18 days prior to exercise. Participants performed one bout of heavy unilateral resistance exercise. Six muscle biopsies were obtained...... from the vastus lateralis muscles of each subject: two before exercise, and four after exercise (4.5 hours and 1, 4 and 7 days). Blood pressure and blood samples were collected at the same time points. Biopsies were sectioned for immunohistochemistry to determine the number of satellite cells...

  18. Lipid emulsions in the treatment of acute poisoning: a systematic review of human and animal studies.

    Science.gov (United States)

    Jamaty, Chloé; Bailey, Benoit; Larocque, Alexandre; Notebaert, Eric; Sanogo, Karine; Chauny, Jean-Marc

    2010-01-01

    To assess the evidence regarding the efficacy and safety of intravenous fat emulsion (IFE) in the management of poisoned patients. We performed a systematic review of the literature with no time or language restriction. The electronic databases were searched from their inception until June 1, 2009 (Medline, EMBASE, ISI web of science, Biological abstract, LILACS, ChemIndex, Toxnet, and Proquest). We also examined the references of identified articles and the gray literature. The target interventions eligible for inclusion were administration of any IFE before, during, or after poisoning in human or animals. All types of studies were reviewed. Eligibility for inclusion and study quality scores, based on criteria by Jadad and the STROBE statement, were evaluated by independent investigators. The primary outcome was mortality. Secondary outcomes included neurologic, hemodynamic, and electrocardiographic variables, as well as adverse effects. Of the 938 publications identified by the search strategies, 74 met the inclusion criteria. We identified 23 animal trials, 50 human, and 1 animal case reports. Overall, the quality of evidence was weak and significant heterogeneity prevented data pooling. Available data suggest some benefits of IFE in bupivacaine, verapamil, chlorpromazine, and some tricyclic antidepressants and beta-blockers toxicity. No trial assessed the safety of IFE in the treatment of acute poisoning. The evidence for the efficacy of IFE in reducing mortality and improving hemodynamic, electrocardiographic, and neurological parameters in the poisoned patients is solely based on animal studies and human case reports. The safety of IFE has not been established.

  19. Human coronaviruses in severe acute respiratory infection (SARI) cases in southwest India.

    Science.gov (United States)

    Suresha, Prabhu G; Akhil, Chameettachal; Anjali, Aithal; Giselle, Dsouza R; Revti, Bhaskar; Arunkumar, Govindakarnavar

    2016-01-01

    Acute viral respiratory infections (AVRI) are a leading cause of morbidity and mortality among all age groups globally. Except for Influenza virus and Respiratory Syncytial virus, mostly viral aetiology of AVRI remains undiagnosed. Lately, human coronaviruses (HCoVs) have emerged as an important aetiology of AVRI. A laboratory based retrospective cross sectional study was conducted in which respiratory samples (throat swabs) of patients (n = 864), with Influenza negative SARI, of all age groups between Jan 2011-Dec 2012 were tested for HCoVs including MERS-CoV using Conventional and real time PCR assays. The prevalence of HCoV among SARI cases was 1.04% (9/864) [95% CI: 0.36-1.72]. Of these four (44.44%) were identified as HCoV OC43, three (33.33%) as HCoV NL63 and two (22.22%) as HCoV 229E. No HCoV HKU1 was detected. The samples were also negative for SARS-CoV and MERS-CoV. The results of this study documents low prevalence of human coronaviruses in SARI cases in south western India and the absence of highly pathogenic human coronaviruses. As the study included only SARI cases the prevalence reported could be an under estimate when it is extrapolated to community. © 2015 Wiley Periodicals, Inc.

  20. Targeting Aberrant Glutathione Metabolism to Eradicate Human Acute Myelogenous Leukemia Cells*

    Science.gov (United States)

    Pei, Shanshan; Minhajuddin, Mohammad; Callahan, Kevin P.; Balys, Marlene; Ashton, John M.; Neering, Sarah J.; Lagadinou, Eleni D.; Corbett, Cheryl; Ye, Haobin; Liesveld, Jane L.; O'Dwyer, Kristen M.; Li, Zheng; Shi, Lei; Greninger, Patricia; Settleman, Jeffrey; Benes, Cyril; Hagen, Fred K.; Munger, Joshua; Crooks, Peter A.; Becker, Michael W.; Jordan, Craig T.

    2013-01-01

    The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34+) leukemic versus normal specimens. Our data indicate that CD34+ AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to compensate for increased oxidative stress in leukemic cells. Consistent with this observation, CD34+ AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared with normal CD34+ cells. These findings led us to hypothesize that AML cells will be hypersensitive to inhibition of glutathione metabolism. To test this premise, we identified compounds such as parthenolide (PTL) or piperlongumine that induce almost complete glutathione depletion and severe cell death in CD34+ AML cells. Importantly, these compounds only induce limited and transient glutathione depletion as well as significantly less toxicity in normal CD34+ cells. We further determined that PTL perturbs glutathione homeostasis by a multifactorial mechanism, which includes inhibiting key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of glutathione. These findings demonstrate that primitive leukemia cells are uniquely sensitive to agents that target aberrant glutathione metabolism, an intrinsic property of primary human AML cells. PMID:24089526

  1. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Francis Richard W

    2010-04-01

    Full Text Available Abstract Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL. However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

  2. Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex.

    Science.gov (United States)

    de Matos, Nuno M P; Hock, Andreas; Wyss, Michael; Ettlin, Dominik A; Brügger, Mike

    2017-09-04

    The trigeminal brainstem sensory nuclear complex is the first central relay structure mediating orofacial somatosensory and nociceptive perception. Animal studies suggest a substantial involvement of neurochemical alterations at such basal CNS levels in acute and chronic pain processing. Translating this animal based knowledge to humans is challenging. Human related examining of brainstem functions are challenged by MR related peculiarities as well as applicability aspects of experimentally standardized paradigms. Based on our experience with an MR compatible human orofacial pain model, the aims of the present study were twofold: 1) from a technical perspective, the evaluation of proton magnetic resonance spectroscopy at 3 T regarding measurement accuracy of neurochemical profiles in this small brainstem nuclear complex and 2) the examination of possible neurochemical alterations induced by an experimental orofacial pain model. Data from 13 healthy volunteers aged 19-46 years were analyzed and revealed high quality spectra with significant reductions in total N-acetylaspartate (N-acetylaspartate + N-acetylaspartylglutamate) (-3.7%, p = 0.009) and GABA (-10.88%, p = 0.041) during the pain condition. These results might reflect contributions of N-acetylaspartate and N-acetylaspartylglutamate in neuronal activity-dependent physiologic processes and/or excitatory neurotransmission, whereas changes in GABA might indicate towards a reduction in tonic GABAergic functioning during nociceptive signaling. Summarized, the present study indicates the applicability of (1)H-MRS to obtain neurochemical dynamics within the human trigeminal brainstem sensory nuclear complex. Further developments are needed to pave the way towards bridging important animal based knowledge with human research to understand the neurochemistry of orofacial nociception and pain. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Human thermal bioclimatic conditions associated with acute cardiovascular syndromes in Crete Island, Greece

    Science.gov (United States)

    Bleta, Anastasia G.; Nastos, Panagiotis T.

    2013-04-01

    The aim of this study is to quantify the association between bioclimatic conditions and daily counts of admissions for non-fatal acute cardiovascular (acute coronary syndrome, arrhythmia, decompensation of heart failure) syndromes (ACS) registered by the two main hospitals in Heraklion, Crete Island, during a five-year period 2008-2012. The bioclimatic conditions analyzed are based on human thermal bioclimatic indices such as the Physiological Equivalent Temperature (PET) and the Universal Thermal Climate Index (UTCI). Mean daily meteorological parameters, such as air temperature, relative humidity, wind speed and cloudiness, were acquired from the meteorological station of Heraklion (Hellenic National Meteorological Service). These parameters were used as input variables in modeling the aforementioned thermal indices, in order to interpret the grade of the thermo-physiological stress. The PET and UTCI analysis was performed by the use of the radiation and bioclimate model, "RayMan", which is well-suited to calculate radiation fluxes and human biometeorological indices. Generalized linear models (GLM) were applied to time series of daily numbers of outpatients with ACS against bioclimatic variations, after controlling for possible confounders and adjustment for season and trends. The interpretation of the results of this analysis suggests a significant association between cold weather and increased coronary heart disease incidence, especially in the elderly and males. Additionally, heat stress plays an important role in the configuration of daily ACS outpatients, even in temperate climate, as that in Crete Island. In this point it is worth mentioning that Crete Island is frequently affected by Saharan outbreaks, which are associated in many cases with miscellaneous phenomena, such as Föhn winds - hot and dry winds - causing extreme bioclimatic conditions (strong heat stress). Taking into consideration the projected increased ambient temperature in the future, ACS

  4. Impact of Human Development Index on the profile and outcomes of patients with acute coronary syndrome.

    Science.gov (United States)

    Roy, Ambuj; Roe, Matthew T; Neely, Megan L; Cyr, Derek D; Zamoryakhin, Dmitry; Fox, Keith A A; White, Harvey D; Armstrong, Paul W; Ohman, E Magnus; Prabhakaran, Dorairaj

    2015-02-01

    To study the impact of national economic and human development status on patient profiles and outcomes in the setting of acute coronary syndrome (ACS). We conducted a retrospective analysis of the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes trial (TRILOGY ACS) population (51 countries; 9301 patients). Outcome measures compared baseline characteristics and clinical outcomes through 30 months by 2010 country-level United Nations Human Development Indices (HDIs) and per-capita gross national income. TRILOGY ACS enrolled 3659 patients from 27 very-high HDI countries, 3744 from 18 high-HDI countries and 1898 from 6 medium-HDI countries. Baseline characteristics of groups varied significantly, with the medium-HDI group having a lower mean age (63.0 years, vs 65.0 and 68.0 years for high-HDI and very-high HDI, respectively; pcountries vs upper-income/middle-income (0.791(95% CI 0.632 to 0.990)) and high-income countries (0.756 (95% CI 0.616 to 0.928)), with differences largely attributable to myocardial infarction rates. Clinical patient profiles differed substantially by country HDI groupings. Lower unadjusted event rates in medium-HDI countries may be explained by younger age and lower comorbidity burden among these countries' patients. This heterogeneity in patient recruitment across country HDI groupings may have important implications for future global ACS trial design. NCT00699998. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Agent-based modeling of endotoxin-induced acute inflammatory response in human blood leukocytes.

    Directory of Open Access Journals (Sweden)

    Xu Dong

    2010-02-01

    Full Text Available Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions.An agent-based modeling (ABM framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (noninfectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades.The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would

  6. Agent-based modeling of endotoxin-induced acute inflammatory response in human blood leukocytes.

    Science.gov (United States)

    Dong, Xu; Foteinou, Panagiota T; Calvano, Steven E; Lowry, Stephen F; Androulakis, Ioannis P

    2010-02-18

    Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear) nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions. An agent-based modeling (ABM) framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (non)infectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades. The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would potentially improve

  7. Molecular characterization of human calicivirus associated with acute diarrheal disease in mexican children

    Directory of Open Access Journals (Sweden)

    Gómez-Santiago Fabián

    2012-02-01

    Full Text Available Abstract Background Human caliciviruses (HuCV are emerging enteric pathogens that are a common cause of diarrhea in humans worldwide. Due to the paucity of information on the molecular characterization of HuCV circulating in Mexico, the aim of this work was to investigate the diversity and molecular epidemiology of the HuCV infection associated with acute diarrheal disease in Mexican children aged up to 5 years. Results Of the 131/414 (32% HuCV positive-specimens analyzed, 128 were identified as Norovirus (NoV and three as Sapovirus (SaV. Of the NoV positive specimens, 118/128 (92% were NoV GII and 10/128(8% were untypeable by RT-PCR in both polymerase and capsid genes, whereas one SaV isolate was further confirmed by sequencing as GI.2. Phylogenetic analysis based on polymerase partial gene sequences from 89/131 (68% HuCV isolates showed that 86/89 (97% belong to NoV GII.4 with three main variant clusters of this genotype, 2/89 (2% to NoV GII.2, and 1/89 (1% to SaV GI.2. Furthermore, partial sequencing of the capsid gene VP1 of 63/131 (48% strains indicated that 61/63 (97% correlated with NoV GII.4, whereas only 2/63 (3% clustered to NoV GII.2. HuCV infections were detected throughout the year, and the highest number of cases positive for NoV was found in children between 7 and 18 months of age (60%. Conclusions This study highlights the usefulness of analyzing both polymerase and capsid genes for molecular characterization of HuCV and demonstrates the relatedness and predominance of NoV GII.4 with acute diarrheal disease in young Mexican children, thus contributing to better understanding of the molecular epidemiology of this disease.

  8. Effect of acute Plasmodium falciparum malaria on reactivation and shedding of the eight human herpes viruses.

    Directory of Open Access Journals (Sweden)

    Arnaud Chêne

    Full Text Available Human herpes viruses (HHVs are widely distributed pathogens. In immuno-competent individuals their clinical outcomes are generally benign but in immuno-compromised hosts, primary infection or extensive viral reactivation can lead to critical diseases. Plasmodium falciparum malaria profoundly affects the host immune system. In this retrospective study, we evaluated the direct effect of acute P. falciparum infection on reactivation and shedding of all known human herpes viruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8. We monitored their presence by real time PCR in plasma and saliva of Ugandan children with malaria at the day of admission to the hospital (day-0 and 14 days later (after treatment, or in children with mild infections unrelated to malaria. For each child screened in this study, at least one type of HHV was detected in the saliva. HHV-7 and HHV-6 were detected in more than 70% of the samples and CMV in approximately half. HSV-1, HSV-2, VZV and HHV-8 were detected at lower frequency. During salivary shedding the highest mean viral load was observed for HSV-1 followed by EBV, HHV-7, HHV-6, CMV and HHV-8. After anti-malarial treatment the salivary HSV-1 levels were profoundly diminished or totally cleared. Similarly, four children with malaria had high levels of circulating EBV at day-0, levels that were cleared after anti-malarial treatment confirming the association between P. falciparum infection and EBV reactivation. This study shows that acute P. falciparum infection can contribute to EBV reactivation in the blood and HSV-1 reactivation in the oral cavity. Taken together our results call for further studies investigating the potential clinical implications of HHVs reactivation in children suffering from malaria.

  9. MicroRNA-223 dose levels fine tune proliferation and differentiation in human cord blood progenitors and acute myeloid leukemia

    NARCIS (Netherlands)

    B. Gentner (Bernhard); N. Pochert (Nicole); A. Rouhi (Arefeh); F. Boccalatte (Francesco); T. Plati (Tiziana); T. Berg (Tobias); S.M. Sun; S.M. Mah (Sarah M.); M. Mirkovic-Hösle (Milijana); J. Ruschmann (Jens); A. Muranyi (Andrew); S. Leierseder (Simon); B. Argiropoulos (Bob); D.T. Starczynowski (Daniel T.); A. Karsan (Aly); M. Heuser (Michael); D. Hogge (Donna); F.D. Camargo (Fernando D.); S. Engelhardt (Stefan); H. Döhner (Hartmut); C. Buske (Christian); M. Jongen-Lavrencic (Mojca); L. Naldini (Luigi); R.K. Humphries (R. Keith); F. Kuchenbauer (Florian)

    2015-01-01

    textabstractA precise understanding of the role of miR-223 in human hematopoiesis and in the pathogenesis of acute myeloid leukemia (AML) is still lacking. By measuring miR-223 expression in blasts from 115 AML patients, we found significantly higher miR-223 levels in patients with favorable

  10. CD47 Is an Adverse Prognostic Factor and Therapeutic Antibody Target on Human Acute Myeloid Leukemia Stem Cells

    NARCIS (Netherlands)

    Majeti, R.; Chao, M.P.; Alizadeh, AA; Pang, W.W.; Jaiswal, S.; Gibbs, K.D.; Rooijen, van N.; Weissman, I.L.

    2009-01-01

    Acute myeloid leukemia (AML) is organized as a cellular hierarchy initiated and maintained by a subset of self-renewing leukemia stem cells (LSC). We hypothesized that increased CD47 expression on human AML LSC contributes to pathogenesis by inhibiting their phagocytosis through the interaction of

  11. Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model.

    Science.gov (United States)

    Kuismanen, Kirsi; Juntunen, Miia; Narra Girish, Nathaniel; Tuominen, Heikki; Huhtala, Heini; Nieminen, Kari; Hyttinen, Jari; Miettinen, Susanna

    2018-01-31

    Anal incontinence is a devastating condition that significantly reduces the quality of life. Our aim was to evaluate the effect of human adipose stem cell (hASC) injections in a rat model for anal sphincter injury, which is the main cause of anal incontinence in humans. Furthermore, we tested if the efficacy of hASCs could be improved by combining them with polyacrylamide hydrogel carrier, Bulkamid®. Human ASCs derived from a female donor were culture expanded in DMEM/F12 supplemented with human platelet lysate. Female virgin Sprague-Dawley rats were randomized into four groups (n = 14-15/group): hASCs in saline or Bulkamid® (3 × 105 /60 μl) and saline or Bulkamid® without cells. Anorectal manometry (ARM) was performed before anal sphincter injury, at two (n=58) and at four weeks after (n = 33). Additionally, the anal sphincter tissue was examined by micro-computed tomography (μCT) and the histological parameters were compared between the groups. The median resting and peak pressure during spontaneous contraction measured by ARM were significantly higher in hASC treatment groups compared with the control groups without hASCs. There was no statistical difference in functional results between the hASC-carrier groups (saline vs. Bulkamid®). No difference was detected in the sphincter muscle continuation between the groups in the histology and μCT analysis. More inflammation was discovered in the group receiving saline with hASC. The hASC injection therapy with both saline and Bulkamid® is a promising nonsurgical treatment for acute anal sphincter injury. Traditional histology combined with the 3D μCT image data lends greater confidence in assessing muscle healing and continuity. Stem Cells Translational Medicine 2018. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  12. Lycopene Pretreatment Ameliorates Acute Ethanol Induced NAD+ Depletion in Human Astroglial Cells

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    Jade Guest

    2015-01-01

    Full Text Available Excessive alcohol consumption is associated with reduced brain volume and cognition. While the mechanisms by which ethanol induces these deleterious effects in vivo are varied most are associated with increased inflammatory and oxidative processes. In order to further characterise the effect of acute ethanol exposure on oxidative damage and NAD+ levels in the brain, human U251 astroglioma cells were exposed to physiologically relevant doses of ethanol (11 mM, 22 mM, 65 mM, and 100 mM for ≤ 30 minutes. Ethanol exposure resulted in a dose dependent increase in both ROS and poly(ADP-ribose polymer production. Significant decreases in total NAD(H and sirtuin 1 activity were also observed at concentrations ≥ 22 mM. Similar to U251 cells, exposure to ethanol (≥22 mM decreased levels of NAD(H in primary human astrocytes. NAD(H depletion in primary astrocytes was prevented by pretreatment with 1 μM of lycopene for 3.5 hours. Unexpectedly, in U251 cells lycopene treatment at concentrations ≥ 5 μM resulted in significant reductions in [NAD(H]. This study suggests that exposure of the brain to alcohol at commonly observed blood concentrations may cause transitory oxidative damage which may be at least partly ameliorated by lycopene.

  13. Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

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    I. K. Hals

    2013-01-01

    Full Text Available Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1–0.3% O2 for 8 h, followed by reoxygenation on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8±3.5% in encapsulated and 42.9±5.2% in nonencapsulated islets (P<0.2. Nonencapsulated islets released 37.7% (median more HMGB1 compared to encapsulated islets after hypoxic culture conditions (P<0.001. Glucose-induced insulin release was marginally affected by hypoxia. Basal oxygen consumption was equally reduced in encapsulated and nonencapsulated islets, by 22.0±6.1% versus 24.8±5.7%. Among 27 tested cytokines/chemokines, hypoxia increased the secretion of IL-6 and IL-8/CXCL8 in both groups of islets, whereas an increase of MCP-1/CCL2 was seen only with nonencapsulated islets. Conclusion. Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation.

  14. Genetic Diversity of Human Adenovirus in Children with Acute Gastroenteritis, Albania, 2013–2015

    Science.gov (United States)

    La Rosa, G.; Della Libera, S.; Petricca, S.; Iaconelli, M.; Donia, D.; Saccucci, P.; Cenko, F.; Xhelilaj, G.; Divizia, M.

    2015-01-01

    The objectives of the present study were to assess the occurrence of human adenoviruses (HAdVs) in paediatric patients with gastroenteritis in Albania and to characterize HAdV strains. Faecal specimens from children admitted with acute gastroenteritis to the Paediatric Hospital in Tirana were screened for HAdV, using broad-range primers targeting the hexon gene, in combination with species-specific primers targeting the fiber gene. Phylogenetic analysis was then performed to assess the genetic relationships among the different sequences and between the sequences of the samples and those of the prototype strains. Adenovirus DNA was detected in 33/142 samples (23.2%); 14 belonged to species F (13 HAdV-41 and 1 HAdV-40), 13 to species C (1 HAdV-1, 8 HAdV-2, and 4 HAdV-5), 5 to species B (HAdV-3), and 1 to species A (HAdV-12). Rotavirus coinfection was present in 9/33 (27.2%) positive samples. In the remaining 24 positive samples (12 enteric—F species; 12 nonenteric—A, B, or C species), HAdVs were detected as unique viral pathogens, suggesting that HAdV may be an important cause of diarrhoea in children requiring hospitalization. This is the first study investigating the presence of human adenoviruses (species A–G) as etiologic agents of viral gastroenteritis in children in Albania. PMID:26339589

  15. Genetic Diversity of Human Adenovirus in Children with Acute Gastroenteritis, Albania, 2013-2015.

    Science.gov (United States)

    La Rosa, G; Della Libera, S; Petricca, S; Iaconelli, M; Donia, D; Saccucci, P; Cenko, F; Xhelilaj, G; Divizia, M

    2015-01-01

    The objectives of the present study were to assess the occurrence of human adenoviruses (HAdVs) in paediatric patients with gastroenteritis in Albania and to characterize HAdV strains. Faecal specimens from children admitted with acute gastroenteritis to the Paediatric Hospital in Tirana were screened for HAdV, using broad-range primers targeting the hexon gene, in combination with species-specific primers targeting the fiber gene. Phylogenetic analysis was then performed to assess the genetic relationships among the different sequences and between the sequences of the samples and those of the prototype strains. Adenovirus DNA was detected in 33/142 samples (23.2%); 14 belonged to species F (13 HAdV-41 and 1 HAdV-40), 13 to species C (1 HAdV-1, 8 HAdV-2, and 4 HAdV-5), 5 to species B (HAdV-3), and 1 to species A (HAdV-12). Rotavirus coinfection was present in 9/33 (27.2%) positive samples. In the remaining 24 positive samples (12 enteric--F species; 12 nonenteric--A, B, or C species), HAdVs were detected as unique viral pathogens, suggesting that HAdV may be an important cause of diarrhoea in children requiring hospitalization. This is the first study investigating the presence of human adenoviruses (species A-G) as etiologic agents of viral gastroenteritis in children in Albania.

  16. Effects of acute alcohol intoxication on growth axis in human adolescents of both sexes.

    Science.gov (United States)

    Frias, J; Torres, J M; Rodriguez, R; Ruiz, E; Ortega, E

    2000-10-20

    We previously reported the deleterious effects of acute alcohol intoxication (AAI) on pituitary-gonadal and pituitary-adrenal axes hormones in human adolescents. In the present paper we studied the effects of AAI on the growth axis hormones, and the possible contribution of the insulin-glucose axis to the alcohol-induced dysfunction of the growth axis in human adolescents. Blood samples were drawn from adolescents that arrived at the emergency department with evident behavioural symptoms of drunkenness (AAI) or with nil consumption of alcohol (controls [C]). AAI produced in the adolescents of both sexes in our series: a decrease in growth hormone (GH) levels, without significant alteration of either insulin-like growth factor-I (IGF-I) or insulin-like growth factor binding protein-3 (IGFBP3); an increase in plasma glucose and a decrease in insulin in the female adolescents but not in the males. Males and females undergo a significant period of bone growth during adolescence. Growth axis hormones play an important role in the pubertal spurt. Thus, ethanol consumption during adolescence could have long-lasting deleterious effects on this aspect of development. In industrialised countries, around 35% of alcohol drinkers are under 16 years old, therefore the result of this study should be made known to adolescents and the appropriate authorities.

  17. Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhao

    2015-01-01

    Full Text Available This study is aimed at investigating whether human umbilical cord mesenchymal stem cell- (hucMSC- derived exosomes (hucMSC-exosomes have a protective effect on acute myocardial infarction (AMI. Exosomes were characterized under transmission electron microscopy and the particles of exosomes were further examined through nanoparticle tracking analysis. Exosomes (400 μg protein were intravenously administrated immediately following ligation of the left anterior descending (LAD coronary artery in rats. Cardiac function was evaluated by echocardiography and apoptotic cells were counted using TUNEL staining. The cardiac fibrosis was assessed using Masson’s trichrome staining. The Ki67 positive cells in ischemic myocardium were determined using immunohistochemistry. The effect of hucMSC-exosomes on blood vessel formation was evaluated through tube formation and migration of human umbilical vein endothelial cells (EA.hy926 cells. The results indicated that ligation of the LAD coronary artery reduced cardiac function and induced cardiomyocyte apoptosis. Administration of hucMSC-exosomes significantly improved cardiac systolic function and reduced cardiac fibrosis. Moreover, hucMSC-exosomes protected myocardial cells from apoptosis and promoted the tube formation and migration of EA.hy926 cells. It is concluded that hucMSC-exosomes improved cardiac systolic function by protecting myocardial cells from apoptosis and promoting angiogenesis. These effects of hucMSC-exosomes might be associated with regulating the expression of Bcl-2 family.

  18. Resveratrol Downregulates Interleukin-6-Stimulated Sonic Hedgehog Signaling in Human Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Yu-Chieh Su

    2013-01-01

    Full Text Available IL-6 and sonic hedgehog (Shh signaling molecules are considered to maintain the growth of cancer stem cells (CSCs. Resveratrol, an important integrant in traditional Chinese medicine, possesses certain antitumor effects. However, the mechanisms on regulating acute myeloid leukemia (AML are unclear. This study first used human subjects to demonstrate that the plasma levels of IL-6 and IL-1β in AML patients were higher and lower, respectively, than healthy donors. The expression of Shh preproproteins, and C- and N-terminal Shh peptides increased in bone marrow and peripheral blood mononuclear cells isolated from AML patients, and the plasma N-Shh secretion was greater. To further clarify the effect of IL-6 and resveratrol in Shh signaling, human AML HL-60 cells were tested. IL-6 upregulated Shh and Gli-1 expression and was accompanied by an increase of cell viability. Resveratrol significantly decreased CSC-related Shh expression, Gli-1 nuclear translocation, and cell viability in IL-6-treated HL-60 cells and had synergistic effect with Shh inhibitor cyclopamine on inhibiting cell growth. Conclusions. IL-6 stimulated the growth of AML cells through Shh signaling, and this effect might be blocked by resveratrol. Further investigations of Shh as a prognostic marker and resveratrol as a therapeutic drug target to CSCs in AML are surely warranted.

  19. Human herpesviruses respiratory infections in patients with acute respiratory distress (ARDS).

    Science.gov (United States)

    Bonizzoli, Manuela; Arvia, Rosaria; di Valvasone, Simona; Liotta, Francesco; Zakrzewska, Krystyna; Azzi, Alberta; Peris, Adriano

    2016-08-01

    Acute respiratory distress syndrome (ARDS) is today a leading cause of hospitalization in intensive care unit (ICU). ARDS and pneumonia are closely related to critically ill patients; however, the etiologic agent is not always identified. The presence of human herpes simplex virus 1, human cytomegalovirus and Epstein-Barr virus in respiratory samples of critically ill patients is increasingly reported even without canonical immunosuppression. The main aim of this study was to better understand the significance of herpesviruses finding in lower respiratory tract of ARDS patients hospitalized in ICU. The presence of this group of herpesviruses, in addition to the research of influenza viruses and other common respiratory viruses, was investigated in respiratory samples from 54 patients hospitalized in ICU, without a known microbiological causative agent. Moreover, the immunophenotype of each patient was analyzed. Herpesviruses DNA presence in the lower respiratory tract seemed not attributable to an impaired immunophenotype, whereas a significant correlation was observed between herpesviruses positivity and influenza virus infection. A higher ICU mortality was significantly related to the presence of herpesvirus infection in the lower respiratory tract as well as to impaired immunophenotype, as patients with poor outcome showed severe lymphopenia, affecting in particular T (CD3+) cells, since the first days of ICU hospitalization. In conclusion, these results indicate that herpesviruses lower respiratory tract infection, which occurs more frequently following influenza virus infection, can be a negative prognostic marker. An independent risk factor for ICU patients with ARDS is an impaired immunophenotype.

  20. Innate, T and B Cell Responses in Acute Human Zika Patients.

    Science.gov (United States)

    Lai, Lilin; Rouphael, Nadine; Xu, Yongxian; Natrajan, Muktha S; Beck, Allison; Hart, Mari; Feldhammer, Matthew; Feldpausch, Amanda; Hill, Charles; Wu, Henry; Fairley, Jessica K; Lankford-Turner, Pamela; Kasher, Nicole; Rago, Patrick; Hu, Yi-Juan; Edupuganti, Srilatha; Patel, Shital M; Murray, Kristy O; Mulligan, Mark J

    2017-08-17

    There is an urgent need for studies of viral persistence and immunity during human Zika infections to inform planning and conduct of vaccine clinical trials. In five returned US travelers with acute symptomatic Zika infection, clinical features, viral RNA levels, and immune responses were characterized. Two pregnant, flavivirus-experienced patients had viral RNA persist in plasma for >44 and >26 days. Three days after symptom onset transient increases in pro-inflammatory monocytes began followed at five days by transient decreases in myeloid dendritic cells. Anti-Zika virus IgM was detected as early as day 7 after symptom onset, persisted beyond 103 days, and remained equivocal through day 172. Zika virus-specific plasmablasts and neutralizing antibodies developed quickly; dengue virus-specific plasmablasts and neutralizing antibodies at high titers developed only in flavivirus-experienced patients. Zika virus- and dengue virus-specific memory B cells developed in both flavivirus-naïve and -experienced patients. CD4+ T cells were moderately activated and produced antiviral cytokines after stimulation with Zika virus C, prM, E, and NS5 peptides in 4/4 patients. In contrast, CD8+ T cells were massively activated but functional virus-specific cells producing cytokines were present in only 2/4 patients assessed. Acute infections with Zika virus modulated antigen-presenting cell populations early. Flavivirus-experienced patients quickly recalled cross-reactive memory B cells to secrete antibodies. Dengue virus-naïve patients made little dengue-specific antibody but developed memory B cells that cross-reacted against dengue virus. Zika virus-specific functional CD4+ T cells were readily detected but few CD8+ T cells specific for the tested peptides were found.

  1. Investigation of functional activity human dental pulp stem cells at acute and chronic pulpitis.

    Science.gov (United States)

    Ustiashvili, M; Kordzaia, D; Mamaladze, M; Jangavadze, M; Sanodze, L

    2014-09-01

    It is already recognized that together with the other connective tissues organ-specific progenic stem cells are also found in postnatal dental pulp. This group of undifferentiated cells is only 1% of total cell population of the pulp. The aim of the study was the identification of stem cells in human dental pulp, detection of their localization and assessment of functional activity during inflammation process and/or at norm. The obtained results showed that at acute pulpitis the pulp stroma is hypocellular in comparison with the norm but cells proliferative activity is low. CD 133 and NCAM (CD 56) positive stem cells were found in perivascularl space of the pulp stroma and in Hohle layer. At process prolongation and transition to the chronic phase pulp stroma is hypercellular, the cells with large, rounded or oval-shaped nuclei with clear chromatin appear together with fibroblasts. They are distributed as about entire thickness of the stroma as especially Hohle layer. In such cells higher proliferative activity (Ki67 expression) was observed. The cells in the mentioned proliferation phase are intensively marked by CD133, the rate of which is high in Hohle layer and along it. A large number of NCAM (CD 56) positive cells appear in pulp stroma. During pulpitis an involvement of stem cells into the process of reparative dentinogenesis should be conducted stepwise. In acute cases of the disease, stem cell perivascularl mobilization and proliferation and its migration to Hohle layer occur in response to irritation /stimulation. Chronification of the process leads not only to the migration of stem cells to the periphery of the pulp but also s their В«maturationВ» (increase of NCAM expression in the stem cells), which causes an increase the number of dentin producing active odontoblasts and initiation of reparative dentinogenesis.

  2. Dynamic regulation of metabolic efficiency explains tolerance to acute hypoxia in humans.

    Science.gov (United States)

    Schiffer, Tomas A; Ekblom, Björn; Lundberg, Jon O; Weitzberg, Eddie; Larsen, Filip J

    2014-10-01

    The maximum power principle dictates that open biological systems tend to self-organize to a level of efficiency that allows maximal power production. Applying this principle to cellular energetics and whole-body physiology would suggest that for every metabolic challenge, an optimal efficiency exists that maximizes power production. On exposure to hypoxia, it would be favorable if metabolic efficiency would rapidly adjust so as to better preserve work performance. We tested this idea in humans by measuring metabolic efficiency and exercise tolerance under normoxic (Fio2=20.9%) and hypoxic (Fio2=16%) conditions, where Fio2 is fraction of inhaled oxygen. The results were compared with respirometric analyses of skeletal muscle mitochondria from the same individuals. We found that among healthy trained subjects (n=14) with a wide range of metabolic efficiency (ME), those with a high ME during normoxic exercise were able to better maintain exercise capacity (Wmax) in hypoxia. On hypoxic exposure, these subjects acutely decreased their efficiency from 19.2 to 17.4%, thereby likely shifting it closer to a degree of efficiency where maximal power production is achieved. In addition, mitochondria from these subjects had a lower intrinsic respiration compared to subjects that showed a large drop in Wmax in hypoxia An acute shift in efficiency was also demonstrated in isolated mitochondria exposed to physiological levels of hypoxia as P/O ratio increased from 0.9 to 1.3 with hypoxic exposure. These findings suggest the existence of a physiological adaptive response by which metabolic efficiency is dynamically optimized to maximize power production. © FASEB.

  3. Prevalence and molecular epidemiology of human coronavirus HKU1 in patients with acute respiratory illness.

    Science.gov (United States)

    Lee, Wan-Ji; Chung, Yoon-Seok; Yoon, Hee Sook; Kang, Chun; Kim, Kisoon

    2013-02-01

    In 2005, human coronavirus HKU1 (HCoV-HKU1) was isolated and identified from a 71-year-old man with pneumonia in Hong Kong. To identify and classify genotypes of HCoV-HKU1 in Korea, a sensitive, specific, and quantitative real-time polymerase chain reaction (PCR) assay was developed and analyzed the sequences of HCoV-HKU1 isolated in Korea. A total of 1,985 respiratory specimens taken from patients with acute respiratory illness were tested for HCoV-HKU1 from January 2007 to May 2008. The major clinical symptoms associated with HCoV-HKU1 infection were examined statistically and sequence variations of the RNA-dependent RNA polymerase (RdRp), spike, and nucleocapsid genes were also analyzed. Fifty cases (2.5%) HCoV-HKU1 were identified by real-time PCR and viral loads ranged from 6.7 × 10(4) to 1.6 × 10(9)  copies/ml. The clinical symptoms of HCoV-HKU1 infection included rhinorrhea (72%), cough (64%), nasal congestion (56%), fever (32%), sputum (30%), sore throat (18%), chills (16%), postnasal discharge (14%), and tonsillar hypertrophy (10%). There was a seasonal distribution of HCoV-HKU1 infection, peaking in winter and spring. Both genotypes A and B were detected but no recombination between them was found. This is the first report on the identification and genotyping of HCoV-HKU1 as a causative agent of acute respiratory illness in Korea. The data suggest that at least two genotypes, A and B, of HCoV-HKU1 with scattered silent mutations were circulating in Korea from 2007 to 2008. Copyright © 2012 Wiley Periodicals, Inc.

  4. Human mesenchymal stem cells attenuate early damage in a ventilated pig model of acute lung injury

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    Yuben Moodley

    2016-07-01

    Full Text Available Acute lung injury/acute respiratory distress syndrome (ALI/ARDS is a major cause of global morbidity and mortality. Mesenchymal stem cells (MSC have shown promise in treating inflammatory lung conditions. We hypothesised that human MSC (hMSC can improve ALI/ARDS through their anti-inflammatory actions. We subjected pigs (n = 6 to intravenous oleic acid (OA injury, ventilation and hMSC infusion, while the controls (n = 5 had intravenous OA, ventilation and an infusion vehicle control. hMSC were infused 1 h after the administration of OA. The animals were monitored for additional 4 h. Nuclear translocation of nuclear factor-light chain enhancer of activated B cells (NF-κB, a transcription factor that mediates several inflammatory pathways was reduced in hMSC treated pigs compared to controls (p = 0.04. There was no significant difference in lung injury, assessed by histological scoring in hMSC treated pigs versus controls (p = 0.063. There was no difference in neutrophil counts between hMSC-treated pigs and controls. Within 4 h, there was no difference in the levels of IL-10 and IL-8 pre- and post-treatment with hMSC. In addition, there was no difference in hemodynamics, lung mechanics or arterial blood gases between hMSC treated animals and controls. Subsequent studies are required to determine if the observed decrease in inflammatory transcription factors will translate into improvement in inflammation and in physiological parameters over the long term.

  5. Kinin B1 receptors contributes to acute pain following minor surgery in humans

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    Brahim Jaime S

    2010-02-01

    Full Text Available Abstract Background Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels. Results Tissue injury resulted in a significant up-regulation in the gene expression of B1 and B2 receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B1 and B2 receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B1 and B2 receptors were correlated. Following tissue injury, B1 ligands des-Arg9-BK and des-Arg10-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B1 receptor but not B2 receptor. Conclusions These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the

  6. Acute passive cigarette smoke exposure and inhaled human insulin (Exubera) pharmacokinetics.

    Science.gov (United States)

    Fountaine, Robert; Milton, Ashley; Checchio, Tina; Wei, Greg; Stolar, Marilyn; Teeter, John; Jaeger, Rudolph; Fryburg, David

    2008-06-01

    Active cigarette smoking is associated with increased permeability of the pulmonary alveolar epithelium, resulting in faster absorption of inhaled drugs such as Exubera (EXU). Absorption of EXU is increased approximately twice to four times as much in chronic smokers compared with nonsmokers. The rate of clearance of radioaerosols such as technetium-labelled diethylenetriamine penta-acetic acid is decreased in response to passive smoke exposure. Passive smoke exposure causes a decrease in lung permeability, an effect opposite to that of active smoking. Acute passive smoke exposure results in a decrease in EXU bioavailability and does not create a risk of hypoglycaemia. These results are consistent with previous studies of radioaerosol lung clearance. AIMS Relative to nonsmokers, the bioavailability of inhaled human insulin (Exubera(R); EXU) is markedly increased in chronic smokers. The pharmacokinetics of EXU following passive cigarette smoke exposure is unknown. METHODS In an open-label, crossover study, healthy nonsmoking volunteers received two treatments in randomized sequence separated by a 2-week wash-out: (i) EXU 3 mg with no passive smoke exposure and (ii) EXU 3 mg after passive smoke exposure (atmospheric nicotine levels 75-125 mug m(-3)) for 2 h. Blood samples were obtained at prespecified times up to 6 h after EXU administration. Twenty-seven subjects completed both study periods. Mean plasma insulin AUC(0-360) decreased by 17% [ratio 83%, 95% confidence interval (CI) 68.8, 99.5] and mean C(max) by 29% (ratio 71%, 95% CI 59.8, 83.1) after passive cigarette smoke exposure. The median (range) t(max) was 60 min (20-120 min) and 75 min (20-360 min) in the EXU with no exposure and EXU passive exposure groups, respectively. EXU was well tolerated. Unlike active chronic smoking, acute passive cigarette smoke exposure modestly decreases EXU bioavailability and thus should not increase hypoglycaemia risk. These results are consistent with those from published

  7. [Different species of human rhinovirus infection in children with acute respiratory tract infections in Beijing].

    Science.gov (United States)

    Song, Ming-hui; Zhao, Lin-qing; Qian, Yuan; Zhu, Ru-nan; Deng, Jie; Wang, Fang; Sun, Yu; Tian, Run

    2013-12-01

    To understand the clinical characteristics of different groups human rhinovirus (HRV)-A, B and C infection in children with acute respiratory tract infections (ARI) in Beijing. Respiratory tract specimens (n = 1412) collected from children with ARI during Jan. 2011 to Dec. 2012 were tested for HRV by using semi-nested PCR. Gene fragments of VP4/VP2 capsid protein amplified from HRV positive specimens were sequenced for HRV genotype confirmation. Then epidemiological characteristics of these HRV-positive cases were analyzed. Among these 1412 specimens tested, 103 (7.3%) were HRV positive, including 54 (52.4%) positive for HRV-A, 14 (13.6%) for HRV-B, 35 (34.0%) for HRV-C determined by sequence analysis. The positive rates of HRV-A, B and C (2.5%, 16/638; 0.3%, 2/638 and 1.3%, 8/638) in children with acute upper respiratory tract infections (URI) were lower than those (5.8%, 36/623; 1.8%, 11/623 and 3.9%, 24/623) in children with acute lower respiratory tract infections (LRI) (P = 0.003, 0.011, 0.003). In children with LRI, the positive rates of HRV-A, C were similar to each other (P = 0.112), and both were higher than that of HRV-B (P = 0.000, P = 0.026). The severity of ARI among children positive for different groups HRV showed no significant difference evaluated by Kruskal-Wallis H test (Hc = 0.044, P > 0.05), as well as that between children co-infected with HRV and other viruses and those infected with HRV only evaluated by Wilcoxon rank sum test (Zc = 0.872, P > 0.05). HRV is one of important pathogens for children with ARI, especially LRI in Beijing. The positive rates of HRV-A and HRV-C are similar to each other, and both are higher than that of HRV-B. No significant difference was shown among children with different HRV genotypes by evaluation of the severity of ARI, and co-infections of HRV with other viruses do not significantly increase the severity of ARI.

  8. Prevalence of human metapneumovirus in children with acute lower respiratory infection in Changsha, China.

    Science.gov (United States)

    Xiao, Ni-guang; Zhang, Bing; Xie, Zhi-ping; Zhou, Qiong-hua; Zhang, Rong-fang; Zhong, Li-li; Ding, Xiao-fang; Li, Jia; Song, Jing-rong; Gao, Han-chun; Hou, Yun-de; Duan, Zhao-jun

    2013-03-01

    Human metapneumovirus (hMPV) causes acute respiratory infections in children. The prevalence and clinical characteristics of hMPV were determined in nasopharyngeal aspirates of children in Changsha, China. Reverse transcription-polymerase chain reaction (RT-PCR) or PCR was employed to screen for both hMPV and other common respiratory viruses in 1,165 nasopharyngeal aspirate specimens collected from children with lower respiratory tract infections from September 2007 to August 2008. All PCR products were sequenced, and demographic and clinical data were collected from all patients. Seventy-six of 1,165 (6.5%) specimens were positive for hMPV, of which 85.5% (65/76) occurred in the winter and spring seasons. The hMPV coinfection rate was 57.9% (44/76), and human bocavirus was the most common virus detected in conjunction with hMPV. Phylogenetic analysis revealed that 94.7% of the hMPV detected were of subgroup A2, 5.3% were subgroup B2, and none belonged to either the A1 or B1 subgroups. No significant differences were found in terms of the frequency of diagnosis and clinical signs between either the co- and mono-infection groups, or between patients with and without underlying diseases. It was concluded that hMPV is an important viral pathogen in pediatric patients with lower respiratory tract infections in Changsha. Only hMPV genotypes A2 and B2 were co-circulating in this locality; human bocavirus was the most common coinfecting virus, and coinfection did not affect disease severity. Copyright © 2013 Wiley Periodicals, Inc.

  9. Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans

    Science.gov (United States)

    van Boheemen, Sander; de Graaf, Miranda; Lauber, Chris; Bestebroer, Theo M.; Raj, V. Stalin; Zaki, Ali Moh; Osterhaus, Albert D. M. E.; Haagmans, Bart L.; Gorbalenya, Alexander E.; Snijder, Eric J.; Fouchier, Ron A. M.

    2012-01-01

    ABSTRACT A novel human coronavirus (HCoV-EMC/2012) was isolated from a man with acute pneumonia and renal failure in June 2012. This report describes the complete genome sequence, genome organization, and expression strategy of HCoV-EMC/2012 and its relation with known coronaviruses. The genome contains 30,119 nucleotides and contains at least 10 predicted open reading frames, 9 of which are predicted to be expressed from a nested set of seven subgenomic mRNAs. Phylogenetic analysis of the replicase gene of coronaviruses with completely sequenced genomes showed that HCoV-EMC/2012 is most closely related to Tylonycteris bat coronavirus HKU4 (BtCoV-HKU4) and Pipistrellus bat coronavirus HKU5 (BtCoV-HKU5), which prototype two species in lineage C of the genus Betacoronavirus. In accordance with the guidelines of the International Committee on Taxonomy of Viruses, and in view of the 75% and 77% amino acid sequence identity in 7 conserved replicase domains with BtCoV-HKU4 and BtCoV-HKU5, respectively, we propose that HCoV-EMC/2012 prototypes a novel species in the genus Betacoronavirus. HCoV-EMC/2012 may be most closely related to a coronavirus detected in Pipistrellus pipistrellus in The Netherlands, but because only a short sequence from the most conserved part of the RNA-dependent RNA polymerase-encoding region of the genome was reported for this bat virus, its genetic distance from HCoV-EMC remains uncertain. HCoV-EMC/2012 is the sixth coronavirus known to infect humans and the first human virus within betacoronavirus lineage C. PMID:23170002

  10. Effect of phenylhexyl isothiocyanate on aberrant histone H3 methylation in primary human acute leukemia

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    Zou Yong

    2012-07-01

    Full Text Available Abstract Background We have previously studied the histone acetylation in primary human leukemia cells. However, histone H3 methylation in these cells has not been characterized. Methods This study examined the methylation status at histone H3 lysine 4 (H3K4 and histone H3 lysine 9 (H3K9 in primary acute leukemia cells obtained from patients and compared with those in the non-leukemia and healthy cells. We further characterized the effect of phenylhexyl isothiocyanate (PHI, Trichostatin A (TSA, and 5-aza-2’-deoxycytidine (5-Aza on the cells. Results We found that methylation of histone H3K4 was virtually undetectable, while methylation at H3K9 was significantly higher in primary human leukemia cells. The histone H3K9 hypermethylation and histone H3K4 hypomethylation were observed in both myeloid and lymphoid leukemia cells. PHI was found to be able to normalize the methylation level in the primary leukemia cells. We further showed that PHI was able to enhance the methyltransferase activity of H3K4 and decrease the activity of H3K9 methyltransferase. 5-Aza had similar effect on H3K4, but minimal effect on H3K9, whereas TSA had no effect on H3K4 and H3K9 methyltransferases. Conclusions This study revealed opposite methylation level of H3K4 and H3K9 in primary human leukemia cells and demonstrated for the first time that PHI has different effects on the methyltransferases for H3K4 and H3K9.

  11. Xenotransplantation of human unrestricted somatic stem cells in a pig model of acute myocardial infarction.

    Science.gov (United States)

    Gahremanpour, Amir; Vela, Deborah; Zheng, Yi; Silva, Guilherme V; Fodor, William; Cardoso, Cristiano O; Baimbridge, Fred; Fernandes, Marlos R; Buja, L Maximilian; Perin, Emerson C

    2013-01-01

    Stem cell therapy may help restore cardiac function after acute myocardial infarction (AMI), but the optimal therapeutic cell type has not been identified. We examined the effects of CD34-/CD45- human unrestricted somatic stem cells (USSCs) in pigs (n = 30) with an AMI created by a 90-min occlusion of the left anterior descending coronary artery. Pigs were randomly assigned to receive either USSCs (302 ± 23 × 10(6) cells) or phosphate-buffered saline via 15 NOGA-guided transendocardial injections 10 days after AMI. Cyclosporine A (10 mg/kg orally, twice a day) was started in all pigs 3 days before control or cell treatment. Cardiac function was assessed by echocardiography before injection and at 4 and 8 weeks after treatment. Serum titers for pig IgG antibodies against USSCs were also measured at these time points and before AMI. Compared with control pigs, USSC-treated pigs showed no significant differences in any of the functional parameters examined. USSC-treated pigs showed variable increases in anti-USSC IgG antibody titers in the blood and chronic inflammatory infiltrates at the cell injection sites. Immunohistochemical studies of the injection sites using human anti-mitochondrial antibodies failed to detect implanted USSCs. We conclude that human USSCs did not improve cardiac function in a pig model of AMI. Cell transplantation in a xenogeneic setting may obscure the benefits of stem cell therapy. © 2013 John Wiley & Sons A/S.

  12. Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota.

    Science.gov (United States)

    von Klitzing, Eliane; Ekmekciu, Ira; Kühl, Anja A; Bereswill, Stefan; Heimesaat, Markus M

    2017-01-01

    Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction. Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum. With respect to the intestinal microbiota composition "humanized" mice display acute ileitis

  13. Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota.

    Directory of Open Access Journals (Sweden)

    Eliane von Klitzing

    Full Text Available Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction.Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based methods. At day 7 post infection (p.i. with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney and systemic compartments including spleen and serum.With respect to the intestinal microbiota composition "humanized" mice display

  14. Human Cytotoxic T Lymphocyte-Mediated Acute Liver Failure and Rescue by Immunoglobulin in Human Hepatocyte Transplant TK-NOG Mice.

    Science.gov (United States)

    Uchida, Takuro; Hiraga, Nobuhiko; Imamura, Michio; Tsuge, Masataka; Abe, Hiromi; Hayes, C Nelson; Aikata, Hiroshi; Ishida, Yuji; Tateno, Chise; Yoshizato, Katsutoshi; Ohdan, Hideki; Murakami, Kazunari; Chayama, Kazuaki

    2015-10-01

    Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) are critical in eliminating infection. We developed an animal model in which HBV-infected human hepatocytes are targeted by HBV-specific CTLs. After HBV inoculation in human hepatocyte-transplanted herpes simplex virus type-1 thymidine kinase-NOG mice, human peripheral blood mononuclear cells (PBMCs) were administered, and albumin, HBV DNA, alanine aminotransferase (ALT), and cytokine levels were analyzed. Histopathological and flow-cytometric analysis of infiltrating human immune cells were performed, and the efficacy of CTL-associated antigen-4 immunoglobulin (CTLA4Ig) against liver damage was evaluated. PBMC treatment resulted in massive hepatocyte damage with elevation of ALT, granzyme A, and gamma interferon and decrease in albumin and HBV DNA. The number of liver-infiltrating human lymphocytes and CD8-positive cells was significantly higher in HBV-infected mice. HBV-specific CTLs were detected by core and polymerase peptide-major histocompatibility complex-tetramer, and the population of regulatory T cells was significantly decreased in HBV-infected mice. Serum hepatitis B surface (HBs) antigen became negative, and HBs antibody appeared. CTLA4Ig treatment strongly inhibited infiltration of mononuclear cells. CTLA4Ig treatment will be used to treat patients who develop severe acute hepatitis B to prevent liver transplantation or lethality. This animal model is useful for virological and immunological analysis of HBV infection and to develop new therapies for severe acute hepatitis B. Without liver transplantation, some HBV-infected patients will die from severe liver damage due to acute overreaction of the immune system. No effective treatment exists, due in part to the lack of a suitable animal model. An animal model is necessary to investigate the mechanism of hepatitis and to develop therapeutic strategies to prevent acute liver failure in HBV infection. We developed an animal model in which

  15. Beyond crisis resource management: new frontiers in human factors training for acute care medicine.

    Science.gov (United States)

    Petrosoniak, Andrew; Hicks, Christopher M

    2013-12-01

    Error is ubiquitous in medicine, particularly during critical events and resuscitation. A significant proportion of adverse events can be attributed to inadequate team-based skills such as communication, leadership, situation awareness and resource utilization. Aviation-based crisis resource management (CRM) training using high-fidelity simulation has been proposed as a strategy to improve team behaviours. This review will address key considerations in CRM training and outline recommendations for the future of human factors education in healthcare. A critical examination of the current literature yields several important considerations to guide the development and implementation of effective simulation-based CRM training. These include defining a priori domain-specific objectives, creating an immersive environment that encourages deliberate practice and transfer-appropriate processing, and the importance of effective team debriefing. Building on research from high-risk industry, we suggest that traditional CRM training may be augmented with new training techniques that promote the development of shared mental models for team and task processes, address the effect of acute stress on team performance, and integrate strategies to improve clinical reasoning and the detection of cognitive errors. The evolution of CRM training involves a 'Triple Threat' approach that integrates mental model theory for team and task processes, training for stressful situations and metacognition and error theory towards a more comprehensive training paradigm, with roots in high-risk industry and cognitive psychology. Further research is required to evaluate the impact of this approach on patient-oriented outcomes.

  16. Acute Alithiasic Cholecystitis and Human Herpes Virus Type-6 Infection: First Case

    Directory of Open Access Journals (Sweden)

    Maria Miguel Gomes

    2016-01-01

    Full Text Available A three-year-old male child presented with erythematous maculopapular nonpruritic generalized rash, poor feeding, vomiting, and cramping generalized abdominal pain. He was previously healthy and there was no family history of immunologic or other diseases. On examination he was afebrile, hemodynamically stable, with painful palpation of the right upper quadrant and positive Murphy’s sign. Laboratory tests revealed elevated inflammatory markers, elevated aminotransferase activity, and features of cholestasis. Abdominal ultrasound showed gallbladder wall thickening of 8 mm with a positive sonographic Murphy’s sign, without gallstones or pericholecystic fluid. Acute Alithiasic Cholecystitis (AAC was diagnosed. Tests for underlying infectious causes were negative except positive blood specimen for Human Herpes Virus Type-6 (HHV-6 by polymerase chain reaction. With supportive therapy the child became progressively less symptomatic with gradual improvement. The child was discharged on the sixth day, asymptomatic and with improved analytic values. Two months later he had IgM negative and IgG positive antibodies (1/160 for HHV-6, which confirmed the diagnosis of previous infection. In a six-month follow-up period he remains asymptomatic. To the best of our knowledge, this represents the first case of AAC associated with HHV-6 infection.

  17. Estimating healthcare costs of acute gastroenteritis and human campylobacteriosis in Switzerland.

    Science.gov (United States)

    Schmutz, C; Mäusezahl, D; Bless, P J; Hatz, C; Schwenkglenks, M; Urbinello, D

    2017-03-01

    Rising numbers of campylobacteriosis case notifications in Switzerland resulted in an increased attention to acute gastroenteritis (AG) in general. Patients with a laboratory-confirmed Campylobacter infection perceive their disease as severe and around 15% of these patients are hospitalized. This study aimed at estimating healthcare costs due to AG and campylobacteriosis in Switzerland. We used official health statistics, data from different studies and expert opinion for estimating individual treatment costs for patients with different illness severity and for extrapolating overall costs due to AG and campylobacteriosis. We estimated that total Swiss healthcare costs resulting from these diseases amount to €29-45 million annually. Data suggest that patients with AG consulting a physician without a stool diagnostic test account for €9·0-24·2 million, patients with a negative stool test result for Campylobacter spp. for €12·3 million, patients testing positive for Campylobacter spp. for €1·8 million and hospitalized campylobacteriosis patients for €6·5 million/year. Healthcare costs of campylobacteriosis are high and most likely increasing in Switzerland considering that campylobacteriosis case notifications steadily increased in the past decade. Costs and potential cost savings for the healthcare system should be considered when designing sectorial and cross-sectorial interventions to reduce the burden of human campylobacteriosis in Switzerland.

  18. Mouse xenograft modeling of human adult acute lymphoblastic leukemia provides mechanistic insights into adult LIC biology

    Science.gov (United States)

    Dey, Aditi; Castleton, Anna Z.; Schwab, Claire; Samuel, Edward; Sivakumaran, Janani; Beaton, Brendan; Zareian, Nahid; Zhang, Christie Yu; Rai, Lena; Enver, Tariq; Moorman, Anthony V.; Fielding, Adele K.

    2014-01-01

    The distinct nature of acute lymphoblastic leukemia (ALL) in adults, evidenced by inferior treatment outcome and different genetic landscape, mandates specific studies of disease-initiating mechanisms. In this study, we used NOD/LtSz-scid IL2Rγ nullc (NSG) mouse xenotransplantation approaches to elucidate leukemia-initiating cell (LIC) biology in primary adult precursor B (pre-B) ALL to optimize disease modeling. In contrast with xenografting studies of pediatric ALL, we found that modification of the NSG host environment using preconditioning total body irradiation (TBI) was indispensable for efficient engraftment of adult non-t(4;11) pre-B ALL, whereas t(4;11) pre-B ALL was successfully reconstituted without this adaptation. Furthermore, TBI-based xenotransplantation of non-t(4;11) pre-B ALL enabled detection of a high frequency of LICs (<1:6900) and permitted frank leukemic engraftment from a remission sample containing drug-resistant minimal residual disease. Investigation of TBI-sensitive stromal-derived factor-1/chemokine receptor type 4 signaling revealed greater functional dependence of non-t(4;11) pre-B ALL on this niche-based interaction, providing a possible basis for the differential engraftment behavior. Thus, our studies establish the optimal conditions for experimental modeling of human adult pre-B ALL and demonstrate the critical protumorogenic role of microenvironment-derived SDF-1 in regulating adult pre-B LIC activity that may present a therapeutic opportunity. PMID:24825861

  19. Effect of peripheral morphine in a human model of acute inflammatory pain

    DEFF Research Database (Denmark)

    Lillesø, J; Hammer, N A; Pedersen, J L

    2000-01-01

    Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h...... before heat injury (47 degrees C, 7 min) and naloxone infiltration s.c. (0.2 mg) 2.5 h after the heat injury. Hyperalgesia to mechanical and heat stimuli were examined using von Frey hairs and thermodes, and pain was rated using a visual analogue scale. The burns produced significant hyperalgesia...

  20. Automaticity in acute ischemia: Bifurcation analysis of a human ventricular model

    Science.gov (United States)

    Bouchard, Sylvain; Jacquemet, Vincent; Vinet, Alain

    2011-01-01

    Acute ischemia (restriction in blood supply to part of the heart as a result of myocardial infarction) induces major changes in the electrophysiological properties of the ventricular tissue. Extracellular potassium concentration ([Ko+]) increases in the ischemic zone, leading to an elevation of the resting membrane potential that creates an “injury current” (IS) between the infarcted and the healthy zone. In addition, the lack of oxygen impairs the metabolic activity of the myocytes and decreases ATP production, thereby affecting ATP-sensitive potassium channels (IKatp). Frequent complications of myocardial infarction are tachycardia, fibrillation, and sudden cardiac death, but the mechanisms underlying their initiation are still debated. One hypothesis is that these arrhythmias may be triggered by abnormal automaticity. We investigated the effect of ischemia on myocyte automaticity by performing a comprehensive bifurcation analysis (fixed points, cycles, and their stability) of a human ventricular myocyte model [K. H. W. J. ten Tusscher and A. V. Panfilov, Am. J. Physiol. Heart Circ. Physiol.AJPHAP0363-613510.1152/ajpheart.00109.2006 291, H1088 (2006)] as a function of three ischemia-relevant parameters [Ko+], IS, and IKatp. In this single-cell model, we found that automatic activity was possible only in the presence of an injury current. Changes in [Ko+] and IKatp significantly altered the bifurcation structure of IS, including the occurrence of early-after depolarization. The results provide a sound basis for studying higher-dimensional tissue structures representing an ischemic heart.

  1. Acute dark chocolate ingestion is beneficial for hemodynamics via enhancement of erythrocyte deformability in healthy humans.

    Science.gov (United States)

    Radosinska, Jana; Horvathova, Martina; Frimmel, Karel; Muchova, Jana; Vidosovicova, Maria; Vazan, Rastislav; Bernatova, Iveta

    2017-03-01

    Erythrocyte deformability is an important property of erythrocytes that considerably affects blood flow and hemodynamics. The high content of polyphenols present in dark chocolate has been reported to play a protective role in functionality of erythrocytes. We hypothesized that chocolate might influence erythrocytes not only after repeated chronic intake, but also immediately after its ingestion. Thus, we determined the acute effect of dark chocolate and milk (with lower content of biologically active substances) chocolate intake on erythrocyte deformability. We also focused on selected factors that may affect erythrocyte deformability, specifically nitric oxide production in erythrocytes and total antioxidant capacity of plasma. We determined posttreatment changes in the mentioned parameters 2hours after consumption of chocolate compared with their levels before consumption of chocolate. In contrast to milk chocolate intake, the dark chocolate led to a significantly higher increase in erythrocyte deformability. Nitric oxide production in erythrocytes was not changed after dark chocolate intake, but significantly decreased after milk chocolate. The plasma total antioxidant capacity remained unaffected after ingestion of both chocolates. We conclude that our hypothesis was confirmed. Single ingestion of dark chocolate improved erythrocyte deformability despite unchanged nitric oxide production and antioxidant capacity of plasma. Increased deformability of erythrocytes may considerably improve rheological properties of blood and thus hemodynamics in humans, resulting in better tissue oxygenation. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Human parechovirus as a minor cause of acute otitis media in children.

    Science.gov (United States)

    Sillanpää, Saara; Oikarinen, Sami; Sipilä, Markku; Seppälä, Elina; Nurminen, Noora; Rautiainen, Markus; Laranne, Jussi; Hyöty, Heikki

    2015-01-01

    Human parechoviruses (HPeVs) cause mild upper respiratory infections, gastrointestinal symptoms, central nervous system infections and some studies have linked them with acute otitis media (AOM). The aim of the present study was to study further the role of HPeV infections in AOM by detecting these viruses directly from middle ear fluid (MEF), respiratory and stool samples collected from children during AOM episodes. A total of 91 MEF samples, 98 nasal swab (NS) samples and 92 stool samples were collected during 100 AOM episodes in a total of 87 children aged between five to 42 months. All specimens were analyzed by real time RT-PCR for the presence of HPeV RNA. HPeV infection was diagnosed in 12 (14%) patients. HPeV RNA was detected in altogether 13 samples, including four MEF samples, three NS samples and six stool samples. One patient was positive in both stool and MEF samples. The results suggest that HPeV may play a role in some AOM cases, but it is not a major cause of AOM in children. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults.

    Science.gov (United States)

    Lippelt, D P; van der Kint, S; van Herk, K; Naber, M

    2016-01-01

    Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2.0-2.5g of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. The null hypothesis that choline does not improve memory performance as compared to placebo was strongly supported by Bayesian statistics. These results are in contrast with animal studies suggesting that choline supplementation boosts memory performance and learning. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants.

  4. No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults.

    Directory of Open Access Journals (Sweden)

    D P Lippelt

    Full Text Available Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2.0-2.5g of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. The null hypothesis that choline does not improve memory performance as compared to placebo was strongly supported by Bayesian statistics. These results are in contrast with animal studies suggesting that choline supplementation boosts memory performance and learning. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants.

  5. [Detection and Analysis of Human Parainfluenza Virus Infection in Hospitalized Adults with Acute Respiratory Tract Infections].

    Science.gov (United States)

    Li, Xing-Qiao; Liu, Xue-Wei; Zhou, Tao; Pei, Xiao-Fang

    2017-11-01

    To investigate the prevalence and gene characteristics of different groups of human parainfluenza virus (HPIV) infection in hospitalized adults with acute respiratory tract infections (ARI). RT-PCR was used to detect HPIV hemagglutinin (HA) DNA,which was extracted from sputum samples of 1 039 adult patients with ARI from March,2014 to June,2016. The HA gene amplified from randomly selected positive samples were sequenced to analyze the homology and variation. 10.6% (110/1 039) of these samples were positive for HPIV,including 8 cases of HPIV-1,22 cases of HPIV-2,46 cases of HPIV-3 and 34 cases of HPIV-4. Detectable rate varied among different groups of HPIV according to seasons of the year and ages of patients. No significant differences were found between the positive samples and the reference sequences. Compared with different reference strains of different regions,the genetic distance of nucleotide is the smallest between the strains tested in this study and the reference strains of other provinces and cities in China. In Chengdu region,HPIV virus is highly detected in ARI,all subtypes were detected with HPIV-3 being the main subtype.

  6. Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis.

    Science.gov (United States)

    Skouras, Christos; Zheng, Xiaozhong; Binnie, Margaret; Homer, Natalie Z M; Murray, Toby B J; Robertson, Darren; Briody, Lesley; Paterson, Finny; Spence, Heather; Derr, Lisa; Hayes, Alastair J; Tsoumanis, Andreas; Lyster, Dawn; Parks, Rowan W; Garden, O James; Iredale, John P; Uings, Iain J; Liddle, John; Wright, Wayne L; Dukes, George; Webster, Scott P; Mole, Damian J

    2016-09-27

    Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R2 = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R2 = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction.

  7. Acute human brain responses to intracortical microelectrode arrays: Challenges and future prospects

    Directory of Open Access Journals (Sweden)

    Eduardo eFernandez

    2014-07-01

    Full Text Available The emerging field of neuroprosthetics is focused on the development of new therapeutic interventions that will be able to restore some lost neural function by selective electrical stimulation or by harnessing activity recorded from populations of neurons. As more and more patients benefit from these approaches, the interest in neural interfaces has grown significantly and a new generation of penetrating microelectrode arrays are providing unprecedented access to the neurons of the CNS. These microelectrodes have active tip dimensions that are similar in size to neurons and because they penetrate the nervous system, they provide selective access to these cells (within a few microns. However, the very long-term viability of chronically implanted microelectrodes and the capability of recording the same spiking activity over long time periods still remain to be established and confirmed in human studies. Here we review the main responses to acute implantation of microelectrode arrays, and emphasize that it will become essential to control the neural tissue damage induced by these intracortical microelectrodes in order to achieve the high clinical potentials accompanying this technology.

  8. HUMAN CALICIVIRUS OUTBREAK OF ACUTE GASTROENTERITIS IN AN AGED-CARE FACILITY

    Directory of Open Access Journals (Sweden)

    Iztok Štrumbelj

    2003-05-01

    Full Text Available Background. Human caliciviruses represent a genetically and antigenetically diverse group of single-stranded RNA viruses associated with acute gastroenteritis in humans. In last two years the number of notified gastroenteric cases in Slovenia is increasing. From January till November 2002 already 574 calicivirus cases have been confirmed. Majority of cases were observed in preschool and school children but no cases were described in the aged-care facility.Methods. An outbreak of gastroenteritis in an aged-care facility occured. After onset of the outbreak an epidemiological questionnaire and inspection of local conditions were realized. Stool samples from home residents were analysed to find out bacteriological and/or viral aetiology. Direct electron microscopy and RT-PCR assay was performed to detect caliciviruses. Viral RNA was amplified using specific primers and PCR products were identified in hybridisation test.Results. The outbreak started suddenly on the second floor, where the attack rate was the highest. On the other floors the illness started later and the attack rate was lower. Sixty-one (40,1% residents from 152 became ill and additionally 15 (22,4% employees from 67. The outbreak ended after ten days. Electron microscopy or/and RT-PCR revealed Norovirus members of family Caliciviridae in 9 of 10 stool specimens. As determined by RT-PCR and hybridisation assay viruses corresponded to genogroup II, genetic cluster 1 (closely related to the Hawaii virus and genetic cluster 4 (closely related to the Lordsdale virus.Conclusions. Presented data support a significant role for caliciviruses as causative agents of gastroenteritis in elderly persons in Slovenia.

  9. Mechanism of cigarette smoke condensate-induced acute inflammatory response in human bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Mohapatra Shyam S

    2002-07-01

    Full Text Available Abstract Background To demonstrate the involvement of tobacco smoking in the pathophysiology of lung disease, the responses of pulmonary epithelial cells to cigarette smoke condensate (CSC — the particulate fraction of tobacco smoke — were examined. Methods The human alveolar epithelial cell line A549 and normal human bronchial epithelial cells (NHBEs were exposed to 0.4 μg/ml CSC, a concentration that resulted in >90% cell survival and Results NHBEs exposed to CSC showed increased expression of the inflammatory mediators sICAM-1, IL-1β, IL-8 and GM-CSF, as determined by RT-PCR. CSC-induced IL-1β expression was reduced by PD98059, a blocker of mitogen-actived protein kinase (MAPK kinase (MEK, and by PDTC, a NFκB inhibitor. Analysis of intracellular signaling pathways, using antibodies specific for phosphorylated MAPKs (extracellular signal-regulated kinase [ERK]-1/2, demonstrated an increased level of phosphorylated ERK1/2 with increasing CSC concentration. Nuclear localization of phosphorylated ERK1/2 was seen within 30 min of CSC exposure and was inhibited by PD98059. Increased phosphorylation and nuclear translocation of IκB was also seen after CSC exposure. A549 cells transfected with a luciferase reporter plasmid containing a NFκB-inducible promoter sequence and exposed to CSC (0.4 μg/ml or TNF-α (50 ng/ml had an increased reporter activity of approximately 2-fold for CSC and 3.5-fold for TNF-α relative to untreated controls. Conclusion The acute phase response of NHBEs to cigarette smoke involves activation of both MAPK and NFκB.

  10. Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice

    Directory of Open Access Journals (Sweden)

    Shanzheng Lu

    2016-10-01

    Full Text Available Abstract Background The endometrial regenerative cell (ERC is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4–induced acute liver injury (ALI. Methods An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4. Transplanted ERCs were intravenously injected (1 million/mouse into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl4 induction. Results ERC treatment effectively decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT and aspartate aminotransferase (AST activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA was increased after ERC treatment. Furthermore, the frequency of CD4+ and CD8+ T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4+CD25+FOXP3+ regulatory T cells (Tregs was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1β, IL-6, and TNF-α but higher level of IL-10 in both serum and liver. Conclusions Human ERCs protect the liver from acute injury

  11. Absence of acute ocular damage in humans after prolonged exposure to intense RF EMF

    Science.gov (United States)

    Adibzadeh, F.; van Rhoon, G. C.; Verduijn, G. M.; Naus-Postema, N. C.; Paulides, M. M.

    2016-01-01

    The eye is considered to be a critical organ when determining safety standards for radio frequency (RF) radiation. Experimental data obtained using animals showed that RF heating of the eye, particularly over a specific threshold, can induce cataracts. During the treatment of cancer in the head and neck by hyperthermia, the eyes receive a considerable dose of RF radiation due to stray radiation from the prolonged (60 min) and intense exposure at 434 MHz of this region. In the current study, we verified the exposure guidelines for humans by determining the association between the electromagnetic and thermal dose in the eyes with the reported ocular effects. We performed a simulation study to retrospectively assess the specific absorption rate (SAR) and temperature increase in the eyes of 16 selected patients (encompassing a total of 74 treatment sessions) whose treatment involved high power delivery as well as a minimal distance between the tumor site and the eye. Our results show that the basic restrictions on the peak 10 g spatial-averaged SAR (10 W kg-1) and peak tissue temperature increase (1 °C) are exceeded by up to 10.4 and 4.6 times, on average, and by at least 6.2 and 1.8 times when considering the lower limit of the 95% confidence interval. Evaluation of the acute effects according to patients’ feedback (all patients), the common toxicity criteria scores (all patients) and an ophthalmology investigation (one patient with the highest exposure) revealed no indication of any serious acute ocular effect, even though the eyes were exposed to high electromagnetic fields, leading to a high thermal dose. We also found that, although there is a strong correlation (R 2  =  0.88) between the predicted induced SAR and temperature in the eye, there are large uncertainties regarding the temperature-SAR relationship. Given this large uncertainty (129%) compared with the uncertainty of 3D temperature simulations (61%), we recommend using temperature

  12. Acute and Non-acute Effects of Cannabis on Human Memory Function: A Critical Review of Neuroimaging Studies

    NARCIS (Netherlands)

    Bossong, M.G.; Jager, G.; Bhattacharyya, S.; Allen, P.

    2014-01-01

    Smoking cannabis produces a diverse range of effects, including impairments in learning and memory. These effects are exerted through action on the endocannabinoid system, which suggests involvement of this system in human cognition. Learning and memory deficits are core symptoms of psychiatric and

  13. Acute hypoxia and cytochrome P450-mediated hepatic drug metabolism in humans

    DEFF Research Database (Denmark)

    Jürgens, Gesche; Christensen, Hanne Rolighed; Brøsen, Kim

    2002-01-01

    Our objective was to investigate the effect of acute hypoxia on the activity of hepatic cytochrome P450 (CYP) enzymes.......Our objective was to investigate the effect of acute hypoxia on the activity of hepatic cytochrome P450 (CYP) enzymes....

  14. A novel RT-multiplex PCR for detection of Aichi virus, human parechovirus, enteroviruses, and human bocavirus among infants and children with acute gastroenteritis.

    Science.gov (United States)

    Pham, Ngan Thi Kim; Trinh, Quang Duy; Chan-It, Wisoot; Khamrin, Pattara; Shimizu, Hideaki; Okitsu, Shoko; Mizuguchi, Masashi; Ushijima, Hiroshi

    2010-10-01

    A novel reverse transcription-multiplex polymerase chain reaction assay was developed to detect Aichi virus, human parechovirus, enteroviruses, and human bocavirus. A mixture of four pairs of published specific primers, 6261 and 6779, ev22(+) and ev22(-), F1 and R1, 188F and 542R, was used to amplify the viral genomes and specifically generate four different amplicon sizes of 519, 270, 440, and 354 bp for Aichi virus, human parechovirus, enteroviruses, and human bocavirus, respectively. A total of 247 fecal specimens previously screened for rotavirus, adenovirus, norovirus, sapovirus, and astrovirus-negative, collected from infants and children with acute gastroenteritis in Japan from July 2007 to June 2008, were tested further for the presence of the four viruses, Aichi virus, human parechovirus, enteroviruses, and human bocavirus, by RT-multiplex PCR. The total detection rate of these viruses was 26.7% (66 out of 247 samples). Of these, HPeV, EVs, and HBoV were identified in 20, 41, and 5 specimens. No Aichi virus was found among these subjects. The sensitivity and specificity of RT-multiplex PCR were assessed and demonstrated a strong validation against RT-monoplex PCR. This is the first report of detecting these types of viruses in fecal samples from infants and children with acute gastroenteritis by RT-multiplex PCR. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  15. Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in Mice

    OpenAIRE

    Toyohara, Takafumi; Mae, Shin-Ichi; Sueta, Shin-Ichi; Inoue, Tatsuyuki; Yamagishi, Yukiko; Kawamoto, Tatsuya; Kasahara, Tomoko; Hoshina, Azusa; Toyoda, Taro; Tanaka, Hiromi; Araoka, Toshikazu; Sato-Otsubo, Aiko; Takahashi, Kazutoshi; Sato, Yasunori; Yamaji, Noboru

    2015-01-01

    Acute kidney injury (AKI) is defined as a rapid loss of renal function resulting from various etiologies, with a mortality rate exceeding 60% among intensive care patients. Because conventional treatments have failed to alleviate this condition, the development of regenerative therapies using human induced pluripotent stem cells (hiPSCs) presents a promising new therapeutic option for AKI. We describe our methodology for generating renal progenitors from hiPSCs that show potential in ameliora...

  16. Downregulation but lack of promoter hypermethylation or somatic mutations of the potential tumor suppressor CXXC5 in MDS and AML with deletion 5q

    DEFF Research Database (Denmark)

    Treppendahl, Marianne Bach; Möllgård, L; Hellström-Lindberg, E

    2013-01-01

    During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells, identify......During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells...

  17. Acute Stress Alters Auditory Selective Attention in Humans Independent of HPA: A Study of Evoked Potentials

    Science.gov (United States)

    Elling, Ludger; Steinberg, Christian; Bröckelmann, Ann-Kathrin; Dobel, Christan; Bölte, Jens; Junghofer, Markus

    2011-01-01

    Background Acute stress is a stereotypical, but multimodal response to a present or imminent challenge overcharging an organism. Among the different branches of this multimodal response, the consequences of glucocorticoid secretion have been extensively investigated, mostly in connection with long-term memory (LTM). However, stress responses comprise other endocrine signaling and altered neuronal activity wholly independent of pituitary regulation. To date, knowledge of the impact of such “paracorticoidal” stress responses on higher cognitive functions is scarce. We investigated the impact of an ecological stressor on the ability to direct selective attention using event-related potentials in humans. Based on research in rodents, we assumed that a stress-induced imbalance of catecholaminergic transmission would impair this ability. Methodology/Principal Findings The stressor consisted of a single cold pressor test. Auditory negative difference (Nd) and mismatch negativity (MMN) were recorded in a tonal dichotic listening task. A time series of such tasks confirmed an increased distractibility occuring 4–7 minutes after onset of the stressor as reflected by an attenuated Nd. Salivary cortisol began to rise 8–11 minutes after onset when no further modulations in the event-related potentials (ERP) occurred, thus precluding a causal relationship. This effect may be attributed to a stress-induced activation of mesofrontal dopaminergic projections. It may also be attributed to an activation of noradrenergic projections. Known characteristics of the modulation of ERP by different stress-related ligands were used for further disambiguation of causality. The conjuncture of an attenuated Nd and an increased MMN might be interpreted as indicating a dopaminergic influence. The selective effect on the late portion of the Nd provides another tentative clue for this. Conclusions/Significance Prior studies have deliberately tracked the adrenocortical influence on cognition

  18. BEC, a Novel Enterotoxin of Clostridium perfringens Found in Human Clinical Isolates from Acute Gastroenteritis Outbreaks

    Science.gov (United States)

    Yonogi, Shinya; Matsuda, Shigeaki; Kawai, Takao; Yoda, Tomoko; Harada, Tetsuya; Kumeda, Yuko; Gotoh, Kazuyoshi; Hiyoshi, Hirotaka; Nakamura, Shota; Kodama, Toshio

    2014-01-01

    Clostridium perfringens is a causative agent of food-borne gastroenteritis for which C. perfringens enterotoxin (CPE) has been considered an essential factor. Recently, we experienced two outbreaks of food-borne gastroenteritis in which non-CPE producers of C. perfringens were strongly suspected to be the cause. Here, we report a novel enterotoxin produced by C. perfringens isolates, BEC (binary enterotoxin of C. perfringens). Culture supernatants of the C. perfringens strains showed fluid-accumulating activity in rabbit ileal loop and suckling mouse assays. Purification of the enterotoxic substance in the supernatants and high-throughput sequencing of genomic DNA of the strains revealed BEC, composed of BECa and BECb. BECa and BECb displayed limited amino acid sequence similarity to other binary toxin family members, such as the C. perfringens iota toxin. The becAB genes were located on 54.5-kb pCP13-like plasmids. Recombinant BECb (rBECb) alone had fluid-accumulating activity in the suckling mouse assay. Although rBECa alone did not show enterotoxic activity, rBECa enhanced the enterotoxicity of rBECb when simultaneously administered in suckling mice. The entertoxicity of the mutant in which the becB gene was disrupted was dramatically decreased compared to that of the parental strain. rBECa showed an ADP-ribosylating activity on purified actin. Although we have not directly evaluated whether BECb delivers BECa into cells, rounding of Vero cells occurred only when cells were treated with both rBECa and rBECb. These results suggest that BEC is a novel enterotoxin of C. perfringens distinct from CPE, and that BEC-producing C. perfringens strains can be causative agents of acute gastroenteritis in humans. Additionally, the presence of becAB on nearly identical plasmids in distinct lineages of C. perfringens isolates suggests the involvement of horizontal gene transfer in the acquisition of the toxin genes. PMID:24664508

  19. Effects of acute methamphetamine on emotional memory formation in humans: encoding vs consolidation.

    Science.gov (United States)

    Ballard, Michael E; Weafer, Jessica; Gallo, David A; de Wit, Harriet

    2015-01-01

    Understanding how stimulant drugs affect memory is important for understanding their addictive potential. Here we examined the effects of acute d-methamphetamine (METH), administered either before (encoding phase) or immediately after (consolidation phase) study on memory for emotional and neutral images in healthy humans. Young adult volunteers (N = 60) were randomly assigned to either an encoding group (N = 29) or a consolidation group (N = 31). Across three experimental sessions, they received placebo and two doses of METH (10, 20 mg) either 45 min before (encoding) or immediately after (consolidation) viewing pictures of emotionally positive, neutral, and negative scenes. Memory for the pictures was tested two days later, under drug-free conditions. Half of the sample reported sleep disturbances following the high dose of METH, which affected their memory performance. Therefore, participants were classified as poor sleepers (less than 6 hours; n = 29) or adequate sleepers (6 or more hours; n = 31) prior to analyses. For adequate sleepers, METH (20 mg) administered before encoding significantly improved memory accuracy relative to placebo, especially for emotional (positive and negative), compared to neutral, stimuli. For poor sleepers in the encoding group, METH impaired memory. METH did not affect memory in the consolidation group regardless of sleep quality. These results extend previous findings showing that METH can enhance memory for salient emotional stimuli but only if it is present at the time of study, where it can affect both encoding and consolidation. METH does not appear to facilitate consolidation if administered after encoding. The study also demonstrates the important role of sleep in memory studies.

  20. Effects of acute methamphetamine on emotional memory formation in humans: encoding vs consolidation.

    Directory of Open Access Journals (Sweden)

    Michael E Ballard

    Full Text Available Understanding how stimulant drugs affect memory is important for understanding their addictive potential. Here we examined the effects of acute d-methamphetamine (METH, administered either before (encoding phase or immediately after (consolidation phase study on memory for emotional and neutral images in healthy humans. Young adult volunteers (N = 60 were randomly assigned to either an encoding group (N = 29 or a consolidation group (N = 31. Across three experimental sessions, they received placebo and two doses of METH (10, 20 mg either 45 min before (encoding or immediately after (consolidation viewing pictures of emotionally positive, neutral, and negative scenes. Memory for the pictures was tested two days later, under drug-free conditions. Half of the sample reported sleep disturbances following the high dose of METH, which affected their memory performance. Therefore, participants were classified as poor sleepers (less than 6 hours; n = 29 or adequate sleepers (6 or more hours; n = 31 prior to analyses. For adequate sleepers, METH (20 mg administered before encoding significantly improved memory accuracy relative to placebo, especially for emotional (positive and negative, compared to neutral, stimuli. For poor sleepers in the encoding group, METH impaired memory. METH did not affect memory in the consolidation group regardless of sleep quality. These results extend previous findings showing that METH can enhance memory for salient emotional stimuli but only if it is present at the time of study, where it can affect both encoding and consolidation. METH does not appear to facilitate consolidation if administered after encoding. The study also demonstrates the important role of sleep in memory studies.

  1. Effects of Acute Methamphetamine on Emotional Memory Formation in Humans: Encoding vs Consolidation

    Science.gov (United States)

    Ballard, Michael E.; Weafer, Jessica; Gallo, David A.; de Wit, Harriet

    2015-01-01

    Understanding how stimulant drugs affect memory is important for understanding their addictive potential. Here we examined the effects of acute d-methamphetamine (METH), administered either before (encoding phase) or immediately after (consolidation phase) study on memory for emotional and neutral images in healthy humans. Young adult volunteers (N = 60) were randomly assigned to either an encoding group (N = 29) or a consolidation group (N = 31). Across three experimental sessions, they received placebo and two doses of METH (10, 20 mg) either 45 min before (encoding) or immediately after (consolidation) viewing pictures of emotionally positive, neutral, and negative scenes. Memory for the pictures was tested two days later, under drug-free conditions. Half of the sample reported sleep disturbances following the high dose of METH, which affected their memory performance. Therefore, participants were classified as poor sleepers (less than 6 hours; n = 29) or adequate sleepers (6 or more hours; n = 31) prior to analyses. For adequate sleepers, METH (20 mg) administered before encoding significantly improved memory accuracy relative to placebo, especially for emotional (positive and negative), compared to neutral, stimuli. For poor sleepers in the encoding group, METH impaired memory. METH did not affect memory in the consolidation group regardless of sleep quality. These results extend previous findings showing that METH can enhance memory for salient emotional stimuli but only if it is present at the time of study, where it can affect both encoding and consolidation. METH does not appear to facilitate consolidation if administered after encoding. The study also demonstrates the important role of sleep in memory studies. PMID:25679982

  2. Prevalence of human metapneumovirus in adults with acute respiratory tract infection in Beijing, China.

    Science.gov (United States)

    Li, Jianguo; Wang, Zhong; Gonzalez, Richard; Xiao, Yan; Zhou, Hongli; Zhang, Jing; Paranhos-Baccala, Glaucia; Vernet, Guy; Jin, Qi; Wang, Jianwei; Hung, Tao

    2012-01-01

    To evaluate the prevalence and clinical manifestations of human metapneumovirus (hMPV) in immunocompetent Chinese adults with acute respiratory tract infections (ARTIs). A reverse transcription PCR (RT-PCR) assay targeting the P gene was developed in this study and used to detect hMPV in nasal and throat swabs collected from 2936 immunocompetent adult patients with ARTIs in Beijing, China between July 2008 and June 2010. Among the 2936 patients studied, 49 (1.7%) were positive for hMPV, of whom 14 (28.6%) were positive for hMPV_A2b, 19 (38.8%) for hMPV_B1, and 16 (32.6%) for hMPV_B2. hMPV_A1 was not detected. An average detection rate of 6.6% was observed in the peak months of the two epidemic seasons studied. The hMPV prevalence was higher in the sampled elderly (>65 years, 3.2%) than in middle aged adults (25-65 years; 2.0%) and teenagers (14-25 years; 0.9%). During the study period, hMPV infections showed a biennial rhythm of seasonality, peaking from November to March in 2008/09 and from March to June in 2010. hMPV infection plays an important role in immunocompetent adults in its epidemic season. The demographic and clinical data presented in this study improves our understanding of the pathogenesis and clinical burden of hMPV infection in adults. Copyright © 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  3. Human bocavirus infection as a cause of severe acute respiratory tract infection in children.

    Science.gov (United States)

    Moesker, F M; van Kampen, J J A; van der Eijk, A A; van Rossum, A M C; de Hoog, M; Schutten, M; Smits, S L; Bodewes, R; Osterhaus, A D M E; Fraaij, P L A

    2015-10-01

    In 2005 human bocavirus (HBoV) was discovered in respiratory tract samples of children. The role of HBoV as the single causative agent for respiratory tract infections remains unclear. Detection of HBoV in children with respiratory disease is frequently in combination with other viruses or bacteria. We set up an algorithm to study whether HBoV alone can cause severe acute respiratory tract infection (SARI) in children. The algorithm was developed to exclude cases with no other likely cause than HBoV for the need for admission to the paediatric intensive care unit (PICU) with SARI. We searched for other viruses by next-generation sequencing (NGS) in these cases and studied their HBoV viral loads. To benchmark our algorithm, the same was applied to respiratory syncytial virus (RSV)-positive patients. From our total group of 990 patients who tested positive for a respiratory virus by means of RT-PCR, HBoV and RSV were detected in 178 and 366 children admitted to our hospital. Forty-nine HBoV-positive patients and 72 RSV-positive patients were admitted to the PICU. We found seven single HBoV-infected cases with SARI admitted to PICU (7/49, 14%). They had no other detectable virus by NGS. They had much higher HBoV loads than other patients positive for HBoV. We identified 14 RSV-infected SARI patients with a single RSV infection (14/72, 19%). We conclude that our study provides strong support that HBoV can cause SARI in children in the absence of viral and bacterial co-infections. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  4. Genetic characterization of human bocavirus among children with severe acute respiratory infection in China.

    Science.gov (United States)

    Wang, Yanqun; Li, Yamin; Liu, Jun; Zhao, Yanjie; Xie, Zhengde; Shen, Jun; Tan, Wenjie

    2016-08-01

    To investigate the genetic character of Human bocavirus (HBoV) among children with severe acute respiratory infection (SARI) in China. We screened 993 respiratory samples for HBoV by PCR among hospitalized children with SARI between September 2007 and March 2014. Four of HBoV1 samples were selected for complete genomes analysis by next-generation sequencing. The results show that 200 (20.1%) out of 993 samples were HBoV-positive, most of these HBoV belong to HBoV1 subtype (n = 197), HBoV2 (n = 1) and HBoV3 (n = 2) were also detected. Fifty (5.04%) of 993 SARI patient were detected as HBoV-positive only. Four HBoV1 genomes in this study were conserved and showed no significant difference among the nucleotide diversity from different regions. Analyses of evolutionary rates showed that NS1 exhibited the highest degree of conservation while the VP1 gene exhibited the fastest rate of evolution at 4.20 × 10(-4) substitutions/site/year. The nucleotide deletions and substitutions occurred in NP1 and VP1 represented novel molecular signatures enabling subtype differentiation between HBoVs. We described some new characteristics in the epidemiology of HBoV among children with SARI, these data will significantly expand the current knowledge of HBoV epidemic and genomic characterization among children with SARI. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  5. Human respiratory syncytial virus and metapneumovirus in patients with acute respiratory infection in Colombia, 2000 - 2011.

    Science.gov (United States)

    Barbosa Ramirez, Juliana; Pulido Dominguez, Paola; Rey Benito, Gloria; Mendez Rico, Jairo; Castellanos, Jaime; Páez Martinez, Andrés

    2014-08-01

    To describe the epidemiology of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) in Colombia from 2000 - 2011, including seasonal trends. Nasopharyngeal aspirates and/or throat swabs from 14 870 patients with acute respiratory infections (ARI) were studied. Two subgroups were analyzed using molecular biology techniques. The first consisted of 264 RSV indirect fluorescence assay (IFA)-positive samples, the second of 264 RSV IFA-negative samples. RSV and hMPV were detected using reverse transcription polymerase chain reaction (RT-PCR). 2 799 samples (18.8%) contained a respiratory virus. RSV was detected by IFA in 1 333 samples (8.9%). RSV was detected by RT-PCR in 192 samples from the RSV IFA-positive subgroup and in 25 samples from the RSV IFA-negative subgroup. hMPV was detected in eight samples from the RSV IFA-positive subgroup and in 11 samples from the RSV IFA-negative subgroup. Among the RSV infections, subtype A was dominant in two-year intervals, subtype B was dominant in one-year intervals. 85.3% of RSV and 74% of hMPV infections occurred in children younger than 5 years old. RSV and hMPV infections were associated with rainy seasons. Co-infection with RSV A and RSV B was detected in two patients. Five cases of co-infection with RSV and hMPV were detected. This report is the first to examine the epidemiology of ARIs in Colombia, with an emphasis on RSV and hMPV. The samples studied here were obtained over a 12-year period and represent all age groups and both genders.

  6. Duodenal fatty acid sensor and transporter expression following acute fat exposure in healthy lean humans.

    Science.gov (United States)

    Cvijanovic, Nada; Isaacs, Nicole J; Rayner, Christopher K; Feinle-Bisset, Christine; Young, Richard L; Little, Tanya J

    2017-04-01

    Free fatty acids (FFAs) and their derivatives are detected by G-protein coupled receptors (GPRs) on enteroendocrine cells, with specific transporters on enterocytes. It is unknown whether acute fat exposure affects FFA sensors/transporters, and whether this relates to hormone secretion and habitual fat intake. We studied 20 healthy participants (10M, 10F; BMI: 22 ± 1 kg/m 2 ; age: 28 ± 2 years), after an overnight fast, on 2 separate days. On the first day, duodenal biopsies were collected endoscopically before, and after, a 30-min intraduodenal (ID) infusion of 10% Intralipid ® , and relative transcript expression of FFA receptor 1 (FFAR1), FFA receptor 4 (FFAR4), GPR119 and the FFA transporter, cluster of differentiation-36 (CD36) was quantified from biopsies. On the second day, ID Intralipid ® was infused for 120-min, and plasma concentrations of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) evaluated. Habitual dietary intake was assessed using food frequency questionnaires (FFQs). ID Intralipid ® increased expression of GPR119, but not FFAR1, FFAR4 and CD36, and stimulated CCK and GLP-1 secretion. Habitual polyunsaturated fatty acid (PUFA) consumption was negatively associated with basal GPR119 expression. GPR119 is an early transcriptional responder to duodenal lipid in lean humans, although this response appeared reduced in individuals with high PUFA intake. These observations may have implications for downstream regulation of gut hormone secretion and appetite. This study was registered as a clinical trial with the Australia and New Zealand Clinical Trial Registry (Trial number: ACTRN12612000376842). Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  7. Renal kallikrein excretion and epigenetics in human acute kidney injury: Expression, mechanisms and consequences

    Directory of Open Access Journals (Sweden)

    Tolwani Ashita

    2011-06-01

    Full Text Available Abstract Background Renal kallikrein (KLK1 synthesis and urinary excretion are reportedly diminished during AKI (acute kidney injury in animal models, and provision of kallikrein abrogates renal injury in this setting, but data in human AKI is limited. Therefore we first examined KLK1 renal excretion in human AKI, and then probed potential endocrine and epigenetic mechanisms for its alterations. Methods KLK1 enzymatic activity excretion was evaluated in urine from patients with established or incipient AKI, versus healthy/non-hospital as well as ICU controls. Endocrine control of KLK1 excretion was then probed by catecholamine and aldosterone measurements in established AKI versus healthy controls. To examine epigenetic control of KLK1 synthesis, we tested blood and urine DNA for changes in promoter CpG methylation of the KLK1 gene, as well as LINE-1 elements, by bisulfite sequencing. Results Patients with early/incipient AKI displayed a modest reduction of KLK1 excretion, but unexpectedly, established AKI displayed substantially elevated urine KLK1 excretion, ~11-fold higher than healthy controls, and ~3-fold greater than ICU controls. We then probed potential mechanisms of the change. Established AKI patients had lower SBP, higher heart rate, and higher epinephrine excretion than healthy controls, though aldosterone excretion was not different. Promoter KLK1 CpG methylation was higher in blood than urine DNA, while KLK1 methylation in blood DNA was significantly higher in established AKI than healthy controls, though KLK1 methylation in urine tended to be higher in AKI, directionally consistent with earlier/incipient but not later/established changes in KLK1 excretion in AKI. On multivariate ANOVA, AKI displayed coordinate changes in KLK1 excretion and promoter methylation, though directionally opposite to expectation. Control (LINE-1 repetitive element methylation in blood and urine DNA was similar between AKI and controls. Conclusions

  8. Inducing Acute Traumatic Coagulopathy In Vitro: The Effects of Activated Protein C on Healthy Human Whole Blood.

    Directory of Open Access Journals (Sweden)

    Benjamin M Howard

    Full Text Available Acute traumatic coagulopathy has been associated with shock and tissue injury, and may be mediated via activation of the protein C pathway. Patients with acute traumatic coagulopathy have prolonged PT and PTT, and decreased activity of factors V and VIII; they are also hypocoagulable by thromboelastometry (ROTEM and other viscoelastic assays. To test the etiology of this phenomenon, we hypothesized that such coagulopathy could be induced in vitro in healthy human blood with the addition of activated protein C (aPC.Whole blood was collected from 20 healthy human subjects, and was "spiked" with increasing concentrations of purified human aPC (control, 75, 300, 2000 ng/mL. PT/PTT, factor activity assays, and ROTEM were performed on each sample. Mixed effect regression modeling was performed to assess the association of aPC concentration with PT/PTT, factor activity, and ROTEM parameters.In all subjects, increasing concentrations of aPC produced ROTEM tracings consistent with traumatic coagulopathy. ROTEM EXTEM parameters differed significantly by aPC concentration, with stepwise prolongation of clotting time (CT and clot formation time (CFT, decreased alpha angle (α, impaired early clot formation (a10 and a20, and reduced maximum clot firmness (MCF. PT and PTT were significantly prolonged at higher aPC concentrations, with corresponding significant decreases in factor V and VIII activity.A phenotype of acute traumatic coagulopathy can be induced in healthy blood by the in vitro addition of aPC alone, as evidenced by viscoelastic measures and confirmed by conventional coagulation assays and factor activity. This may lend further mechanistic insight to the etiology of coagulation abnormalities in trauma, supporting the central role of the protein C pathway. Our findings also represent a model for future investigations in the diagnosis and treatment of acute traumatic coagulopathy.

  9. Etiology of acute conjunctivitis due to coxsackievirus A24 variant, human adenovirus, herpes simplex virus, and Chlamydia in Beijing, China.

    Science.gov (United States)

    Li, Jie; Yang, Yongsheng; Lin, Changying; Li, Weihong; Yang, Yang; Zhang, Yong; Jia, Lei; Li, Xitai; Chen, Lijuan; Wang, Quanyi

    2014-01-01

    Acute conjunctivitis is a common disease associated with high morbidity and economic burden. To clarify the etiological characteristics of acute conjunctivitis in Beijing, surveillance of acute conjunctivitis was conducted from July to October during 2007-2012 by collecting eye swabs from patients treated at surveillance hospitals affiliated with a surveillance program of 18 districts Center for Disease Prevention and Control in Beijing. Coxsackievirus A24 variant (CA24v), enterovirus 70 (EV70), human adenovirus (HAdV), herpes simplex virus (HSV), and chlamydia were identified by PCR. Phylogenetic analysis of the VP1 region of CA24v was conducted. Comparisons of proportions and statistical significance were performed using the chi-square test. HAdV was found to be the most prevalent pathogen, followed by CA24v, chlamydia, and HSV. Significant differences in the symptoms of ocular pain, photophobia, and epiphora were identified among the 4 agents. The prevalence of HAdV- and CA24v-mediated conjunctivitis peaked in July or August and September or October, respectively. Nucleotide sequences of the VP1 regions among the isolated CA24v strains shared 92.8%-100% homology. In conclusion, HAdV followed by CA24v, chlamydia, and HSV were the most common causative agents of acute conjunctivitis in Beijing. Comprehensive, continuous surveillance and advanced laboratory techniques are needed for further studies.

  10. Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body Irradiation with Bone Marrow Sparing.

    Science.gov (United States)

    Cohen, Eric P; Hankey, Kim G; Bennett, Alexander W; Farese, Ann M; Parker, George A; MacVittie, Thomas J

    2017-12-01

    The development of medical countermeasures against acute and delayed multi-organ injury requires animal models predictive of the human response to radiation and its treatment. Late chronic injury is a well-known feature of radiation nephropathy, but acute kidney injury has not been reported in an appropriate animal model. We have established a single-fraction partial-body irradiation model with minimal marrow sparing in non-human primates. Subject-based medical management was used including parenteral fluids according to prospective morbidity criteria. We show herein that 10 or 11 Gy exposures caused both acute and chronic kidney injury. Acute and chronic kidney injury appear to be dose-independent between 10 and 11 Gy. Acute kidney injury was identified during the first 50 days postirradiation and appeared to resolve before the occurrence of chronic kidney injury, which was progressively more severe up to 180 days postirradiation, which was the end of the study. These findings show that mitigation of the acute radiation syndrome by medical management will unmask delayed late effects that occur months after partial-body irradiation. They further emphasize that both acute and chronic changes in kidney function must be taken into account in the use and timing of mitigators and medical management for acute radiation syndrome and delayed effects of acute radiation exposure (DEARE).

  11. Proteomic analysis of human acute leukemia cells: insight into their classification.

    Science.gov (United States)

    Cui, Jiu-Wei; Wang, Jie; He, Kun; Jin, Bao-Feng; Wang, Hong-Xia; Li, Wei; Kang, Li-Hua; Hu, Mei-Ru; Li, Hui-Yan; Yu, Ming; Shen, Bei-Fen; Wang, Guan-Jun; Zhang, Xue-Min

    2004-10-15

    French-American-British (FAB) classification of acute leukemia with genetic heterogeneity is important for treatment and prognosis. However, the distinct protein profiles that contribute to the subtypes and facilitate molecular definition of acute leukemia classification are still unclear. The proteins of leukemic cells from 61 cases of acute leukemia characterized by FAB classification were separated by two-dimensional electrophoresis, and the differentially expressed protein spots were identified by both matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) and tandem electrospray ionization MS (ESI-MS/MS). The distinct protein profiles of acute leukemia FAB types or subtypes were successfully explored, including acute myeloid leukemia (AML), its subtypes (M2, M3, and M5) and acute lymphoid leukemia (ALL), which were homogeneous within substantial samples of the respective subgroups but clearly differed from all other subgroups. We found a group of proteins that were highly expressed in M2 and M3, rather than other subtypes. Among them, myeloid-related proteins 8 and 14 were first reported to mark AML differentiation and to differentiate AML from ALL. Heat shock 27 kDa protein 1 and other proteins that are highly expressed in ALL may play important roles in clinically distinguishing AML from ALL. Another set of proteins up-regulated was restricted to granulocytic lineage leukemia. High-level expression of NM23-H1 was found in all but the M3a subtype, with favorable prognosis. These data have implications in delineating the pathways of aberrant gene expression underlying the pathogenesis of acute leukemia and could facilitate molecular definition of FAB classification. The extension of the present analysis to currently less well-defined acute leukemias will identify additional subgroups.

  12. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

    Science.gov (United States)

    Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

    2011-11-01

    Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

  13. Pro-apoptotic activity of α-bisabolol in preclinical models of primary human acute leukemia cells

    Directory of Open Access Journals (Sweden)

    Fato Romana

    2011-04-01

    Full Text Available Abstract Background We previously demonstrated that the plant-derived agent α-bisabolol enters cells via lipid rafts, binds to the pro-apoptotic Bcl-2 family protein BID, and may induce apoptosis. Here we studied the activity of α-bisabolol in acute leukemia cells. Methods We tested ex vivo blasts from 42 acute leukemias (14 Philadelphia-negative and 14 Philadelphia-positive B acute lymphoid leukemias, Ph-/Ph+B-ALL; 14 acute myeloid leukemias, AML for their sensitivity to α-bisabolol in 24-hour dose-response assays. Concentrations and time were chosen based on CD34+, CD33+my and normal peripheral blood cell sensitivity to increasing α-bisabolol concentrations for up to 120 hours. Results A clustering analysis of the sensitivity over 24 hours identified three clusters. Cluster 1 (14 ± 5 μM α-bisabolol IC50 included mainly Ph-B-ALL cells. AML cells were split into cluster 2 and 3 (45 ± 7 and 65 ± 5 μM IC50. Ph+B-ALL cells were scattered, but mainly grouped into cluster 2. All leukemias, including 3 imatinib-resistant cases, were eventually responsive, but a subset of B-ALL cells was fairly sensitive to low α-bisabolol concentrations. α-bisabolol acted as a pro-apoptotic agent via a direct damage to mitochondrial integrity, which was responsible for the decrease in NADH-supported state 3 respiration and the disruption of the mitochondrial membrane potential. Conclusion Our study provides the first evidence that α-bisabolol is a pro-apoptotic agent for primary human acute leukemia cells.

  14. Effects of recombinant human brain natriuretic peptide on renal function in patients with acute heart failure following myocardial infarction.

    Science.gov (United States)

    Wang, Yanbo; Gu, Xinshun; Fan, Weize; Fan, Yanming; Li, Wei; Fu, Xianghua

    2016-01-01

    To investigate the effect of recombinant human brain natriuretic peptide (rhBNP) on renal function in patients with acute heart failure (AHF) following acute myocardial infarction (AMI). Consecutive patients with AHF following AMI were enrolled in this clinical trial. Eligible patients were randomly assigned to receive rhBNP (rhBNP group) or nitroglycerin (NIT group). Patients in the rhBNP group received rhBNP 0.15 μg /kg bolus injection after randomization followed by an adjusted-dose (0.0075-0.020 μg/kg/min) for 72 hours, while patients in NIT received infusion of nitroglycerin with an adjusted-dose (10-100 μg/kg/min) for 72 hours in NIT group. Standard clinical and laboratory data were collected. The levels of serum creatinine (SCr), urea, β-2 microglobulin and cystatin C were measured at baseline and repeated at the end of the 24, 48 and 72 hours after infusion. The primary end point was the incidence of acute renal dysfunction, which was defined as an increase in SCr > 0.5 mg/dl (> 44.2 μmol/L) or 25% above baseline SCr value. The occurrence of major adverse cardiac event (MACE) was followed up for 1 month. Of the 50 patients enrolled, 26 were randomly assigned to rhBNP and 24 to nitroglycerin (NIT). There were no significant differences in baseline characteristics between the two groups (all P > 0.05). The baseline concentrations of SCr, urea, β-2 microglobulin and cystatin C at admission were similar in the two groups. However, the concentrations of SCr and urea were significantly higher in rhBNP group than those in NIT group at hour 24 and 48 after treatments (all P acute renal dysfuntion in rhBNP group was higher (9/26 vs. 2/24, P = 0.040). The results of multiple logistic regression found that the use of rhBNP was an independent predictor of acute renal dysfunction in patients with AHF following AMI (OR, 0.162; 95% CI, 0.029 to 0.909; P = 0.039). the incidence of acute renal dysfuntion in rhBNP group was higher, and the use of rhBNP was an

  15. Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota

    Science.gov (United States)

    von Klitzing, Eliane; Ekmekciu, Ira; Kühl, Anja A.; Bereswill, Stefan

    2017-01-01

    Background Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction. Methodology/Principal findings Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum. Conclusion/Significance With respect to the intestinal

  16. Systemic administration of a novel human umbilical cord mesenchymal stem cells population accelerates the resolution of acute liver injury

    Directory of Open Access Journals (Sweden)

    Burra Patrizia

    2012-07-01

    Full Text Available Abstract Background Hepatocytes and stem cells transplantation may be an alternative to liver transplantation in acute or chronic liver disease. We aimed to evaluate the therapeutic potential of mesenchymal stem cells from human umbilical cord (UCMSCs, a readily available source of mesenchymal stem cells, in the CCl4-induced acute liver injury model. Methods Mesenchymal stem cells profile was analyzed by flow cytometry. In order to evaluate the capability of our UCMSCs to differentiate in hepatocytes, cells were seeded on three different supports, untreated plastic support, MatrigelTM and human liver acellular matrix. Cells were analyzed by immunocitochemistry for alpha-fetoprotein and albumin expression, qPCR for hepatocyte markers gene expression, Periodic Acid-Schiff staining for glycogen storage, ELISA for albumin detection and colorimetric assay for urea secretion. To assess the effects of undifferentiated UCMSCs in hepatic regeneration after an acute liver injury, we transplanted them via tail vein in mice injected intraperitoneally with a single dose of CCl4. Livers were analyzed by histological evaluation for damage quantification, immunostaining for Kupffer and stellate cells/liver myofibroblasts activation and for UCMSCs homing. Pro- and anti-inflammatory cytokines gene expression was evaluated by qPCR analysis and antioxidant enzyme activity was measured by catalase quantification. Data were analyzed by Mann–Whitney U-test, Kruskal-Wallis test and Cuzick’s test followed by Bonferroni correction for multiple comparisons. Results We have standardized the isolation procedure to obtain a cell population with hepatogenic properties prior to in vivo transplantation. When subjected to hepatogenic differentiation on untreated plastic support, UCMSCs differentiated in hepatocyte-like cells as demonstrated by their morphology, progressive up-regulation of mature hepatocyte markers, glycogen storage, albumin and urea secretion. However

  17. Erythropoietin receptor in human skeletal muscle and the effects of acute and long-term injections with recombinant human erythropoietin on the skeletal muscle

    DEFF Research Database (Denmark)

    Lundby, Carsten; Hellsten, Ylva; Jensen, Mie B. F.

    2008-01-01

    The presence and potential physiological role of the erythropoietin receptor (Epo-R) were examined in human skeletal muscle. In this study we demonstrate that Epo-R is present in the endothelium, smooth muscle cells, and in fractions of the sarcolemma of skeletal muscle fibers. To study...... the potential effects of Epo in human skeletal muscle, two separate studies were conducted: one to study the acute effects of a single Epo injection on skeletal muscle gene expression and plasma hormones and another to study the effects of long-term (14 wk) Epo treatment on skeletal muscle structure. Subjects....... In conclusion, the Epo-R is present in the vasculature and myocytes in human skeletal muscle, suggesting a role in both cell types. In accordance, a single injection of Epo regulates myoglobin, MRF-4, and transferrin receptor mRNA levels. However, in contrast to our hypothesis, prolonged Epo administration had...

  18. Effect of acute hypobaric hypoxia on the endothelial glycocalyx and digital reactive hyperemia in humans

    DEFF Research Database (Denmark)

    Johansson, Pär I; Bergström, Anita; Aachmann-Andersen, Niels Jacob

    2014-01-01

    INTRODUCTION: Hypoxia is associated with increased capillary permeability. This study tested whether acute hypobaric hypoxia involves degradation of the endothelial glycocalyx. METHODS: We exposed 12 subjects to acute hypobaric hypoxia (equivalent to 4500 m for 2-4 h) and measured venous blood....../nitrate decreased from 23 (18-27) μM at baseline to 19 (14-24) μM and 18 (14-21) μM in hypoxia and recovery, respectively (p pre-occlusion ratio (reactive hyperemia index, RHI) decreased from 1.80 (1.52-2.07) in normoxia to 1.62 (1.28-1.96) after 2...

  19. The acute phase protein Serum Amyloid A induces lipolysis and inflammation in human adipocytes through distinct pathways.

    Directory of Open Access Journals (Sweden)

    Aurélie Faty

    Full Text Available BACKGROUND: The acute phase response (APR is characterized by alterations in lipid and glucose metabolism leading to an increased delivery of energy substrates. In adipocytes, there is a coordinated decrease in Free Fatty acids (FFAs and glucose storage, in addition to an increase in FFAs mobilization. Serum Amyloid A (SAA is an acute phase protein mainly associated with High Density Lipoproteins (HDL. We hypothesized that enrichment of HDL with SAA, during the APR, could be implicated in the metabolic changes occurring in adipocytes. METHODOLOGY/PRINCIPAL FINDINGS: In vitro differentiated human adipocytes (hMADS were treated with SAA enriched HDL or recombinant SAA and the metabolic phenotype of the cells analyzed. In hMADS, SAA induces an increased lipolysis through an ERK dependent pathway. At the molecular level, SAA represses PPARγ2, C/EBPα and SREBP-1c gene expression, three transcription factors involved in adipocyte differentiation or lipid synthesis. In addition, the activation of the NF-κB pathway by SAA leads to the induction of pro-inflammatory cytokines and chemokines, as in the case of immune cells. These latter findings were replicated in freshly isolated mature human adipocytes. CONCLUSIONS/SIGNIFICANCE: Besides its well-characterized role in cholesterol metabolism, SAA has direct metabolic effects on human adipocytes. These metabolic changes could be at least partly responsible for alterations of adipocyte metabolism observed during the APR as well as during pathophysiological conditions such as obesity and conditions leading to insulin resistant states.

  20. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

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    Xiaolin He

    Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  1. Genetic diversity and clinical impact of human rhinoviruses in hospitalized and outpatient children with acute respiratory infection, Argentina.

    Science.gov (United States)

    Marcone, Débora Natalia; Culasso, Andrés; Carballal, Guadalupe; Campos, Rodolfo; Echavarría, Marcela

    2014-12-01

    Human rhinoviruses (HRV) are recognized as a cause of upper and lower acute respiratory infections (ARI). The circulating species and their clinical impact were not described in Argentina. To describe the molecular epidemiology of HRV in children and to determine the association of HRV species with outcome and severity. Hospitalized and outpatients children infections. This study highlights the clinical impact of HRV in children without comorbidities as a cause of lower ARI and hospitalization. The high frequency of HRV infections may be associated with the simultaneous circulation of genotypes and their high turnover rate. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. The hairless guinea-pig as a model for treatment of acute irritation in humans

    DEFF Research Database (Denmark)

    Andersen, F; Hedegaard, K; Fullerton, A

    2006-01-01

    % isopropyl palmitate (IPP cream), 10% glycerol (glycerol cream), 19.5% canola oil (canola oil cream) or 0.5% (-)-alpha-bisabolol (bisabolol cream). METHODS: Acute irritation was induced by occlusive tests with 1% sodium lauryl sulfate aq. in both HLGP and HV, and in HV also by using nonanoic acid in n...

  3. Local production of interleukin-6 during acute rejection in human renal allografts

    NARCIS (Netherlands)

    Raasveld, M. H.; Weening, J. J.; Kerst, J. M.; Surachno, S.; ten Berge, R. J.

    1993-01-01

    Interleukin-6 is involved in T-cell activation and possibly plays a role in the pathogenesis of acute rejection of transplanted organs. This is indicated by elevated levels of interleukin-6 in serum and urine of renal allograft recipients, and elevated amounts of mRNA for interleukin-6 in all

  4. Effect of acute metabolic acid/base shifts on the human airway calibre.

    NARCIS (Netherlands)

    Brijker, F.; Elshout, F.J.J. van den; Heijdra, Y.F.; Bosch, F.H.; Folgering, H.T.M.

    2001-01-01

    Acute metabolic alkalosis (NaHCO(3)), acidosis (NH(4)Cl), and placebo (NaCl) were induced in 15 healthy volunteers (12 females, median age 34 (range 24-56) years) in a double blind, placebo controlled study to evaluate the presence of the effects on airway calibre. Acid-base shifts were determined

  5. Recombinant human C1-inhibitor prevents acute antibody-mediated rejection in alloimmunized baboons

    NARCIS (Netherlands)

    Tillou, Xavier; Poirier, Nicolas; Le Bas-Bernardet, Stephanie; Hervouet, Jeremy; Minault, David; Renaudin, Karine; Vistoli, Fabio; Karam, Georges; Daha, Mohamed; Soulillou, Jean Paul; Blancho, Gilles

    Acute antibody-mediated rejection is an unsolved issue in transplantation, especially in the context of pretransplant immunization. The deleterious effect of preformed cytotoxic anti-HLA antibodies through complement activation is well proven, but very little is known concerning complement blockade

  6. Acute exercise induces FGF21 expression in mice and in healthy humans.

    Directory of Open Access Journals (Sweden)

    Kook Hwan Kim

    Full Text Available Fibroblast growth factor 21 (FGF21 plays an important role in the regulation of energy homeostasis during starvation and has an excellent therapeutic potential for the treatment of type 2 diabetes in rodents and monkeys. Acute exercise affects glucose and lipid metabolism by increasing glucose uptake and lipolysis. However, it is not known whether acute exercise affects FGF21 expression. Here, we showed that serum FGF21 level is increased in mice after a single bout of acute exercise, and that this is accompanied by increased serum levels of free fatty acid, glycerol and ketone body. FGF21 gene expression was induced in the liver but not in skeletal muscle and white adipose tissue of mice after acute exercise, and further, the gene expression levels of hepatic peroxisome proliferator-activated receptor α (PPARα and activating transcription factor 4 (ATF4 were also increased. In addition, we observed increased FGF21 level in serum of healthy male volunteers performing a treadmill run at 50 or 80% VO2max. These results suggest that FGF21 may also be associated with exercise-induced lipolysis in addition to increased catecholamines and reduced insulin.

  7. CITED2-mediated human hematopoietic stem cell maintenance is critical for acute myeloid leukemia

    NARCIS (Netherlands)

    Korthuis, P. M.; Berger, G.; Bakker, B.; Rozenyeld-Geugien, M.; Jaques, J.; de Haan, G.; Schuringa, J. J.; Vellenga, E.; Schepers, H.

    As the transcriptional coactivator CITED2 (CBP/p300-interacting-transactivator-with-an ED-rich-tail 2) can be overexpressed in acute myeloid leukemia (AML) cells, we analyzed the consequences of high CITED2 expression in normal and AML cells. CITED2 overexpression in normal CD34(+) cells resulted in

  8. Prevalence and molecular characterization of human rhinovirus in stool samples of individuals with and without acute gastroenteritis.

    Science.gov (United States)

    Khoonta, Prapaporn; Linsuwanon, Piyada; Posuwan, Nawarat; Vongpunsawad, Sompong; Payungporn, Sunchai; Poovorawan, Yong

    2017-05-01

    Human rhinovirus (RV) most often causes mild upper respiratory tract infection. Although RV is routinely isolated from the respiratory tract, few studies have examined RV in other types of clinical samples. The prevalence of RV was examined in 1,294 stool samples collected mostly from children with acute gastroenteritis residing in Bangkok and Khon Kaen province of Thailand between January 2010 and October 2014. In addition, 591 samples from hand-foot-mouth disease (HFMD) or herpangina patients who do not have gastroenteritis served as a comparison group. Samples were initially screened by semi-nested PCR for the RV 5'UTR through the VP2 capsid region. RV genotyping and phylogenetic analysis were performed on the VP4/VP2 regions. Among children with acute gastroenteritis, RV was found in 2.3% (30/1,294) of stool samples, which comprised 47% (14/30) RV-A, 17% (5/30) RV-B, and 37% (11/30) RV-C. In the comparison group, 0.8% (5/591) was RV-positive and RV-C (3/5) was the major species found. Interestingly, RV was recovered more often from children with acute gastroenteritis than from those with HFMD or herpangina. As many as 31 RV types were present in the gastroenteritis stools, which were different than the types found in those with HFMD or herpangina. J. Med. Virol. 89:801-808, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Structural and functional changes of the human macula during acute exposure to high altitude.

    Directory of Open Access Journals (Sweden)

    M Dominik Fischer

    Full Text Available BACKGROUND: This study aimed to quantify structural and functional changes at the macula during acute exposure to high altitude and to assess their structure/function relationship. This work is related to the Tuebingen High Altitude Ophthalmology (THAO study. METHODOLOGY/PRINCIPAL FINDINGS: Spectral domain optical coherence tomography and microperimetry were used to quantify changes of central retinal structure and function in 14 healthy subjects during acute exposure to high altitude (4559 m. High-resolution volume scans and fundus-controlled microperimetry of the posterior pole were performed in addition to best-corrected visual acuity (BCVA measurements and assessment of acute mountain sickness. Analysis of measurements at altitude vs. baseline revealed increased total retinal thickness (TRT in all four outer ETDRS grid subfields during acute altitude exposure (TRT(outer = 2.80 ± 1.00 μm; mean change ± 95%CI. This change was inverted towards the inner four subfields (TRT(inner = -1.89 ± 0.97 μm with significant reduction of TRT in the fovea (TRT(foveal = -6.62 ± 0.90 μm at altitude. BCVA revealed no significant difference compared to baseline (0.06 ± 0.08 logMAR. Microperimetry showed stable mean sensitivity in all but the foveal subfield (MS(foveal = -1.12 ± 0.68 dB. At baseline recordings before and >2 weeks after high altitude exposure, all subjects showed equal levels with no sign of persisting structural or functional sequels. CONCLUSIONS/SIGNIFICANCE: During acute exposure to high altitude central retinal thickness is subject to minor, yet statistically significant changes. These alterations describe a function of eccentricity with an increase in regions with relatively higher retinal nerve fiber content and vascular arcades. However, these changes did not correlate with measures of central retinal function or acute mountain sickness. For the first time a quantitative approach has been used to assess these changes during acute

  10. YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils

    DEFF Research Database (Denmark)

    Volck, B; Price, P A; Johansen, J S

    1998-01-01

    YKL-40, also called human cartilage glycoprotein-39 (HC gp-39), is a member of family 18 glycosyl hydrolases. YKL-40 is secreted by chondrocytes, synovial cells, and macrophages, and recently it has been reported that YKL-40 has a role as an autoantigen in rheumatoid arthritis (RA). The function...... YKL-40 at the myelocyte-metamyelocyte stage, the stage of maturation at which other specific granule proteins are formed. Assuming that YKL-40 has a role as an autoantigen in RA by inducing T cell-mediated autoimmune response, YKL-40 released from neutrophils in the inflamed joint could be essential...

  11. Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fang (UMM)

    2008-09-23

    It is believed that a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), was passed from palm civets to humans and caused the epidemic of SARS in 2002 to 2003. The major species barriers between humans and civets for SARS-CoV infections are the specific interactions between a defined receptor-binding domain (RBD) on a viral spike protein and its host receptor, angiotensin-converting enzyme 2 (ACE2). In this study a chimeric ACE2 bearing the critical N-terminal helix from civet and the remaining peptidase domain from human was constructed, and it was shown that this construct has the same receptor activity as civet ACE2. In addition, crystal structures of the chimeric ACE2 complexed with RBDs from various human and civet SARS-CoV strains were determined. These structures, combined with a previously determined structure of human ACE2 complexed with the RBD from a human SARS-CoV strain, have revealed a structural basis for understanding the major species barriers between humans and civets for SARS-CoV infections. They show that the major species barriers are determined by interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479 and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced salt bridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479 and 487. These results enhance our understanding of host adaptations and cross-species infections of SARS-CoV and other emerging animal viruses.

  12. [Relationship between viral load of human bocavirus and clinical characteristics in children with acute lower respiratory tract infection].

    Science.gov (United States)

    Ding, Xiao-Fang; Zhang, Bing; Zhong, Li-Li; Xie, Le-Yun; Xiao, Ni-Guang

    2017-03-01

    To investigate the prevalence of human bocavirus (HBoV) in children with acute lower respiratory tract infection and to explore the relationship between the viral load of HBoV and the clinical characteristics of acute lower respiratory tract infection in children. A total of 1 554 nasopharyngeal aspirates from children who were hospitalized due to acute lower respiratory tract infection between March 2011 and March 2014 were collected. Quantitative real-time PCR was used to detect 12 RNA and 2 DNA viruses, adenovirus (ADV) and HBoV, and to measure the viral load of HBoV in HBoV-positive children. A comprehensive analysis was performed with reference to clinical symptoms and indicators. In the 1 554 specimens, 1 212 (77.99%) were positive for viruses, and 275 (17.70%) were HBoV-positive. In HBoV-positive cases, 94.9% were aged infection, and 230 (83.64%) had mixed infection. There was no significant difference in viral load between children with single infection and mixed infection (P>0.05). The patients with fever had a significantly higher viral load than those without fever (Pacute lower respiratory tract infection (P>0.05). HBoV is one of the important pathogens of acute lower respiratory tract infection in children. Children with a higher viral load of HBoV are more likely to experience symptoms such as fever and wheezing. However, the severity of disease and mixed infection are not significantly related to viral load.

  13. Misdiagnosis of cerebral malaria initially as acute psychotic disorder and later as human rabies: a case report.

    Science.gov (United States)

    Mudiyanselage, Meththananda Herath Herath; Weerasinghe, Nayani Prasangika; Pathirana, Kithsiri; Dias, Hasini

    2016-08-11

    Cerebral malaria is arguably one of the most common non-traumatic encephalopathies in the developing world. Unless the diagnosis of cerebral malaria is made promptly, the consequence could be disastrous. Even though the diagnosis of cerebral malaria can be made relatively easily in majority of cases atypical presentation can often lead to misdiagnosis or delayed diagnosis. We report a case of an uncommon presentation of Plasmodium falciparum infection in a 17-year-old school girl with altered sensorium, seizures and phobic spasms. A previously healthy 17-year-old school girl was admitted to our hospital with acute condition characterised by comatose state, recurrent seizures and phobic spasms. She initially presented to a local hospital with agitation and over talkativeness and was diagnosed as having an acute psychotic state. Few days later she became drowsy and developed recurrent seizures and marked phobic spasms which prompted the treating physician to diagnose human rabies. However, further investigations carried out in our unit (including rapid antigenic test for P. falciparum and peripheral blood smear) were positive for P. falciparum. She was treated as for cerebral malaria with intravenous quinine and discharge from hospital with no residual neurological deficit. Atypical presentation of cerebral malaria can often lead to misdiagnosis. This patient presented with encephalopathic illness with phobic spasms was initially misdiagnosed as human rabies. Therefore, the physicians in malarial endemic areas should be vigilant of similar presentations and should consider cerebral malaria as a possibility.

  14. Acute effects of thermally processed pili (Canarium ovatum, Engl.) pomace drink on plasma antioxidant and polyphenol status in humans.

    Science.gov (United States)

    Arenas, Elizabeth Hashim; Trinidad, Trinidad Palad

    2017-01-01

    Pili (Canarium ovatum, Engl.) pomace is an underutilized agricultural waste that possesses great potential to be regarded as a functional food ingredient. The aim of this study was to measure the polyphenol content and antioxidant activity of pili pomace drink and determine the influence of heating on these parameters. Moreover, it sought to assess the acute effects of thermally processed pili pomace drink on plasma antioxidant and polyphenol status in humans. Ten healthy adults received a single dose (130 ml) of pili pomace drink following an overnight fasting, and blood was collected at 0, 30, 60, 120 and 240 min after ingestion of pili pomace. Plasma total polyphenol content was measured using Folin-Ciocalteu method, while total antioxidant capacity (TAC) was determined using ferric reducing antioxidant power (FRAP) assay in uricase-treated and untreated plasma samples. Significant changes in plasma antioxidant and polyphenol levels were observed, reaching maximum levels at 120 and between 30 - 60 min, respectively (p<0.05). Both plasma polyphenols and TAC remained significantly above baseline values throughout the entire test period (p<0.05). Results raised the possibility that an acute consumption of this phenolic-rich pili pomace drink may enhance plasma antioxidant and polyphenol status in humans. Future studies on other unidentified metabolites from pili pomace that may have enhanced the antioxidant activity of plasma should be done.

  15. GABAergic modulation of human social interaction in a prisoner’s dilemma model via acute administration of alprazolam

    Science.gov (United States)

    Lane, Scott D.; Gowin, Joshua L.

    2010-01-01

    Recent work in neuroeconomics has utilized game theory paradigms to examine neural systems that subserve human social interaction and decision making. Attempts to modify social interaction through pharmacological manipulation have been less common. Here we show dose-dependent modification of human social behavior in a prisoner’s dilemma (PD) model following acute administration of the GABA-A modulating benzodiazepine alprazolam. Nine healthy adults received doses of placebo, 0.5, 1.0, and 2.0 mg alprazolam in a counterbalanced within-subject design, while completing multiple test blocks per day on an iterated PD game. During test blocks in which peak subjective effects of alprazolam were reported, cooperative choices were significantly decreased as a function of dose. Consistent with previous reports showing that high acute doses of GABA-modulating drugs are associated with violence and other antisocial behavior, our data suggest that at sufficiently high doses, alprazolam can decrease cooperation. These behavioral changes may be facilitated by changes in inhibitory control facilitated by GABA. Game theory paradigms may prove useful in behavioral pharmacology studies seeking to measure social interaction, and may help inform the emerging field of neuroeconomics. PMID:19667972

  16. Acute limb heating improves macro- and microvascular dilator function in the leg of aged humans.

    Science.gov (United States)

    Romero, Steven A; Gagnon, Daniel; Adams, Amy N; Cramer, Matthew N; Kouda, Ken; Crandall, Craig G

    2017-01-01

    Local heating of an extremity increases blood flow and vascular shear stress throughout the arterial tree. Local heating acutely improves macrovascular dilator function in the upper limbs of young healthy adults through a shear stress-dependent mechanism but has no such effect in the lower limbs of this age group. The effect of acute limb heating on dilator function within the atherosclerotic prone vasculature of the lower limbs of aged adults is unknown. Therefore, the purpose of this study was to test the hypothesis that acute lower limb heating improves macro- and microvascular dilator function within the leg vasculature of aged adults. Nine young and nine aged adults immersed their lower limbs at a depth of ~33 cm into a heated (~42°C) circulated water bath for 45 min. Before and 30 min after heating, macro (flow-mediated dilation)- and microvascular (reactive hyperemia) dilator functions were assessed in the lower limb, following 5 min of arterial occlusion, via Doppler ultrasound. Compared with preheat, macrovascular dilator function was unchanged following heating in young adults (P = 0.6) but was improved in aged adults (P = 0.04). Similarly, microvascular dilator function, as assessed by peak reactive hyperemia, was unchanged following heating in young adults (P = 0.1) but was improved in aged adults (P age dependent manner. We demonstrate that lower limb heating acutely improves macro- and microvascular dilator function within the atherosclerotic prone vasculature of the leg in aged adults. These findings provide evidence for a potential therapeutic use of chronic lower limb heating to improve vascular health in primary aging and various disease conditions. Copyright © 2017 the American Physiological Society.

  17. Comparison of acute cardiovascular responses to water immersion and head-down tilt in humans

    DEFF Research Database (Denmark)

    Shiraishi, Makoto; Schou, Morten; Gybel, Mikkel

    2002-01-01

    , and renin activity were suppressed similarly. Mean arterial pressure decreased by 9 mmHg (P hypothesis......The hypothesis was tested that acute water immersion to the neck (WI) compared with 6 degrees head-down tilt (HDT) induces a more pronounced distension of the heart and lower plasma levels of vasoconstrictor hormones. Ten healthy males underwent 30 min of HDT, WI, and a seated control (randomized...

  18. Personality and the acute subjective effects of d-amphetamine in humans

    OpenAIRE

    Kirkpatrick, Matthew G; Johanson, Chris-Ellyn; de Wit, Harriet

    2013-01-01

    There is evidence that subjective responses to psychoactive drugs are related to personality traits. Here, we extend previous findings by examining personality measures in relation to acute responses to d-amphetamine (AMPH) in a large sample of healthy volunteers. Healthy adults (n=286) completed the Multidimensional Personality Questionnaire Brief Form (MPQ-BF) and participated in four sessions during which they received oral AMPH (0, 5,10, 20 mg), under double-blind conditions. Subjective r...

  19. Kefir induces apoptosis and inhibits cell proliferation in human acute erythroleukemia.

    Science.gov (United States)

    Jalali, Fatemeh; Sharifi, Mohammadreza; Salehi, Rasoul

    2016-01-01

    Acute erythroleukemia is an uncommon subtype of acute myeloid leukemia which has been considered to be a subtype of AML with a worse prognosis. Intensive chemotherapy is the first line of treatment. In recent years, the effect of kefir on some malignancies has been experimented. Kefir is a kind of beverage, which obtained by incubation of kefir grains with raw milk. Kefir grains are a symbiotic complex of different kinds of yeasts and bacteria, especially lactic acid bacteria which gather in a mostly carbohydrate matrix, named kefiran. We investigated the effect of kefir on acute erythroleukemia cell line (KG-1) and peripheral blood mononuclear cells (PBMCs). The cell line and PBMCs were treated with different doses of kefir and milk and incubated for three different times. We used Polymixin B to block the lipopolysaccharide and NaOH (1 mol/l) to neutralize the acidic media. Viability was detected by MTT assay. Apoptosis and necrosis were assessed by annexin-propidium iodide staining. Our results showed that kefir induced apoptosis and necrosis in KG-1 cell line. It was revealed that kefir decreased proliferation in erythroleukemia cell line. We did not observe a remarkable effect of kefir on PBMCs. Our study suggested that kefir may have potential to be an effective treatment for erythroleukemia.

  20. Erythrocyte membrane fluidity and indices of plasmatic oxidative damage after acute physical exercise in humans.

    Science.gov (United States)

    Berzosa, C; Gómez-Trullén, E M; Piedrafita, E; Cebrián, I; Martínez-Ballarín, E; Miana-Mena, F J; Fuentes-Broto, L; García, J J

    2011-06-01

    Optimal levels of membrane fluidity are essential for numerous cell functions including cell growth, solute transport and signal transduction. Since exercise enhances free radical production, our aim was to evaluate in healthy male subjects the effects of an acute bout of maximal and submaximal exercise on the erythrocyte membrane fluidity and its possible relation to the oxidative damage overproduction due to exercise. Subjects (n = 34) performed three cycloergometric tests: a continuous progressive exercise, a strenuous exercise until exhaustion and an acute bout of exercise at an intensity corresponding to 70% of maximal work capacity for 30 min. Venous blood samples were collected before and immediately after these exercises. Erythrocyte membrane fluidity was assessed by fluorescence spectroscopy. Plasma malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations and carbonyl content of plasmatic proteins were used as an index of lipid and protein oxidation, respectively. Exercise produced a dramatic drop in the erythrocyte membrane fluidity as compared to resting time, but this was not accompanied by significant changes in the plasmatic MDA and 4-HDA concentrations. The highest erythrocyte membrane rigidity was detected immediately after strenuous exercise until exhaustion was performed. Protein carbonyl levels were higher after exhaustive exercises than at rest. Continuous progressive and strenuous exercises until exhaustion, but not submaximal workload, resulted in a significant enhanced accumulation of carbonylated proteins in the plasma. These findings are consistent with the idea that exercise exaggerates oxidative damage, which may contribute, at least partially, to explain the rigidity in the membrane of the erythrocytes due to acute exercise.

  1. Effects of acute exercise on flow-mediated dilatation in healthy humans.

    Science.gov (United States)

    Dawson, Ellen A; Green, Daniel J; Cable, N Timothy; Thijssen, Dick H J

    2013-12-01

    Although the effects of exercise training on vascular function have been well studied, less is known about the effects of acute exercise bouts. This synthesis summarizes and integrates knowledge derived from papers relating acute impacts of exercise on artery function, specifically endothelial function assessed by flow-mediated dilatation (FMD). We propose that an immediate decrease in FMD ("nadir") occurs soon after exercise cessation and that this is followed by a (supra)normalization response. The magnitude of the nadir and (supra)normalization and duration of this biphasic pattern of response appears to be influenced by numerous factors, including the nature of the exercise stimulus (e.g., type, duration, intensity), the subject population (e.g., trained vs. untrained), and various methodological factors. The impact of these factors on the biphasic pattern are most likely mediated through stimuli that underpin altered FMD postexercise, including shear and oxidative stress, changes in arterial diameter, and antioxidant status. We propose that a combination of these stimuli act synergistically to balance the vasomotor responses postexercise. Finally, we discuss the potential (clinical) relevance of the biphasic response after acute exercise, as the immediate nadir may represent an essential response for subsequent training-induced adaptations but may also represent a transient period of increased cardiovascular risk leading to the "exercise paradox."

  2. Cytokine responses in acute and persistent human parvovirus B19 infection

    DEFF Research Database (Denmark)

    Isa, A; Lundqvist, A; Lindblom, A

    2007-01-01

    The aim of this study was to characterize the proinflammatory and T helper (Th)1/Th2 cytokine responses during acute parvovirus B19 (B19) infection and determine whether an imbalance of the Th1/Th2 cytokine pattern is related to persistent B19 infection. Cytokines were quantified by multiplex beads...... immunoassay in serum from B19-infected patients and controls. The cytokine responses were correlated with B19 serology, quantitative B19 DNA levels and clinical symptoms. In addition to a proinflammatory response, elevated levels of the Th1 type of cytokines interleukin (IL)-2, IL-12 and IL-15 were evident...... at time of the initial peak of B19 viral load in a few patients during acute infection. This pattern was seen in the absence of an interferon (IFN)-gamma response. During follow-up (20-130 weeks post-acute infection) some of these patients had a sustained Th1 cytokine response. The Th1 cytokine response...

  3. The Role of Human Coronaviruses in Children Hospitalized for Acute Bronchiolitis, Acute Gastroenteritis, and Febrile Seizures: A 2-Year Prospective Study.

    Directory of Open Access Journals (Sweden)

    Monika Jevšnik

    Full Text Available Human coronaviruses (HCoVs are associated with a variety of clinical presentations in children, but their role in disease remains uncertain. The objective of our prospective study was to investigate HCoVs associations with various clinical presentations in hospitalized children up to 6 years of age. Children hospitalized with acute bronchiolitis (AB, acute gastroenteritis (AGE, or febrile seizures (FS, and children admitted for elective surgical procedures (healthy controls were included in the study. In patients with AB, AGE, and FS, a nasopharyngeal (NP swab and blood sample were obtained upon admission and the follow-up visit 14 days later, whereas in children with AGE a stool sample was also acquired upon admission; in healthy controls a NP swab and stool sample were taken upon admission. Amplification of polymerase 1b gene was used to detect HCoVs in the specimens. HCoVs-positive specimens were also examined for the presence of several other viruses. HCoVs were most often detected in children with FS (19/192, 9.9%, 95% CI: 6-15%, followed by children with AGE (19/218, 8.7%, 95% CI: 5.3-13.3% and AB (20/308, 6.5%, 95% CI: 4.0-9.8%. The presence of other viruses was a common finding, most frequent in the group of children with AB (19/20, 95%, 95% CI: 75.1-99.8%, followed by FS (10/19, 52.6%, 95% CI: 28.9-75.6% and AGE (7/19, 36.8%, 95% CI: 16.3-61.6%. In healthy control children HCoVs were detected in 3/156 (1.9%, 95% CI: 0.4-5.5% NP swabs and 1/150 (0.7%, 95% CI: 0.02-3.3% stool samples. It seems that an etiological role of HCoVs is most likely in children with FS, considering that they had a higher proportion of positive HCoVs results than patients with AB and those with AGE, and had the highest viral load; however, the co-detection of other viruses was 52.6%.ClinicalTrials.gov NCT00987519.

  4. Pulmonary Inflammatory Responses to Acute Meteorite Dust Exposures - Implications for Human Space Exploration

    Science.gov (United States)

    Harrington, A. D.; McCubbin, F. M.; Vander Kaaden, K. E.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

    2018-01-01

    New initiatives to send humans to Mars within the next few decades are illustrative of the resurgence of interest in space travel. However, as with all exploration, there are risks. The Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts.

  5. Inheritable stimulatory effects of caffeine on steroidogenic acute regulatory protein expression and cortisol production in human adrenocortical cells.

    Science.gov (United States)

    Ping, Jie; Lei, You-Ying; Liu, Lian; Wang, Ting-ting; Feng, Ying-hong; Wang, Hui

    2012-01-05

    Caffeine is the most widely consumed psychoactive substance in the world. It can elevate the level of glucocorticoid which is involved in metabolism regulation, stress response, and immune function. However, the specific mechanism has yet to be elucidated. Glucocorticoid is steroid hormone synthesized in adrenal cortex and the key rate-limiting step in its biosynthesis is mediated by steroidogenic acute regulatory protein (StAR). This study was designed to investigate the direct effects and inheritable epigenetic mechanisms of caffeine on cortisol production and StAR expression in human adrenocortical cells. The human adrenocortical cell line NCI-H295A was cultured with 0.4-40μM caffeine. There was a significant increase of the cortisol production in cells. In both acutely and chronically caffeine-treated cell groups, mRNA and protein expressions of StAR were stimulated in a dose-dependent manner. DNA methylation detection via bisulfite-sequencing PCR (BSP) uncovered a single site CpG demethylation at nt -682 within the StAR promoter region. Then we investigated how long the increased StAR expression and the single CpG demethylation could last. The caffeine was withdrawn after 48h of treatment and then the cells were continually subcultured for up to 5 and 10 passages, respectively. The results showed that the StAR expression at post-caffeine passage 10 still increased, as compared with that in the control. The caffeine-induced demethylation at nt -682 in StAR promoter underwent a similar time course as StAR expression does. The present study reveals the direct effect and possible inheritable epigenetic mechanism of caffeine on steroidogenesis in human adrenocortical cells and has implications for our understanding of the consumption of caffeine. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans.

    Directory of Open Access Journals (Sweden)

    Thomas C Darton

    2015-09-01

    Full Text Available Iron is a key pathogenic determinant of many infectious diseases. Hepcidin, the hormone responsible for governing systemic iron homeostasis, is widely hypothesized to represent a key component of nutritional immunity through regulating the accessibility of iron to invading microorganisms during infection. However, the deployment of hepcidin in human bacterial infections remains poorly characterized. Typhoid fever is a globally significant, human-restricted bacterial infection, but understanding of its pathogenesis, especially during the critical early phases, likewise is poorly understood. Here, we investigate alterations in hepcidin and iron/inflammatory indices following experimental human typhoid challenge.Fifty study participants were challenged with Salmonella enterica serovar Typhi and monitored for evidence of typhoid fever. Serum hepcidin, ferritin, serum iron parameters, C-reactive protein (CRP, and plasma IL-6 and TNF-alpha concentrations were measured during the 14 days following challenge. We found that hepcidin concentrations were markedly higher during acute typhoid infection than at baseline. Hepcidin elevations mirrored the kinetics of fever, and were accompanied by profound hypoferremia, increased CRP and ferritin, despite only modest elevations in IL-6 and TNF-alpha in some individuals. During inflammation, the extent of hepcidin upregulation associated with the degree of hypoferremia.We demonstrate that strong hepcidin upregulation and hypoferremia, coincident with fever and systemic inflammation, are hallmarks of the early innate response to acute typhoid infection. We hypothesize that hepcidin-mediated iron redistribution into macrophages may contribute to S. Typhi pathogenesis by increasing iron availability for macrophage-tropic bacteria, and that targeting macrophage iron retention may represent a strategy for limiting infections with macrophage-tropic pathogens such as S. Typhi.

  7. Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans.

    Science.gov (United States)

    Darton, Thomas C; Blohmke, Christoph J; Giannoulatou, Eleni; Waddington, Claire S; Jones, Claire; Sturges, Pamela; Webster, Craig; Drakesmith, Hal; Pollard, Andrew J; Armitage, Andrew E

    2015-09-01

    Iron is a key pathogenic determinant of many infectious diseases. Hepcidin, the hormone responsible for governing systemic iron homeostasis, is widely hypothesized to represent a key component of nutritional immunity through regulating the accessibility of iron to invading microorganisms during infection. However, the deployment of hepcidin in human bacterial infections remains poorly characterized. Typhoid fever is a globally significant, human-restricted bacterial infection, but understanding of its pathogenesis, especially during the critical early phases, likewise is poorly understood. Here, we investigate alterations in hepcidin and iron/inflammatory indices following experimental human typhoid challenge. Fifty study participants were challenged with Salmonella enterica serovar Typhi and monitored for evidence of typhoid fever. Serum hepcidin, ferritin, serum iron parameters, C-reactive protein (CRP), and plasma IL-6 and TNF-alpha concentrations were measured during the 14 days following challenge. We found that hepcidin concentrations were markedly higher during acute typhoid infection than at baseline. Hepcidin elevations mirrored the kinetics of fever, and were accompanied by profound hypoferremia, increased CRP and ferritin, despite only modest elevations in IL-6 and TNF-alpha in some individuals. During inflammation, the extent of hepcidin upregulation associated with the degree of hypoferremia. We demonstrate that strong hepcidin upregulation and hypoferremia, coincident with fever and systemic inflammation, are hallmarks of the early innate response to acute typhoid infection. We hypothesize that hepcidin-mediated iron redistribution into macrophages may contribute to S. Typhi pathogenesis by increasing iron availability for macrophage-tropic bacteria, and that targeting macrophage iron retention may represent a strategy for limiting infections with macrophage-tropic pathogens such as S. Typhi.

  8. The acute environment, rather than T cell subset pre-commitment, regulates expression of the human T cell cytokine amphiregulin.

    Directory of Open Access Journals (Sweden)

    Yilin Qi

    Full Text Available Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals. We showed previously that the epidermal growth factor family member Amphiregulin is expressed by T cell receptor-activated mouse CD4 T cells, particularly Th2 cells, and helps eliminate helminth infection. Here we report a detailed analysis of the regulation of Amphiregulin expression by human T cell subsets. Signaling through the T cell receptor induced Amphiregulin expression by most or all T cell subsets in human peripheral blood, including naive and memory CD4 and CD8 T cells, Th1 and Th2 in vitro T cell lines, and subsets of memory CD4 T cells expressing several different chemokine receptors and cytokines. In these different T cell types, Amphiregulin synthesis was inhibited by an antagonist of protein kinase A, a downstream component of the cAMP signaling pathway, and enhanced by ligands that increased cAMP or directly activated protein kinase A. Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines. Thus, in contrast to mouse T cells, Amphiregulin synthesis by human T cells is regulated more by acute signals than pre-commitment of T cells to a particular cytokine pattern. This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses.

  9. Effect of acute hypobaric hypoxia on the endothelial glycocalyx and digital reactive hyperemia in humans

    Directory of Open Access Journals (Sweden)

    Pär I Johansson

    2014-11-01

    Full Text Available Introduction: Hypoxia is associated with increased capillary permeability. This study tested whether acute hypobaric hypoxia involves degradation of the endothelial glycocalyx. Methods: We exposed 12 subjects to acute hypobaric hypoxia (equivalent to 4,500 m for 2-4 hours and measured venous blood concentrations of biomarkers reflecting endothelial and glycocalyx degradation (catecholamines, syndecan-1, soluble CD40 ligand, protein C, soluble thrombomodulin, tissue-type plasminogen activators, histone-complexed DNA fragments and nitrite/nitrate. Endothelial function was assessed by the hyperemic response to brachial artery occlusion by peripheral arterial tonometry. Results: Compared with normoxic baseline levels, hypoxia increased concentrations of syndecan-1 from 22 (95% confidence interval: 17-27 to 25 (19-30 ng/ml (p < 0.02 and protein C from 76 (70-83 % to 81 (74-88 % (p < 0.02. Nitrite/nitrate decreased from 23 (18-27 μM at baseline to 19 (14-24 μM and 18 (14-21 μM in hypoxia and recovery, respectively (p < 0.05. Other biomarkers remained unchanged. The post-occlusion/pre-occlusion ratio (reactive hyperemia index, RHI decreased from 1.80 (1.52–2.07 in normoxia to 1.62 (1.28–1.96 after 2 to 4 hours of hypobaric hypoxia and thereafter increased to 2.43 (1.99-2.86 during normoxic recovery (p < 0.01. Conclusions: The increase in syndecan-1 and protein C suggests that acute hypobaric hypoxia produces minor degree of glycocalyx degradation and overall cellular damage. After hypoxia RHI rebounded to higher than baseline levels suggesting improved endothelial functionality.

  10. Alterations of consciousness and mystical-type experiences after acute LSD in humans.

    Science.gov (United States)

    Liechti, Matthias E; Dolder, Patrick C; Schmid, Yasmin

    2017-05-01

    Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. Acute mystical-type experiences that are acutely induced by hallucinogens are thought to contribute to their potential therapeutic effects. However, no data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness. Additionally, LSD dose- and concentration-response functions with regard to alterations of consciousness are lacking. We conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 μg LSD in 24 and 16 subjects, respectively. Acute effects of LSD were assessed using the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical Experience Questionnaire (MEQ) after 200 μg. On the MEQ, 200 μg LSD induced mystical experiences that were comparable to those in patients who underwent LSD-assisted psychotherapy but were fewer than those reported for psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 μg compared with 100 μg. Plasma levels of LSD were not positively correlated with its effects, with the exception of ego dissolution at 100 μg. Mystical-type experiences were infrequent after LSD, possibly because of the set and setting used in the present study. LSD may produce greater or different alterations of consciousness at 200 μg (i.e., a dose that is currently used in psychotherapy in Switzerland) compared with 100 μg (i.e., a dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD, whereas more robustly induced effects of LSD may not result in such associations.

  11. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Kim, Yu-Sok; Krogh-Madsen, Rikke

    2012-01-01

    Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic...... and cerebrovascular variables following acute (30,000 IU/d for 3 d; n=8) and chronic (5000 IU/week for 13 wk; n=8) administration of EPO, while the responsiveness of the vasculature was challenged during cycling exercise, with and without hypoxia. Prolonged administration of EPO increased hematocrit from 42.5 ± 3...

  12. Assessment of acute and chronic toxicity of doxorubicin in human induced pluripotent stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Louisse, Jochem; Wüst, Rob C I; Pistollato, Francesca; Palosaari, Taina; Barilari, Manuela; Macko, Peter; Bremer, Susanne; Prieto, Pilar

    2017-08-01

    The present study assesses acute and chronic toxicity of doxorubicin in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), with the aim to obtain in vitro biomarkers that can be used as readouts to predict in vivo cardiotoxicity. Possible acute toxicity was investigated by assessing effects on the beating rate and the field potential duration (FPD) of doxorubicin-exposed cardiomyocytes by measuring electrical activity using multi-electrode array (MEA) analyses. No effects on the beating rate and FPD were found at concentrations up to 6μM, whereas at 12μM no electrical activity was recorded, indicating that the cardiomyocytes stopped beating. Acute and chronic effects of doxorubicin on mitochondria, which have been reported to be affected in doxorubicin-induced cardiotoxicity, were assessed using high content imaging techniques. To this end hiPSC-CMs were exposed to 150 or 300nM doxorubicin using both single dosing (3h and 2days) and repetitive dosing (3 times, of 2days each), including washout studies to assess delayed effects (assessment at day 14) and effects on cell number, mitochondrial density, mitochondrial membrane potential, mitochondrial superoxide levels and mitochondrial calcium levels were assessed. No effects of doxorubicin were found on mitochondrial density and mitochondrial superoxide levels, whereas doxorubicin reduced cell survival and slightly altered mitochondrial membrane potential and mitochondrial calcium levels, which was most profound in the washout studies. Altogether, the results of the present study show that concentrations of doxorubicin in the micromolar range were required to affect electrical activity of hiPSC-CMs, whereas nanomolar concentrations already affected cell viability and caused mitochondrial disturbances. Integration of these data with other in vitro data may enable the selection of a series of in vitro biomarkers that can be used as readouts to screen chemicals for possible cardiotoxicity

  13. Prevalence of human rhinovirus in children admitted to hospital with acute lower respiratory tract infections in Changsha, China.

    Science.gov (United States)

    Zeng, Sai-Zhen; Xiao, Ni-Guang; Xie, Zhi-Ping; Xie, Guang-Cheng; Zhong, Li-Li; Wang, Juan; Huang, Han; Zhang, Bing; Duan, Zhao-Jun

    2014-11-01

    Human rhinovirus (HRV) is a causative agent of acute respiratory tract infections. This study analyzed the prevalence and clinical characteristics of three HRV groups (HRV-A, -B, and -C) among 1,165 children aged 14 years or younger who were hospitalized with acute lower respiratory tract infection in China. PCR or reverse transcription-PCR was performed to detect 14 respiratory viruses in nasopharyngeal aspirates collected from September 2007 to August 2008 in Changsha, China. HRV was detected in 202 (17.3%) of the 1,165 children; 25.3% of the HRV-positive children were 13-36 months of age (χ(2)  = 22.803, P = 0.000). HRV was detected year round and peaked between September and December. Fifty-three percent of the HRV-positive samples were also positive for other respiratory viruses; respiratory syncytial virus (RSV) was the most common secondary virus. Phylogenetic analysis using the VP4/VP2 region grouped the HRV-positive strains as follows: 101 HRV-A (50.0%), 21 HRV-B (10.4%), and 80 HRV-C (39.6%). HRV-A infections occurred predominantly in spring and autumn, and the peak prevalence of HRV-C was in early winter and late autumn. HRV-B infections were less common in spring (χ(2)  = 31.914, P = 0.000). No significant difference in clinical severity or presentation was found between patients with HRV single infection and HRV co-detections. Furthermore, the clinical characterizations did not differ among the three HRV species. These results suggest that HRV-C is an important viral agent along with HRV-A and HRV-B and that among hospitalized children with acute lower respiratory tract infection in China, the three HRV genotypes have similar clinical characteristics. © 2014 Wiley Periodicals, Inc.

  14. Improved memory for reward cues following acute buprenorphine administration in humans

    NARCIS (Netherlands)

    Syal, Supriya; Ipser, Jonathan; Terburg, David; Solms, Mark; Panksepp, Jaak; Malcolm-Smith, Susan; Bos, Peter A.; Montoya, Estrella R.; Stein, Dan J.; van Honk, Jack

    2015-01-01

    In rodents, there is abundant evidence for the involvement of the opioid system in the processing of reward cues, but this system has remained understudied in humans. In humans, the happy facial expression is a pivotal reward cue. Happy facial expressions activate the brain's reward system and are

  15. Lifelong training preserves some redox-regulated adaptive responses after an acute exercise stimulus in aged human skeletal muscle.

    Science.gov (United States)

    Cobley, J N; Sakellariou, G K; Owens, D J; Murray, S; Waldron, S; Gregson, W; Fraser, W D; Burniston, J G; Iwanejko, L A; McArdle, A; Morton, J P; Jackson, M J; Close, G L

    2014-05-01

    Several redox-regulated responses to an acute exercise bout fail in aged animal skeletal muscle, including the ability to upregulate the expression of antioxidant defense enzymes and heat shock proteins (HSPs). These findings are generally derived from studies on sedentary rodent models and thus may be related to reduced physical activity and/or intraspecies differences as opposed to aging per se. This study, therefore, aimed to determine the influence of age and training status on the expression of HSPs, antioxidant enzymes, and NO synthase isoenzymes in quiescent and exercised human skeletal muscle. Muscle biopsy samples were obtained from the vastus lateralis before and 3 days after an acute high-intensity-interval exercise bout in young trained, young untrained, old trained, and old untrained subjects. Levels of HSP72, PRX5, and eNOS were significantly higher in quiescent muscle of older compared with younger subjects, irrespective of training status. 3-NT levels were elevated in muscles of the old untrained but not the old trained state, suggesting that lifelong training may reduce age-related macromolecule damage. SOD1, CAT, and HSP27 levels were not significantly different between groups. HSP27 content was upregulated in all groups studied postexercise. HSP72 content was upregulated to a greater extent in muscle of trained compared with untrained subjects postexercise, irrespective of age. In contrast to every other group, old untrained subjects failed to upregulate CAT postexercise. Aging was associated with a failure to upregulate SOD2 and a downregulation of PRX5 in muscle postexercise, irrespective of training status. In conclusion, lifelong training is unable to fully prevent the progression toward a more stressed muscular state as evidenced by increased HSP72, PRX5, and eNOS protein levels in quiescent muscle. Moreover, lifelong training preserves some (e.g., CAT) but not all (e.g., SOD2, HSP72, PRX5) of the adaptive redox-regulated responses after an

  16. High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples

    Science.gov (United States)

    Payton, Jacqueline E.; Grieselhuber, Nicole R.; Chang, Li-Wei; Murakami, Mark; Geiss, Gary K.; Link, Daniel C.; Nagarajan, Rakesh; Watson, Mark A.; Ley, Timothy J.

    2009-01-01

    Acute promyelocytic leukemia (APL) is characterized by the t(15;17) chromosomal translocation, which results in fusion of the retinoic acid receptor α (RARA) gene to another gene, most commonly promyelocytic leukemia (PML). The resulting fusion protein, PML-RARA, initiates APL, which is a subtype (M3) of acute myeloid leukemia (AML). In this report, we identify a gene expression signature that is specific to M3 samples; it was not found in other AML subtypes and did not simply represent the normal gene expression pattern of primary promyelocytes. To validate this signature for a large number of genes, we tested a recently developed high throughput digital technology (NanoString nCounter). Nearly all of the genes tested demonstrated highly significant concordance with our microarray data (P < 0.05). The validated gene signature reliably identified M3 samples in 2 other AML datasets, and the validated genes were substantially enriched in our mouse model of APL, but not in a cell line that inducibly expressed PML-RARA. These results demonstrate that nCounter is a highly reproducible, customizable system for mRNA quantification using limited amounts of clinical material, which provides a valuable tool for biomarker measurement in low-abundance patient samples. PMID:19451695

  17. Muscle-specific acute changes in passive stiffness of human triceps surae after stretching.

    Science.gov (United States)

    Hirata, Kosuke; Miyamoto-Mikami, Eri; Kanehisa, Hiroaki; Miyamoto, Naokazu

    2016-05-01

    It remains unclear whether the acute effect of stretching on passive muscle stiffness differs among the synergists. We examined the muscle stiffness responses of the medial (MG) and lateral gastrocnemii (LG), and soleus (Sol) during passive dorsiflexion before and after a static stretching by using ultrasound shear wave elastography. Before and after a 5-min static stretching by passive dorsiflexion, shear modulus of the triceps surae and the Achilles tendon (AT) during passive dorsiflexion in the knee extended position were measured in 12 healthy subjects. Before the static stretching, shear modulus was the greatest in MG and smallest in Sol. The stretching induced significant reductions in shear modulus of MG, but not in shear modulus of LG and Sol. The slack angle was observed at more plantar flexed position in the following order: AT, MG, LG, and Sol. After the stretching, the slack angles of each muscle and AT were significantly shifted to more dorsiflexed positions with a similar extent. When considering the shift in slack angle, the change in MG shear modulus became smaller. The present study indicates that passive muscle stiffness differs among the triceps surae, and that the acute effect of a static stretching is observed only in the stiff muscle. However, a large part of the reduction of passive muscle stiffness at a given joint angle could be due to an increase in the slack length.

  18. Consumption of flavanol-rich cocoa acutely increases microcirculation in human skin.

    Science.gov (United States)

    Neukam, Karin; Stahl, Wilhelm; Tronnier, Hagen; Sies, Helmut; Heinrich, Ulrike

    2007-02-01

    Long term cocoa ingestion leads to an increased resistance against UV-induced erythema and a lowered transepidermal water loss. To investigate the acute effects of a single dose of cocoa rich in flavanols on dermal microcirculation. In a crossover design study, 10 healthy women ingested a cocoa drink (100 ml) with high (329 mg) or low (27 mg) content of flavanols. The major flavanol monomer in both drinks was epicatechin, 61 mg in the high flavanol, and 6.6 mg in the low flavanol product per 100 ml. Dermal blood flow and oxygen saturation of hemoglobin were examined by laser Doppler flowmetry and spectroscopically at 1 mm skin depth at t = 0, 1, 2, 4, and 6 h. At the same time points, plasma levels of total epicatechin (free compound plus conjugates) were measured by means of HPLC. Subsequent to the intake of high flavanol cocoa, dermal blood flow was significantly increased by 1.7-fold at t = 2 h and oxygen saturation was elevated 1.8-fold. No statistically significant changes were found upon intake of low flavanol cocoa. Maximum plasma levels of total epicatechin were observed 1 h after ingestion of the high flavanol cocoa drink, 11.6 +/- 7.4 nmol/l at baseline, and 62.9 +/- 35.8 nmol/l at 1 h. No change of total epicatechin was found in the low flavanol group. Flavanol-rich cocoa consumption acutely increases dermal blood flow and oxygen saturation.

  19. Acute and chronic effects of hyperbaric oxygen therapy on blood circulation of human muscle and tendon in vivo.

    Science.gov (United States)

    Kubo, Keitaro; Ikebukuro, Toshihiro

    2012-10-01

    This study aimed to investigate the acute and chronic effects of hyperbaric oxygen therapy on blood circulation of human muscle and tendon in vivo. Using near-infrared spectroscopy and red laser lights, we determined acute changes in blood volume (THb) and oxygen saturation (StO2) of the medial gastrocnemius muscle and Achilles tendon during 60 minutes of hyperbaric oxygen therapy (1.3 atm absolute and 50% O2, experiment 1). In addition, we determined the chronic effects of hyperbaric oxygen therapy (60 minutes, 2 times per week, 6 weeks) on THb and StO2 of muscle and tendon (experiment 2). In experiment 1, THb of the muscle increased gradually from resting level, but StO2 did not change. On the other hand, THb and StO2 of the tendon increased during hyperbaric oxygen therapy. In experiment 2, the pattern of changes in the measured variables during 60 minutes of therapy was similar for both the muscle and tendon between the first and last therapies. During resting, THb and StO2 of the tendon were significantly lower after 6 weeks of therapy, although those of the muscle were not. In conclusion, oxygen saturation of the tendon increased during hyperbaric oxygen therapy, whereas that of the muscle did not. This result would be related to the difference in the treated effects between muscle and tendon. However, oxygen saturation of the tendon, but not the muscle, during resting decreased after 6 weeks of therapy.

  20. Monitoring of human herpesviruses-6 and -7 DNA in saliva samples during the acute and convalescent phases of exanthem subitum.

    Science.gov (United States)

    Miyazaki, Yuki; Namba, Hikaru; Torigoe, Sadayoshi; Watanabe, Masahiro; Yamashita, Nobuko; Ogawa, Hirohito; Morishima, Tsuneo; Yamada, Masao

    2017-04-01

    The amounts of the DNAs of human herpesviruses-6 (HHV-6) and -7 (HHV-7) in saliva samples were monitored during the acute and convalescent phases of exanthem subitum (ES) to elucidate the kinetics of virus shedding after ES. A total of 247 saliva samples were collected from 17 children (5 males and 12 females: 8-31 months old at onset). The monitoring period ranged from 152 to 721 days after onset, and in 15 children it was longer than 1 year. Among the 17 cases, 16 were attributed to HHV-6B, while a single case was attributed to HHV-7. Detection rates and average amounts of HHV-6 DNA in saliva samples after ES attributed to HHV-6B were low in the acute phase, increased to the maximum in the convalescent phase at 3-7 months, and then decreased. In addition, to investigate the source of infection, saliva samples from the older siblings (age 3-9 years) and parents of ES patients and children with a history of ES were also examined. The detection rate of HHV-6 DNA in saliva samples from 3- to 9-year-old children was significantly higher than the rate in adult saliva samples. Taken together, these findings suggest that the saliva of children in the convalescent phase of ES might be a more likely source of HHV-6 infection than that of adults. J. Med. Virol. 89:696-702, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Acute nonlymphocytic leukemia in adults: correlations with Q-banded chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Golomb, H.M.; Vardiman, J.; Rowley, J.D.

    1976-07-01

    Chromosome banding patterns were obtained for 50 of 55 consecutive adult patients with acute nonlymphocytic leukemia during a 5-yr period. Twenty-two of the 50 cases were diagnosed as acute myelocytic leukemia (AML), 24 as acute myelomonocytic leukemia (AMMol), 2 as acute promyelocytic leukemia (APL), and 2 as erythroleukemia. Twenty-five patients had initial chromosome abnormalities, and five more patients developed abnormalities during the course of the disease. The median survival of patients with normal chromosomes initially (group 1) was 10 mo, whereas that of patients with abnormal chromosomes initially (group II) was 2 mo. Similar times were obtained for treated patients with AML and AMMol. However, when the AML patients were separated into those with and those without a chromosome abnormality, the median survival times were markedly different (2 mo versus 18 mo, respectively). Patients with AMMol demonstrated no difference in median survival times when subgrouped according to the presence or absence of chromosome abnormalities. The treated group II patients whose marrow samples had only abnormal metaphases had a poorer response (10 percent complete remission) and median survival (2 mo) than the group II patients who had at least one normal metaphase (42 percent complete remission with a median survival of 9 mo). The two cases of APL demonstrated a deletion of the long arm of No. 17 which occurred in the same region of the chromosome in each case. Both patients had similar clinical histories, with disseminated intravascular coagulation, and neither responded to therapy.

  2. Rotavirus specific plasma secretory immunoglobulin in children with acute gastroenteritis and children vaccinated with an attenuated human rotavirus vaccine.

    Science.gov (United States)

    Herrera, Daniel; Vásquez, Camilo; Corthésy, Blaise; Franco, Manuel A; Angel, Juana

    2013-11-01

    Rotavirus (RV)-specific secretory immunoglobulin (RV-SIg) has been previously detected in serum of naturally RV infected children and shown to reflect the intestinal Ig immune response. Total plasma SIgA and plasma RV-SIg were evaluated by ELISA in children with gastroenteritis due or not due to RV infection and in 50 children vaccinated with the attenuated RIX4414 human RV vaccine and 62 placebo recipients. RV-SIg was only detected in children with evidence of previous RV infection or with acute RV gastroenteritis. Vaccinees had higher RV-SIg titers than placebo recipients and RV-SIg titers increased after the second vaccine dose. RV-SIg measured after the second dose correlated with protection when vaccinees and placebo recipients were analyzed jointly. RV-SIg may serve as a valuable correlate of protection for RV vaccines.

  3. Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors.

    Science.gov (United States)

    Rodrigues, Robim M; Sachinidis, Agapios; De Boe, Veerle; Rogiers, Vera; Vanhaecke, Tamara; De Kock, Joery

    2015-09-01

    Besides their role in the elucidation of pathogenic processes of medical and pharmacological nature, biomarkers can also be used to document specific toxicological events. Hepatic cells generated from human skin-derived precursors (hSKP-HPC) were previously shown to be a promising in vitro tool for the evaluation of drug-induced hepatotoxicity. In this study, their capacity to identify potential liver-specific biomarkers at the gene expression level was investigated with particular emphasis on acute liver failure (ALF). To this end, a set of potential ALF-specific biomarkers was established using clinically relevant liver samples obtained from patients suffering from hepatitis B-associated ALF. Subsequently, this data was compared to data obtained from primary human hepatocyte cultures and hSKP-HPC, both exposed to the ALF-inducing reference compound acetaminophen. It was found that both in vitro systems revealed a set of molecules that was previously identified in the ALF liver samples. Yet, only a limited number of molecules was common between both in vitro systems and the ALF liver samples. Each of the in vitro systems could be used independently to identify potential toxicity biomarkers related to ALF. It seems therefore more appropriate to combine primary human hepatocyte cultures with complementary in vitro models to efficiently screen out potential hepatotoxic compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Preliminary evidence that ketamine inhibits spreading depolarizations in acute human brain injury

    DEFF Research Database (Denmark)

    Sakowitz, Oliver W; Kiening, Karl L; Krajewski, Kara L

    2009-01-01

    by the noncompetitive N-methyl-d-aspartate receptor antagonist ketamine. This restored electrocorticographic activity. CONCLUSIONS: These anecdotal electrocorticographic findings suggest that ketamine has an inhibitory effect on spreading depolarizations in humans. This is of potential interest for future...

  5. Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in Mice.

    Science.gov (United States)

    Toyohara, Takafumi; Mae, Shin-Ichi; Sueta, Shin-Ichi; Inoue, Tatsuyuki; Yamagishi, Yukiko; Kawamoto, Tatsuya; Kasahara, Tomoko; Hoshina, Azusa; Toyoda, Taro; Tanaka, Hiromi; Araoka, Toshikazu; Sato-Otsubo, Aiko; Takahashi, Kazutoshi; Sato, Yasunori; Yamaji, Noboru; Ogawa, Seishi; Yamanaka, Shinya; Osafune, Kenji

    2015-09-01

    Acute kidney injury (AKI) is defined as a rapid loss of renal function resulting from various etiologies, with a mortality rate exceeding 60% among intensive care patients. Because conventional treatments have failed to alleviate this condition, the development of regenerative therapies using human induced pluripotent stem cells (hiPSCs) presents a promising new therapeutic option for AKI. We describe our methodology for generating renal progenitors from hiPSCs that show potential in ameliorating AKI. We established a multistep differentiation protocol for inducing hiPSCs into OSR1+SIX2+ renal progenitors capable of reconstituting three-dimensional proximal renal tubule-like structures in vitro and in vivo. Moreover, we found that renal subcapsular transplantation of hiPSC-derived renal progenitors ameliorated the AKI in mice induced by ischemia/reperfusion injury, significantly suppressing the elevation of blood urea nitrogen and serum creatinine levels and attenuating histopathological changes, such as tubular necrosis, tubule dilatation with casts, and interstitial fibrosis. To our knowledge, few reports demonstrating the therapeutic efficacy of cell therapy with renal lineage cells generated from hiPSCs have been published. Our results suggest that regenerative medicine strategies for kidney diseases could be developed using hiPSC-derived renal cells. This report is the first to demonstrate that the transplantation of renal progenitor cells differentiated from human induced pluripotent stem (iPS) cells has therapeutic effectiveness in mouse models of acute kidney injury induced by ischemia/reperfusion injury. In addition, this report clearly demonstrates that the therapeutic benefits come from trophic effects by the renal progenitor cells, and it identifies the renoprotective factors secreted by the progenitors. The results of this study indicate the feasibility of developing regenerative medicine strategy using iPS cells against renal diseases.

  6. Distal promoter regions are responsible for differential regulation of human orosomucoid-1 and -2 gene expression and acute phase responses.

    Science.gov (United States)

    Sai, Kimie; Kurose, Kouichi; Koizumi, Tomoko; Katori, Noriko; Sawada, Jun-ichi; Matsumura, Yasuhiro; Saijo, Nagahiro; Yamamoto, Noboru; Tamura, Tomohide; Okuda, Haruhiro; Saito, Yoshiro

    2014-01-01

    Human orosomucoid (ORM) is a major acute-phase plasma protein, encoded by 2 highly homologous genes, ORM1 and ORM2. Human ORM induction is assumed to be regulated by each proximal promoter region, where putative glucocorticoid responsive elements and CCAAT/enhancer binding protein (C/EBP)β binding sites are located. However, the details of the differential regulation of these genes remain unknown. To explore this, we assessed the role of the distal promoter region of each ORM in HeLa cells. Luciferase-reporter activities of full constructs, containing approximately 1.1 kbp (FULL), and those of deletion constructs, containing up to 188 bp region (DEL) upstream of the transcription start sites of ORM1 and ORM2 were compared under both basal and inducer-treated conditions. For ORM1 and ORM2 DEL constructs, significantly increased activities after dexamethasone (DEX) treatments (alone and combined with interleukin (IL)-1β) were observed. Significantly higher FULL construct activities than DEL construct activities were observed for ORM1 after IL-1β treatment, while those for ORM2 were significantly lower at basal level and after DEX treatments. Upon C/EBPβ overexpression, FULL construct activities were significantly higher than those of DEL constructs at basal level and after IL-1β treatment for ORM1, and at basal level and after inducer-treatments for ORM2. Higher transcription-induction activity in the distal promoter region was evident for ORM1 in the absence of C/EBPβ overexpression, and for ORM2 under C/EBPβ overexpression conditions. These findings suggest that the ORM distal promoter region differentially regulates expression of ORM genes at basal level and in acute phase responses.

  7. Evolution of the human fear-circuitry and acute sociogenic pseudoneurological symptoms: the Neolithic balanced-polymorphism hypothesis.

    Science.gov (United States)

    Bracha, H Stefan; Yoshioka, Dawn T; Masukawa, Nicole K; Stockman, Deborah J J

    2005-10-01

    In light of the increasing threat of large-scale massacres such as terrorism against non-combatants (civilians), more attention is warranted not only to posttraumatic stress disorder (PTSD) but also to acute sociogenic pseudoneurological ("conversion") symptoms, especially epidemic sociogenic symptoms. We posit that conversion disorders are etiologically related to specific evolutionary pressures (inescapable threats to life) in the late stage of the human environment of evolutionary adaptedness (EEA). Bracha et al. have recently argued that from the neuroevolutionary perspective, medically unexplained efferent vasovagal syncope and medically unexplained craniofacial musculoskeletal pain in young otherwise healthy individuals, may be taxonomized as stress and fear-circuitry disorders. In the present article, we extend neuroevolutionary perspectives to acute pseudoneurological sociogenic ("conversive") symptoms: psychogenic non-epileptic attacks ("pseudoseizures"), epidemic sociogenic disorders (DSM-IV-TR Epidemic "Hysteria"), conversive motor deficits (pseudo-paralysis and pseudo-cerebellar symptoms), and psychogenic blindness. We hypothesize that these perplexing pseudoneurological stress-triggered symptoms, which constitute psychopathology in extant humans, are traceable to allele-variant polymorphisms which spread during the Neolithic EEA. During Neolithic warfare, conversive symptoms may have increased the survival odds for some non-combatants by visually (i.e., "non-verbally") signaling to predatory conspecifics that one does not present a danger. This is consistent with the age and sex pattern of conversive disorders. Testable and falsifiable predictions are presented; e.g., at the genome-transcriptome interface, one of the major oligogenic loci involved in conversive spectrum disorders may carry a developmentally sensitive allele in a stable polymorphism (balanced polymorphism) in which the gene expression mechanism is gradually suppressed by pleiotropic

  8. KRAS (G12D Cooperates with AML1/ETO to Initiate a Mouse Model Mimicking Human Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Shanmin Zhao

    2014-01-01

    Full Text Available Background/Aims: It has been demonstrated that KRAS mutations represent about 90% of cancer-associated mutations, and that KRAS mutations play an essential role in neoplastic transformation. Cancer-associated RAS mutations occur frequently in acute myeloid leukemia (AML, suggesting a functional role for Ras in leukemogenesis. Methods: We successfully established a mouse model of human leukemia by transplanting bone marrow cells co-transfected with the K-ras (G12D mutation and AML1/ETO fusion protein. Results: Mice transplanted with AML/ETO+KRAS co-transduced cells had the highest mortality rate than mice transplanted with AML/ETO- or KRAS-transduced cells (115d vs. 150d. Upon reaching a terminal disease stage, EGFP-positive cells dominated their spleen, lymph nodes, peripheral blood and central nervous system tissue. Immunophenotyping, cytologic analyses revealed that AML/ETO+KRAS leukemias predominantly contained immature myeloid precursors (EGFP+/c-Kit+/Mac-1-/Gr-1-. Histologic analyses revealed that massive leukemic infiltrations were closely packed in dense sheets that effaced the normal architecture of spleen and thymus in mice transplanted with AML1/ETO + KRAS co-transduced cells. K-ras mRNA and protein expression were upregulated in bone marrow cells of the K-ras group and AML1/ETO + Kras group. The phosphorylation of MEK/ERK was significantly enhanced in the AML1/ETO + Kras group. The similar results of the AML1/ETO + Nras group were consistent with those reported previously. Conclusion: Co-transduction of KrasG12D and AML1/ETO induces acute monoblastic leukemia. Since expression of mutant K-ras alone was insufficient to induce leukemia, this model may be useful for investigating the multi-step leukemogenesis model of human leukemia.

  9. Telomere dynamics in human mesenchymal stem cells after exposure to acute oxidative stress

    DEFF Research Database (Denmark)

    Harbo, M.; Koelvraa, S.; Serakinci, N.

    2012-01-01

    mesenchymal stem cells, either primary or hTERT immortalized, were exposed to sub-lethal doses of hydrogen peroxide, and the short term effect on telomere dynamics was monitored by Universal STELA and TRF measurements. Both telomere measures were then correlated with the percentage of senescent cells...... estimated by senescence-associated beta-galactosidase staining. The exposure to acute oxidative stress resulted in an increased number of ultra-short telomeres, which correlated strongly with the percentage of senescent cells, whereas a correlation between mean telomere length and the percentage...... of senescent cells was absent. Based on the findings in the present study, it seems reasonable to conclude that Universal STELA is superior to TRF in detecting telomere damage caused by exposure to oxidative stress. The choice of method should therefore be considered carefully in studies examining stress...

  10. Development of ML390: A Human DHODH Inhibitor That Induces Differentiation in Acute Myeloid Leukemia.

    Science.gov (United States)

    Lewis, Timothy A; Sykes, David B; Law, Jason M; Muñoz, Benito; Rustiguel, Joane K; Nonato, Maria Cristina; Scadden, David T; Schreiber, Stuart L

    2016-12-08

    Homeobox transcription factor A9 (HoxA9) is overexpressed in 70% of patients diagnosed with acute myeloid leukemia (AML), whereas only a small subset of AML patients respond to current differentiation therapies. A cell line overexpressing HoxA9 was derived from the bone marrow of a lysozyme-GFP mouse. In this fashion, GFP served as an endogenous reporter of differentiation, permitting a high-throughput phenotypic screen against the MLPCN library. Two chemical scaffolds were optimized for activity yielding compound ML390, and genetic resistance and sequencing efforts identified dihydroorotate dehydrogenase (DHODH) as the target enzyme. The DHODH inhibitor brequinar works against these leukemic cells as well. The X-ray crystal structure of ML390 bound to DHODH elucidates ML390s binding interactions.

  11. Suppression of blood monocyte and neutrophil chemotaxis in acute human malaria

    DEFF Research Database (Denmark)

    Nielsen, H; Kharazmi, A; Theander, T G

    1986-01-01

    tested monocyte chemotactic responsiveness in 19 patients with acute primary attack malaria. In addition, the neutrophil chemotaxis was measured in 12 patients. Before the initiation of antimalarial treatment a significant depression of monocyte chemotaxis was observed in approximately half...... suppressed. The monocyte chemotaxis was followed in 14 of the patients, during treatment and after complete recovery. After 3 days of treatment the response had improved in most of the patients, and after 7 days all patients had a normal monocyte chemotaxis, which remained normal after one month....... No significant differences between P. falciparum and P. vivax/ovale malaria was observed with respect to blood monocyte chemotactic responsiveness. Neutrophil chemotaxis in patients with P. falciparum infections was similarly suppressed before treatment (54% of controls), was still defective after 3 days...

  12. Nerve growth factor receptor gene is at human chromosome region 17q12-17q22, distal to the chromosome 17 breakpoint in acute leukemias

    Energy Technology Data Exchange (ETDEWEB)

    Huebner, K.; Isobe, M.; Chao, M.; Bothwell, M.; Ross, A.H.; Finan, J.; Hoxie, J.A.; Sehgal, A.; Buck, C.R.; Lanahan, A.

    1986-03-01

    Genomic and cDNA clones for the human nerve growth factor receptor have been used in conjunction with somatic cell hybrid analysis and in situ hybridization to localize the nerve growth factor receptor locus to human chromosome region 17q12-q22. Additionally, part, if not all, of the nerve growth factor receptor locus is present on the translocated portion of 17q (17q21-qter) from a poorly differential acute leukemia in which the chromosome 17 breakpoint was indistinguishable cytogenetically from the 17 breakpoint observed in the t(15;17)(q22;q21) translocation associated with acute promyelocytic leukemia. Thus the nerve growth factor receptor locus may be closely distal to the acute promyelocytic leukemia-associated chromosome 17 breakpoint at 17q21.

  13. Acute effects of cigarette smoke on three-dimensional cultures of normal human oral mucosa.

    Science.gov (United States)

    Gualerzi, Alice; Sciarabba, Michele; Tartaglia, Gianluca; Sforza, Chiarella; Donetti, Elena

    2012-05-01

    Human oral mucosa is the combustion chamber of cigarette, but scanty evidence is available about the early smoke effects. The present work aimed at evaluating from a morphological point of view whole smoke early effects on epithelial intercellular adhesion and keratinocyte terminal differentiation in a three-dimensional model of human oral mucosa. Biopsies of keratinized oral mucosa of healthy nonsmoking women (n = 5) were collected. After culturing in a Transwell system, one fragment of each biopsy was exposed to the smoke of one single cigarette; the remnant represented the internal control. The distribution of epithelial differentiation markers (keratin-10, K10, and keratin-14, K14, for suprabasal and basal cells respectively), desmosomes (desmoglein-1, desmoglein-3), tight junctions (occludin), adherens junctions (E-cadherin, β-catenin), and apoptotic cells (p53, caspase 3) were evaluated by immunofluorescence. Quantitative analysis of K14 immunolabeling revealed an overexpression in the suprabasal layers as early as 3 h after smoke exposure, without impairment of the epithelial junctional apparatus and apoptosis induction. These results suggested that the first significant response to cigarette smoke came from the basal and suprabasal layers of the human oral epithelium. The considered model maintained the three-dimensional arrangement of the human mucosa in the oral cavity and mimicked the inhalation/exhalation cycle during the exposure to cigarette smoke, offering a good possibility to extrapolate the reported observations to humans.

  14. Acute systemic insulin intolerance does not alter the response of the Akt/GSK-3 pathway to environmental hypoxia in human skeletal muscle

    DEFF Research Database (Denmark)

    D'Hulst, Gommaar; Sylow, Lykke; Hespel, Peter

    2015-01-01

    PURPOSE: To investigate how acute environmental hypoxia regulates blood glucose and downstream intramuscular insulin signaling after a meal in healthy humans. METHODS: Fifteen subjects were exposed for 4 h to normoxia (NOR) or to normobaric hypoxia (HYP, FiO2 = 0.11) in a randomized order 40 min ...

  15. Evaluation of sorivudine (BV-araU) versus acyclovir in the treatment of acute localized herpes zoster in human immunodeficiency virus-infected adults

    NARCIS (Netherlands)

    Bodsworth, NJ; Boag, F; Burdge, D; Genereux, M; Borleffs, JCC; Evans, BA; Modai, J; Colebunders, R; Thomas, M; DeHertogh, D; Pacelli, L; Thomis, J; Knight, E.L.; McNulty, AM; Delaney, C; VanHove, D; Sacks, S; Gage, L; McLeod, A; DiazMitoma, F; Fong, J; MacFadden, D; Martel, A; Rachlis, A; Salit, [No Value; Shafran, S; Szabo, J; Toma, E; Deschenes, L; Gill, J; Lalonde, R; Kaufhold, R; Molina, JM; Dellamonica, P; Rozenbaum, W; Kolsters, FP; Meenhorst, PL; Danner, S; Sprenger, HG; EllisPegler, RB; Moragas, J; Moyle, G; Colman, J; Parnell, A; McLean, KA; Holmes, DA; Kitchen, C.M.R.; Linde, A; Dahl, H; Dwyer, D

    The clinical efficacy and safety of sorivudine as treatment for acute cutaneous tester in human immunodeficiency virus-infected adults was compared with that of acyclovir in a double-blinded randomized study, A total of 125 patients with laboratory-confirmed tester rash present for less than or

  16. THE DNA-BINDING PROTEIN PUL57 OF HUMAN CYTOMEGALOVIRUS IS A MAJOR TARGET ANTIGEN FOR THE IMMUNOGLOBULIN-M ANTIBODY-RESPONSE DURING ACUTE INFECTION

    NARCIS (Netherlands)

    VORNHAGEN, R; HINDERER, W; SONNEBORN, HH; BEIN, G; MATTER, L; THE, TH; JAHN, G; PLACHTER, B

    A small polypeptide from pUL57 of human cytomegalovirus was identified as a major target for the immunoglobulin M antibody response. This antigen seems to be superior to antigenic fragments from pp150 and p52 in the identification of sera from acutely infected patients. It may therefore represent an

  17. Acute black tea consumption improves cutaneous vascular function in healthy middle-aged humans.

    Science.gov (United States)

    Woodward, Kirsty A; Hopkins, Nicola D; Draijer, Richard; de Graaf, Young; Low, David A; Thijssen, Dick H J

    2016-12-22

    Dietary flavonoids, such as those present in black tea, are associated with reduced risk of cardiovascular disease (CVD), possibly through improving nitric oxide (NO) mediated vascular function. The aim of this study was to examine the effect of acute black tea ingestion on cutaneous microvascular function. Twenty healthy participants (58 ± 5 y, 9 men) attended two experimental trials (tea, placebo), 7-days apart in a randomised, controlled, double-blind, cross-over design. Participants ingested a single dose of 200 ml black tea or placebo, followed by assessment of forearm cutaneous perfusion using laser-Doppler flowmetry (LDF) using three distinct heating protocols, enabling us to distinguish between axon- and endothelium-dependent vasodilation: 1. rapid 42°C, 2. rapid 39°C and 3. gradual 42°C. On the contralateral arm, full-field laser perfusion imaging (FLPI) was used to assess forearm perfusion during gradual 42°C. Data were presented as cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC (%CVCmax). Rapid local heating to 39°C or 42°C demonstrated no effect of tea for flux, CVC or %CVCmax (all P > 0.05). Gradual local heating to 42 °C, however, produced a higher skin blood flow following black tea ingestion for absolute CVC (P = 0.04) when measured by LDF, and higher absolute flux (P < 0.001) and CVC (P < 0.001) measured with FLPI. No effect of tea was found for %CVCmax when assessed by either LDF or FLPI. Acute tea ingestion enhanced cutaneous vascular responses to gradual local heating to 42 °C in healthy, middle-aged participants, possibly through a mechanism related to activation of endothelium-derived chemical mediators, such as NO. These improvements may contribute to the cardiovascular health benefits of regular tea ingestion. Copyright © 2016. Published by Elsevier Ltd.

  18. Anatomic pathways of peripancreatic fluid draining to mediastinum in recurrent acute pancreatitis: visible human project and CT study.

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    Haotong Xu

    Full Text Available BACKGROUND: In past reports, researchers have seldom attached importance to achievements in transforming digital anatomy to radiological diagnosis. However, investigators have been able to illustrate communication relationships in the retroperitoneal space by drawing potential routes in computerized tomography (CT images or a virtual anatomical atlas. We established a new imaging anatomy research method for comparisons of the communication relationships of the retroperitoneal space in combination with the Visible Human Project and CT images. Specifically, the anatomic pathways of peripancreatic fluid extension to the mediastinum that may potentially transform into fistulas were studied. METHODS: We explored potential pathways to the mediastinum based on American and Chinese Visible Human Project datasets. These drainage pathways to the mediastinum were confirmed or corrected in CT images of 51 patients with recurrent acute pancreatitis in 2011. We also investigated whether additional routes to the mediastinum were displayed in CT images that were not in Visible Human Project images. PRINCIPAL FINDINGS: All hypothesized routes to the mediastinum displayed in Visible Human Project images, except for routes from the retromesenteric plane to the bilateral retrorenal plane across the bilateral fascial trifurcation and further to the retrocrural space via the aortic hiatus, were confirmed in CT images. In addition, route 13 via the narrow space between the left costal and crural diaphragm into the retrocrural space was demonstrated for the first time in CT images. CONCLUSION: This type of exploration model related to imaging anatomy may be used to support research on the communication relationships of abdominal spaces, mediastinal spaces, cervical fascial spaces and other areas of the body.

  19. Human cord blood progenitors with high aldehyde dehydrogenase activity improve vascular density in a model of acute myocardial infarction

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    Creer Michael H

    2010-03-01

    Full Text Available Abstract Human stem cells from adult sources have been shown to contribute to the regeneration of muscle, liver, heart, and vasculature. The mechanisms by which this is accomplished are, however, still not well understood. We tested the engraftment and regenerative potential of human umbilical cord blood-derived ALDHhiLin-, and ALDHloLin- cells following transplantation to NOD/SCID or NOD/SCID β2m null mice with experimentally induced acute myocardial infarction. We used combined nanoparticle labeling and whole organ fluorescent imaging to detect human cells in multiple organs 48 hours post transplantation. Engraftment and regenerative effects of cell treatment were assessed four weeks post transplantation. We found that ALDHhiLin- stem cells specifically located to the site of injury 48 hours post transplantation and engrafted the infarcted heart at higher frequencies than ALDHloLin- committed progenitor cells four weeks post transplantation. We found no donor derived cardiomyocytes and few endothelial cells of donor origin. Cell treatment was not associated with any detectable functional improvement at the four week endpoint. There was, however, a significant increase in vascular density in the central infarct zone of ALDHhiLin- cell-treated mice, as compared to PBS and ALDHloLin- cell-treated mice. Conclusions Our data indicate that adult human stem cells do not become a significant part of the regenerating tissue, but rapidly home to and persist only temporarily at the site of hypoxic injury to exert trophic effects on tissue repair thereby enhancing vascular recovery.

  20. Impact of training status on LPS-induced acute inflammation in humans

    DEFF Research Database (Denmark)

    Olesen, Jesper; Biensø, Rasmus Sjørup; Meinertz, S.

    2015-01-01

    The aim of the present study was to examine the impact of training status on the ability to induce a lipopolysaccharide (LPS)-induced inflammatory response systemically as well as in skeletal muscle (SkM) and adipose tissue (AT) in human subjects. Methods: Seventeen young (23.8 ± 2.5 years of age...

  1. Retrograde flow and shear rate acutely impair endothelial function in humans.

    NARCIS (Netherlands)

    Thijssen, D.H.J.; Dawson, E.A.; Tinken, T.M.; Cable, N.T.; Green, D.J.

    2009-01-01

    Changes in arterial shear stress induce functional and structural vasculature adaptations. Recent studies indicate that substantial retrograde flow and shear can occur through human conduit arteries. In animals, retrograde shear is associated with atherogenic effects. The aim of this study was to

  2. Acute maternal rehydration increases the urine production rate in the near-term human fetus

    NARCIS (Netherlands)

    Haak, MC; Aarnoudse, JG; Oosterhof, H.

    OBJECTIVE: We sought to investigate the effect of a decrease of maternal plasma osmolality produced by hypotonic rehydration on the fetal urine production rate in normal near-term human fetuses. STUDY DESIGN: Twenty-one healthy pregnant women attending the clinic for antenatal care were studied

  3. Task shifting: Meeting the human resources needs for acute and emergency care in Africa

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    Benjamin Terry

    2012-12-01

    Full Text Available The enormous shortage of health workers in sub-Saharan Africa (SSA is a major contributor to the unacceptably high rates of morbidity and mortality in the region. This is especially true for patients whose illnesses and injuries require time-sensitive interventions. To address the crisis, a number of countries have utilized “task-shifting” in various health disciplines where they call upon other cadres, often nurses, to assume new roles and responsibilities that are not traditionally within their scope of practice. This practice has been shown to increase access, to be cost-effective and of high-quality. A literature review was undertaken to better understand the implications of task-shifting on emergency medical care in Africa. This review demonstrates that, while task-shifting has been used effectively for specific emergency procedures in specialty fields such as obstetrics and surgery, to date there are no studies on the use of task-shifting to treat the acute, undifferentiated patient in SSA. Task shifting is a potential solution to help address the very limited access to emergency care across SSA, but requires further study to ensure effective implementation.

  4. Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency

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    Alvaro Muñoz-López

    2016-10-01

    Full Text Available Induced pluripotent stem cells (iPSCs are a powerful tool for disease modeling. They are routinely generated from healthy donors and patients from multiple cell types at different developmental stages. However, reprogramming leukemias is an extremely inefficient process. Few studies generated iPSCs from primary chronic myeloid leukemias, but iPSC generation from acute myeloid or lymphoid leukemias (ALL has not been achieved. We attempted to generate iPSCs from different subtypes of B-ALL to address the developmental impact of leukemic fusion genes. OKSM(L-expressing mono/polycistronic-, retroviral/lentiviral/episomal-, and Sendai virus vector-based reprogramming strategies failed to render iPSCs in vitro and in vivo. Addition of transcriptomic-epigenetic reprogramming “boosters” also failed to generate iPSCs from B cell blasts and B-ALL lines, and when iPSCs emerged they lacked leukemic fusion genes, demonstrating non-leukemic myeloid origin. Conversely, MLL-AF4-overexpressing hematopoietic stem cells/B progenitors were successfully reprogrammed, indicating that B cell origin and leukemic fusion gene were not reprogramming barriers. Global transcriptome/DNA methylome profiling suggested a developmental/differentiation refractoriness of MLL-rearranged B-ALL to reprogramming into pluripotency.

  5. Therapeutic Effects of Myeloid Cell Leukemia-1 siRNA on Human Acute Myeloid Leukemia Cells

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    Hadi Karami

    2014-05-01

    Full Text Available Purpose: Up-regulation of Mcl-1, a known anti-apoptotic protein, is associated with the survival and progression of various malignancies including leukemia. The aim of this study was to explore the effect of Mcl-1 small interference RNA (siRNA on the proliferation and apoptosis of HL-60 acute myeloid leukemia (AML cells. Methods: siRNA transfection was performed using Lipofectamine™2000 reagent. Relative mRNA and protein expressions were quantified by quantitative real-time PCR and Western blotting, respectively. Trypan blue assay was performed to assess tumor cell proliferation after siRNA transfection. The cytotoxic effect of Mcl-1 siRNA on leukemic cells was measured using MTT assay. Apoptosis was detected using ELISA cell death assay. Results: Mcl-1 siRNA clearly lowered both Mcl-1 mRNA and protein levels in a time-dependent manner, leading to marked inhibition of cell survival and proliferation. Furthermore, Mcl-1 down-regulation significantly enhanced the extent of HL-60 apoptotic cells. Conclusion: Our results suggest that the down-regulation of Mcl-1 by siRNA can effectively trigger apoptosis and inhibit the proliferation of leukemic cells. Therefore, Mcl-1 siRNA may be a potent adjuvant in AML therapy.

  6. Personality and the acute subjective effects of d-amphetamine in humans.

    Science.gov (United States)

    Kirkpatrick, Matthew G; Johanson, Chris-Ellyn; de Wit, Harriet

    2013-03-01

    There is evidence that subjective responses to psychoactive drugs are related to personality traits. Here, we extend previous findings by examining personality measures in relation to acute responses to d-amphetamine (AMPH) in a large sample of healthy volunteers. Healthy adults (n=286) completed the Multidimensional Personality Questionnaire Brief Form (MPQ-BF) and participated in four sessions during which they received oral AMPH (0, 5, 10, 20 mg), under double-blind conditions. Subjective responses to the drug were measured using the Profile of Mood States, Addiction Research Center Inventory, and Drug Effects Questionnaire. Drug responses were reduced via principal components analysis to three higher-order factors ('Euphoria', 'Arousal', 'Dysphoria'). Participants were rank ordered on selected MPQ-BF scales; the top and bottom third on each trait were compared on the drug response factors. High trait physical fearlessness was significantly associated with greater amphetamine-related Arousal, and high trait reward sensitivity was significantly associated with greater Euphoria. In addition, high trait impulsivity was significantly associated with greater Arousal and Euphoria. These results provide further evidence that individual differences in the subjective effects of AMPH are partially explained by differences in personality, and are consistent with the idea that both personality and responses to stimulants depend upon shared neurochemical systems.

  7. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor–modified T cells

    Science.gov (United States)

    Gill, Saar; Tasian, Sarah K.; Ruella, Marco; Shestova, Olga; Li, Yong; Porter, David L.; Carroll, Martin; Danet-Desnoyers, Gwenn; Scholler, John; Grupp, Stephan A.; June, Carl H.

    2014-01-01

    Many patients with acute myeloid leukemia (AML) are incurable with chemotherapy and may benefit from novel approaches. One such approach involves the transfer of T cells engineered to express chimeric antigen receptors (CARs) for a specific cell-surface antigen. This strategy depends upon preferential expression of the target on tumor cells. To date, the lack of AML-specific surface markers has impeded development of such CAR-based approaches. CD123, the transmembrane α chain of the interleukin-3 receptor, is expressed in the majority of AML cells but is also expressed in many normal hematopoietic cells. Here, we show that CD123 is a good target for AML-directed CAR therapy, because its expression increases over time in vivo even in initially CD123dim populations, and that human CD123-redirected T cells (CART123) eradicate primary AML in immunodeficient mice. CART123 also eradicated normal human myelopoiesis, a surprising finding because anti-CD123 antibody-based strategies have been reportedly well tolerated. Because AML is likely preceded by clonal evolution in “preleukemic” hematopoietic stem cells, our observations support CART123 as a viable AML therapy, suggest that CART123-based myeloablation may be used as a novel conditioning regimen for hematopoietic cell transplantation, and raise concerns for the use of CART123 without such a rescue strategy. PMID:24596416

  8. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells.

    Science.gov (United States)

    Gill, Saar; Tasian, Sarah K; Ruella, Marco; Shestova, Olga; Li, Yong; Porter, David L; Carroll, Martin; Danet-Desnoyers, Gwenn; Scholler, John; Grupp, Stephan A; June, Carl H; Kalos, Michael

    2014-04-10

    Many patients with acute myeloid leukemia (AML) are incurable with chemotherapy and may benefit from novel approaches. One such approach involves the transfer of T cells engineered to express chimeric antigen receptors (CARs) for a specific cell-surface antigen. This strategy depends upon preferential expression of the target on tumor cells. To date, the lack of AML-specific surface markers has impeded development of such CAR-based approaches. CD123, the transmembrane α chain of the interleukin-3 receptor, is expressed in the majority of AML cells but is also expressed in many normal hematopoietic cells. Here, we show that CD123 is a good target for AML-directed CAR therapy, because its expression increases over time in vivo even in initially CD123(dim) populations, and that human CD123-redirected T cells (CART123) eradicate primary AML in immunodeficient mice. CART123 also eradicated normal human myelopoiesis, a surprising finding because anti-CD123 antibody-based strategies have been reportedly well tolerated. Because AML is likely preceded by clonal evolution in "preleukemic" hematopoietic stem cells, our observations support CART123 as a viable AML therapy, suggest that CART123-based myeloablation may be used as a novel conditioning regimen for hematopoietic cell transplantation, and raise concerns for the use of CART123 without such a rescue strategy.

  9. Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.

    Science.gov (United States)

    Kasper, Katherine J; Zeppa, Joseph J; Wakabayashi, Adrienne T; Xu, Stacey X; Mazzuca, Delfina M; Welch, Ian; Baroja, Miren L; Kotb, Malak; Cairns, Ewa; Cleary, P Patrick; Haeryfar, S M Mansour; McCormick, John K

    2014-05-01

    Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as 'trademark' virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II) molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS), how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6) mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC -II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms.

  10. Time-Dependent Alterations of MMPs, TIMPs and Tendon Structure in Human Achilles Tendons after Acute Rupture.

    Science.gov (United States)

    Minkwitz, Susann; Schmock, Aysha; Kurtoglu, Alper; Tsitsilonis, Serafeim; Manegold, Sebastian; Wildemann, Britt; Klatte-Schulz, Franka

    2017-10-20

    A balance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) is required to maintain tendon homeostasis. Variation in this balance over time might impact on the success of tendon healing. This study aimed to analyze structural changes and the expression profile of MMPs and TIMPs in human Achilles tendons at different time-points after rupture. Biopsies from 37 patients with acute Achilles tendon rupture were taken at surgery and grouped according to time after rupture: early (2-4 days), middle (5-6 days), and late (≥7 days), and intact Achilles tendons served as control. The histological score increased from the early to the late time-point after rupture, indicating the progression towards a more degenerative status. In comparison to intact tendons, qRT-PCR analysis revealed a significantly increased expression of MMP-1, -2, -13, TIMP-1, COL1A1, and COL3A1 in ruptured tendons, whereas TIMP-3 decreased. Comparing the changes over time post rupture, the expression of MMP-9, -13, and COL1A1 significantly increased, whereas MMP-3 and -10 expression decreased. TIMP expression was not significantly altered over time. MMP staining by immunohistochemistry was positive in the ruptured tendons exemplarily analyzed from early and late time-points. The study demonstrates a pivotal contribution of all investigated MMPs and TIMP-1, but a minor role of TIMP-2, -3, and -4, in the early human tendon healing process.

  11. Plumbagin exerts an immunosuppressive effect on human T-cell acute lymphoblastic leukemia MOLT-4 cells

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    Bae, Kyoung Jun; Lee, Yura [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of); Kim, Soon Ae [Department of Pharmacology, School of Medicine, Daejeon 34824 (Korea, Republic of); Kim, Jiyeon, E-mail: yeon@eulji.ac.kr [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of)

    2016-04-22

    Of the hematological disorders typified by poor prognoses and survival rates, T-cell acute lymphoblastic leukemia (T-ALL) is one of the most commonly diagnosed. Despite the development of new therapeutic agents, the treatment options for this cancer remain limited. In this manuscript, we investigated the anti-proliferative effects of plumbagin, mediated by the activation of mitogen-activated protein kinase (MAPK) pathways, and inhibition of NF-κB signaling; the human T-ALL MOLT-4 cell line was used as our experimental system. Plumbagin is a natural, plant derived compound, which exerts an anti-proliferative activity against many types of human cancer. Our experiments confirm that plumbagin induces a caspase-dependent apoptosis of MOLT-4 cells, with no significant cytotoxicity seen for normal peripheral blood mononuclear cells (PBMCs). Plumbagin also inhibited LPS-induced phosphorylation of p65, and the transcription of NF-κB target genes. Our results now show that plumbagin is a potent inhibitor of the NF-κB signaling pathway, and suppressor of T-ALL cell proliferation. - Highlights: • Plumbagin induces caspase-dependent apoptosis in T-ALL MOLT-4 cells. • Plumbagin activates phosphorylation of stress-activated protein kinase (SAPK) JNK and p38. • Plumbagin inhibits LPS-mediated NF-κB signaling cascade. • Plumbagin inhibits LPS-mediated transcriptional activity of pro-inflammatory cytokines.

  12. A Rapid Culture Technique Produces Functional Dendritic-Like Cells from Human Acute Myeloid Leukemia Cell Lines

    Directory of Open Access Journals (Sweden)

    Jian Ning

    2011-01-01

    Full Text Available Most anti-cancer immunotherapeutic strategies involving dendritic cells (DC as vaccines rely upon the adoptive transfer of DC loaded with exogenous tumour-peptides. This study utilized human acute myeloid leukemia (AML cells as progenitors from which functional dendritic-like antigen presenting cells (DLC were generated, that constitutively express tumour antigens for recognition by CD8+ T cells. DLC were generated from AML cell lines KG-1 and MUTZ-3 using rapid culture techniques and appropriate cytokines. DLC were evaluated for their cell-surface phenotype, antigen uptake and ability to stimulate allogeneic responder cell proliferation, and production of IFN-γ; compared with DC derived from normal human PBMC donors. KG-1 and MUTZ-3 DLC increased expression of CD80, CD83, CD86, and HLA-DR, and MUTZ-3 DLC downregulated CD14 and expressed CD1a. Importantly, both KG-1 and MUTZ-3-derived DLC promoted proliferation of allogeneic responder cells more efficiently than unmodified cells; neither cells incorporated FITC-labeled dextran, but both stimulated IFN-γ production from responding allogeneic CD8+ T cells. Control DC produced from PBMC using the FastDC culture also expressed high levels of critical cell surface ligands and demonstrated good APC function. This paper indicates that functional DLC can be cultured from the AML cell lines KG-1 and MUTZ-3, and FastDC culture generates functional KG-1 DLC.

  13. Time-Dependent Alterations of MMPs, TIMPs and Tendon Structure in Human Achilles Tendons after Acute Rupture

    Science.gov (United States)

    Minkwitz, Susann; Schmock, Aysha; Kurtoglu, Alper; Tsitsilonis, Serafeim; Manegold, Sebastian; Klatte-Schulz, Franka

    2017-01-01

    A balance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) is required to maintain tendon homeostasis. Variation in this balance over time might impact on the success of tendon healing. This study aimed to analyze structural changes and the expression profile of MMPs and TIMPs in human Achilles tendons at different time-points after rupture. Biopsies from 37 patients with acute Achilles tendon rupture were taken at surgery and grouped according to time after rupture: early (2–4 days), middle (5–6 days), and late (≥7 days), and intact Achilles tendons served as control. The histological score increased from the early to the late time-point after rupture, indicating the progression towards a more degenerative status. In comparison to intact tendons, qRT-PCR analysis revealed a significantly increased expression of MMP-1, -2, -13, TIMP-1, COL1A1, and COL3A1 in ruptured tendons, whereas TIMP-3 decreased. Comparing the changes over time post rupture, the expression of MMP-9, -13, and COL1A1 significantly increased, whereas MMP-3 and -10 expression decreased. TIMP expression was not significantly altered over time. MMP staining by immunohistochemistry was positive in the ruptured tendons exemplarily analyzed from early and late time-points. The study demonstrates a pivotal contribution of all investigated MMPs and TIMP-1, but a minor role of TIMP-2, -3, and -4, in the early human tendon healing process. PMID:29053586

  14. Acute Human Lethal Toxicity of Agricultural Pesticides: A Prospective Cohort Study

    Science.gov (United States)

    Senarathna, Lalith; Mohamed, Fahim; Gawarammana, Indika; Bowe, Steven J.; Manuweera, Gamini; Buckley, Nicholas A.

    2010-01-01

    Background Agricultural pesticide poisoning is a major public health problem in the developing world, killing at least 250,000–370,000 people each year. Targeted pesticide restrictions in Sri Lanka over the last 20 years have reduced pesticide deaths by 50% without decreasing agricultural output. However, regulatory decisions have thus far not been based on the human toxicity of formulated agricultural pesticides but on the surrogate of rat toxicity using pure unformulated pesticides. We aimed to determine the relative human toxicity of formulated agricultural pesticides to improve the effectiveness of regulatory policy. Methods and Findings We examined the case fatality of different agricultural pesticides in a prospective cohort of patients presenting with pesticide self-poisoning to two clinical trial centers from April 2002 to November 2008. Identification of the pesticide ingested was based on history or positive identification of the container. A single pesticide was ingested by 9,302 patients. A specific pesticide was identified in 7,461 patients; 1,841 ingested an unknown pesticide. In a subset of 808 patients, the history of ingestion was confirmed by laboratory analysis in 95% of patients. There was a large variation in case fatality between pesticides—from 0% to 42%. This marked variation in lethality was observed for compounds within the same chemical and/or WHO toxicity classification of pesticides and for those used for similar agricultural indications. Conclusion The human data provided toxicity rankings for some pesticides that contrasted strongly with the WHO toxicity classification based on rat toxicity. Basing regulation on human toxicity will make pesticide poisoning less hazardous, preventing hundreds of thousands of deaths globally without compromising agricultural needs. Ongoing monitoring of patterns of use and clinical toxicity for new pesticides is needed to identify highly toxic pesticides in a timely manner. Please see later in the

  15. Acute stress reduces wound-induced activation of microbicidal potential of ex vivo isolated human monocyte-derived macrophages.

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    Ulrike Kuebler

    Full Text Available BACKGROUND: Psychological stress delays wound healing but the precise underlying mechanisms are unclear. Macrophages play an important role in wound healing, in particular by killing microbes. We hypothesized that (a acute psychological stress reduces wound-induced activation of microbicidal potential of human monocyte-derived macrophages (HMDM, and (b that these reductions are modulated by stress hormone release. METHODS: Fourty-one healthy men (mean age 35 ± 13 years were randomly assigned to either a stress or stress-control group. While the stress group underwent a standardized short-term psychological stress task after catheter-induced wound infliction, stress-controls did not. Catheter insertion was controlled. Assessing the microbicidal potential, we investigated PMA-activated superoxide anion production by HMDM immediately before and 1, 10 and 60 min after stress/rest. Moreover, plasma norepinephrine and epinephrine and salivary cortisol were repeatedly measured. In subsequent in vitro studies, whole blood was incubated with norepinephrine in the presence or absence of phentolamine (norepinephrine blocker before assessing HMDM microbicidal potential. RESULTS: Compared with stress-controls, HMDM of the stressed subjects displayed decreased superoxide anion-responses after stress (p's <.05. Higher plasma norepinephrine levels statistically mediated lower amounts of superoxide anion-responses (indirect effect 95% CI: 4.14-44.72. Norepinephrine-treated HMDM showed reduced superoxide anion-production (p<.001. This effect was blocked by prior incubation with phentolamine. CONCLUSIONS: Our results suggest that acute psychological stress reduces wound-induced activation of microbicidal potential of HMDM and that this reduction is mediated by norepinephrine. This might have implications for stress-induced impairment in wound healing.

  16. Effect of Acetazolamide and Gingko Biloba on the Human Pulmonary Vascular Response to an Acute Altitude Ascent

    Science.gov (United States)

    Ke, Tao; Wang, Jiye; Swenson, Erik R.; Zhang, Xiangnan; Hu, Yunlong; Chen, Yaoming; Liu, Mingchao; Zhang, Wenbin; Zhao, Feng; Shen, Xuefeng; Yang, Qun

    2013-01-01

    Abstract Ke, Tao, Jiye Wang, Erik R. Swenson, Xiangnan Zhang, Yunlong Hu, Yaoming Chen, Mingchao Liu, Wenbin Zhang, Feng Zhao, Xuefeng Shen, Qun Yang, Jingyuan Chen, and Wenjing Luo. Effect of acetazolamide and gingko biloba on the human pulmonary vascular response to an acute altitude ascent. High Alt Med Biol 14:162–167, 2013.—Acetazolamide and gingko biloba are the two most investigated drugs for the prevention of acute mountain sickness (AMS). Evidence suggests that they may also reduce pulmonary artery systolic pressure (PASP). To investigate whether these two drugs for AMS prevention also reduce PASP with rapid airlift ascent to high altitude, a randomized controlled trial was conducted on 28 healthy young men with acetazolamide (125 mg bid), gingko biloba (120 mg bid), or placebo for 3 days prior to airlift ascent (397 m) and for the first 3 days at high altitude (3658 m). PASP, AMS, arterial oxygen saturation (Sao2), mean arterial pressure (MAP), heart rate (HR), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF) were assessed both at 397 m and 3658 m. HR, PEF, and PASP increased with altitude exposure (pbiloba (mean at 3658 m, 33.7 mm Hg, p=0.001; incremental change, 13.1 mm Hg, 95%CI., 9.6–16.5 mm Hg, p=0.002), and with placebo (mean at 3658 m, 34.7 mm Hg, pgingko biloba, mitigates the early increase of PASP in a quick ascent profile. PMID:23795737

  17. Functional assessment of the acute local and distal transplantation of human neural stem cells after spinal cord injury.

    Science.gov (United States)

    Cheng, Ivan; Mayle, Robert E; Cox, Christopher A; Park, Don Y; Smith, Robert L; Corcoran-Schwartz, Ian; Ponnusamy, Karthikeyan E; Oshtory, Rayshad; Smuck, Matthew W; Mitra, Raj; Kharazi, Alexander I; Carragee, Eugene J

    2012-11-01

    Spinal cord injury can lead to severe functional impairments secondary to axonal damage, neuronal loss, and demyelination. The injured spinal cord has limited regrowth of damaged axons. Treatment remains controversial, given inconsistent functional improvement. Previous studies demonstrated functional recovery of rats with spinal cord contusion after transplantation of rat fetal neural stem cells. We hypothesized that acute transplantation of human fetal neural stem cells (hNSCs) both locally at the injury site as well as distally via intrathecal injection would lead to improved functional recovery compared with controls. Twenty-four adult female Long-Evans hooded rats were randomized into four groups with six animals in each group: two experimental and two control. Functional assessment was measured after injury and then weekly for 6 weeks using the Basso, Beattie, and Bresnahan Locomotor Rating Score. Data were analyzed using two-sample t test and linear mixed-effects model analysis. Posterior exposure and laminectomy at T10 level was used. Moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor with 10-g weight dropped from a height of 25 mm. Experimental subjects received either a subdural injection of hNSCs locally at the injury site or intrathecal injection of hNSCs through a separate distal laminotomy. Controls received control media injection either locally or distally. Statistically significant functional improvement was observed in local or distal hNSCs subjects versus controls (p=.034 and 0.016, respectively). No significant difference was seen between local or distal hNSC subjects (p=.66). Acute local and distal transplantation of hNSCs into the contused spinal cord led to significant functional recovery in the rat model. No statistical difference was found between the two techniques. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Metabolomics reveals increased isoleukotoxin diol (12,13-DHOME) in human plasma after acute Intralipid infusion.

    Science.gov (United States)

    Edwards, Lindsay M; Lawler, Nathan G; Nikolic, Sonja B; Peters, James M; Horne, James; Wilson, Richard; Davies, Noel W; Sharman, James E

    2012-09-01

    Intralipid is a fat emulsion that is regularly infused into humans and animals. Despite its routine use, Intralipid infusion can cause serious adverse reactions, including immunosuppression. Intralipid is a complex mix of proteins, lipids, and other small molecules, and the effect of its infusion on the human plasma metabolome is unknown. We hypothesized that untargeted metabolomics of human plasma after an Intralipid infusion would reveal novel insights into its effects. We infused Intralipid and saline into 10 healthy men in a double-blind, placebo-controlled experiment and used GC/MS, LC/MS, and NMR to profile the small-molecule composition of their plasma before and after infusion. Multivariate statistical analysis of the 40 resulting plasma samples revealed that after Intralipid infusion, a less-well-characterized pathway of linoleic acid metabolism had resulted in the appearance of (9Z)-12,13-dihydroxyoctadec-9-enoic acid (12,13-DHOME, P plasma 12,13-DHOME. Given that 12,13-DHOME is known to directly affect neutrophil function, we conclude that untargeted metabolomics may have revealed a hitherto-unknown mechanism of intralipid-induced immunosuppression.

  19. Human performance under sustained operations and acute sleep deprivation conditions: toward a model of controlled attention.

    Science.gov (United States)

    Pilcher, June J; Band, David; Odle-Dusseau, Heather N; Muth, Eric R

    2007-05-01

    Although a number of studies have examined the effects of sleep deprivation on performance, the results are not easily explained. The purpose of the current study was to examine the effects of sustained operations and acute sleep deprivation on tasks that require a wide range of information processing. The current study also provided preliminary data on the use of the controlled attention model to better understand the effects of sleep deprivation. There were 24 college students who were paid to remain awake for one night and complete a variety of cognitive and vigilance tasks. Each task was administered four times during the night, once in each testing session (17:30-21:30, 21:45-01:45, 02:30-06:30, and 06:45-10:45). All tasks were counterbalanced across the testing sessions. The data were converted to z-scores and repeated-measures ANOVAs were completed. Performance did not significantly decrease on the more complex cognitive tasks over the night of sleep deprivation. Performance on the vigilance tasks decreased significantly across the night. Examining the characteristics of the cognitive tasks indicated that although they required different types of processing, they encouraged the participants to remain attentive to and engaged in the task. In contrast, the vigilance tasks were less intrinsically interesting and engaging. Thus, it seems likely that the participants were less capable of maintaining attention on the vigilance tasks than the cognitive tasks. These results indicate that a controlled attention model may be useful in better understanding the effects of sustained operations and sleep deprivation on performance.

  20. Regulation of cancer stem cell properties by CD9 in human B-acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Hiroto [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Wilson Xu, C. [Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States); Naito, Motohiko [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Nishida, Hiroko [Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan); Okamoto, Toshihiro; Ghani, Farhana Ishrat; Iwata, Satoshi [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Inukai, Takeshi; Sugita, Kanji [Department of Pediatrics, School of Medicine, University of Yamanashi, Yamanashi (Japan); Morimoto, Chikao, E-mail: morimoto@ims.u-tokyo.ac.jp [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States)

    2011-05-27

    Highlights: {yields} We performed more detailed analysis of CD9 function for CSC properties in B-ALL. {yields} Leukemogenic fusion/Src family proteins were markedly regulated in the CD9{sup +} cells. {yields} Proliferation of B-ALL cells was inhibited by anti-CD9 monoclonal antibody. {yields} Knockdown of CD9 by RNAi remarkably reduced the leukemogenic potential. {yields} CD9-knockdown affected the expression and phosphorylation of Src family and USP22. -- Abstract: Although the prognosis of acute lymphoblastic leukemia (ALL) has improved considerably in recent years, some of the cases still exhibit therapy-resistant. We have previously reported that CD9 was expressed heterogeneously in B-ALL cell lines and CD9{sup +} cells exhibited an asymmetric cell division with greater tumorigenic potential than CD9{sup -} cells. CD9{sup +} cells were also serially transplantable in immunodeficient mice, indicating that CD9{sup +} cell possess self-renewal capacity. In the current study, we performed more detailed analysis of CD9 function for the cancer stem cell (CSC) properties. In patient sample, CD9 was expressed in the most cases of B-ALL cells with significant correlation of CD34-expression. Gene expression analysis revealed that leukemogenic fusion proteins and Src family proteins were significantly regulated in the CD9{sup +} population. Moreover, CD9{sup +} cells exhibited drug-resistance, but proliferation of bulk cells was inhibited by anti-CD9 monoclonal antibody. Knockdown of CD9 remarkably reduced the leukemogenic potential. Furthermore, gene ablation of CD9 affected the expression and tyrosine-phosphorylation of Src family proteins and reduced the expression of histone-deubiquitinase USP22. Taken together, our results suggest that CD9 links to several signaling pathways and epigenetic modification for regulating the CSC properties of B-ALL.

  1. A STUDY OF THE PROTEOLYTIC FERMENTS OF THE LARGE LYMPHOCYTES IN A CASE OF ACUTE LEUKAEMIA.

    Science.gov (United States)

    Longcope, W T; Donhauser, J L

    1908-09-05

    The leucocytes of the blood of normal individuals and of patients showing a marked polymorphonuclear leucocytosis contain enzymes capable of digesting coagulated blood serum in neutral, alkaline or acid solutions. The cells in pus that is composed principally of polymorphonuclear leucocytes and the leucocytes of the circulating blood in myelogeneous leukaemia contain similar proteolytic enzymes, which act best when the reaction is alkaline. The leucocytes of the circulating blood and of the enlarged lymph nodes from a case of large cell, acute, lymphatic leukaemia contain proteolytic enzymes that act qualitatively in much the same way as the leucocytes of pus and as the white corpuscles of the blood in myelogenous leukaemia. These large lymphocytes in acute lymphatic leukaemia can be differentiated biologically from the small lymphocytes in chronic lymphatic leukaemia which possess no proteolytic enzymes, and from the large endothelioid cells of the hyperplastic lymph glands which are proteolytic only in the presence of acid. These results seem to show that the large cells of the so-called acute lymphatic leukaemia are not true lymphocytes, but are nearly related to the granular myelocytes and should probably be considered as the forerunners to these cells.

  2. Human Platelets Express Functional Thymic Stromal Lymphopoietin Receptors: a Potential Role in Platelet Activation in Acute Coronary Syndrome

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    Boyuan Wang

    2013-12-01

    Full Text Available Background: Thymic stromal lymphopoietin (TSLP has been shown to be expressed in various inflammatory tissues, such as human atherosclerotic plaques. Many types of myeloid cells involved in atherosclerosis, including mast cells, lymphocytes, dendritic cells and monocytes/macrophages, present TSLP receptors (TSLPR. However, it is unknown whether platelets, which also play important roles in atherothrombosis, express TSLPR. Methods and Results: We applied flow cytometry and western blotting to show that TSLPR was expressed on the surface of human platelets. Following the addition of TSLP to platelets, the expression of CD62P, CD63, PAC-1 and p-Akt as well as aggregation and ATP release were increased significantly. A TSLPR antibody and a PI3K (phosphatidylinositol 3-kinase enzyme inhibitor (LY294002 significantly inhibited the platelet activation induced by TSLP. The expression of TSLPR, CD62P and CD63 and the increment of the expression of CD62P and CD63 induced by TSLP in the acute coronary syndrome (ACS group were markedly higher than those in the control group and the stable angina pectoris (SAP group. The expression and the increment of the expression of CD62P and CD63 induced by TSLP were positively correlated with the expression of TSLPR. Conclusion: Human platelets express functional TSLPR, which can be activated by TSLP to promote platelet activation. TSLP/TSLPR functions via activating the PI3K/AKT pathway, and this signalling pathway may be one of the mechanisms involved in thrombosis in ACS. In coronary disease patients, the determination of TSLPR in platelets may help to identify the risk of ACS.

  3. Molecular typing and epidemiology profiles of human adenovirus infection among paediatric patients with severe acute respiratory infection in China.

    Science.gov (United States)

    Li, Yamin; Zhou, Weimin; Zhao, Yanjie; Wang, Yanqun; Xie, Zhengde; Lou, Yongliang; Tan, Wenjie

    2015-01-01

    Human adenoviruses (HAdVs) have been recognised as pathogens that cause a broad spectrum of diseases. The studies on HAdV infection among children with severe acute respiratory infection (SARI) are limited. To investigate the prevalence, epidemiology, and genotype of HAdV among children with SARI in China. Nasopharyngeal aspirates (NPAs) or induced sputum (IS) was collected from hospitalised children with SARIs in Beijing (representing Northern China; n = 259) and Zhejiang Province (representing Eastern China; n = 293) from 2007 to 2010. The prevalence of HAdV was screened by polymerase chain reaction (PCR), followed by sequence typing of PCR fragments that targeted the second half of the hexon gene. In addition, co-infection with other human respiratory viruses, related epidemiological profiles and clinical presentations were investigated. In total, 76 (13.8%) of 552 SARI patients were positive for HAdV, and the infection rates of HAdV in Northern and Eastern China were 20.1% (n = 52) and 8.2% (n = 24), respectively. HAdV co-infection with other respiratory viruses was frequent (infection rates: Northern China, 90.4%; Eastern China, 70.8%). The peak seasons for HAdV-B infection was winter and spring. Additionally, members of multiple species (Human mastadenovirus B, C, D and E) were circulating among paediatric patients with SARI, of which HAdV-B (34/52; 65.4%) and HAdV-C (20/24, 83.3%) were the most predominant in Northern and Eastern China, respectively. These findings provide a benchmark for future epidemiology and prevention strategies for HAdV.

  4. Monocyte subset accumulation in the human heart following acute myocardial infarction and the role of the spleen as monocyte reservoir.

    Science.gov (United States)

    van der Laan, Anja M; Ter Horst, Ellis N; Delewi, Ronak; Begieneman, Mark P V; Krijnen, Paul A J; Hirsch, Alexander; Lavaei, Mehrdad; Nahrendorf, Matthias; Horrevoets, Anton J; Niessen, Hans W M; Piek, Jan J

    2014-02-01

    Monocytes are critical mediators of healing following acute myocardial infarction (AMI), making them an interesting target to improve myocardial repair. The purpose of this study was a gain of insight into the source and recruitment of monocytes following AMI in humans. Post-mortem tissue specimens of myocardium, spleen and bone marrow were collected from 28 patients who died at different time points after AMI. Twelve patients who died from other causes served as controls. The presence and localization of monocytes (CD14(+) cells), and their CD14(+)CD16(-) and CD14(+)CD16(+) subsets, were evaluated by immunohistochemical and immunofluorescence analyses. CD14(+) cells localized at distinct regions of the infarcted myocardium in different phases of healing following AMI. In the inflammatory phase after AMI, CD14(+) cells were predominantly located in the infarct border zone, adjacent to cardiomyocytes, and consisted for 85% (78-92%) of CD14(+)CD16(-) cells. In contrast, in the subsequent post-AMI proliferative phase, massive accumulation of CD14(+) cells was observed in the infarct core, containing comparable proportions of both the CD14(+)CD16(-) [60% (31-67%)] and CD14(+)CD16(+) subsets [40% (33-69%)]. Importantly, in AMI patients, of the number of CD14(+) cells was decreased by 39% in the bone marrow and by 58% in the spleen, in comparison with control patients (P = 0.02 and <0.001, respectively). Overall, this study showed a unique spatiotemporal pattern of monocyte accumulation in the human myocardium following AMI that coincides with a marked depletion of monocytes from the spleen, suggesting that the human spleen contains an important reservoir function for monocytes.

  5. Molecular basis of arsenite (As+3-induced acute cytotoxicity in human cervical epithelial carcinoma cells

    Directory of Open Access Journals (Sweden)

    Muhammad Nauman Arshad

    2015-04-01

    Full Text Available Background: Rapid industrialization is discharging toxic heavy metals into the environment, disturbing human health in many ways and causing various neurologic, cardiovascular, and dermatologic abnormalities and certain types of cancer. The presence of arsenic in drinking water from different urban and rural areas of the major cities of Pakistan, for example, Lahore, Faisalabad, and Kasur, was found to be beyond the permissible limit of 10 parts per billion set by the World Health Organization. Therefore the present study was initiated to examine the effects of arsenite (As+3 on DNA biosynthesis and cell death. Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and flow cytometry. Results: We show that As+3 ions have a dose- and time-dependent cytotoxic effect through the activation of the caspase-dependent apoptotic pathway. In contrast to previous research, the present study was designed to explore the early cytotoxic effects produced in human cells during exposure to heavy dosage of As+3 (7.5 µg/ml. Even treatment for 1 h significantly increased the mRNA levels of p21 and p27 and caspases 3, 7, and 9. It was interesting that there was no change in the expression levels of p53, which plays an important role in G2/M phase cell cycle arrest. Conclusion: Our results indicate that sudden exposure of cells to arsenite (As+3 resulted in cytotoxicity and mitochondrial-mediated apoptosis resulting from up-regulation of caspases.

  6. Pulmonary Inflammatory Responses To Acute Meteorite Dust Exposures - Implications For Human Space Exploration

    Science.gov (United States)

    Harrington, A. D.; McCubbin, F. M.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

    2017-01-01

    The previous manned missions to the Moon represent milestones of human ingenuity, perseverance, and intellectual curiosity. However, one of the major ongoing concerns is the array of hazards associated with lunar surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness" (Figure 1). It was further reported that the allergic response to the dust worsened with each exposure. The lack of gravity exacerbated the exposure, requiring the astronauts to wear their helmet within the module in order to avoid breathing the irritating particles. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment. Studies on the lunar highland regolith indicate that the dust is not only respirable but also reactive, and previous studies concluded that it is moderately toxic; generating a greater response than titanium oxide but a lower response than quartz. The presence of reactive oxygen species (ROS) on the surface of the dust has been implicated. However, there is actually little data related to physicochemical characteristics of particulates and pulmonary toxicity, especially as it relates to celestial dust exposure. As a direct response to this deficit, the present study evaluates the role of a particulate's innate geochemical features (e.g., bulk chemistry, internal composition, morphology, size, and reactivity) in generating adverse toxicological responses in vitro and in vivo. This highly interdisciplinary study evaluates the relative

  7. Acute Meteorite Dust Exposure and Pulmonary Inflammation - Implications for Human Space Exploration

    Science.gov (United States)

    Harrington, A. D.; McCubbin, F. M.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

    2017-01-01

    The previous manned missions to the Moon represent milestones of human ingenuity, perseverance, and intellectual curiosity. However, one of the major ongoing concerns is the array of hazards associated with lunar surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness [1-3]" (Figure 1). It was further reported that the allergic response to the dust worsened with each exposure [4]. The lack of gravity exacerbated the exposure, requiring the astronauts to wear their helmet within the module in order to avoid breathing the irritating particles [1]. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern [5]. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment. Studies on the lunar highland regolith indicate that the dust is not only respirable but also reactive [2, 6-9], and previous studies concluded that it is moderately toxic; generating a greater response than titanium oxide but a lower response than quartz [6]. The presence of reactive oxygen species (ROS) on the surface of the dust has been implicated. However, there is actually little data related to physicochemical characteristics of particulates and pulmonary toxicity, especially as it relates to celestial dust exposure. As a direct response to this deficit, the present study evaluates the role of a particulate's innate geochemical features (e.g., bulk chemistry, internal composition, morphology, size, and reactivity) in generating adverse toxicological responses in vitro and in vivo. This highly interdisciplinary

  8. Cytomegalovirus infection presenting as acute periodontal infection in a patient infected with the human immunodeficiency virus.

    Science.gov (United States)

    Dodd, C L; Winkler, J R; Heinic, G S; Daniels, T E; Yee, K; Greenspan, D

    1993-04-01

    During childhood, many people acquire primary infection with cytomegalovirus (CMV), one of the herpes viruses. If they later become immunosuppressed, such as occurs with human immunodeficiency virus (HIV) infection, CMV is likely to become reactivated. Severe disease caused by CMV is life-threatening in the HIV-infected population. CMV retinitis, gastritis, colitis, pneumonia, encephalitis and hepatitis have all been reported, but oral lesions due to infection with CMV are rarely reported. We report a case of oral CMV infection which at first was clinically indistinguishable from HIV-associated periodontal disease.

  9. Kudzu extract treatment does not increase the intoxicating effects of acute alcohol in human volunteers.

    Science.gov (United States)

    Penetar, David M; Maclean, Robert R; McNeil, Jane F; Lukas, Scott E

    2011-04-01

    Isoflavone administration in the form of a purified extract from the herbal medication kudzu root has been shown to reduce, but not eliminate, alcohol consumption in alcohol-abusing and alcohol-dependent men. The precise mechanism of this action is unknown, but 1 possible explanation for these results is that the isoflavones in kudzu might actually increase the intensity or duration of alcohol's effects and thus delay the desire for subsequent drinks. This study was designed to test this hypothesis. Twelve (12) healthy adult men and women (27.5 ± 1.89 years old) who consumed moderate amounts of alcohol (7.8 ± 0.63 drinks/wk) participated in a double-blinded, placebo-controlled crossover study in which they were treated with either kudzu extract (total isoflavone dose of 750 mg/d) or matched placebo for 9 days. On days 8 and 9, participants received an acute challenge of ethyl alcohol (either 0.35 or 0.7 g/kg alcohol). During the challenges, the following measures were collected: subjective effects, psychomotor (body sway), cognitive performance (vigilance/reaction time), physiological measures (heart rate and skin temperature), and plasma ethanol concentration. Alcohol resulted in a dose-related alteration in subjective measures of intoxication, impairment of stance stability, and vigilance/reaction time. Kudzu extract did not alter participants' subjective responses to the alcohol challenge or to alcohol's effects on stance stability or vigilance/reaction time. However, individuals treated with kudzu extract experienced a slightly more rapid rise in plasma ethanol levels, but only after the 0.7 g/kg dose. This transient effect during the first 30 minutes of the ascending plasma alcohol curve lasted only 10-15 minutes; there were no differences in peak plasma alcohol levels or alcohol elimination kinetics. Additionally, kudzu pretreatment enhanced the effects of the 0.7 g/kg dose of alcohol on heart rate and skin temperature. These data suggest that individuals

  10. Cardiac αVβ3integrin expression following acute myocardial infarction in humans.

    Science.gov (United States)

    Jenkins, William S A; Vesey, Alex T; Stirrat, Colin; Connell, Martin; Lucatelli, Christophe; Neale, Anoushka; Moles, Catriona; Vickers, Anna; Fletcher, Alison; Pawade, Tania; Wilson, Ian; Rudd, James H F; van Beek, Edwin J R; Mirsadraee, Saeed; Dweck, Marc R; Newby, David E

    2017-04-01

    Maladaptive repair contributes towards the development of heart failure following myocardial infarction (MI). The α v β 3 integrin receptor is a key mediator and determinant of cardiac repair. We aimed to establish whether α v β 3 integrin expression determines myocardial recovery following MI. 18 F-Fluciclatide (a novel α v β 3 -selective radiotracer) positron emission tomography (PET) and CT imaging and gadolinium-enhanced MRI (CMR) were performed in 21 patients 2 weeks after ST-segment elevation MI (anterior, n=16; lateral, n=4; inferior, n=1). CMR was repeated 9 months after MI. 7 stable patients with chronic total occlusion (CTO) of a major coronary vessel and nine healthy volunteers underwent a single PET/CT and CMR. 18 F-Fluciclatide uptake was increased at sites of acute infarction compared with remote myocardium (tissue-to-background ratio (TBR mean ) 1.34±0.22 vs 0.85±0.17; pinfarction in patients with CTO, with activity similar to the myocardium of healthy volunteers (TBR mean 0.71±0.06 vs 0.70±0.03, p=0.83). 18 F-Fluciclatide uptake occurred at sites of regional wall hypokinesia (wall motion index≥1 vs 0; TBR mean 0.93±0.31 vs 0.80±0.26 respectively, pinfarction. Importantly, although there was no correlation with infarct size (r=0.03, p=0.90) or inflammation (C reactive protein, r=-0.20, p=0.38), 18 F-fluciclatide uptake was increased in segments displaying functional recovery (TBR mean 0.95±0.33 vs 0.81±0.27, p=0.002) and associated with increase in probability of regional recovery. 18 F-Fluciclatide uptake is increased at sites of recent MI acting as a biomarker of cardiac repair and predicting regions of recovery. NCT01813045; Post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Human Respiratory Syncytial Virus load normalized by cell quantification as predictor of acute respiratory tract infection.

    Science.gov (United States)

    Gómez-Novo, Miriam; Boga, José A; Álvarez-Argüelles, Marta E; Rojo-Alba, Susana; Fernández, Ana; Menéndez, María J; de Oña, María; Melón, Santiago

    2018-01-05

    Human respiratory syncytial virus (HRSV) is a common cause of respiratory infections. The main objective is to analyze the prediction ability of viral load of HRSV normalized by cell number in respiratory symptoms. A prospective, descriptive and analytical study was performed. From 7307 respiratory samples processed between December 2014 to April 2016, 1019 HRSV-positive samples, were included in this study. Low respiratory tract infection was present in 729 patients (71.54%). Normalized HRSV load was calculated by quantification of HRSV genome and human β-globin gene and expressed as log10 copies/1000 cells. HRSV mean loads were 4.09 ± 2.08 and 4.82 ± 2.09 log10 copies/1000 cells in the 549 pharyngeal and 470 nasopharyngeal samples, respectively (p respiratory tract infection and 4.22 ± 2.28 log10 copies/1000 cells with upper respiratory tract infection or febrile syndrome (p < 0.05). A possible cut off value to predict LRTI evolution was tentatively established. Normalization of viral load by cell number in the samples is essential to ensure an optimal virological molecular diagnosis avoiding that the quality of samples affects the results. A high viral load can be a useful marker to predict disease progression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase.

    Science.gov (United States)

    Khan, Sitara G; Melikian, Narbeh; Shabeeh, Husain; Cabaco, Ana R; Martin, Katherine; Khan, Faisal; O'Gallagher, Kevin; Chowienczyk, Philip J; Shah, Ajay M

    2017-09-01

    Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion (P nitric oxide synthase in the human coronary circulation.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/. Copyright © 2017 the American Physiological Society.

  13. Retrograde flow and shear rate acutely impair endothelial function in humans.

    Science.gov (United States)

    Thijssen, Dick H J; Dawson, Ellen A; Tinken, Toni M; Cable, N Timothy; Green, Daniel J

    2009-06-01

    Changes in arterial shear stress induce functional and structural vasculature adaptations. Recent studies indicate that substantial retrograde flow and shear can occur through human conduit arteries. In animals, retrograde shear is associated with atherogenic effects. The aim of this study was to examine the impact of incremental levels of retrograde shear on endothelial function in vivo. On 3 separate days, we examined bilateral brachial artery flow-mediated dilation, an index of NO-mediated endothelial function, in healthy men (24+/-3 years) before and after a 30-minute intervention consisting of cuff inflation to 25, 50, or 75 mm Hg. Cuff inflations resulted in "dose"-dependent increases in retrograde shear rate, compared with the noncuffed arm, within subjects (P<0.001). Flow-mediated dilation in the cuffed arm did not change in response to the 25-mm Hg stimulus but decreased significantly after both the 50- and 75-mm Hg interventions (P<0.05). The decrease in flow-mediated dilation after the 75-mm Hg intervention was significantly larger than that observed after a 50-mm Hg intervention (P=0.03). In the noncuffed arm, no changes in shear rate or flow-mediated dilation were observed. These results demonstrate that an increase in retrograde shear rate induces a dose-dependent attenuation of endothelial function in humans. This finding contributes to our understanding regarding the possible detrimental effects of retrograde shear rate in vivo.

  14. The first imported human case of Yersinia pseudotuberculosis serotype O1 septicemia presents with acute appendicitis-like syndrome in Taiwan

    Directory of Open Access Journals (Sweden)

    Chung-Hsu Lai

    2014-09-01

    Full Text Available Human nonplague yersiniosis occurs more commonly in temperate regions than in tropical or subtropical regions. In Taiwan, which is located in a subtropical region of Southeast Asia, only environmental isolates and human infection of Yersinia enterocolitica were reported, but a human case of Y. pseudotuberculosis infection had not been identified. We report the first person with Y. pseudotuberculosis serotype O1 septicemia who presented with acute appendicitis-like syndrome and who was probably contracted the infection via ingestion of raw foods in a barbecue restaurant in Japan.

  15. Evolution of IgG antibody response against Toxoplasma gondii tissue cyst in acute and chronic human infections

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    Margarita VILLAVEDRA

    1998-03-01

    Full Text Available The recognition profile of the tissue cysts antigens by IgG antibodies was studied during acute and chronic human toxoplasmic infection. Thus the IgG response against Toxoplasma gondii was investigated by immunoblotting in two patients accidentally infected with the RH strain as well as in group of naturally infected patients at acute and chronic phase. There was an overall coincidence of molecular mass among antigens of tachyzoites and tissue cysts recognized by these sera, however, they appear not to be the same molecules. The response against tissue cysts starts early during acute infection, and the reactivity of antibodies is strong against a wide range of antigens. Six bands (between 82 and 151 kDa were exclusively recognized by chronic phase sera but only the 132 kDa band was positive in more than 50% of the sera analysed. A mixture of these antigens could be used to discriminate between the two infection phases. The most important antigens recognized by the acute and the chronic phase sera were 4 clusters in the ranges 20-24 kDa, 34-39 kDa, 58-80 kDa and 105-130 kDa as well as two additional antigens of 18 and 29 kDa. Both accidentally infected patients and some of the naturally infected patients showed a weak specific response against tissue cyst antigens.O reconhecimento do perfil dos antígenos de cistos tissulares pelos anticorpos IgG foi estudado durante a infecção toxoplasmótica aguda e crônica. Assim a resposta de IgG contra Toxoplasma gondii foi investigada pelo "immunoblotting" em dois pacientes acidentalmente infectados com a variedade RH bem como em grupos de pacientes naturalmente infectados nas fases aguda e crônica. Houve uma coincidência global da massa molecular entre antígenos de taquizoitas e cistos tissulares reconhecidos por estes soros, todavia, eles parecem não ser as mesmas moléculas. A resposta contra cistos tissulares começa precocemente durante a infecção aguda e a reatividade de anticorpos é forte

  16. Inhibitory effect of human recombinant interferon gamma on synthesis of acute phase proteins in human hepatoma Hep G2 cells stimulated by leukocyte cytokines, TNF alpha and IFN-beta 2/BSF-2/IL-6.

    Science.gov (United States)

    Magielska-Zero, D; Bereta, J; Czuba-Pelech, B; Pajdak, W; Gauldie, J; Koj, A

    1988-07-01

    Supernatants from endotoxin-stimulated human leukemic cells and human recombinant interferon-beta 2 similarly enhance synthesis of alpha 1-antichymotrypsin and haptoglobin but suppress synthesis of albumin in cultured Hep G2 cells. Human recombinant tumor necrosis factor only slightly affects production of alpha 1-antichymotrypsin and albumin in a similar manner as leukocyte cytokines. In distinction, recombinant human interferon-gamma profoundly inhibits synthesis of alpha 1-antichymotrypsin, and especially of haptoglobin, but stimulates production of alpha 2-macroglobulin thus modulating the acute phase response of these cells.

  17. Fabrication of Anti-human Cardiac Troponin I Immunogold Nanorods for Sensing Acute Myocardial Damage

    Directory of Open Access Journals (Sweden)

    Fan X

    2009-01-01

    Full Text Available Abstract A facile, rapid, solution-phase method of detecting human cardiac troponin I for sensing myocardial damage has been described using gold nanorods-based biosensors. The sensing is demonstrated by the distinct change of the longitudinal surface plasmon resonance wavelength of the gold nanorods to specific antibody–antigen binding events. For a higher sensitivity, the aspect ratio of gold nanorods is increased up to ca 5.5 by simply adding small amount of HCl in seed-mediated growth solution. Experimental results show that the detecting limit of the present method is 10 ng/mL. Contrast tests reveal that these gold nanorods-based plasmonic biosensors hold much higher sensitivity than that of conventionally spherical gold nanoparticles.

  18. Phylogenetic analysis of human metapneumovirus among children with acute respiratory infections in Kuala Lumpur, Malaysia.

    Science.gov (United States)

    Nor'e, S S; Sam, I C; Mohamad Fakri, E F; Hooi, P S; Nathan, A M; de Bruyne, J A; Jafar, F; Hassan, A; AbuBakar, S; Chan, Y F

    2014-09-01

    Human metapneumovirus (HMPV) is a recently discovered cause of viral respiratory infections. We describe clinical and molecular epidemiology of HMPV cases diagnosed in children with respiratory infection at University of Malaya Medical Centre, Kuala Lumpur, Malaysia. The prevalence rate of HMPV between 2010 and 2012 was 1.1%, and HMPV contributed 6.5% of confirmed viral respiratory infections. The HMPV patients had a median age of 1.6 years, and a median hospital admission of 4 days. The most common clinical presentations were fever, rhinitis, pneumonia, vomiting/diarrhoea, and bronchiolitis. Based on the partial sequences of F fusion gene from 26 HMPV strains, 14 (54%) were subgenotype A2b, which was predominant in 2010; 11 (42%) were subgenotype B1, which was predominant in 2012; and 1 (4%) was subgenotype A2a. Knowledge of the circulating subgenotypes in Malaysia, and the displacement of predominant subgenotypes within 3 years, is useful data for future vaccine planning.

  19. Acute exposure to evening blue-enriched light impacts on human sleep.

    Science.gov (United States)

    Chellappa, Sarah L; Steiner, Roland; Oelhafen, Peter; Lang, Dieter; Götz, Thomas; Krebs, Julia; Cajochen, Christian

    2013-10-01

    Light in the short wavelength range (blue light: 446-483 nm) elicits direct effects on human melatonin secretion, alertness and cognitive performance via non-image-forming photoreceptors. However, the impact of blue-enriched polychromatic light on human sleep architecture and sleep electroencephalographic activity remains fairly unknown. In this study we investigated sleep structure and sleep electroencephalographic characteristics of 30 healthy young participants (16 men, 14 women; age range 20-31 years) following 2 h of evening light exposure to polychromatic light at 6500 K, 2500 K and 3000 K. Sleep structure across the first three non-rapid eye movement non-rapid eye movement - rapid eye movement sleep cycles did not differ significantly with respect to the light conditions. All-night non-rapid eye movement sleep electroencephalographic power density indicated that exposure to light at 6500 K resulted in a tendency for less frontal non-rapid eye movement electroencephalographic power density, compared to light at 2500 K and 3000 K. The dynamics of non-rapid eye movement electroencephalographic slow wave activity (2.0-4.0 Hz), a functional index of homeostatic sleep pressure, were such that slow wave activity was reduced significantly during the first sleep cycle after light at 6500 K compared to light at 2500 K and 3000 K, particularly in the frontal derivation. Our data suggest that exposure to blue-enriched polychromatic light at relatively low room light levels impacts upon homeostatic sleep regulation, as indexed by reduction in frontal slow wave activity during the first non-rapid eye movement episode. © 2013 European Sleep Research Society.

  20. Disaturated-phosphatidylcholine and surfactant protein-B turnover in human acute lung injury and in control patients.

    Science.gov (United States)

    Simonato, Manuela; Baritussio, Aldo; Ori, Carlo; Vedovelli, Luca; Rossi, Sandra; Dalla Massara, Lorenza; Rizzi, Sabina; Carnielli, Virgilio P; Cogo, Paola E

    2011-03-24

    Patients with adult respiratory distress syndrome (ARDS) and acute lung injury (ALI) have low concentrations of disaturated-phosphatidylcholine and surfactant protein-B in bronchoalveolar lavage fluid. No information is available on their turnover. To analyze disaturated-phosphatidylcholine and surfactant protein-B turnover in patients with ARDS/ALI and in human adults with normal lungs (controls). 2H2O as precursor of disaturated-phosphatidylcholine-palmitate and 113C-Leucine as precursor of surfactant protein-B were administered intravenously to 12 patients with ARDS/ALI and to 8 controls. Disaturated-phosphatidylcholine and surfactant protein-B were isolated from serial tracheal aspirates, and their fractional synthetic rate was derived from the 2H and 13C enrichment curves, obtained by gas chromatography mass spectrometry. Disaturated-phosphatidylcholine, surfactant protein-B, and protein concentrations in tracheal aspirates were also measured. 1) Surfactant protein-B turned over at faster rate than disaturated-phosphatidylcholine both in ARDS/ALI patients and in controls. 2) In patients with ARDS/ALI the fractional synthesis rate of disaturated-phosphatidylcholine was 3.1 times higher than in controls (p phosphatidylcholine and surfactant protein-B in tracheal aspirates were markedly and significantly reduced (17% and 40% of the control values respectively). 1) Disaturated-phosphatidylcholine and surfactant protein-B have a different turnover both in healthy and diseased lungs. 2) In ARDS/ALI the synthesis of these two surfactant components may be differently regulated.

  1. Human Rhinovirus Association with Influenza-Like Illness and Symptomatic Treatment for Acute Respiratory Infection in a Brazilian Southern City

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    Fernando Seiji Morais

    2017-09-01

    Full Text Available Acute respiratory infections (ARI are the world’s leading cause of morbidity and mortality. ARI impairs children’s education and have a huge impact on the economy. Human rhinovirus (HRV is the most prevalent agent of ARI. In this study, a clinical and epidemiological surveillance in outpatients was carried to investiga-te the involvement of HRV in ARI cases in the city of Guarapuava, a Brazilian southern city. Attention was also given to the most common medications used for treating ARI symptoms. Samples from 135 patients were col-lected from Apr to Dec from 2014, HRV was identified in nearly 20% of samples, with symptoms ranging from common cold to Influenza-like Illness (ILI and was more frequent in individuals with 10 or less years-old. Ne-arly two thirds of patients reported use of at least one class of drug during the ARI episodes, such as analgesi-cs, cough and cold preparations, and NSAIDs. In some cases and with no justifiable reason, patients also repor-ted the use of antibiotics, possibly contributing to the development of bacterial resistance. These results show a significant detection rate of HRV in ARI cases, and highlight the impact of this virus in the local population.

  2. Multifaceted therapeutic benefits of factors derived from stem cells from human exfoliated deciduous teeth for acute liver failure in rats.

    Science.gov (United States)

    Matsushita, Yoshihiro; Ishigami, Masatoshi; Matsubara, Kohki; Kondo, Megumi; Wakayama, Hirotaka; Goto, Hidemi; Ueda, Minoru; Yamamoto, Akihito

    2017-06-01

    In acute liver failure (ALF), a poorly controlled innate immune response causes massive hepatic destruction, which elicits a systemic inflammatory response, progressive multiple organ failure and ultimate sudden death. Although the liver has inherent tissue-repairing activities, its regeneration during ALF fails, and orthotopic liver transplantation is the only curative approach. Here we show that a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED-derived serum-free conditioned medium (SHED-CM) into the d-galactosamine-induced rat model of ALF markedly improved the condition of the injured liver and the animals' survival rate. The engraftment of infused SHEDs was very low, and both SHEDs and SHED-CM exerted similar levels of therapeutic effect, suggesting that the SHEDs reversed ALF by paracrine mechanisms. Importantly, SHED-CM attenuated the ALF-induced pro-inflammatory response and generated an anti-inflammatory/tissue-regenerating environment, which was accompanied by the induction of anti-inflammatory M2-like hepatic macrophages. Secretome analysis by cytokine antibody array revealed that the SHED-CM contained multiple tissue-regenerating factors with known roles in anti-apoptosis/hepatocyte protection, angiogenesis, macrophage differentiation and the proliferation/differentiation of liver progenitor cells. Taken together, our findings suggest that SHEDs produce factors that provide multifaceted therapeutic benefits for AFL. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Detection of human bocavirus from children and adults with acute respiratory tract illness in Guangzhou, southern China

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    Liu Wen-Kuan

    2011-12-01

    Full Text Available Abstract Background Human bocavirus (HBoV is a newly discovered parvovirus associated with acute respiratory tract illness (ARTI and gastrointestinal illness. Our study is the first to analyze the characteristics of HBoV-positive samples from ARTI patients with a wide age distribution from Guangzhou, southern China. Methods Throat swabs (n=2811 were collected and analyzed from children and adults with ARTI over a 13-month period. The HBoV complete genome from a 60 year-old female patient isolate was also determined. Results HBoV DNA was detected in 65/2811 (2.3% samples, of which 61/1797 were from children (Mycoplasma pneumoniae had the highest frequency of 16.9% (11/65. Upper and lower respiratory tract illness were common symptoms, with 19/65 (29.2% patients diagnosed with pneumonia by chest radiography. All four adult patients had systemic influenza-like symptoms. Phylogenetic analysis of the complete genome revealed a close relationship with other HBoVs, and a more distant relationship with HBoV2 and HBoV3. Conclusions HBoV was detected from children and adults with ARTI from Guangzhou, southern China. Elderly people were also susceptive to HBoV. A single lineage of HBoV was detected among a wide age distribution of patients with ARTI.

  4. Genome sequence of human adenovirus type 55, a re-emergent acute respiratory disease pathogen in China.

    Science.gov (United States)

    Zhang, Qiwei; Seto, Donald; Cao, Bin; Zhao, Suhui; Wan, Chengsong

    2012-11-01

    Human adenovirus type 55 (HAdV-B55) is an acute respiratory disease (ARD) pathogen first completely characterized in China (2006). This is a unique Trojan horse microbe with the virus neutralization attribute of a renal pathogen and the cell tropism and clinical attributes of a respiratory pathogen, bypassing herd immunity. It appeared to be an uncommon pathogen, with earlier putative, sporadic occurrences in Spain (1969) and Turkey (2004); these isolates were incompletely characterized using only two epitopes. Reported here is the genome of a second recent isolate (China, 2011), indicating that it may occur more frequently. The availability of this HAdV-B55 genome provides a foundation for studying adenovirus molecular evolution, the dynamics of epidemics, and patterns of pathogen emergence and re-emergence. These data facilitate studies to predict genome recombination between adenoviruses, as well as sequence divergence rates and hotspots, all of which are important for vaccine development and because HAdVs are used for epitope and/or gene delivery vectors.

  5. CD166(pos) subpopulation from differentiated human ES and iPS cells support repair of acute lung injury.

    Science.gov (United States)

    Soh, Boon Seng; Zheng, Dahai; Li Yeo, Julie Su; Yang, Henry He; Ng, Shi Yan; Wong, Lan Hiong; Zhang, Wencai; Li, Pin; Nichane, Massimo; Asmat, Atasha; Wong, Poo Sing; Wong, Peng Cheang; Su, Lin Lin; Mantalaris, Sakis A; Lu, Jia; Xian, Wa; McKeon, Frank; Chen, Jianzhu; Lim, Elaine Hsuen; Lim, Bing

    2012-12-01

    Previous efforts to derive lung progenitor cells from human embryonic stem (hES) cells using embryoid body formation or stromal feeder cocultures had been limited by low efficiencies. Here, we report a step-wise differentiation method to drive both hES and induced pluripotent stem (iPS) cells toward the lung lineage. Our data demonstrated a 30% efficiency in generating lung epithelial cells (LECs) that expresses various distal lung markers. Further enrichment of lung progenitor cells using a stem cell marker, CD166 before transplantation into bleomycin-injured NOD/SCID mice resulted in enhanced survivability of mice and improved lung pulmonary functions. Immunohistochemistry of lung sections from surviving mice further confirmed the specific engraftment of transplanted cells in the damaged lung. These cells were shown to express surfactant protein C, a specific marker for distal lung progenitor in the alveoli. Our study has therefore demonstrated the proof-of-concept of using iPS cells for the repair of acute lung injury, demonstrating the potential usefulness of using patient's own iPS cells to prevent immune rejection which arise from allogenic transplantation.

  6. CD166pos Subpopulation From Differentiated Human ES and iPS Cells Support Repair of Acute Lung Injury

    Science.gov (United States)

    Soh, Boon Seng; Zheng, Dahai; Li Yeo, Julie Su; Yang, Henry He; Ng, Shi Yan; Wong, Lan Hiong; Zhang, Wencai; Li, Pin; Nichane, Massimo; Asmat, Atasha; Wong, Poo Sing; Wong, Peng Cheang; Su, Lin Lin; Mantalaris, Sakis A; Lu, Jia; Xian, Wa; McKeon, Frank; Chen, Jianzhu; Lim, Elaine Hsuen; Lim, Bing

    2012-01-01

    Previous efforts to derive lung progenitor cells from human embryonic stem (hES) cells using embryoid body formation or stromal feeder cocultures had been limited by low efficiencies. Here, we report a step-wise differentiation method to drive both hES and induced pluripotent stem (iPS) cells toward the lung lineage. Our data demonstrated a 30% efficiency in generating lung epithelial cells (LECs) that expresses various distal lung markers. Further enrichment of lung progenitor cells using a stem cell marker, CD166 before transplantation into bleomycin-injured NOD/SCID mice resulted in enhanced survivability of mice and improved lung pulmonary functions. Immunohistochemistry of lung sections from surviving mice further confirmed the specific engraftment of transplanted cells in the damaged lung. These cells were shown to express surfactant protein C, a specific marker for distal lung progenitor in the alveoli. Our study has therefore demonstrated the proof-of-concept of using iPS cells for the repair of acute lung injury, demonstrating the potential usefulness of using patient's own iPS cells to prevent immune rejection which arise from allogenic transplantation. PMID:22968480

  7. Disaturated-phosphatidylcholine and Surfactant protein-B turnover in human acute lung injury and in control patients

    Directory of Open Access Journals (Sweden)

    Rizzi Sabina

    2011-03-01

    Full Text Available Abstract Background Patients with Adult Respiratory Distress Syndrome (ARDS and Acute Lung Injury (ALI have low concentrations of disaturated-phosphatidylcholine and surfactant protein-B in bronchoalveolar lavage fluid. No information is available on their turnover. Objectives To analyze disaturated-phosphatidylcholine and surfactant protein-B turnover in patients with ARDS/ALI and in human adults with normal lungs (controls. Methods 2H2O as precursor of disaturated-phosphatidylcholine-palmitate and 113C-Leucine as precursor of surfactant protein-B were administered intravenously to 12 patients with ARDS/ALI and to 8 controls. Disaturated-phosphatidylcholine and surfactant protein-B were isolated from serial tracheal aspirates, and their fractional synthetic rate was derived from the 2H and 13C enrichment curves, obtained by gas chromatography mass spectrometry. Disaturated-phosphatidylcholine, surfactant protein-B, and protein concentrations in tracheal aspirates were also measured. Results 1 Surfactant protein-B turned over at faster rate than disaturated-phosphatidylcholine both in ARDS/ALI patients and in controls. 2 In patients with ARDS/ALI the fractional synthesis rate of disaturated-phosphatidylcholine was 3.1 times higher than in controls (p Conclusions 1 Disaturated-phosphatidylcholine and surfactant protein-B have a different turnover both in healthy and diseased lungs. 2 In ARDS/ALI the synthesis of these two surfactant components may be differently regulated.

  8. Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells.

    Science.gov (United States)

    Ye, Lei; Chang, Ying-Hua; Xiong, Qiang; Zhang, Pengyuan; Zhang, Liying; Somasundaram, Porur; Lepley, Mike; Swingen, Cory; Su, Liping; Wendel, Jacqueline S; Guo, Jing; Jang, Albert; Rosenbush, Daniel; Greder, Lucas; Dutton, James R; Zhang, Jianhua; Kamp, Timothy J; Kaufman, Dan S; Ge, Ying; Zhang, Jianyi

    2014-12-04

    Human induced pluripotent stem cells (hiPSCs) hold promise for myocardial repair following injury, but preclinical studies in large animal models are required to determine optimal cell preparation and delivery strategies to maximize functional benefits and to evaluate safety. Here, we utilized a porcine model of acute myocardial infarction (MI) to investigate the functional impact of intramyocardial transplantation of hiPSC-derived cardiomyocytes, endothelial cells, and smooth muscle cells, in combination with a 3D fibrin patch loaded with insulin growth factor (IGF)-encapsulated microspheres. hiPSC-derived cardiomyocytes integrated into host myocardium and generated organized sarcomeric structures, and endothelial and smooth muscle cells contributed to host vasculature. Trilineage cell transplantation significantly improved left ventricular function, myocardial metabolism, and arteriole density, while reducing infarct size, ventricular wall stress, and apoptosis without inducing ventricular arrhythmias. These findings in a large animal MI model highlight the potential of utilizing hiPSC-derived cells for cardiac repair. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Effect of combination antiretroviral therapy on T-cell immunity in acute human immunodeficiency virus type 1 infection.

    Science.gov (United States)

    Malhotra, U; Berrey, M M; Huang, Y; Markee, J; Brown, D J; Ap, S; Musey, L; Schacker, T; Corey, L; McElrath, M J

    2000-01-01

    T-cell responses were evaluated prospectively in 41 patients with acute human immunodeficiency virus type 1 (HIV-1) infection (30 untreated and 11 receiving zidovudine, lamivudine, and indinavir) and in 38 uninfected adults. By 6-12 months, treated patients had significantly greater median Candida and tetanus lymphoproliferative responses (stimulation index [SI], 76 and 55, respectively) than did untreated patients (SI, 7 and 6, P=.02 and.001, respectively), and the responses of treated patients surpassed those of uninfected adults (SI, 19 and 32, P= .002 and .101, respectively). Unlike the patients in the untreated group, the patients in the treated group mounted a 6-fold increased HIV-1 p24 response (SI increase, 1.0 to 5.7, P= .01) within 3 months. HIV-1-specific cytotoxicity remained detectable in most treated patients. Thus, combination therapy administered within 3-4 months of infection was associated with improved T-cell memory responses that were distinct from those of untreated patients. The amplified HIV-1-specific T-cell responses may help maintain cytotoxic activities.

  10. Assessment of Acute and Chronic Pharmacological Effects on Energy Expenditure and Macronutrient Oxidation in Humans: Responses to Ephedrine

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    Antonella Napolitano

    2011-01-01

    Full Text Available Evidence of active brown adipose tissue in human adults suggests that this may become a pharmacological target to induce negative energy balance. We have explored whole-body indirect calorimetry to detect the metabolic effects of thermogenic drugs through administration of ephedrine hydrochloride and have assessed ephedrine's merits as a comparator compound in the evaluation of novel thermogenic agents. Volunteers randomly given ephedrine hydrochloride 15 mg QID (n=8 or placebo (n=6 were studied at baseline and after 1-2 and 14-15 days of treatment. We demonstrate that overnight or 23-hour, 2% energy expenditure (EE and 5% fat (FO or CHO oxidation effects are detectable both acutely and over 14 days. Compared to placebo, ephedrine increased EE and FO rates overnight (EE 63 kJ day 2, EE 105 kJ, FO 190 kJ, day 14, but not over 23 h. We conclude that modest energy expenditure and fat oxidation responses to pharmacological interventions can be confidently detected by calorimetry in small groups. Ephedrine should provide reliable data against which to compare novel thermogenic compounds.

  11. Development and Retranslational Validation of an In Vitro Model to Characterize Acute Infections in Large Human Joints

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    Ingo H. Pilz

    2014-01-01

    Full Text Available Bacterial infections can destroy cartilage integrity, resulting in osteoarthritis. Goal was to develop an in vitro model with in vivo validation of acute joint inflammation. Inflammation in cocultivated human synovial fibroblasts (SFB, chondrocytes (CHDR, and mononuclear cells (MNC was successively relieved for 10 days. Articular effusions from patients with (n=7 and without (n=5 postoperative joint infection in healthy patients (ASA 1-2 were used as model validation. Inflammation in vitro resulted in an enormous increase in IL-1 and a successive reduction in SFB numbers. CHDR however, maintained metabolic activity and proteoglycan synthesis. While concentrations of bFGF in vivo and in vitro rose consistently, the mRNA increase was only moderate. Concurring with our in vivo data, cartilage-specific IGF-1 steadily increased, while IGF-1 mRNA in the CHDR and SFB did not correlate with protein levels. Similarly, aggrecan (ACAN protein concentrations increased in vivo and failed to correlate in vitro with gene expression in either the CHDR or the SFB, indicating extracellular matrix breakdown. Anabolic cartilage-specific BMP-7 with highly significant intra-articular levels was significantly elevated in vitro on day 10 following maximum inflammation. Our in vitro model enables us to validate early inflammation of in vivo cell- and cytokine-specific regulatory patterns. This trial is registered with MISSinG, DRKS 00003536.

  12. Development and retranslational validation of an in vitro model to characterize acute infections in large human joints.

    Science.gov (United States)

    Pilz, Ingo H; Mehlhorn, Alexander; Dovi-Akue, David; Langenmair, Elia Raoul; Südkamp, Norbert P; Schmal, Hagen

    2014-01-01

    Bacterial infections can destroy cartilage integrity, resulting in osteoarthritis. Goal was to develop an in vitro model with in vivo validation of acute joint inflammation. Inflammation in cocultivated human synovial fibroblasts (SFB), chondrocytes (CHDR), and mononuclear cells (MNC) was successively relieved for 10 days. Articular effusions from patients with (n = 7) and without (n = 5) postoperative joint infection in healthy patients (ASA 1-2) were used as model validation. Inflammation in vitro resulted in an enormous increase in IL-1 and a successive reduction in SFB numbers. CHDR however, maintained metabolic activity and proteoglycan synthesis. While concentrations of bFGF in vivo and in vitro rose consistently, the mRNA increase was only moderate. Concurring with our in vivo data, cartilage-specific IGF-1 steadily increased, while IGF-1 mRNA in the CHDR and SFB did not correlate with protein levels. Similarly, aggrecan (ACAN) protein concentrations increased in vivo and failed to correlate in vitro with gene expression in either the CHDR or the SFB, indicating extracellular matrix breakdown. Anabolic cartilage-specific BMP-7 with highly significant intra-articular levels was significantly elevated in vitro on day 10 following maximum inflammation. Our in vitro model enables us to validate early inflammation of in vivo cell- and cytokine-specific regulatory patterns. This trial is registered with MISSinG, DRKS 00003536.

  13. The role of serotonin in reward, punishment and behavioural inhibition in humans: insights from studies with acute tryptophan depletion.

    Science.gov (United States)

    Faulkner, Paul; Deakin, J F William

    2014-10-01

    Deakin and Graeff proposed that forebrain 5-hydroxytryptamine (5-HT) projections are activated by aversive events and mediate anticipatory coping responses including avoidance learning and suppression of the fight-flight escape/panic response. Other theories proposed 5-HT mediates aspects of behavioural inhibition or reward. Most of the evidence comes from rodent studies. We review 36 experimental studies in humans in which the technique of acute tryptophan depletion (ATD) was used to explicitly address the role of 5-HT in response inhibition, punishment and reward. ATD did not cause disinhibition of responding in the absence of rewards or punishments (9 studies). A major role for 5-HT in reward processing is unlikely but further tests are warranted by some ATD findings. Remarkably, ATD lessened the ability of punishments (losing points or notional money) to restrain behaviour without affecting reward processing in 7 studies. Two of these studies strongly indicate that ATD blocks 5-HT mediated aversively conditioned Pavlovian inhibition and this can explain a number of the behavioural effects of ATD. Copyright © 2014. Published by Elsevier Ltd.

  14. Pathological changes in acute experimental toxoplasmosis with Toxoplasma gondii strains obtained from human cases of congenital disease.

    Science.gov (United States)

    Pinheiro, Breno Veloso; Noviello, Maria de Lourdes Meirelles; Cunha, Mariana Maciel; Tavares, Alice Thomaz; Carneiro, Ana Carolina Aguiar Vasconcelos; Arantes, Rosa Maria Esteves; Vitor, Ricardo Wagner Almeida

    2015-09-01

    There is a lack of studies using Toxoplasma gondii strains isolated from human patients. Here, we present a pathological study of three strains obtained from human cases of congenital toxoplasmosis in Brazil using inbred mice after oral infection with 10 tissue cysts. Multiplex-nested PCR-RFLP of eleven loci revealed atypical genotypes commonly found in Brazil: toxodb #8 for TgCTBr5 and TgCTBr16 strains and toxodb #11 for the TgCTBr9 strain. BALB/c and C57BL/6 mice were evaluated for survival and histological changes during the acute phase of the disease. All mice inoculated with the non-virulent TgCTBR5 strain survived after 30 days, although irreversible tissue damage was found. In contrast, no mice were resistant to infection with the highly virulent TgCTBR9 strain. The TgCTBr16 strain resulted in 80% survival in mice. However, this strain presented low infectivity, especially by the oral route of infection. Despite being identified with the same genotype, TgCTBr5 and TgCTBr16 strains showed biological differences. Histopathologic analysis revealed liver and lungs to be the most affected organs, and the pattern of tissue injury was similar to that found in mice inoculated perorally with strains belonging to clonal genotypes. However, there was a variation in the intensity of ileum lesions according to T. gondii strain and mouse lineage. C57BL/6 mice showed higher susceptibility than BALB/c for histological lesions. Taken together, these results revealed that the pathogenesis of T. gondii strains belonging to atypical genotypes can induce similar tissue damage to those from clonal genotypes, although intrinsic aspects of the strains seem critical to the induction of ileitis in the infected host. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Binding to histo-blood group antigen-expressing bacteria protects human norovirus from acute heat stress

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    Dan eLi

    2015-07-01

    Full Text Available This study aims to investigate if histo-blood group antigen (HBGA expressing bacteria have any protective role on human norovirus (NoV from acute heat stress. Eleven bacterial strains were included, belonging to Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Clostridium difficile, Bifidobacterium adolescentis, and Bifidobacterium longum. HBGA expression of the bacteria as well as binding of human NoV virus-like particles (VLPs, GI.1 and GII.4 strains to the bacteria were detected by flow cytometry. NoV VLPs pre-incubated with HBGA expressing or non-HBGA expressing bacteria were heated and detected by both direct ELISA and porcine gastric mucin-binding assay. The NoV-binding abilities of the bacteria correlated well with their HBGA expression profiles. Two HBGA expressing E.coli (LMG8223 and LFMFP861, both GI.1 and GII.4 binders and one non-HBGA expressing E.coli (ATCC8739, neither GI.1 nor GII.4 binder were selected for the heat treatment test with NoV VLPs. Compared with the same cell numbers of non-HBGA expressing E.coli, the presence of HBGA-expressing E.coli could always maintain higher antigen integrity, as well as mucin-binding ability of NoV VLPs of both GI.1 and GII.4 after heat-treatment at 90°C for 2 min. These results indicate that HBGA-expressing bacteria may protect NoVs during the food processing treatments, thereby facilitating their transmission.

  16. Extraocular light via the ear canal does not acutely affect human circadian physiology, alertness and psychomotor vigilance performance.

    Science.gov (United States)

    Bromundt, Vivien; Frey, Sylvia; Odermatt, Jonas; Cajochen, Christian

    2014-04-01

    We aimed at testing potential effects of extraocular bright light via the ear canals on human evening melatonin levels, sleepiness and psychomotor vigilance performance. Twenty healthy young men and women (10/10) kept a regular sleep-wake cycle during the 2-week study. The volunteers reported to the laboratory on three evenings, 2 h 15 min before usual bedtime, on average at 21:45 h. They were exposed to three different light conditions, each lasting for 12 min: extraocular bright light via the ear canal, ocular bright light as an active control condition and a control condition (extraocular light therapy device with completely blacked out LEDs). The timing of exposure was on average from 22:48 to 23:00 h. During the 2-h protocol, saliva samples were collected in 15-min intervals for melatonin assays along with subjective sleepiness ratings, and the volunteers performed a 10-min visual psychomotor vigilance task (PVT) prior to and after each light condition. The evening melatonin rise was significantly attenuated after the 12-min ocular bright light exposure while no significant changes were observed after the extraocular bright light and sham light condition. Subjective sleepiness decreased immediately over a short period only after ocular light exposure. No significant differences were observed for mean reaction times and the number of lapses for the PVT between the three light conditions. We conclude that extraocular transcranial light exposure in the late evening does not suppress melatonin, reduce subjective sleepiness or improve performance, and therefore, does not acutely influence the human circadian timing system.

  17. Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism.

    Science.gov (United States)

    Farge, Thomas; Saland, Estelle; de Toni, Fabienne; Aroua, Nesrine; Hosseini, Mohsen; Perry, Robin; Bosc, Claudie; Sugita, Mayumi; Stuani, Lucille; Fraisse, Marine; Scotland, Sarah; Larrue, Clément; Boutzen, Héléna; Féliu, Virginie; Nicolau-Travers, Marie-Laure; Cassant-Sourdy, Stéphanie; Broin, Nicolas; David, Marion; Serhan, Nizar; Sarry, Audrey; Tavitian, Suzanne; Kaoma, Tony; Vallar, Laurent; Iacovoni, Jason; Linares, Laetitia K; Montersino, Camille; Castellano, Rémy; Griessinger, Emmanuel; Collette, Yves; Duchamp, Olivier; Barreira, Yara; Hirsch, Pierre; Palama, Tony; Gales, Lara; Delhommeau, François; Garmy-Susini, Barbara H; Portais, Jean-Charles; Vergez, François; Selak, Mary; Danet-Desnoyers, Gwenn; Carroll, Martin; Récher, Christian; Sarry, Jean-Emmanuel

    2017-07-01

    Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be enriched in quiescent immature leukemic stem cells (LSC). To validate this hypothesis in vivo, we developed a clinically relevant chemotherapeutic approach treating patient-derived xenografts (PDX) with cytarabine (AraC). AraC residual AML cells are enriched in neither immature, quiescent cells nor LSCs. Strikingly, AraC-resistant preexisting and persisting cells displayed high levels of reactive oxygen species, showed increased mitochondrial mass, and retained active polarized mitochondria, consistent with a high oxidative phosphorylation (OXPHOS) status. AraC residual cells exhibited increased fatty-acid oxidation, upregulated CD36 expression, and a high OXPHOS gene signature predictive for treatment response in PDX and patients with AML. High OXPHOS but not low OXPHOS human AML cell lines were chemoresistant in vivo. Targeting mitochondrial protein synthesis, electron transfer, or fatty-acid oxidation induced an energetic shift toward low OXPHOS and markedly enhanced antileukemic effects of AraC. Together, this study demonstrates that essential mitochondrial functions contribute to AraC resistance in AML and are a robust hallmark of AraC sensitivity and a promising therapeutic avenue to treat AML residual disease.Significance: AraC-resistant AML cells exhibit metabolic features and gene signatures consistent with a high OXPHOS status. In these cells, targeting mitochondrial metabolism through the CD36-FAO-OXPHOS axis induces an energetic shift toward low OXPHOS and strongly enhanced antileukemic effects of AraC, offering a promising avenue to design new therapeutic strategies and fight AraC resistance in AML. Cancer Discov; 7(7); 716-35. ©2017 AACR.See related commentary by Schimmer, p. 670This article is highlighted in the In This Issue feature, p. 653. ©2017 American Association for Cancer Research.

  18. Human parainfluenza virus types 1-4 in hospitalized children with acute lower respiratory infections in China.

    Science.gov (United States)

    Xiao, Ni-Guang; Duan, Zhao-Jun; Xie, Zhi-Ping; Zhong, Li-Li; Zeng, Sai-Zhen; Huang, Han; Gao, Han-Chun; Zhang, Bing

    2016-12-01

    Human parainfluenza viruses (HPIVs) are an important cause of acute lower respiratory tract infections (ALRTIs). HPIV-4, a newly identified virus, has been associated with severe ALRTIs recently. A total of 771 nasopharyngeal aspirate samples were collected from hospitalized children between March 2010 and February 2011. HPIVs were detected by Nest-PCR, and other known respiratory viruses were detected by RT-PCR and PCR. All amplification products were sequenced. HPIVs were detected in 151 (19.58%) patients, of whom 28 (3.63%) were positive for HPIV-4, 12(1.55%) for HPIV-1, 4 (0.51%) for HPIV-2, and 107 (13.87%) for HPIV-3. Only three were found to be co-infected with different types of HPIVs. All HPIV-positive children were under 5 years of age, with the majority being less than 1 year. Only the detection rate of HPIV-3 had a significant statistical difference (χ 2  = 29.648, P = 0.000) between ages. HPIV-3 and HPIV-4 were detected during the summer. Sixty (39.74%) were co-infected with other respiratory viruses, and human rhinovirus (HRV) was the most common co-infecting virus. The most frequent clinical diagnosis was bronchopneumonia, and all patients had cough; some patients who were infected with HPIV-3 and HPIV-4 had polypnea and cyanosis. No significant difference was found in clinical manifestations between those who were infected with HPIV-4 and HPIV-3. Two genotypes for HPIV-4 were prevalent, although HPIV-4a dominated. HPIV-4 is an important virus for children hospitalized with ALRTIs in China. HRV was the most common co-infecting virus. Two genotypes for HPIV-4 are prevalent, HPIV-4a dominated. J. Med. Virol. 88:2085-2091, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Clinical features of human metapneumovirus genotypes in children with acute lower respiratory tract infection in Changsha, China.

    Science.gov (United States)

    Zeng, Sai-Zhen; Xiao, Ni-Guang; Zhong, Li-Li; Yu, Tian; Zhang, Bing; Duan, Zhao-Jun

    2015-11-01

    To explore the epidemiological and clinical features of different human metapneumovirus (hMPV) genotypes in hospitalized children. Reverse transcription polymerase chain reaction (RT-PCR) or PCR was employed to screen for both hMPV and other common respiratory viruses in 2613 nasopharyngeal aspirate specimens collected from children with lower respiratory tract infections from September 2007 to February 2011 (a period of 3.5 years). The demographics and clinical presentations of patients infected with different genotypes of hMPV were compared. A total of 135 samples were positive for hMPV (positive detection rate: 5.2%). Co-infection with other viruses was observed in 45.9% (62/135) of cases, and human bocavirus was the most common additional respiratory virus. The most common symptoms included cough, fever, and wheezing. The M gene was sequenced for 135 isolates; of these, genotype A was identified in 72.6% (98/135) of patients, and genotype B was identified in 27.4% (37/135) of patients. The predominant genotype of hMPV changed over the 3.5-year study period from genotype A2b to A2b or B1 and then to predominantly B1. Most of clinical features were similar between patients infected with different hMPV genotypes. These results suggested that hMPV is an important viral pathogen in pediatric patients with acute lower respiratory tract infection in Changsha. The hMPV subtypes A2b and B1 were found to co-circulate. The different hMPV genotypes exhibit similar clinical characteristics. © 2015 Wiley Periodicals, Inc.

  20. Bacterial Superantigens Promote Acute Nasopharyngeal Infection by Streptococcus pyogenes in a Human MHC Class II-Dependent Manner

    Science.gov (United States)

    Kasper, Katherine J.; Zeppa, Joseph J.; Wakabayashi, Adrienne T.; Xu, Stacey X.; Mazzuca, Delfina M.; Welch, Ian; Baroja, Miren L.; Kotb, Malak; Cairns, Ewa; Cleary, P. Patrick; Haeryfar, S. M. Mansour; McCormick, John K.

    2014-01-01

    Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as ‘trademark’ virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II) molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS), how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6) mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC –II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms. PMID:24875883

  1. Biochemical pharmacology and resistance to 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine, a novel analogue of cladribine in human leukemic cells.

    Science.gov (United States)

    Lotfi, K; Månsson, E; Spasokoukotskaja, T; Pettersson, B; Liliemark, J; Peterson, C; Eriksson, S; Albertioni, F

    1999-09-01

    The objective of the present study was to investigate the biochemical pharmacology of 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine (CAFdA)--a fluorinated analogue of cladribine [2-chloro-2'-deoxyadenosine, Leustatin (CdA)] with improved acid and metabolic stability--in human leukemic cell lines and in mononuclear cells isolated from patients with chronic lymphocytic leukemia (CLL) and acute myelocytic leukemia (AML). We have also made and characterized two cell lines that are not sensitive to the growth inhibitory and cytotoxic effects of CAFdA. Incubation of cells isolated from the blood of CLL and AML patients with various concentrations of CdA or of CAFdA accumulated CdA and CAFdA nucleotides in a dose-dependent manner. A significantly higher rate of phosphorylation to monophosphates was observed for CAFdA than for CdA in cells from CLL patients (n = 14; P = 0.04). The differences in the phosphorylation were even more pronounced for the respective triphosphates in both CLL (n = 14; P = 0.001) and AML (n = 4; P = 0.04) cells. Retention of CAFdA 5'-triphosphate (CAFdATP) was also longer than that for CdA 5'-triphosphate (CdATP) in cells from leukemic patients. The relative efficacy of CAFdA as a substrate for purified recombinant deoxycytidine kinase (dCK), the key enzyme in the activation of nucleoside analogues, was very high and exceeded that of CdA as well as the natural substrate, deoxycytidine, by a factor of 2 and 8, respectively. The Km for CAFdA with dCK was also lower than that for CdA, as measured in crude extracts from the human acute lymphoblastic leukemia cell line CCRF-CEM and the promyelocytic leukemia cell line HL60. Acquired resistance to CAFdA in HL60 and in CCRF-CEM cell lines was directly correlated to the decreased activity of the nucleoside phosphorylating enzyme, dCK. Resistant cells also showed a considerable degree of cross-resistance to analogues that were activated by dCK. These observations demonstrated that dCK phosphorylates CAFd

  2. Acute Post-Prandial Cognitive Effects of Brown Seaweed Extract in Humans

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    Crystal F. Haskell-Ramsay

    2018-01-01

    Full Text Available (Polyphenols and, specifically, phlorotannins present in brown seaweeds have previously been shown to inhibit α-amylase and α-glucosidase, key enzymes involved in the breakdown and intestinal absorption of carbohydrates. Related to this are observations of modulation of post-prandial glycemic response in mice and increased insulin sensitivity in humans when supplemented with seaweed extract. However, no studies to date have explored the effect of seaweed extract on cognition. The current randomized, placebo-controlled, double-blind, parallel groups study examined the impact of a brown seaweed extract on cognitive function post-prandially in 60 healthy adults (N = 30 per group. Computerized measures of episodic memory, attention and subjective state were completed at baseline and 5 times at 40 min intervals over a 3 h period following lunch, with either seaweed or placebo consumed 30 min prior to lunch. Analysis was conducted with linear mixed models controlling for baseline. Seaweed led to significant improvements to accuracy on digit vigilance (p = 0.035 and choice reaction time (p = 0.043 tasks. These findings provide the first evidence for modulation of cognition with seaweed extract. In order to explore the mechanism underlying these effects, future research should examine effects on cognition in parallel with blood glucose and insulin responses.

  3. Radioiodine plus recombinant human thyrotropin do not cause acute airway compression and are effective in reducing multinodular goiter

    Energy Technology Data Exchange (ETDEWEB)

    Albino, C.C., E-mail: ccalbino@uol.com.b [Instituto de Diabetes e Endocrinologia de Maringa, PR (Brazil); Graf, H.; Paz-Filho, G. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Hospital das Clinicas. Servico de Endocrinologia e Metabologia; Diehl, L.A. [Universidade Estadual de Londrina (UEL), PR (Brazil); Olandoski, M.; Sabbag, A. [Pontificia Univ. Catolica do Parana (PUCPR), Curitiba, PR (Brazil). Nucleo de Bioestatistica; Buchpiguel, C. [Universidade de Sao Paulo (USP), SP (Brazil). Dept. de Radiologia

    2006-03-15

    Recombinant human thyrotropin (rhTSH) reduces the activity of radioiodine required to treat multinodular goiter (MNG), but acute airway compression can be a life-threatening complication. In this prospective, randomized, double-blind, placebo-controlled study, we assessed the efficacy and safety (including airway compression) of different doses of rhTSH associated with a fixed activity of {sup 131}I for treating MNG. Euthyroid patients with MNG (69.3 +- 62.0 mL, 20 females, 2 males, 64 +- 7 years) received 0.1 mg (group I, N = 8) or 0.01 mg (group II, N = 6) rhTSH or placebo (group III, N = 8), 24 h before 1.11 GBq {sup 131}I. Radioactive iodine uptake was determined at baseline and 24 h after rhTSH and thyroid volume (TV, baseline and 6 and 12 months after treatment) and tracheal cross-sectional area (TCA, baseline and 2, 7, 180, and 360 days after rhTSH) were determined by magnetic resonance; antithyroid antibodies and thyroid hormones were determined at frequent intervals. After 6 months, TV decreased significantly in groups I (28.5 +- 17.6%) and II (21.6 +- 17.8%), but not in group III (2.7 +- 15.3%). After 12 months, TV decreased significantly in groups I (36.7 +- 18.1%) and II (37.4 +- 27.1%), but not in group III (19.0 +- 24.3%). No significant changes in TCA were observed. T3 and free T4 increased transiently during the first month. After 12 months, 7 patients were hypothyroid (N 3 in group I and N = 2 in groups II and III). rhTSH plus a 1.11-GBq fixed {sup 131}I activity did not cause acute or chronic changes in TCA. After 6 and 12 months, TV reduction was more pronounced among patients treated with rhTSH plus {sup 131}I (author)

  4. Lectin-binding sites in the epithelium of normal human appendix vermiformis and in acute appendicitis.

    Science.gov (United States)

    Brinck, U; Bosbach, R; Korabiowska, M; Schauer, A; Gabius, H J

    1995-01-01

    By using histochemical methods, the binding pattern of various lectins in the epithelium of normal human appendix vermiformis was assessed. In addition to plant and invertebrate sugar receptors with nominal monosaccharide specificity for alpha-L-Fuc (UEA-I), alpha-D-Man and alpha-D-Gluc (Con A), alpha-D-GalNAc (DBA), D-GalNAc (SBA, HPA) beta-D-Gal (RCA-I) and D-Gal (VAA), a mammalian beta-galactoside-specific lectin (MW, 14 kDa) was included in the applied panel. The apical surface of enterocytes presented binding sites for RCA-I on all cells, binding sites of UEA-I, DBA, SBA, HPA and VAA heterogeneously and no binding sites of Con A and 14 kDa. Binding sites of DBA, SBA, HPA, VAA and RCA-I within enterocytes were located primarily focally in a supranuclear position, whereas Con A and 14 kDa bound to the cytoplasm both in apical and basal cell parts. In the follicle-associated epithelium more enterocytes expressed SBA- and VAA-binding sites than in the crypt epithelium. No differences between the lectin-binding pattern of M-cells and enterocytes were found in the follicle-associated epithelium. Intraepithelial macrophages were heterogeneously positive for the full panel of applied lectins. In contrast, intraepithelial lymphatic cells expressed binding sites only for RCA-I and less prominently for Con A, VAA and 14 kDa. Goblet cell mucus contained lectin-binding sites in a heterogeneous manner: binding sites for Con A were not detected in goblet cells for DBA, SBA, VAA and 14 kDa in less than 20%, for UEA-I in 20-40%, for HPA in 40-60% and for RCA-I in 60-100% of the goblet cells. Secreted mucus differed in its lectin-binding capacity from intracellular goblet cell mucus selectively by an increase of UEA-I, SBA- and RCA-I-binding sites and a lack of 14 kDa-binding sites. Comparative study of lectin binding to goblet cell mucin in another region of the large intestine, namely the rectosigmoid, demonstrated that DBA, SBA and 14 kDa bound mainly to the distal colon

  5. Acute hypoxia influences collagen and matrix metalloproteinase expression by human keratoconus cells in vitro.

    Science.gov (United States)

    McKay, Tina B; Hjortdal, Jesper; Priyadarsini, Shrestha; Karamichos, Dimitrios

    2017-01-01

    Keratoconus (KC) is a progressive corneal ectasia linked to thinning of the central cornea. Hard contact lenses, rigid gas permeable lenses, and scleral lenses are the primary treatment modalities for early to mid- stages of KC to correct refractive error and astigmatism that develops as a result of an irregular corneal structure. These treatments are associated with significant drawbacks, including reduced availability of the tear film and oxygen to the corneal epithelium and stroma. However, it remains unknown whether hypoxia affects corneal integrity in the KC pathobiology. A number of studies have associated elevated oxidative stress with KC both in vitro and ex vivo. We hypothesized that KC-derived corneal fibroblasts are more susceptible to hypoxia-induced oxidative stress compared to healthy controls leading to exacerbation of corneal thinning in KC. This study investigated the effects of hypoxia on ECM secretion, assembly, and matrix metalloproteinase (MMP) expression in human corneal fibroblasts from healthy controls (HCFs) and KC patients (HKCs) in vitro. HCFs and HKCs were cultured in 3D constructs for 3 weeks and maintained or transferred to normoxic (21% O2) or hypoxic (2% O2) conditions, respectively, for 1 additional week. At the 4 week time-point, constructs were isolated and probed for Collagen I, III, and V, keratocan and MMP-1, -2, -3, -9, and -13, as well as hypoxia markers, hypoxia inducible factor-1α and lactoferrin. Conditioned media was also collected and probed for Collagen I, III, and V by Western blot. Thickness of the ECM assembled by HCFs and HKCs was measured using immunofluorescence microscopy. Results showed that hypoxia significantly reduced Collagen I secretion in HKCs, as well as upregulated the expression of MMP-1 and -2 with no significant effects on MMP-3, -9, or -13. ECM thickness was reduced in both cell types following 1 week in a low oxygen environment. Our study shows that hypoxia influences collagen and MMP expression by

  6. Human amnion cells reverse acute and chronic pulmonary damage in experimental neonatal lung injury

    Directory of Open Access Journals (Sweden)

    Dandan Zhu

    2017-11-01

    Full Text Available Abstract Background Despite advances in neonatal care, bronchopulmonary dysplasia (BPD remains a significant contributor to infant mortality and morbidity. While human amnion epithelial cells (hAECs have shown promise in small and large animal models of BPD, there is scarce information on long-term benefit and clinically relevant questions surrounding administration strategy remain unanswered. In assessing the therapeutic potential of hAECs, we investigated the impact of cell dosage, administration routes and timing of treatment in a pre-clinical model of BPD. Methods Lipopolysaccharide was introduced intra-amniotically at day 16 of pregnancy prior to exposure to 65% oxygen (hyperoxia at birth. hAECs were administered either 12 hours (early or 4 days (late after hyperoxia commenced. Collective lung tissues were subjected to histological analysis, multikine ELISA for inflammatory cytokines, FACS for immune cell populations and 3D lung stem cell culture at neonatal stage (postnatal day 7 and 14. Invasive lung function test and echocardiography were applied at 6 and 10 weeks of age. Results hAECs improved the tissue-to-airspace ratio and septal crest density in a dose-dependent manner, regardless of administration route. Early administration of hAECs, coinciding with the commencement of postnatal hyperoxia, was associated with reduced macrophages, dendritic cells and natural killer cells. This was not the case if hAECs were administered when lung injury was established. Fittingly, early hAEC treatment was more efficacious in reducing interleukin-1β, tumour necrosis factor alpha and monocyte chemoattractant protein-1 levels. Early hAEC treatment was also associated with reduced airway hyper-responsiveness and normalisation of pressure–volume loops. Pulmonary hypertension and right ventricle hypertrophy were also prevented in the early hAEC treatment group, and this persisted until 10 weeks of age. Conclusions Early hAEC treatment appears to

  7. Unsuccessful Detection of Plant MicroRNAs in Beer, Extra Virgin Olive Oil and Human Plasma After an Acute Ingestion of Extra Virgin Olive Oil.

    Science.gov (United States)

    Micó, Victor; Martín, Roberto; Lasunción, Miguel A; Ordovás, Jose M; Daimiel, Lidia

    2016-03-01

    The recent description of the presence of exogenous plant microRNAs from rice in human plasma had profound implications for the interpretation of microRNAs function in human health. If validated, these results suggest that food should not be considered only as a macronutrient and micronutrient supplier but it could also be a way of genomic interchange between kingdoms. Subsequently, several studies have tried to replicate these results in rice and other plant foods and most of them have failed to find plant microRNAs in human plasma. In this scenario, we aimed to detect plant microRNAs in beer and extra virgin olive oil (EVOO)--two plant-derived liquid products frequently consumed in Spain--as well as in human plasma after an acute ingestion of EVOO. Our hypothesis was that microRNAs present in beer and EVOO raw material could survive manufacturing processes, be part of these liquid products, be absorbed by human gut and circulate in human plasma. To test this hypothesis, we first optimized the microRNA extraction protocol to extract microRNAs from beer and EVOO, and then tried to detect microRNAs in those samples and in plasma samples of healthy volunteers after an acute ingestion of EVOO.

  8. DISTINCT PHENOTYPES OF INFILTRATING CELLS DURING ACUTE AND CHRONIC LUNG REJECTION IN HUMAN HEART-LUNG TRANSPLANTS

    NARCIS (Netherlands)

    WINTER, JB; CLELLAND, C; GOUW, ASH; PROP, J

    1995-01-01

    To differentiate between acute and chronic lung rejection in an early stage, phenotypes of infiltrating inflammatory cells were analyzed in 34 transbronchial biopsies (TBBs) of 24 patients after heart-lung transplantation. TBBs were taken during during acute lung rejection and chronic lung

  9. An unusual case of primary human immunodeficiency virus infection presenting as mononucleosis-like syndrome and acute aseptic meningoencephalitis. Report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Marcelo Corti

    2014-01-01

    Full Text Available Clinical presentation of primary human immunodeficiency virus (HIV infection includes a wide spectrum of manifestations from asymptomatic infection to a symptomatic and severe illness. Central nervous system involvement should be always considered as a severe clinical form of primary HIV infection. Physicians should be aware to the broad clinical spectrum of primary HIV infection. We report a case of a female with diagnosis of mononucleosis-like syndrome and acute aseptic meningoencephalitis during primary HIV infection.

  10. Acute upregulation of PGC-1α mRNA correlates with training-induced increases in SDH activity in human skeletal muscle.

    Science.gov (United States)

    Bonafiglia, Jacob T; Edgett, Brittany A; Baechler, Brittany L; Nelms, Matthew W; Simpson, Craig A; Quadrilatero, Joe; Gurd, Brendon J

    2017-06-01

    The purpose of the present study was to determine if acute responses in PGC-1α, VEGFA, SDHA, and GPD1-2 mRNA expression predict their associated chronic skeletal muscle molecular (SDH-GPD activity and substrate storage) and morphological (fibre-type composition and capillary density) adaptations following training. Skeletal muscle biopsies were collected from 14 recreationally active men (age: 22.0 ± 2.4 years) before (PRE) and 3 h after (3HR) the completion of an acute bout of sprint interval training (SIT) (eight 20-s intervals at ∼170% peak oxygen uptake work rate separated by 10 s of recovery). Participants then completed 6 weeks of SIT 4 times per week with additional biopsies after 2 (MID) and 6 (POST) weeks of training. Acute increases in PGC-1α mRNA strongly predicted increases in SDH activity (a marker of oxidative capacity) from PRE and MID to POST (PRE-POST: r = 0.81, r2 = 0.65, p < 0.01; MID-POST: r = 0.79, r2 = 0.62, p < 0.01) and glycogen content from MID to POST (r = 0.60, r2 = 0.36, p < 0.05). No other significant relationships were found between acute responses in PGC-1α, VEGFA, SDHA, and GPD1-2 mRNA expression and chronic adaptations to training. These results suggest that acute upregulation of PGC-1α mRNA relates to the magnitude of subsequent training-induced increases in oxidative capacity, but not other molecular and morphological chronic skeletal muscle adaptations. Additionally, acute mRNA responses in PGC-1α correlated with VEGFA, but not SDHA, suggesting a coordinated upregulation between PGC-1α and only some of its proposed targets in human skeletal muscle.

  11. Recombinant human activated protein C in the treatment of acute respiratory distress syndrome: a randomized clinical trial.

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    Alexander D Cornet

    Full Text Available RATIONALE: Pulmonary coagulopathy may play a pathogenetic role in acute respiratory distress syndrome (ARDS, by contributing to alveolocapillary inflammation and increased permeability. Recombinant human activated protein C (rh-APC may inhibit this process and thereby improve patient outcome. METHODS: A prospective randomized, saline-controlled, single-blinded clinical trial was performed in the intensive care units of two university hospitals, and patients with ARDS were included within 24 h after meeting inclusion criteria. INTERVENTION: A 4-day course of intravenous rh-APC (24 mcg/kg/h (n = 33 versus saline (n = 38. OUTCOMES: The primary outcome parameter was the pulmonary leak index (PLI of 67Gallium-transferrin as a measure of alveolocapillary permeability and secondary outcomes were disease severity scores and ventilator-free days, among others. RESULTS: Baseline characteristics were similar; in 87% of patients the PLI was above normal and in 90% mechanical or non-invasive ventilation was instituted at a median lung injury score of 2.5. There was no evidence that Rh-APC treatment affected the PLI or attenuated lung injury and sequential organ failure assessment scores. Mean ventilator-free days amounted to 14 (rh-APC and 12 days (saline, P = 0.35. 28-day mortality was 6% in rh-APC- and 18% in saline-treated patients (P = 0.12. There was no difference in bleeding events. The study was prematurely discontinued because rh-APC was withdrawn from the market. CONCLUSION: There is no evidence that treatment with intravenous rh-APC during 4 days for infectious or inflammatory ARDS ameliorates increased alveolocapillary permeability or the clinical course of ARDS patients. We cannot exclude underpowering. TRIAL REGISTRATION: Nederlands Trial Register ISRCTN 52566874.

  12. Developing the catecholamines hypothesis for the acute exercise-cognition interaction in humans: Lessons from animal studies.

    Science.gov (United States)

    McMorris, Terry

    2016-10-15

    The catecholamines hypothesis for the acute exercise-cognition interaction in humans fails to adequately explain the interaction between peripherally circulating catecholamines and brain concentrations; how different exercise intensities×durations affect different cognitive tasks; and how brain catecholamines, glucocorticoids, BDNF and 5-hydroxytryptamine interact. A review of the animal literature was able to clarify many of the issues. Rodent studies showed that facilitation of cognition during short to moderate duration (SMD), moderate exercise could be accounted for by activation of the locus coeruleus via feedback from stretch reflexes, baroreceptors and, post-catecholamines threshold, β-adrenoceptors on the vagus nerve. SMD, moderate exercise facilitates all types of task by stimulation of the reticular system by norepinephrine (NE) but central executive tasks are further facilitated by activation of α2A-adrenoceptors and D1-dopaminergic receptors in the prefrontal cortex, which increases the signal to 'noise' ratio. During long-duration, moderate exercise and heavy exercise, brain concentrations of glucocorticoids and 5-hydroxytryptamine, the latter in moderate exercise only, also increase. This further increases catecholamines release. This results in increased activation of D1-receptors and α1-adrenoceptors, in the prefrontal cortex, which dampens all neural activity, thus inhibiting central executive performance. However, activation of β- and α1-adrenoceptors can positively affect signal detection in the sensory cortices, hence performance of perception/attention and autonomous tasks can be facilitated. Animal studies also show that during long-duration, moderate exercise and heavy exercise, NE activation of β-adrenoceptors releases cAMP, which modulates the signaling and trafficking of the BDNF receptor Trk B, which facilitates long-term potentiation. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. IRF-3, IRF-7, and IPS-1 promote host defense against acute human metapneumovirus infection in neonatal mice.

    Science.gov (United States)

    Spann, Kirsten M; Loh, Zhixuan; Lynch, Jason P; Ullah, Ashik; Zhang, Vivian; Baturcam, Engin; Werder, Rhiannon B; Khajornjiraphan, Natthida; Rudd, Penny; Loo, Yeuh-Ming; Suhrbier, Andreas; Gale, Michael; Upham, John W; Phipps, Simon

    2014-06-01

    Human metapneumovirus (hMPV) is a leading cause of respiratory tract disease in children and is associated with acute bronchiolitis, pneumonia, and asthma exacerbations, yet the mechanisms by which the host immune response to hMPV is regulated are poorly understood. By using gene-deleted neonatal mice, we examined the contributions of the innate receptor signaling molecules interferon (IFN)-β promoter stimulator 1 (IPS-1), IFN regulatory factor (IRF) 3, and IRF7. Viral load in the lungs was markedly greater in IPS-1(-/-) > IRF3/7(-/-) > IRF3(-/-), but not IRF7(-/-), mice compared with wild-type mice. IFN-β and IFN-λ2/3 (IL-28A/B) production was attenuated in the bronchoalveolar lavage fluid in all factor-deficient mice compared with wild-type mice at 1 day after infection, although IFN-λ2/3 was greater in IRF3/7(-/-) mice at 5 days after infection. IRF7(-/-) and IRF3/7(-/-) mice presented with airway eosinophilia, whereas only IRF3/7(-/-) mice developed an exaggerated type 1 and 17 helper T-cell response, characterized by natural killer T-cell and neutrophilic inflammation. Despite having the highest viral load, IPS-1(-/-) mice did not develop a proinflammatory cytokine or granulocytic response to hMPV infection. Our findings demonstrate that IFN-β, but not IFN-λ2/3, produced via an IPS-1-IRF3 signaling pathway, is important for hMPV clearance. In the absence of a robust type I IFN-α/β response, targeting the IPS-1 signaling pathway may limit the overexuberant inflammatory response that occurs as a consequence of viral persistence. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. Epidemiological aspects of human rotavirus infection in children hospitalized with acute gastroenteritis in an area of northern Italy.

    Science.gov (United States)

    Medici, Maria Cristina; Martinelli, Monica; Arcangeletti, Maria Cristina; Pinardi, Federica; De Conto, Flora; Dodi, Icilio; Virdis, Raffaele; Abelli, Laura Anna; Aloisi, Annalisa; Zerbini, Laura; Valcavi, Pierpaolo; Calderaro, Adriana; Bernasconi, Sergio; Izzi, Gian Carlo; Dettori, Giuseppe; Chezzi, Carlo

    2004-08-01

    Human rotavirus (HRV) is recognized as the most common cause of severe gastroenteritis in children under 5 years of age. Due to the lack of recent reports about the surveillance of HRV infection in Italy, in this study we assessed the prevalence rate of HRV infection on 1,340 stool samples belonging to 1,264 pediatric patients hospitalized with acute gastroenteritis in the period January 2000--December 2002. The stool samples were submitted to virological investigations by electron microscopy (EM) and conventional cell culture, as well as from January 2002 by RT-PCR for norovirus detection. Reovirus-like particles observed by EM were identified by electropherotyping. Single HRV infections were detected in 302 cases (23.9%, ranging from 19.1% in 2000 to 30.2% in 2001). Mixed infections were observed in 28 cases in which HRV was found to be associated with adenovirus in 16 cases (1.3%), with picornavirus in 4 (0.3%), and with norovirus in 8 (2.1% of the 388 cases examined in 2002). The 3 major epidemic periods of HRV infections were March--May 2000 (66 cases), December 2000--May 2001 (128 cases) and September 2001--April 2002 (105 cases) with peaks in March, January and March, and January, respectively. In the periods of major incidence, single HRV infection accounted even for 52.5% of the gastroenteritis cases monthly examined. According to age distribution, 68.9% (208 cases) of HRV infected children was under 4 years (69.6%: 230/330 cases, including mixed infections) and 16.9% (51 cases) was in the 5-12-year age-group. The epidemiological aspects of HRV infection, also compared to other enteric virus infections, will contribute to assess the magnitude of the problem of HRV in different settings and to devise strategies for intervention.

  15. Prevalence and genetic diversity analysis of human coronavirus OC43 among adult patients with acute respiratory infections in Beijing, 2012.

    Science.gov (United States)

    Hu, Qin; Lu, Roujian; Peng, Kun; Duan, Xijie; Wang, Yanqun; Zhao, Yanjie; Wang, Wen; Lou, Yongliang; Tan, Wenjie

    2014-01-01

    To determine the prevalence, epidemiology and genetic diversity of human coronavirus OC43 (HCoV-OC43) among adult patients with acute respiratory infections (ARI) in Beijing,five hundred and fifty-nine nasopharyngeal swab samples were collected from adult patients with ARI in Beijing. The prevalence of HCoV-OC43 infection among these patients was assessed using two different OneStep reverse transcription polymerase chain reaction (RT-PCR) assays. The epidemiological profiles of the patients with HCoV-OC43 infection were described. Partial S and N genes of HCoV-OC43 circulating strains were sequenced followed by phylogenetic analysis and amino acid alignment. Our results showed that the prevalence of HCoV-OC43 infection was 12.52% (95% CI: 9.78-15.26%), and the epidemic peak occurred in autumn. Fifty partial S and 40 partial N fragments were obtained from these patients. Phylogenetic analysis based on neighbour-joining method showed that at least three distinct clusters (A, B, C/D) of HCoV-OC43 strains were circulating among adult patients with ARI in Beijing. In addition, some novel unique clusters (UNT) of HCoV-OC43 were found in the S- and N-based phylogenetic trees. Furthermore, consensus amino acids substitutes for each cluster were also found after alignment of partial S or N sequence coding region in this study. In conclusion, we herein describe the prevalence of HCoV-OC43 among adult patients and provide substantial evidence for the genetic diversity of HCoV-OC43 circulating in Beijing.

  16. Prevalence and genetic diversity analysis of human coronavirus OC43 among adult patients with acute respiratory infections in Beijing, 2012.

    Directory of Open Access Journals (Sweden)

    Qin Hu

    Full Text Available To determine the prevalence, epidemiology and genetic diversity of human coronavirus OC43 (HCoV-OC43 among adult patients with acute respiratory infections (ARI in Beijing,five hundred and fifty-nine nasopharyngeal swab samples were collected from adult patients with ARI in Beijing. The prevalence of HCoV-OC43 infection among these patients was assessed using two different OneStep reverse transcription polymerase chain reaction (RT-PCR assays. The epidemiological profiles of the patients with HCoV-OC43 infection were described. Partial S and N genes of HCoV-OC43 circulating strains were sequenced followed by phylogenetic analysis and amino acid alignment. Our results showed that the prevalence of HCoV-OC43 infection was 12.52% (95% CI: 9.78-15.26%, and the epidemic peak occurred in autumn. Fifty partial S and 40 partial N fragments were obtained from these patients. Phylogenetic analysis based on neighbour-joining method showed that at least three distinct clusters (A, B, C/D of HCoV-OC43 strains were circulating among adult patients with ARI in Beijing. In addition, some novel unique clusters (UNT of HCoV-OC43 were found in the S- and N-based phylogenetic trees. Furthermore, consensus amino acids substitutes for each cluster were also found after alignment of partial S or N sequence coding region in this study. In conclusion, we herein describe the prevalence of HCoV-OC43 among adult patients and provide substantial evidence for the genetic diversity of HCoV-OC43 circulating in Beijing.

  17. Prevalence and clinical and molecular characterization of human metapneumovirus in children with acute respiratory infection in China.

    Science.gov (United States)

    Xiao, Ni-guang; Xie, Zhi-ping; Zhang, Bing; Yuan, Xin-hui; Song, Jing-rong; Gao, Han-chun; Zhang, Rong-fang; Hou, Yun-de; Duan, Zhao-jun

    2010-02-01

    Human metapneumovirus (HMPV), a newly discovered paramyxovirus, has been associated with acute respiratory tract infections (ARTIs). However, the prevalence and molecular characteristics of HMPV in China are still unclear. A total of 661 nasopharyngeal aspirates (NPA) specimens were collected from 661 children with ARTIs between December 2006 and November 2008. Specimens were screened for HMPV by reverse transcription-polymerase reaction. All positive amplification products were confirmed by sequencing. HMPV was detected in 45 patients (6.80%) of the 661 children. The HMPV-infected patients were from 29 days to 9 years of age. A high incidence of HMPV infection (84.4%) was observed during the winter-spring season. Of the 45 HMPV-positive patients, 25 (55.6%) were co-infected with other respiratory viruses, and respiratory syncytial virus (RSV) was the most common additional respiratory virus. The most common clinical diagnosis was bronchopneumonia (57.8%) and cough (88.9%) was the most common clinical symptom. Phylogenetic analysis of the F gene revealed that 80% of the HMPV detected were A2, 2.2% were A1, and 17.8% were B1. Statistical analyses showed that sex, ages, seasons, and severity of the disease did not correlate with HMPV genotype (P = 0.986, 0.347, 0.660, 0.252), but viral coinfection with HMPV increased hospitalization rates (P = 0.005). HMPV was frequently detected in the pediatric patients with ARTI in China. RSV was the most common coinfection virus and coinfection increased hospitalization rates. All HMPV subgroups except B2 cocirculated and there was no association found between HMPV genotypes and severity of disease.

  18. Prevalence and clinical characteristics of human CoV-HKU1 in children with acute respiratory tract infections in China.

    Science.gov (United States)

    Jin, Yu; Song, Jing-Rong; Xie, Zhi-Ping; Gao, Han-Chun; Yuan, Xin-Hui; Xu, Zi-Qian; Yan, Kun-Long; Zhao, Yang; Xiao, Ni-Guang; Hou, Yun-De; Duan, Zhao-Jun

    2010-10-01

    Human CoV-HKU1 (HCoV-HKU1) has been isolated from a 71-year-old man with pneumonia; however, the impact and role of emerging HCoV-HKU1 have not been defined in children with acute respiratory tract infection (ARTI). To investigate the Prevalence and clinical characteristics of HCoV-HKU1 in children with ARTI in Lanzhou, China. The reverse transcription polymerase chain reaction (RT-PCR) or PCR was employed to screen HCoV-HKU1 and other common respiratory viruses in 645 nasopharyngeal aspirate (NPA) specimens collected from children with ARTI from November 2006 to October 2008. All PCR positive products were sequenced. And the demographic and clinical data were collected for all patients. Nineteen of 645 (2.95%) specimens tested positive for HCoV-HKU1, and all HCoV-HKU1 positive specimens were distributed in the winter and spring season. The HCoV-HKU1 co-infection rate with other respiratory viruses was 47.37% (9/19). There was no statistically significant difference in the detection rate between groups by age or gender, except between patients with and without underlying diseases. The phylogenetic analysis indicated that HCoV-HKU1 genotype B was circulating in the years 2007 and 2008 in children with ARTI in Lanzhou, China. HCoV-HKU1 is an uncommon virus existing among Chinese children with ARTI. Children with underlying diseases are more vulnerable to viral infection. Only HCoV-HKU1 genotype B circulated locally. Copyright © 2010. Published by Elsevier B.V.

  19. Biodiversity and clinico-demographic characteristics of human rhinoviruses from hospitalized children with acute lower respiratory tract infections in Malaysia.

    Science.gov (United States)

    Etemadi, Mohammad Reza; Othman, Norlijah; Savolainen-Kopra, Carita; Sekawi, Zamberi; Wahab, NoraAbd; Sann, Lye Munn

    2013-12-01

    There is accumulating evidence that human rhinovirus (HRV) causes acute lower respiratory tract infections (ALRTI). Recently, HRV-C was identified as a new species of HRV, but its spectrum of clinical disease is not well understood. We investigated the molecular epidemiology, demographic and clinical characteristics of HRVs among hospitalized children with ALRIs. One hundred and sixty-five nasopharangeal aspirates taken from children respiratory viruses were also investigated using semi-nested multiplex RT-PCR assay. Clinical parameters were analyzed between HRV, RSV and IFV-A mono-infections and between HRV species. HRV was detected in 54 (33%) patients for both single (36 samples) and multiple (18 samples) infections, 61.1% (22/36) represents HRV-A strains while the remaining 14 HRV-C. Strain P51 was the first reported representative of HRV98. The majority of the single HRV cases were in the second half of infancy; HRV-C occurred among older children compared with HRV-A. HRV children were admitted significantly earlier and less febrile than RSV and IFV-A infection. HRV-C infected children were more likely to have rhonchi and vomiting as compared to HRV-A. Pneumonia was the most common discharge diagnosis followed by bronchiolitis and post-viral wheeze in HRV patients. Our study showed high prevalence of HRVs and detection of HRV-C among hospitalized children with ALRTIs in Malaysia. Analysis of clinical parameters suggested specific features associated with HRVs infections and specific HRV groups. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  20. The role of human adenoviruses type 41 in acute diarrheal disease in Minas Gerais after rotavirus vaccination

    Directory of Open Access Journals (Sweden)

    Thaís Aparecida Vieira Reis

    2016-03-01

    Full Text Available Abstract Human adenovirus species F (HAdV-F type 40 and 41 are commonly associated with acute diarrheal disease (ADD across the world. Despite being the largest state in southeastern Brazil and having the second largest number of inhabitants, there is no information in the State of Minas Gerais regarding the role of HAdV-F in the etiology of ADD. This study was performed to determine the prevalence, to verify the epidemiological aspects of infection, and to characterize the strains of human adenoviruses (HAdV detected. A total of 377 diarrheal fecal samples were obtained between January 2007 and August 2011 from inpatient and outpatient children of age ranging from 0 to 12 years. All samples were previously tested for rotavirus, norovirus, and astrovirus, and 314 of 377 were negative. The viral DNA was extracted, amplified using the polymerase chain reaction and the HAdV-positive samples were sequenced and phylogenetically analyzed. Statistical analyses were performed using the Chi-square test (p < 0.05, considering two conditions: the total of samples tested (377 and the total of negative samples for the remaining viruses tested (314. The overall prevalence of HAdV was 12.47% (47/377; and in 76.60% (36/47 of the positive samples, this virus was the only infectious agent detected. The phylogenetic analysis of partial sequences of 32 positive samples revealed that they all clustered with the HAdV-F type 41. The statistical analysis showed that there was no correlation between the onset of the HAdV infection and the origin of the samples (inpatients or outpatients in the two conditions tested: the total of samples tested (p = 0.598 and the total of negative samples for the remaining viruses tested (p = 0.614. There was a significant association in the occurrence of infection in children aged 0–12 months for the condition 1 (p = 0.030 as well as condition 2 (p = 0.019. The occurrence of infections due to HAdV did not coincide with a pattern of

  1. Cytotoxic capacity of IL-15-stimulated cytokine-induced killer cells against human acute myeloid leukemia and rhabdomyosarcoma in humanized preclinical mouse models

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    Eva eRettinger

    2012-04-01

    Full Text Available Allogeneic stem cell transplantation (allo-SCT has become an important treatment modality for patients with high risk acute myeloid leukemia (AML and is also under investigation for soft tissue sarcomas. The therapeutic success is still limited by minimal residual disease (MRD status ultimately leading to patients’ relapse. Adoptive donor lymphocyte infusions (DLI based on MRD status using IL-15-expanded cytokine-induced killer (CIK cells may prevent relapse without causing graft-versus-host-disease (GvHD. To generate preclinical data we developed mouse models to study anti-leukemic- and anti-tumor-potential of CIK cells in vivo. Immunodeficient mice (NOD/SCID/IL2Rγc-, NSG were injected intravenously with human leukemic cell lines THP-1, SH-2 and with human rhabdomyosarcoma (RMS cell lines RH41 and RH30 at minimal doses required for leukemia or tumor engraftment. Mice transplanted with THP-1 or RH41 cells were randomly assigned for analysis of CIK cell treatment. Organs of mice were analyzed by flow cytometry as well as quantitative polymerase chain reaction (qPCR for engraftment of malignant cells and CIK cells. Potential of CIK cells to induce GvHD was determined by histological analysis. Tissues of the highest degree of THP-1 cell expansion included bone marrow (BM followed by liver, lung, spleen, peripheral blood (PB, and brain. RH30 and RH41 engraftment mainly took place in liver and lung, but was also detectable in spleen and PB. In spite of delayed CIK cell expansion compared with malignant cells, CIK cells injected at an effector to target cell (E:T ratio of 1:1 were sufficient for significant reduction of RH41 cells, whereas against fast-expanding THP-1 cells an E:T ratio of 250:1 was needed to achieve comparable results. Our preclinical in vivo mouse models showed a reliably 100% engraftment of malignant cells which is essential for analysis of anti-cancer therapy. Furthermore our data demonstrated that IL-15-activated CIK cells

  2. Quantitative analysis of human herpesvirus-6 genome in blood and bone marrow samples from Tunisian patients with acute leukemia: a follow-up study

    Directory of Open Access Journals (Sweden)

    Faten Nefzi

    2012-11-01

    Full Text Available Abstract Background Infectious etiology in lymphoproliferative diseases has always been suspected. The pathogenic roles of human herpesvirus-6 (HHV-6 in acute leukemia have been of great interest. Discordant results to establish a link between HHV-6 activation and the genesis of acute leukemia have been observed. The objective of this study was to evaluate a possible association between HHV-6 infection and acute leukemia in children and adults, with a longitudinal follow-up at diagnosis, aplasia, remission and relapse. Methods HHV-6 load was quantified by a quantitative real-time PCR in the blood and bone marrow samples from 37 children and 36 adults with acute leukemia: 33 B acute lymphoblastic leukemia (B-ALL, 6 T acute lymphoblastic leukemia (T-ALL, 34 acute myeloid leukemia (AML. Results HHV-6 was detected in 15%, 8%, 30% and 28% of the blood samples at diagnosis, aplasia, remission and relapse, respectively. The median viral loads were 138, 244, 112 and 78 copies/million cells at diagnosis, aplasia, remission and relapse, respectively. In the bone marrow samples, HHV-6 was detected in 5%, 20% and 23% of the samples at diagnosis, remission and relapse, respectively. The median viral loads were 34, 109 and 32 copies/million cells at diagnosis, remission and relapse, respectively. According to the type of leukemia at diagnosis, HHV-6 was detected in 19% of the blood samples and in 7% of the bone marrow samples (with median viral loads at 206 and 79 copies/million cells, respectively from patients with B-ALL. For patients with AML, HHV-6 was present in 8% of the blood samples and in 4% of the bone marrow samples (with median viral loads at 68 and 12 copies/million cells, respectively. HHV-6 was more prevalent in the blood samples from children than from adults (25% and 9%, respectively and for the bone marrow (11% and 0%, respectively. All typable HHV-6 were HHV-6B species. No link was shown between neither the clinical symptoms nor the

  3. Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans.

    OpenAIRE

    Skene, D J; Bojkowski, C J; Arendt, J

    1994-01-01

    1. Acute administration of the specific serotonin uptake inhibitor, fluvoxamine (100 mg at 16.00 h), markedly increased nocturnal plasma melatonin concentrations, with high levels extending into the morning hours. 2. Acute administration of the noradrenaline uptake inhibitor, desipramine (DMI) (100 mg at 16.00 h), increased evening plasma melatonin concentrations. 3. Both drug treatments increased the duration of melatonin secretion, fluvoxamine significantly delaying the offset time and DMI ...

  4. Complete genome sequence, lifestyle, and multi-drug resistance of the human pathogen Corynebacterium resistens DSM 45100 isolated from blood samples of a leukemia patient

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    Schröder Jasmin

    2012-04-01

    Full Text Available Abstract Background Corynebacterium resistens was initially recovered from human infections and recognized as a new coryneform species that is highly resistant to antimicrobial agents. Bacteremia associated with this organism in immunocompromised patients was rapidly fatal as standard minocycline therapies failed. C. resistens DSM 45100 was isolated from a blood culture of samples taken from a patient with acute myelocytic leukemia. The complete genome sequence of C. resistens DSM 45100 was determined by pyrosequencing to identify genes contributing to multi-drug resistance, virulence, and the lipophilic lifestyle of this newly described human pathogen. Results The genome of C. resistens DSM 45100 consists of a circular chromosome of 2,601,311 bp in size and the 28,312-bp plasmid pJA144188. Metabolic analysis showed that the genome of C. resistens DSM 45100 lacks genes for typical sugar uptake systems, anaplerotic functions, and a fatty acid synthase, explaining the strict lipophilic lifestyle of this species. The genome encodes a broad spectrum of enzymes ensuring the availability of exogenous fatty acids for growth, including predicted virulence factors that probably contribute to fatty acid metabolism by damaging host tissue. C. resistens DSM 45100 is able to use external L-histidine as a combined carbon and nitrogen source, presumably as a result of adaptation to the hitherto unknown habitat on the human skin. Plasmid pJA144188 harbors several genes contributing to antibiotic resistance of C. resistens DSM 45100, including a tetracycline resistance region of the Tet W type known from Lactobacillus reuteri and Streptococcus suis. The tet(W gene of pJA144188 was cloned in Corynebacterium glutamicum and was shown to confer high levels of resistance to tetracycline, doxycycline, and minocycline in vitro. Conclusions The detected gene repertoire of C. resistens DSM 45100 provides insights into the lipophilic lifestyle and virulence functions of

  5. Inhibitors of ORAI1 Prevent Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models.

    Science.gov (United States)

    Wen, Li; Voronina, Svetlana; Javed, Muhammad A; Awais, Muhammad; Szatmary, Peter; Latawiec, Diane; Chvanov, Michael; Collier, David; Huang, Wei; Barrett, John; Begg, Malcolm; Stauderman, Ken; Roos, Jack; Grigoryev, Sergey; Ramos, Stephanie; Rogers, Evan; Whitten, Jeff; Velicelebi, Gonul; Dunn, Michael; Tepikin, Alexei V; Criddle, David N; Sutton, Robert

    2015-08-01

    Sustained activation of the cytosolic calcium concentration induces injury to pancreatic acinar cells and necrosis. The calcium release-activated calcium modulator ORAI1 is the most abundant Ca(2+) entry channel in pancreatic acinar cells; it sustains calcium overload in mice exposed to toxins that induce pancreatitis. We investigated the roles of ORAI1 in pancreatic acinar cell injury and the development of acute pancreatitis in mice. Mouse and human acinar cells, as well as HEK 293 cells transfected to express human ORAI1 with human stromal interaction molecule 1, were hyperstimulated or incubated with human bile acid, thapsigargin, or cyclopiazonic acid to induce calcium entry. GSK-7975A or CM_128 were added to some cells, which were analyzed by confocal and video microscopy and patch clamp recordings. Acute pancreatitis was induced in C57BL/6J mice by ductal injection of taurolithocholic acid 3-sulfate or intravenous' administration of cerulein or ethanol and palmitoleic acid. Some mice then were given GSK-7975A or CM_128, which inhibit ORAI1, at different time points to assess local and systemic effects. GSK-7975A and CM_128 each separately inhibited toxin-induced activation of ORAI1 and/or activation of Ca(2+) currents after Ca(2+) release, in a concentration-dependent manner, in mouse and human pancreatic acinar cells (inhibition >90% of the levels observed in control cells). The ORAI1 inhibitors also prevented activation of the necrotic cell death pathway in mouse and human pancreatic acinar cells. GSK-7975A and CM_128 each inhibited all local and systemic features of acute pancreatitis in all 3 models, in dose- and time-dependent manners. The agents were significantly more effective, in a range of parameters, when given at 1 vs 6 hours after induction of pancreatitis. Cytosolic calcium overload, mediated via ORAI1, contributes to the pathogenesis of acute pancreatitis. ORAI1 inhibitors might be developed for the treatment of patients with pancreatitis

  6. The in vivo evaluation of the therapeutic potential of human adipose tissue-derived mesenchymal stem cells for acute liver disease.

    Science.gov (United States)

    Katsuda, Takeshi; Kurata, Hayato; Tamai, Rie; Banas, Agnieszka; Ishii, Tsuyoshi; Ishikawa, Shumpei; Ochiya, Takahiro

    2014-01-01

    Mesenchymal stem cells (MSCs) have emerged as an attractive candidate for cell therapy applications. In the prior decade, many animal studies have demonstrated that MSCs are therapeutically beneficial for the treatment of liver disease. The carbon tetrachloride (CCl4)-induced acute hepatitis model has been the most widely used model in these studies. Our group has utilized the CCl4-induced mouse hepatitis model to study the therapeutic potential of human adipose tissue-derived MSCs (hADSCs). We have demonstrated that systemically administered hADSCs engrafted into the damaged liver and promoted tissue repair. This phenomenon likely reflected the paracrine effects of the administered hADSCs. In this chapter, we describe a method to evaluate the therapeutic efficacy of the systemic administration of hADSCs in the CCl4-induced mouse model of acute hepatitis.

  7. [DNA damage and repair induced by acute exposure of microwave from mobile phone on cultured human lens epithelial cells].

    Science.gov (United States)

    Sun, Li-xia; Yao, Ke; Jiang, Huai; He, Ji-liang; Lu, De-qiang; Wang, Kai-jun; Li, Hong-wu

    2006-12-01

    To investigate the effects of acute exposure of low-power 217 Hz modulated 1. 8 GHz microwave radiation on the DNA damage of human lens epithelial cells (hLECs) and repair. Cultured hLECs were exposed to 217 Hz modulated 1. 8 GHz microwave radiation at SAR (specific absorption rate) of 1. 0, 2. 0, 3. O0 and 4. 0 W/kg for 2 hours in an sXc-1800 incubator and irradiate system, the DNA single strand breaks were detected with comet assay ( single-cell gel electrophoresis) in sham-irradiated cells and irradiated cells incubated for varying periods: 0, 30 and 60 minutes after irradiation. Images of comets were digitized and analyzed using an Imagine-pro plus software, and the indexes used in this study were tail length (TL) and tail moment (TM). BrdU was added into the medium with additional one hour incubation after radiation, the cell proliferation rate was determined using a BrdU-kit. The difference of DNA-breaks between the exposure and sham exposure groups induced by 1.0 and 2.0 W/kg irradiation were not significant in each time points (P > 0.05) ; there were significant difference in both groups at the exposure dose of 3. 0 and 4. 0 W/kg immediately and at the time of 30 minutes after irradiation (P detected in 3.0 W/kg group (P > 0. 05) compared with control, but the evidence of significant DNA damage still existed in 4. 0 W/kg group at the same time point. Cell proliferation rate had no significant difference when the application of SAR was 0. 05) , however the cell proliferation was decreased significantly at the dose of 4. 0 W/kg irradiation ( P DNA damage was induced using comet assay after 2 hours irradiation of 1. 8 GHz microwave on hLECs at the dose SAR DNA damage and inhibition of hLECs proliferation.

  8. A rapid crosstalk of human gammadelta T cells and monocytes drives the acute inflammation in bacterial infections.

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    Matthias Eberl

    2009-02-01

    Full Text Available Vgamma9/Vdelta2 T cells are a minor subset of T cells in human blood and differ from other T cells by their immediate responsiveness to microbes. We previously demonstrated that the primary target for Vgamma9/Vdelta2 T cells is (E-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP, an essential metabolite produced by a large range of pathogens. Here we wished to study the consequence of this unique responsiveness in microbial infection. The majority of peripheral Vgamma9/Vdelta2 T cells shares migration properties with circulating monocytes, which explains the presence of these two distinct blood cell types in the inflammatory infiltrate at sites of infection and suggests that they synergize in anti-microbial immune responses. Our present findings demonstrate a rapid and HMB-PP-dependent crosstalk between Vgamma9/Vdelta2 T cells and autologous monocytes that results in the immediate production of inflammatory mediators including the cytokines interleukin (IL-6, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, and oncostatin M (OSM; the chemokines CCL2, CXCL8, and CXCL10; and TNF-related apoptosis-inducing ligand (TRAIL. Moreover, under these co-culture conditions monocytes differentiate within 18 hours into inflammatory dendritic cells (DCs with antigen-presenting functions. Addition of further microbial stimuli (lipopolysaccharide, peptidoglycan induces CCR7 and enables these inflammatory DCs to trigger the generation of CD4(+ effector alphabeta T cells expressing IFN-gamma and/or IL-17. Importantly, our in vitro model replicates the responsiveness to microbes of effluent cells from peritoneal dialysis (PD patients and translates directly to episodes of acute PD-associated bacterial peritonitis, where Vgamma9/Vdelta2 T cell numbers and soluble inflammatory mediators are elevated in patients infected with HMB-PP-producing pathogens. Collectively, these findings suggest a direct link between invading pathogens, microbe

  9. Acute myocardial infarction activates distinct inflammation and proliferation pathways in circulating monocytes, prior to recruitment, and identified through conserved transcriptional responses in mice and humans

    Science.gov (United States)

    Ruparelia, Neil; Godec, Jernej; Lee, Regent; Chai, Joshua T.; Dall'Armellina, Erica; McAndrew, Debra; Digby, Janet E.; Forfar, J. Colin; Prendergast, Bernard D.; Kharbanda, Rajesh K.; Banning, Adrian P.; Neubauer, Stefan; Lygate, Craig A.; Channon, Keith M.; Haining, Nicholas W.; Choudhury, Robin P.

    2015-01-01

    Aims Monocytes play critical roles in tissue injury and repair following acute myocardial infarction (AMI). Specifically targeting inflammatory monocytes in experimental models leads to reduced infarct size and improved healing. However, data from humans are sparse, and it remains unclear whether monocytes play an equally important role in humans. The aim of this study was to investigate whether the monocyte response following AMI is conserved between humans and mice and interrogate patterns of gene expression to identify regulated functions. Methods and results Thirty patients (AMI) and 24 control patients (stable coronary atherosclerosis) were enrolled. Female C57BL/6J mice (n = 6/group) underwent AMI by surgical coronary ligation. Myocardial injury was quantified by magnetic resonance imaging (human) and echocardiography (mice). Peripheral monocytes were isolated at presentation and at 48 h. RNA from separated monocytes was hybridized to Illumina beadchips. Acute myocardial infarction resulted in a significant peripheral monocytosis in both species that positively correlated with the extent of myocardial injury. Analysis of the monocyte transcriptome following AMI demonstrated significant conservation and identified inflammation and mitosis as central processes to this response. These findings were validated in both species. Conclusions Our findings show that the monocyte transcriptome is conserved between mice and humans following AMI. Patterns of gene expression associated with inflammation and proliferation appear to be switched on prior to their infiltration of injured myocardium suggesting that the specific targeting of inflammatory and proliferative processes in these immune cells in humans are possible therapeutic strategies. Importantly, they could be effective in the hours after AMI. PMID:25982896

  10. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

    OpenAIRE

    Chan, Michael C. W.; Kuok, Denise I. T.; Leung, Connie Y. H.; Hui, Kenrie P. Y.; Valkenburg, Sophie A.; Lau, Eric H. Y.; Nicholls, John M.; Fang, Xiaohui; Guan, Yi; Lee, Jae W.; Chan, Renee W. Y.; Webster, Robert G.; Matthay, Michael A.; Peiris, J. S. Malik

    2016-01-01

    Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstr...

  11. Effect of recombinant human brain natriuretic peptide-assisted interventional treatment on prognosis of acute myocardial infarction patients complicated with cardiogenic shock

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    Xi-Zhou Chen

    2016-01-01

    Full Text Available Objective: To analyze the effect of recombinant human brain natriuretic peptide-assisted interventional treatment on prognosis of acute myocardial infarction patients complicated with cardiogenic shock. Methods: A total of 112 cases of inpatients treated in Cardiology Department of our hospital from March 2013 to March 2015 were selected, all of whom had acute myocardial infarction within 12 hours of onset and received direct PCI treatment. They were divided into observation group and control group according to random number table, each group with 56 cases, control group received conventional interventional treatment and observation group received recombinant human brain natriuretic peptide-assisted interventional treatment. Then differences of regional myocardial deformability, myocardial enzyme spectrum indicators, brain natriuretic peptide and inflammatory factors, blood sugar and stress hormones as well as myocardial infarction prognosis-associated indexes, etc, between two groups after treatment were compared. Results: After treatment, LVEF, SRs, SRe and Sra levels of observation group were higher than those of control group, WMSI level was lower than that of control group; serum myocardial enzyme spectrum indicators CK, CK-MB, AST and LDH values were lower than those of control group; serum BNP, CRP, TNF-α and IL-6 levels were lower than those of control group; serum cortisol, growth hormone and glucagon levels were lower than those of control group, insulin level was higher than that of control group; FT3 and IGF-1 levels were higher than those of control group, sPLA2 and Hcy levels were lower than those of control group. Conclusion: Recombinant human brain natriuretic peptide-assisted interventional treatment for acute myocardial infarction patients complicated with cardiogenic shock can reduce myocardial function injury, protect normal myocardial function and optimize patients’ long-term prognosis; it has active clinical significance.

  12. Molecular and clinical evaluation of the acute human parvovirus B19 infection: comparison of two cases in children with sickle cell disease and discussion of the literature

    Directory of Open Access Journals (Sweden)

    Svetoslav Nanev Slavov

    2013-02-01

    Full Text Available Human parvovirus B19 is a well-known cause of severe conditions in patients with sickle cell disease, but the molecular mechanisms of the infection are insufficiently understood. The different clinical outcome of the acute parvovirus B19 infection in two pediatric patients with sickle cell disease has been examined. One of them developed life-threatening condition requiring emergency transfusions, while the other had asymptomatic infection, diagnosed occasionally. Both cases had high viral load and identical subgenotype, indicating that the viral molecular characteristics play a minimal role in the infection outcome.

  13. Fatal acute myocarditis and fulminant hepatic failure in an infant with pandemic human influenza A, H1N1 (2009 virus infection

    Directory of Open Access Journals (Sweden)

    Mortada H.F. El-Shabrawi

    2011-04-01

    Full Text Available We report the clinical presentation of a 10 month-old infant who succumbed with acute myocarditis and fulminant hepatic failure associated with a virologically confirmed human influenza A, H1N1 (2009 virus infection. To date, this is the first pediatric patient presenting with this fatal combination of complications during the current H1N1 pandemic. Therefore, we recommend meticulous assessment and follow up of the cardiac status, liver enzymes and coagulation profile in all pediatric patients with severe H1N1 influenza infection.

  14. 'Spreading depression of Leão' and its emerging relevance to acute brain injury in humans

    DEFF Research Database (Denmark)

    Lauritzen, Martin; Strong, Anthony J

    2017-01-01

    A new research field in translational neuroscience has opened as a result of the recognition since 2002 that "spreading depression of Leão" can be detected in many patients with acute brain injury, whether vascular and spontaneous, or traumatic in origin, as well as in those many individuals...

  15. Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans

    DEFF Research Database (Denmark)

    Steensberg, Adam; Fischer, Christian P; Sacchetti, Massimo

    2003-01-01

    The cytokine interleukin (IL)-6 has recently been linked with type 2 diabetes mellitus and has been suggested to affect glucose metabolism. To determine whether acute IL-6 administration affects whole-body glucose kinetics or muscle glucose uptake, 18 healthy young men were assigned to one of thr...

  16. Exenatide, a Glucagon-like Peptide-1 Receptor Agonist, Acutely Inhibits Intestinal Lipoprotein Production in Healthy Humans

    NARCIS (Netherlands)

    Xiao, Changting; Bandsma, Robert H. J.; Dash, Satya; Szeto, Linda; Lewis, Gary F.

    Objective-Incretin-based therapies for the treatment of type 2 diabetes mellitus improve plasma lipid profiles and postprandial lipemia, but their exact mechanism of action remains unclear. Here, we examined the acute effect of the glucagon-like peptide-1 receptor agonist, exenatide, on intestinal

  17. Pro- and anti-angiogenic factors in human skeletal muscle in response to acute exercise and training

    DEFF Research Database (Denmark)

    Høier, Birgitte; Nordsborg, Nikolai; Andersen, Søren

    2012-01-01

    to acute exercise increased similarly (>6-fold; P TSP-1) and Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in muscle, were unaffected by training, whereas e......NOS protein levels in muscle increased by 50% (P TSP-1. After training, TIMP-1mRNA content increased with exercise (P

  18. Insulin acutely upregulates protein expression of the fatty acid transporter CD36 in human skeletal muscle in vivo

    NARCIS (Netherlands)

    Corpeleijn, E.; Pelsers, M. M. A. L.; Soenen, S.; Mensink, M.; Bouwman, F. G.; Kooi, M. E.; Saris, W. H. M.; Glatz, J. F. C.; Blaak, E. E.

    Enhanced fatty acid uptake may lead to the accumulation of lipid intermediates. This is related to insulin resistance and type 2 diabetes mellitus. Rodent studies suggest that fatty acid transporters are acutely regulated by insulin. We investigated differences in fatty acid transporter content

  19. Increased oxidative stress and anaerobic energy release, but blunted Thr172-AMPKα phosphorylation, in response to sprint exercise in severe acute hypoxia in humans.

    Science.gov (United States)

    Morales-Alamo, David; Ponce-González, Jesús Gustavo; Guadalupe-Grau, Amelia; Rodríguez-García, Lorena; Santana, Alfredo; Cusso, Maria Roser; Guerrero, Mario; Guerra, Borja; Dorado, Cecilia; Calbet, José A L

    2012-09-01

    AMP-activated protein kinase (AMPK) is a major mediator of the exercise response and a molecular target to improve insulin sensitivity. To determine if the anaerobic component of the exercise response, which is exaggerated when sprint is performed in severe acute hypoxia, influences sprint exercise-elicited Thr(172)-AMPKα phosphorylation, 10 volunteers performed a single 30-s sprint (Wingate test) in normoxia and in severe acute hypoxia (inspired Po(2): 75 mmHg). Vastus lateralis muscle biopsies were obtained before and immediately after 30 and 120 min postsprint. Mean power output and O(2) consumption were 6% and 37%, respectively, lower in hypoxia than in normoxia. O(2) deficit and muscle lactate accumulation were greater in hypoxia than in normoxia. Carbonylated skeletal muscle and plasma proteins were increased after the sprint in hypoxia. Thr(172)-AMPKα phosphorylation was increased by 3.1-fold 30 min after the sprint in normoxia. This effect was prevented by hypoxia. The NAD(+)-to-NADH.H(+) ratio was reduced (by 24-fold) after the sprints, with a greater reduction in hypoxia than in normoxia (P exercise in human skeletal muscle is altered in severe acute hypoxia, which abrogated Thr(172)-AMPKα phosphorylation, likely due to lower LKB1 activation by SIRT1.

  20. Acute Bronchitis

    Science.gov (United States)

    ... of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your cough ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when people ...

  1. The effect of acute moderate psychological stress on working memory-related neural activity is modulated by a genetic variation in catecholaminergic function in humans

    Directory of Open Access Journals (Sweden)

    Shaozheng eQin

    2012-05-01

    Full Text Available Acute stress has an important impact on higher-order cognitive functions supported by the prefrontal cortex (PFC such as working memory (WM. In rodents, such effects are mediated by stress-induced alterations in catecholaminergic signaling, but human data in support of this notion is lacking. A common variation in the gene encoding Catechol-O-methyltransferase (COMT is known to affect basal catecholaminergic availability and PFC functions. Here, we investigated whether this genetic variation (Val158Met modulates effects of stress on WM-related prefrontal activity in humans. In a counterbalanced crossover design, 41 healthy young men underwent functional Magnetic Resonance Imaging (fMRI while performing a numerical N-back WM task embedded in a stressful or neutral context. Moderate psychological stress was induced by a well-controlled procedure involving viewing strongly aversive (versus emotionally neutral movie material in combination with a self-referencing instruction. Acute stress resulted in genotype-dependent effects on WM performance and WM-related activation in the dorsolateral PFC, with a relatively negative impact of stress in COMT Met-homozygotes as opposed to a relatively positive effect in Val-carriers. A parallel interaction was found for WM-related deactivation in the anterior medial temporal lobe. Our findings suggest that individuals with higher baseline catecholaminergic availability (COMT Met-homozygotes appear to reach a supraoptimal state under moderate levels of stress. In contrast, individuals with lower baselines (Val-carriers may reach an optimal state. Thus, our data show that effects of acute stress on higher-order cognitive functions vary depending on catecholaminergic availability at baseline, and thereby corroborate animal models of catecholaminergic signaling that propose a non-linear relationship between catecholaminergic activity and prefrontal functions.

  2. Reproducibility of the acute rejection diagnosis in human cardiac allografts. The Stanford Classification and the International Grading System

    DEFF Research Database (Denmark)

    Nielsen, H; Sørensen, Flemming Brandt; Nielsen, B

    1993-01-01

    Transplantation has become an accepted treatment of many cardiac end-stage diseases. Acute cellular rejection accounts for 15% to 20% of all graft failures. The first grading system of acute cellular rejection, the Stanford Classification, was introduced in 1979, and since then many other grading...... systems have evolved. Most recently, the International Grading System was introduced in The Journal of Heart and Lung Transplantation. In this study the interobserver reproducibility of both the Stanford Classification and the International Grading System is evaluated using Kappa statistics. Three...... observers evaluated 168 endomyocardial biopsy specimens according to the Stanford Classification and 100 endomyocardial biopsy specimens according to the International Grading System. The evaluation was carried out blindly. Kappa values of 54.1% and 51.5%, respectively, were obtained, both significantly...

  3. Serum neopterin and soluble CD163 as markers of macrophage activation in paracetamol (acetaminophen)-induced human acute liver injury.

    Science.gov (United States)

    Craig, D G; Lee, P; Pryde, E A; Hayes, P C; Simpson, K J

    2013-12-01

    Macrophage activation is implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS) following paracetamol (acetaminophen) overdose (POD). Neopterin is synthesised from macrophages and reflects the intensity of monocyte/macrophage activation. Soluble CD163 (sCD163) is a marker of alternatively activated M2 macrophages. To examine neopterin and sCD163 levels in a cohort of acute liver injury patients. Consecutive patients (n = 41, (18 (43.9%) male) with acute liver injury were enrolled. Neopterin and sCD163 levels were measured by ELISA. A total of 24/33 (72.7%) POD patients developed hepatic encephalopathy (HE), and therefore acute liver failure. Both neopterin and sCD163 levels were significantly higher in PODs compared with chronic liver disease (neopterin P paracetamol overdose, and reflect the degree of macrophage activation in this condition. Serum neopterin in particular may have value as an early proxy marker of macrophage activation following paracetamol overdose. © 2013 John Wiley & Sons Ltd.

  4. How the brain connects in response to acute stress: A review at the human brain systems level.

    Science.gov (United States)

    van Oort, J; Tendolkar, I; Hermans, E J; Mulders, P C; Beckmann, C F; Schene, A H; Fernández, G; van Eijndhoven, P F

    2017-10-24

    The brain's response to stress is a matter of extensive neurocognitive research in an attempt to unravel the mechanistic underpinnings of neural adaptation. In line with the broadly defined concept of acute stress, a wide variety of induction procedures are used to mimic stress experimentally. We set out to review commonalities and diversities of the stress-related functional activity and connectivity changes of functional brain networks in healthy adults across procedures. The acute stress response is consistently associated with both increased activity and connectivity in the salience network (SN) and surprisingly also with increased activity in the default mode network (DMN), while most studies show no changes in the central executive network. These results confirm earlier findings of an essential, coordinating role of the SN in the acute stress response and indicate a dynamic role of the DMN whose function is less clear. Moreover, paradigm specific brain responses have to be taken into account when investigating the role and the within and between network connectivity of these three networks. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Improvement and application of an acute blood stasis rat model aligned with the 3Rs (reduction, refinement and replacement) of humane animal experimentation.

    Science.gov (United States)

    Huang, Shuai; Xu, Feng; Wang, Yin-Ye; Shang, Ming-Ying; Wang, Chao-Qun; Wang, Xuan; Cai, Shao-Qing

    2014-12-23

    To establish a novel cardiocentesis method for withdrawing venous blood from the right atrium, and to improve an acute blood stasis rat model using an ice bath and epinephrine hydrochloride (Epi) while considering the 3Rs (reduction, refinement, and replacement) of humane animal experimentation. An acute blood stasis model was established in male Sprague-Dawley rats by subcutaneous injection (s.c.) Epi (1.2 mg/kg) administration at 0 h, followed by a 5-min exposure to an ice-bath at 2 h and s.c. Epi administration at 4 h. Control rats received physiological saline. Rats were fasted overnight and treated with Angelicae Sinensis Lateralis Radix (ASLR) and Pheretima the following day. Venous blood was collected using our novel cardiocentesis method and used to test whole blood viscosity (WBV), prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) content. The rats survived the novel cardiocentesis technique; WBV value returned to normal while hematological parameters such as hemoglobin level and red blood cell count were restored to >94% of the corresponding values in normal rats following a 14-day recovery. Epi (1.2 mg/kg, s.c.) combined with a 5-min exposure to the ice bath replicated the acute blood stasis rat model and was associated with the highest WBV value. In rats showing acute blood stasis, ASLR treatment [4 g/(kg·d) for 8 days] decreased WBV by 9.98%, 11.09%, 9.34%, 9.00%, 7.66%, and 7.03% (P<0.05), while Pheretima treatment [2.6 g/(kg·d), for 8 days] decreased WBV by 25.49%, 25.94%, 16.28%, 17.76%, 11.07%, and 7.89% (P<0.01) at shear rates of 1, 3, 10, 30, 100, and 180 s-1, respectively. Furthermore, Pheretima treatment increased APTT significantly (P<0.01). We presented a stable, reproducible, and improved acute blood stasis rat model, which could be applied to screen drugs for promoting blood circulation and eliminating blood stasis.

  6. Recombinant human erythropoietin pretreatment attenuates acute renal tubular injury against ischemia-reperfusion by restoring transient receptor potential channel-6 expression and function in collecting ducts.

    Science.gov (United States)

    Shen, Sai'e; Jin, Yi; Li, Weiyan; Liu, Xiaoming; Zhang, Tingting; Xia, Weiliang; Wang, Yingwei; Ma, Ke

    2014-10-01

    Acute renal tubular injury is a serious complication in the postoperative period, which is associated with high mortality and increased ICU stay. We aimed to demonstrate the protective effect of rhEPO against acute tubular injury induced by ischemia-reperfusion and to explore the mechanism of canonical transient receptor potential channel-6. Randomized laboratory animal study. Animal research laboratory. Male Sprague-Dawley rats were randomly divided into three groups: the sham group, the control group, and the rhEPO group. Experimental acute tubular injury was established in rats by bilateral renal arterial occlusion for 30 minutes followed by reperfusion. Blood samples were obtained for cystatin-C and neutrophil gelatinase-associated lipocalin measurements by enzyme-linked immunosorbance assays. Seventy-two hours after reperfusion, urine samples were collected for osmolality and fractional excretion of sodium (%) assays on a chemistry analyzer. Kidneys were harvested at 24, 48, and 72 hours after reperfusion. Transient receptor potential channel-6, aquaporin-2, and Na,K-ATPase expression in collecting ducts were studied by immunofluorescence and Western blot. Coimmunoprecipitations were also performed to identify the possible signalplex relation between transient receptor potential channel-6 and aquaporin-2 or Na,K-ATPase channels. RhEPO pretreatment significantly inhibited serum cystatin-C (2 hr: 453 ± 64 μg/L vs 337 ± 28 μg/L, p human erythropoietin greatly improved the ischemia-reperfusion-induced attenuation of transient receptor potential channel-6 expression (48 hr: 42% ± 2% vs 67% ± 2% and 72 hr: 55% ± 2% vs 66% ± 2%), as well as aquaporin-2 and Na,K-ATPase expression in collecting ducts. Transient receptor potential channel-6 functionally interacted with Na,K-ATPase but not aquaporin-2. Recombinant human erythropoietin pretreatment at the dose of 5,000 IU/kg potently prevented ischemia-reperfusion-induced acute tubular injury, which might be

  7. Acute alcohol intake induces SOCS1 and SOCS3 and inhibits cytokine-induced STAT1 and STAT3 signaling in human monocytes.

    Science.gov (United States)

    Norkina, Oxana; Dolganiuc, Angela; Catalano, Donna; Kodys, Karen; Mandrekar, Pranoti; Syed, Amber; Efros, Marian; Szabo, Gyongyi

    2008-09-01

    Acute alcohol consumption is associated with induction of immuno-inhibitory cytokines and down-regulation of pro-inflammatory responses to various pathogens. We previously reported that alcohol activates janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling leading to IL-10 induction. The JAK-STAT pathway also activates its own negative regulators, suppressors of cytokine signaling (SOCS) 1 and SOCS3. SOCS proteins are inducible inhibitors that negatively regulate STAT3/STAT1 signaling pathways induced by cytokines, IL-6 or IFNs. Here we aimed to explore the effect of acute alcohol on induction of SOCS1/SOCS3 and regulation of STAT3/STAT1 pathways induced by IL-6 or IFNs in human monocytes. Blood samples from normal volunteers were collected before and 24 hours after consumption of 2 ml vodka/kg body weight. For in vitro experiments human monocytes were pretreated with ethanol (EtOH) followed by stimulation with cytokines; proteins were analyzed by Western blot, nuclear protein binding to DNA by EMSA, and RNA by real time PCR. Acute in vivo or in vitro alcohol treatment increased both SOCS1 and SOCS3 RNA expression in monocytes. Alcohol treatment resulted in increased STAT3 and STAT1 DNA binding capacity. Activation of both STAT1 and STAT3 has been shown to induce SOCS1/3. We hypothesized that induction of SOCS proteins by alcohol in turn may lead to modulation of cytokine signaling through STAT1 and STAT3. Indeed, we observed significant down-regulation of IL-6-, IFNalpha- and IFNgamma-induced STAT1 DNA binding as well as inhibition of IL-6- and IFNgamma-induced STAT3 when alcohol was added to monocytes 3 hours prior to the cytokine stimulation. Consistent with inhibition of IL-6-induced STAT3 DNA binding in alcohol-pretreated cells, the levels of IL-6-dependent genes, MCP-1 and ICAM-1, was reduced after IL-6 stimulation. Similar to EtOH alone, combined EtOH+IL-6 simulation resulted in increased expression of both SOCS3 and SOCS1 genes

  8. Oridonin effectively reverses the drug resistance of cisplatin involving induction of cell apoptosis and inhibition of MMP expression in human acute myeloid leukemia cells

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    2017-03-01

    Full Text Available Cisplatin is the first generation platinum-based chemotherapy agent. However, the extensive application of cisplatin inevitably causes drug resistance, which is a major obstacle to cancer chemotherapy. Oridonin is a diterpenoid isolated from Rabdosia rubescens with potent anticancer activity. The aim of our study is to investigate the role of oridonin to reverse the cisplatin-resistance in human acute myeloid leukemia (AML cells. The effect of oridonin on human AML cell proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays in cisplatin-resistant human AML cells. Furthermore, cell apoptosis was examined by flow cytometry. The inhibitive effect of oridonin in vivo was determined using xenografted nude mice. In addition, the expressions of MMP2 and MMP9 were detected by Western blot. There was a synergistic antitumor effect between cisplatin and oridonin on cisplatin-resistant human AML cells in vitro and in vivo. In addition, the combination of cisplatin and oridonin synergistically induced cell apoptosis. Furthermore, the combination treatment not only inhibited AML cell migration and invasion, but more significantly, decreased the expressions of MMP2 and MMP9 proteins. Our results suggest that the synergistic effect between both agents is likely to be driven by the inhibition of MMP expression and the resulting increased apoptosis.

  9. Depression of Complement Regulatory Factors in Rat and Human Renal Grafts Is Associated with the Progress of Acute T-Cell Mediated Rejection.

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    Kazuaki Yamanaka

    Full Text Available The association of complement with the progression of acute T cell mediated rejection (ATCMR is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs in acute T-cell mediated rejection using rat and human renal allografts.We prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP by immunohistochemical staining in human renal grafts and their clinical course.qRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry, was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate.We conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR.

  10. Human umbilical cord mesenchymal stem cells and derived hepatocyte-like cells exhibit similar therapeutic effects on an acute liver failure mouse model.

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    Ruiping Zhou

    Full Text Available Mesenchymal stem cells (MSCs have exhibited therapeutic effects in multiple animal models so that are promising liver substitute for transplantation treatment of end-stage liver diseases. However, it has been shown that over-manipulation of these cells increased their tumorigenic potential, and that reducing the in vitro culture time could minimize the risk. In this study, we used a D-galactosamine plus lipopolysaccharide (Gal/LPS-induced acute liver failure mouse model, which caused death of about 50% of the mice with necrosis of more than 50% hepatocytes, to compare the therapeutic effects of human umbilical cord MSCs (hUCMSCs before and after induction of differentiation into hepatocyte (i-Heps. Induction of hUCMSCs to become i-Heps was achieved by treatment of the cells with a group of growth factors within 4 weeks. The resulted i-Heps exhibited a panel of human hepatocyte biomarkers including cytokeratin (hCK-18, α-fetoprotein (hAFP, albumin (hALB, and hepatocyte-specific functions glycogen storage and urea metabolism. We demonstrated that transplantation of both cell types through tail vein injection rescued almost all of the Gal/LPS-intoxicated mice. Although both cell types exhibited similar ability in homing at the mouse livers, the populations of the hUCMSCs-derived cells, as judged by expressing hAFP, hCK-18 and human hepatocyte growth factor (hHGF, were small. These observations let us to conclude that the hUCMSCs was as effective as the i-Heps in treatment of the mouse acute liver failure, and that the therapeutic effects of hUCMSCs were mediated largely via stimulation of host hepatocyte regeneration, and that delivery of the cells through intravenous injection was effective.

  11. [Protective effect of intraperitoneal transplantation of human liver-derived stem cells at different times against concanavalin A-induced acute liver injury in mice].

    Science.gov (United States)

    Bi, Y Z; Fan, Z; Chen, D F; Li, S S; Wang, Q Y; Gao, P F; Wang, Q Q; Duan, Z P; Chen, Y; Kong, L B; Wang, Y B; Hong, F

    2017-03-20

    Objective: To investigate the protective effect of intraperitoneal transplantation of human liver-derived stem cells at different times against concanavalin A (ConA)-induced acute liver injury in mice. Methods: A total of 88 male C57BL/6 mice were randomly divided into normal control group (group C), ConA model group (group M), and human liver-derived stem cells (HYX1)+ConA group (group E); according to the interval between phosphate buffer/HYX1 injection and ConA injection, Groups M and E were further divided into 3-hour groups (M1 and E1 groups), 6-hour groups (M2 and E2 groups), 12-hour groups (M3 and E3 groups), 24-hour groups (M4 and E4 groups), and 48-hour groups (M5 and E5 groups). The levels of alanine aminotransferase (ALT), aspartate transaminase (AST), and total bilirubin (TBil) in peripheral blood were measured, liver tissue sections were used to observe pathological changes, and the Ishak score for liver inflammation was determined. The independent samples t-test was used for comparison between groups, and P 0.05). The pathological sections of liver tissue showed that compared with group M, group E had significant reductions in the degree of necrosis and Ishak score (both P transplantation of human liver-derived stem cells has a protective effect against ConA-induced acute liver injury in mice, and the injection at 6 and 12 hours in advance has the best protective effect.

  12. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo.

    Science.gov (United States)

    Chan, Michael C W; Kuok, Denise I T; Leung, Connie Y H; Hui, Kenrie P Y; Valkenburg, Sophie A; Lau, Eric H Y; Nicholls, John M; Fang, Xiaohui; Guan, Yi; Lee, Jae W; Chan, Renee W Y; Webster, Robert G; Matthay, Michael A; Peiris, J S Malik

    2016-03-29

    Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium's protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.

  13. Brain and skin do not contribute to the systemic rise in erythropoietin during acute hypoxia in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Nordsborg, Nikolai; Taudorf, Sarah

    2012-01-01

    Erythropoietin (EPO) preserves arterial oxygen content by controlling red blood cell and plasma volumes. Synthesis of EPO was long thought to relate inversely to renal oxygenation, but in knockout mice, brain and skin have been identified as essential for the acute hypoxic EPO response. Whether...... hypoxia with or without breathing oxygen-enriched air to ensure systemic normoxemia. With 9 h of hypoxia, arterial EPO increased (from 6.0±2.2 to 22.0±6.0 mU/ml, n=11, P...

  14. Acute hepatitis C in persons infected with the human immunodeficiency virus (HIV: The "Real-life Setting" proves the concept

    Directory of Open Access Journals (Sweden)

    Obermeier M

    2011-05-01

    Full Text Available Abstract Objectives Outbreaks of sexually transmitted acute HCV infection have been described recently in several cities in the western world. The epidemic affects mainly MSM who are coinfected with HIV and is supposably linked to certain sexual risk practices. Here, we compared our findings with current knowledge and recommendations. Methods HIV-positive patients with the diagnosis of acute HCV infection were included in the retrospective analysis. The patients came from outpatient infectious disease centers in northern German cities. We looked at markers of HIV and HCV infection and compared patients who received treatment and those who did not. Treated patients were followed up to 72 weeks. Results Three hundred nineteen HIV-positive patients with the diagnosis of acute hepatitis C between 2001 and 2008 and were included in the analysis. All patients were male, 315 (99% patients were of caucasian origin, 296 (93% declared homosexual contacts as a risk factor for HCV infection, intravenous drug use was declared in 3 (1% cases. Median age at HCV diagnosis was 40 years (range 20-69 years. Median HCV viral load was 1.2 × 106 IU/mL, 222 patients (70% had HCV genotype 1, 59 (18% genotype 4. The median time of HIV infection was 5.5 years (range 0 to 22.4 years. Median HIV viral load was 110 copies/mL (range 25 to 10 × 106 copies/mL. The median CD 4 count was 461 cells/mm3 (range 55- 1331 cells/mm3. Two hundred and fourty-six patients (77% received anti-HCV treatment, and 175 (55% had completed therapy by the time of the analysis. Median treatment duration was 33 weeks (IQR 24.1-49.9. 93 of the 175 treated patients (53% reached a sustained virological response (SVR. In the multivariate analysis, ART at diagnosis, HCV RNA drop at week 12, hemoglobin levels and higher platelets were associated with SVR. Treatment duration was significantly higher in the SVR group (40.6 weeks vs 26.6 weeks, p Conclusions Our findings confirm that acute hepatitis C in

  15. Ficolin-1 is present in a highly mobilizable subset of human neutrophil granules and associates with the cell surface after stimulation with fMLP

    DEFF Research Database (Denmark)

    Rørvig, Sara; Honoré, Christian Le Fèvre; Larsson, Lars-Inge

    2009-01-01

    FCN1 gene expression largely in myelocytes, metamyelocytes, and band cells with a profile quite similar to that of gelatinase. In accordance with this, biosynthesis studies of neutrophils precursor cells showed that ficolin-1 was primarily synthesized in myelocytes, metamyelocytes, and band cells...

  16. A large outbreak of acute gastroenteritis caused by the human norovirus GII.17 strain at a university in Henan Province, China.

    Science.gov (United States)

    Huang, Xue-Yong; Su, Jia; Lu, Qian-Chao; Li, Shi-Zheng; Zhao, Jia-Yong; Li, Meng-Lei; Li, Yi; Shen, Xiao-Jing; Zhang, Bai-Fan; Wang, Hai-Feng; Mu, Yu-Jiao; Wu, Shu-Yu; Du, Yan-Hua; Liu, Li-Cheng; Chen, Wei-Jun; Klena, John David; Xu, Bian-Li

    2017-02-01

    Human noroviruses are a major cause of viral gastroenteritis and are the main etiological agents of acute gastroenteritis outbreaks. An increasing number of outbreaks and sporadic cases of norovirus have been reported in China in recent years. There was a large acute gastroenteritis outbreak at a university in Henan Province, China in the past five years. We want to identify the source, transmission routes of the outbreak by epidemiological investigation and laboratory testing in order to provide the effective control measures. The clinical cases were investigated, and analysed by descriptive epidemiological methods according to factors such as time, department, grade and so on. Samples were collected from clinical cases, healthy persons, the environment, water, and food at the university. These samples were tested for potential bacteria and viruses. The samples that tested positive for norovirus were selected for whole genome sequencing and the sequences were then analysed. From 4 March to 3 April 2015, a total of 753 acute diarrhoea cases were reported at the university; the attack rate was 3.29%. The epidemic curve showed two peaks, with the main peak occurring between 10 and 20 March, accounting for 85.26% of reported cases. The rates of norovirus detection in samples from confirmed cases, people without symptoms, and environmental samples were 32.72%, 17.39%, and 9.17%, respectively. The phylogenetic analysis showed that the norovirus belonged to the genotype GII.17. This is the largest and most severe outbreak caused by genotype GII.17 norovirus in recent years in China. The GII.17 viruses displayed high epidemic activity and have become a dominant strain in China since the winter of 2014, having replaced the previously dominant GII.4 Sydney 2012 strain.

  17. High-intensity exercise acutely decreases the membrane content of MCT1 and MCT4 and buffer capacity in human skeletal muscle.

    Science.gov (United States)

    Bishop, David; Edge, Johann; Thomas, Claire; Mercier, Jacques

    2007-02-01

    The regulation of intracellular pH during intense muscle contractions occurs via a number of different transport systems [e.g., monocarboxylate transporters (MCTs)] and via intracellular buffering (beta m(in vitro)). The aim of this study was to investigate the effects of an acute bout of high-intensity exercise on both MCT relative abundance and beta m(in vitro) in humans. Six active women volunteered for this study. Biopsies of the vastus lateralis were obtained at rest and immediately after 45 s of exercise at 200% of maximum O2 uptake. Beta m(in vitro) was determined by titration, and MCT relative abundance was determined in membrane preparations by Western blots. High-intensity exercise was associated with a significant decrease in both MCT1 (-24%) and MCT4 (-26%) and a decrease in beta m(in vitro) (-11%; 135 +/- 3 to 120 +/- 2 micromol H+ x g dry muscle(-1) x pH(-1); P < 0.05). These changes were consistently observed in all subjects, and there was a significant correlation between changes in MCT1 and MCT4 relative abundance (R2 = 0.92; P < 0.05). In conclusion, a single bout of high-intensity exercise decreased both MCT relative abundance in membrane preparations and beta m(in vitro). Until the time course of these changes has been established, researchers should consider the possibility that observed training-induced changes in MCT and beta m(in vitro) may be influenced by the acute effects of the last exercise bout, if the biopsy is taken soon after the completion of the training program. The implications that these findings have for lactate (and H+) transport following acute, exhaustive exercise warrant further investigation.

  18. High-intensity interval training in hypoxia does not affect muscle HIF responses to acute hypoxia in humans.

    Science.gov (United States)

    De Smet, Stefan; D'Hulst, Gommaar; Poffé, Chiel; Van Thienen, Ruud; Berardi, Emanuele; Hespel, Peter

    2018-02-08

    The myocellular response to hypoxia is primarily regulated by hypoxia-inducible factors (HIFs). HIFs thus conceivably are implicated in muscular adaptation to altitude training. Therefore, we investigated the effect of hypoxic versus normoxic training during a period of prolonged hypoxia ('living high') on muscle HIF activation during acute ischaemia. Ten young male volunteers lived in normobaric hypoxia for 5 weeks (5 days per week, ~ 15.5 h per day, FiO2: 16.4-14.0%). One leg was trained in hypoxia (TRHYP, 12.3% FiO2) whilst the other leg was trained in normoxia (TRNOR, 20.9% FiO2). Training sessions (3 per week) consisted of intermittent unilateral knee extensions at 20-25% of the 1-repetition maximum. Before and after the intervention, a 10-min arterial occlusion and reperfusion of the leg was performed. Muscle oxygenation status was continuously measured by near-infrared spectroscopy. Biopsies were taken from m. vastus lateralis before and at the end of the occlusion. Irrespective of training, occlusion elevated the fraction of HIF-1α expressing myonuclei from ~ 54 to ~ 64% (P Training in both TRNOR and TRHYP raised muscular oxygen extraction rate upon occlusion by ~ 30%, whilst muscle hyperperfusion immediately following the occlusion increased by ~ 25% in either group (P training during 'living high' altered muscle HIF translocation, stabilisation, or transcription in response to acute hypoxia induced by arterial occlusion.

  19. Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans.

    Science.gov (United States)

    Skene, D J; Bojkowski, C J; Arendt, J

    1994-01-01

    1. Acute administration of the specific serotonin uptake inhibitor, fluvoxamine (100 mg at 16.00 h), markedly increased nocturnal plasma melatonin concentrations, with high levels extending into the morning hours. 2. Acute administration of the noradrenaline uptake inhibitor, desipramine (DMI) (100 mg at 16.00 h), increased evening plasma melatonin concentrations. 3. Both drug treatments increased the duration of melatonin secretion, fluvoxamine significantly delaying the offset time and DMI significantly advancing the onset time. 4. The stimulatory effect of DMI on plasma melatonin was mirrored by increased urinary 6-sulphatoxymelatonin (aMT6s) excretion. 5. On the contrary, there was no correlation between plasma melatonin and urinary aMT6s concentrations following fluvoxamine treatment, suggesting that fluvoxamine may inhibit the metabolism of melatonin. 6. Treatment with DMI increased plasma cortisol concentrations in the evening and early morning, treatment with fluvoxamine increased plasma cortisol at 03.00 h, 10.00 h and 11.00 h. 7. The drug treatments affected different aspects of the nocturnal plasma melatonin profile suggesting that the amplitude of the melatonin rhythm may depend upon serotonin availability and/or melatonin metabolism whilst the onset of melatonin production depends upon noradrenaline availability. PMID:8186063

  20. Acute effect of static stretching on passive stiffness of the human gastrocnemius fascicle measured by ultrasound shear wave elastography.

    Science.gov (United States)

    Hirata, Kosuke; Kanehisa, Hiroaki; Miyamoto, Naokazu

    2017-03-01

    Passive muscle stiffness and muscle architecture at a given joint angle, as well as slack angle of the muscle have been shown to change after an acute bout of stretching. However, it remains unclear whether passive muscle stiffness at a given fascicle length is reduced after stretching. We aimed to elucidate the acute effect of static stretching on the passive fascicle stiffness using ultrasound shear wave elastography. Shear modulus, fascicle length, and slack angle of the medial gastrocnemius (MG) as well as passive plantar flexion torque during passive dorsiflexion were measured before and after a 5-min static stretching in 14 healthy males. After stretching, passive torques were significantly reduced at >50% of range of motion (ROM). Shear modulus at a given fascicle length was significantly reduced at >80% of the change in fascicle length during passive dorsiflexion. Slack angle of MG was observed at the middle part of ROM and significantly shifted toward more dorsiflexed position after stretching. The present study showed the significant effectiveness of static stretching on the passive fascicle stiffness. Furthermore, the present results suggest that both the shift in slack angle and the reduction in passive fascicle stiffness contribute to produce the change in passive torque-joint angle relationship during passive dorsiflexion. Notably, the contribution of the reduced passive fascicle stiffness to the decrease in passive torque is substantial over the latter part of ROM.

  1. Alcohol-associated acute head trauma in human subjects is associated with early deficits in serum ionized Mg and Ca.

    Science.gov (United States)

    Altura, B M; Memon, Z S; Altura, B T; Cracco, R Q

    1995-01-01

    Acute head trauma (AHT) (caused by motor vehicle accidents that did not produce loss of consciousness or observed brain lesions on CT scan, or falls) was found to result in early (1-8 h after injury) serum deficits in ionized magnesium (IMg2+) and ionized calcium (ICa2+) assessed with ion-selective electrodes (ISEs). Total Mg (TMg) and other electrolytes as well as serum biochemical analytes were all within the normal reference ranges. AHT patients with acute alcohol intoxication (BAC > or = 150 mg/dl) or alcohol abuse (BAC > 200 mg/dl) demonstrated deficits (15-35% less than normal) in IMg2+, but serum TMg levels were normal as were electrolytes and serum biochemical analytes. AHT patients with alcohol intoxication or alcohol abuse required hospitalization for 1-3 days prior to release, whereas AHT patients without alcohol intoxication were released in less than 24 h. The ICa2+/IMg2+ ratio, a sign of increased vascular tone and vascular reactivity, was significantly elevated in AHT patients with alcohol intoxication but not in AHT patients without alcohol intoxication or abuse. These serum divalent cation changes early after traumatic brain injury could be of considerable practicable diagnostic value in the assessment of alcohol-associated head injury. Use of ion-selective electrodes to accurately measure IMg2+ could serve as a logical basis for monitoring the response of the body to AHT.

  2. Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors.

    Science.gov (United States)

    Bhattacharyya, Sagnik; Egerton, Alice; Kim, Euitae; Rosso, Lula; Riano Barros, Daniela; Hammers, Alexander; Brammer, Michael; Turkheimer, Federico E; Howes, Oliver D; McGuire, Philip

    2017-11-03

    Use of Cannabis, the most widely used illicit drug worldwide, is associated with acute anxiety, and anxiety disorders following regular use. The precise neural and receptor basis of these effects have not been tested in man. Employing a combination of functional MRI (fMRI) and positron emission tomography (PET), we investigated whether the effects of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on anxiety and on amygdala response while processing fearful stimuli were related to local availability of its main central molecular target, cannabinoid-1 (CB1) receptors in man. Fourteen healthy males were studied with fMRI twice, one month apart, following an oral dose of either delta-9-THC (10 mg) or placebo, while they performed a fear-processing task. Baseline availability of the CB1 receptor was studied using PET with [(11)C]MePPEP, a CB1 inverse agonist radioligand. Relative to the placebo condition, delta-9-THC induced anxiety and modulated right amygdala activation while processing fear. Both these effects were positively correlated with CB1 receptor availability in the right amygdala. These results suggest that the acute effects of cannabis on anxiety in males are mediated by the modulation of amygdalar function by delta-9-THC and the extent of these effects are related to local availability of CB1 receptors.

  3. Chronic levothyroxine and acute T3 treatments enhance the amplitude and time course of uterine contractions in human.

    Science.gov (United States)

    Corriveau, Stéphanie; Pasquier, Jean-Charles; Blouin, Simon; Bellabarba, Diego; Rousseau, Éric

    2013-03-01

    This study compares the functional consequences of levothyroxine (T4) treatment during pregnancy as well as the acute affects of triiodothyronine (T3) on spontaneous uterine contractile activities observed in vitro. Uterine biopsies were obtained from consenting women undergoing elective caesarean at term (n = 28). Spontaneous contractile activities from T4-treated pregnant women (n = 8) were compared with control patients (n = 20) by isometric tension measurements. Effects of acute T3 and T4 on control tissues were also monitored. Area under the curve, amplitude, time to peak, duration, and frequency were quantified. In uterine strips from women treated for hypothyroidism, phasic uterine contractions of larger amplitude (+77%) were observed, with a prolonged duration at 90% relaxation (+138%) and reduced frequency (-55%) compared with values of the control group. The addition of exogenous T3 in vitro on control strips induced a significant increase in the duration of the contractions and a significant decrease in frequency (P uterine contractions' time course to ensure a tighter followup at the end of pregnancy to achieve safer delivery.

  4. The role of leptin in human lipid and glucose metabolism: the effects of acute recombinant human leptin infusion in young healthy males

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2011-01-01

    Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents.......Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents....

  5. Different mechanisms causing loss of mismatched human leukocyte antigens in relapsing t(6;11)(q27;q23) acute myeloid leukemia after haploidentical transplantation.

    Science.gov (United States)

    Tamaki, Hiroya; Fujioka, Tatsuya; Ikegame, Kazuhiro; Yoshihara, Satoshi; Kaida, Katsuji; Taniguchi, Kyoko; Kato, Ruri; Tokugawa, Taduko; Nakata, Jun; Inoue, Takayuki; Yano, Aya; Eguchi, Ryoji; Okada, Masaya; Maruya, Etsuko; Saji, Hiroh; Ogawa, Hiroyasu

    2012-12-01

    Mismatched human leukocyte antigens (HLAs) on leukemic cells can be targeted by donor T cells in HLA-mismatched/haploidentical stem cell transplantation. In two cases of acute myeloid leukemia with t(6;11)(q27;q23) abnormality presented here, flow cytometry analysis showed a lack of HLA-A unshared between recipients and donors in relapsing leukemic cells after HLA-haploidentical transplantation. However, high-resolution HLA genotyping showed that one case lacked a corresponding HLA haplotype, whereas the other preserved it. These cases suggest that leukemic cells, which lacked mismatched HLA expression, might have an advantage in selective expansion under donor T-cell immune surveillance after HLA-haploidentical transplantation. Most importantly, down-regulation of unshared HLA expression potentially occurs by genetic alterations other than loss of HLA alleles. © 2012 John Wiley & Sons A/S.

  6. Acute moderate elevation of TNF-{alpha} does not affect systemic and skeletal muscle protein turnover in healthy humans

    DEFF Research Database (Denmark)

    Petersen, Anne Marie; Plomgaard, Peter; Fischer, Christian P

    2009-01-01

    Context: Skeletal muscle wasting has been associated with elevations in circulating inflammatory cytokines, in particular TNF-alpha. Objective: In this study, we investigated whether TNF-alpha affects human systemic and skeletal muscle protein turnover, via a 4 hours recombinant human TNF...... of either rhTNF-alpha (700 ng.m(-2).h(-1)) or 20% human albumin (Control) which was the vehicle of rhTNF-alpha. Systemic and skeletal muscle protein turnover were estimated by a combination of tracer dilution methodology (primed continuous infusion of L-[ring-(2)H5]phenylalanine and L-[(15)N...... with the phenylalanine 3-compartment model showed similar muscle synthesis, breakdown and net muscle degradation after 2 hours basal and after 4 hours Control or rhTNF-alpha infusion. Conclusion: This study is the first to show in humans that TNF-alpha does not affect systemic and skeletal muscle protein turnover, when...

  7. Imaging and modeling of acute pressure-induced changes of collagen and elastin microarchitectures in pig and human resistance arteries

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Leurgans, Thomas M; Spronck, Bart

    2017-01-01

    The impact of disease related changes in the extracellular matrix (ECM) on the mechanical properties of human resistance arteries largely remains to be established. Resistance arteries from both pig and human parietal pericardium (PRA) display a different ECM microarchitecture compared to frequen......The impact of disease related changes in the extracellular matrix (ECM) on the mechanical properties of human resistance arteries largely remains to be established. Resistance arteries from both pig and human parietal pericardium (PRA) display a different ECM microarchitecture compared...... to frequently used rodent mesenteric arteries. We hypothesized that the biaxial mechanics of PRA mirror pressure induced changes in the ECM microarchitecture. This was tested using isolated pig PRA as model system, integrating vital imaging, pressure myography and mathematical modeling. Collagenase and elastase...

  8. A human-like H1N2 influenza virus detected during an outbreak of acute respiratory disease in swine in Brazil.

    Science.gov (United States)

    Schaefer, Rejane; Rech, Raquel Rubia; Gava, Danielle; Cantão, Mauricio Egídio; da Silva, Marcia Cristina; Silveira, Simone; Zanella, Janice Reis Ciacci

    2015-01-01

    Passive monitoring for detection of influenza A viruses (IAVs) in pigs has been carried out in Brazil since 2009, detecting mostly the A(H1N1)pdm09 influenza virus. Since then, outbreaks of acute respiratory disease suggestive of influenza A virus infection have been observed frequently in Brazilian pig herds. During a 2010-2011 influenza monitoring, a novel H1N2 influenza virus was detected in nursery pigs showing respiratory signs. The pathologic changes were cranioventral acute necrotizing bronchiolitis to subacute proliferative and purulent bronchointerstitial pneumonia. Lung tissue samples were positive for both influenza A virus and A(H1N1)pdm09 influenza virus based on RT-qPCR of the matrix gene. Two IAVs were isolated in SPF chicken eggs. HI analysis of both swine H1N2 influenza viruses showed reactivity to the H1δ cluster. DNA sequencing was performed for all eight viral gene segments of two virus isolates. According to the phylogenetic analysis, the HA and NA genes clustered with influenza viruses of the human lineage (H1-δ cluster, N2), whereas the six internal gene segments clustered with the A(H1N1)pdm09 group. This is the first report of a reassortant human-like H1N2 influenza virus derived from pandemic H1N1 virus causing an outbreak of respiratory disease in pigs in Brazil. The emergence of a reassortant IAV demands the close monitoring of pigs through the full-genome sequencing of virus isolates in order to enhance genetic information about IAVs circulating in pigs.

  9. Hyperglycemia acutely lowers the postprandial excursions of glucagon-like Peptide-1 and gastric inhibitory polypeptide in humans

    DEFF Research Database (Denmark)

    Vollmer, Kirsten; Gardiwal, Husai; Menge, Bjoern A

    2009-01-01

    INTRODUCTION: Impaired secretion of glucagon-like peptide 1 (GLP-1) has been suggested to contribute to the deficient incretin effect in patients with type 2 diabetes. It is unclear whether this is a primary defect or a consequence of the hyperglycemia in type 2 diabetes. We examined whether acute...... hyperglycemia reduces the postprandial excursions of gastric inhibitory polypeptide (GIP) and GLP-1, and if so, whether this can be attributed to changes in gastric emptying. PATIENTS AND METHODS: Fifteen nondiabetic individuals participated in a euglycemic clamp and a hyperglycemic clamp experiment, carried...... the hyperglycemic clamp experiments and 83 +/- 3 mg/dl during the euglycemia (P hyperglycemia, but meal ingestion led to a decline in glucose requirements in both experiments (P

  10. Detection and genotyping of human respiratory viruses in clinical specimens from children with acute respiratory tract infections.

    Science.gov (United States)

    Culebras, Esther; Betriu, Carmen; Vázquez-Cid, Emilia; López-Varela, Elisa; Rueda, Santiago; Picazo, Juan J

    2013-03-01

    Respiratory virus infections are a major health concern and represent the primary cause of testing consultation and hospitalization for young children. The application of nucleic acid amplification technology, particularly multiplex PCR coupled with fluidic or fixed microarrays, provides an important new approach for the detection of multiple respiratory viruses in a single test. The aim of this study was to analyze respiratory samples from children with acute respiratory tract infection (ARTI) using a commercial array-based method (CLART(®) PneumoVir Genomica, Coslada, Spain). These tests were used to identify viruses in 281 nasopharyngeal samples obtained from children affected by ARTI. Samples were obtained form October 2008 to April 2009. Viruses were identified in 80% of the studied ARTI providing useful information on clinical features and epidemiology of specific agents affecting children in cold months. Multiple viral infections were found in 33.45% of the specimens.

  11. Differentiation of human acute myeloid leukaemia cells in primary culture in response to cotylenin A, a plant growth regulator.

    Science.gov (United States)

    Yamada, K; Honma, Y; Asahi, K I; Sassa, T; Hino, K I; Tomoyasu, S

    2001-09-01

    Cotylenin A, which has a diterpenoid tricarbocyclic skeleton, has been isolated as a plant growth regulator, has been shown to affect several physiological processes of higher plants and have differentiation-inducing activity in several myeloid leukaemia cell lines. We examined the effect of cotylenin A on the differentiation of leukaemic cells that were freshly isolated from acute myeloid leukaemia (AML) patients in primary culture. Cotylenin A significantly stimulated both functional and morphological differentiation of leukaemia cells in 9 out of 12 cases. This differentiation-inducing activity was more potent than those of all-trans retinoic acid and 1alpha,25-dihydroxyvitamin D3 (VD3). Treatment with a combination of cotylenin A and VD3 was more effective than cotylenin A or VD3 alone at inducing the monocytic differentiation of AML cells.

  12. Adherence, enterotoxigenicity, invasiveness and serogroups in Campylobacter jejuni and Campylobacter coli strains from adult humans with acute enterocolitis.

    Science.gov (United States)

    Lindblom, G B; Cervantes, L E; Sjögren, E; Kaijser, B; Ruiz-Palacios, G M

    1990-02-01

    Two hundred Campylobacter jejuni and Campylobacter coli strains from the same number of adult Swedish patients with acute enterocolitis were tested regarding adherence to and invasiveness in HEp-2 cells and for enterotoxigenicity by the CHO-cell assay. The serogroup characteristics, heat-stable and heat-labile, for each strain were also investigated. Eighty-four percent of the strains were classified as C. jejuni and 16 percent as C. coli. All of the strains were adherent to HEp-2 cells, 39% were invasive and 31.5% enterotoxigenic. We found significantly more invasive strains in the non-enterotoxigenic group than in the enterotoxigenic one. There would seem to be no correlation between enterotoxigenicity or invasiveness and serogroup. The results of this study suggest the existence of multiple mechanisms for C. jejuni- and C. coli-induced diarrhoea and that the mechanisms may differ from one strain to another.

  13. Psychomotor performance in relation to acute oral administration of Delta9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects.

    Science.gov (United States)

    Roser, Patrik; Gallinat, Jürgen; Weinberg, Gordon; Juckel, Georg; Gorynia, Inge; Stadelmann, Andreas M

    2009-08-01

    Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users. The high levels of central cannabinoid (CB(1)) receptors in the basal ganglia, the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity. Based on the close relationship between cannabis use, the endogenous cannabinoid system and motor disturbances found in schizophrenia, we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-handed volunteers (age 27.9 +/- 2.9 years, 12 male) by comparing Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and standardized cannabis extract containing Delta(9)-THC and cannabidiol. Psychomotor performance was assessed by using a finger tapping test series. Cannabis extract, but not Delta(9)-THC, revealed a significant reduction of right-hand tapping frequencies that was also found in schizophrenia. As to the pure Delta(9)-THC condition, left-hand tapping frequencies were correlated with the plasma concentrations of the Delta(9)-THC metabolite 11-OH-THC. These effects are thought to be related to cannabinoid actions on CB(1) receptors in the basal ganglia, the cerebral cortex and the cerebellum. Our data further demonstrate that acute CB(1) receptor activation under the cannabis extract condition may also affect intermanual coordination (IMC) as an index of interhemispheric transfer. AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve. This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum.

  14. Allium compounds, dipropyl and dimethyl thiosulfinates as antiproliferative and differentiating agents of human acute myeloid leukemia cell lines

    Directory of Open Access Journals (Sweden)

    Faten Merhi

    2008-08-01

    Full Text Available Faten Merhi1, Jacques Auger2, Francine Rendu1, Brigitte Bauvois11UMR 7131 UPMC Paris Universitas/CNRS, Groupe Hospitalier Broussais-HEGP, Paris, France; 2University F. Rabelais, IRBI, UPRESA CNRS 6035, Tours, FranceAbstract: Epidemiologic studies support the premise that Allium vegetables may lower the risk of cancers. The beneficial effects appear related to the organosulfur products generated upon processing of Allium. Leukemia cells from patients with acute myeloid leukemia (AML display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation. Whether the sulfur-containing molecules thiosulfinates (TS, diallyl TS (All2TS, dipropyl TS (Pr2TS and dimethyl TS (Me2TS, are able to exert chemopreventative activity against AML is presently unknown. The present study was an evaluation of proliferation, cytotoxicity, differentiation and secretion of AML cell lines (U937, NB4, HL-60, MonoMac-6 in response to treatment with these TS and their related sulfides (diallylsulfide, diallyl disulfide, dipropyl disulfide, dimethyl disulfide. As assessed by flow cytometry, ELISA, gelatin zymogaphy and RT-PCR, we showed that Pr2TS and Me2TS, but not All2TS and sulfides, 1 inhibited cell proliferation in dose- and time-dependent manner and this process was neither due to cytotoxicity nor apoptosis, 2 induced macrophage maturation, and 3 inhibited the levels of secreted MMP-9 (protein and activity and TNF-α protein, without altering mRNA levels. By establishing for the first time that Pr2TS and Me2TS affect proliferation, differentiation and secretion of leukemic cell lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML.Keywords: acute myeloid leukemia, thiosulfinate, proliferation, differentiation, matrix metalloproteinase-9

  15. Regulation of Lipolysis and Adipose Tissue Signaling during Acute Endotoxin-Induced Inflammation: A Human Randomized Crossover Trial.

    Science.gov (United States)

    Rittig, Nikolaj; Bach, Ermina; Thomsen, Henrik Holm; Pedersen, Steen Bønlykke; Nielsen, Thomas Sava; Jørgensen, Jens O; Jessen, Niels; Møller, Niels

    2016-01-01

    Lipolysis is accelerated during the acute phase of inflammation, a process being regulated by pro-inflammatory cytokines (e.g. TNF-α), stress-hormones, and insulin. The intracellular mechanisms remain elusive and we therefore measured pro- and anti-lipolytic signaling pathways in adipocytes after in vivo endotoxin exposure. Eight healthy, lean, male subjects were investigated using a randomized cross over trial with two interventions: i) bolus injection of saline (Placebo) and ii) bolus injection of lipopolysaccharide endotoxin (LPS). A 3H-palmitate tracer was used to measure palmitate rate of appearance (Rapalmitate) and indirect calorimetry was performed to measure energy expenditures and lipid oxidation rates. A subcutaneous abdominal fat biopsy was obtained during both interventions and subjected to western blotting and qPCR quantifications. LPS caused a mean increase in serum free fatty acids (FFA) concentrations of 90% (CI-95%: 37-142, p = 0.005), a median increase in Rapalmitate of 117% (CI-95%: 77-166, ptrend towards elevated pHSL at ser552 (p = 0.09) and cAMP-dependent protein kinase A (PKA) phosphorylation of perilipin 1 (PLIN1) (p = 0.09). Phosphatase and tensin homolog (PTEN) also tended to increase (p = 0.08) while phosphorylation of Akt at Thr308 tended to decrease (p = 0.09) during LPS compared with Placebo. There was no difference between protein or mRNA expression of ATGL, G0S2, and CGI-58. LPS stimulated lipolysis in adipose tissue and is associated with increased pHSL and signs of increased PLIN1 phosphorylation combined with a trend toward decreased insulin signaling. The combination of these mechanisms appear to be the driving forces behind the increased lipolysis observed in the early stages of acute inflammation and sepsis. ClinicalTrials.gov NCT01705782.

  16. Optical coherence tomography: a reliable alternative to invasive histological assessment of acute wound healing in human skin?

    Science.gov (United States)

    Greaves, N S; Benatar, B; Whiteside, S; Alonso-Rasgado, T; Baguneid, M; Bayat, A

    2014-04-01

    Gold-standard assessment of acute wound healing has traditionally been through histological analysis of biopsied tissue. However, this process is invasive with recognized side-effects. Optical coherence tomography (OCT) is a noninvasive technique generating high-resolution real-time images of cutaneous architecture. To compare OCT with histological assessment of in vivo acute wound healing and ascertain the level of agreement between modalities for measurement of defined cutaneous structures. Punch biopsies (5 mm) were harvested from 50 healthy volunteers. Wounds healed by secondary intention until they were re-excised 7, 14, 21 or 28 days later depending on random group allocation. Wounds were assessed weekly for 6 weeks using OCT and compared with histological findings derived from time-matched biopsies. Dimensions of four cutaneous structures were measured using both modalities and the level of agreement was established by Bland-Altman analysis. The mean greyscale value (MGV) of the upper reticular dermis was derived from OCT images at all time points. Both techniques showed anatomical congruity in normal and wounded skin with correlating architectural changes associated with inflammatory, proliferative and remodelling wound healing phases. MGV was significantly increased 6 weeks after wounding (P = 0·001) and may represent a novel measure of wound fibrosis. Despite good association of histomorphometric values with low but consistent bias (range -4·181 to 0·431 μm), Bland-Altman plots demonstrated poor agreement between OCT and histology. Optical coherence tomography enabled accurate assessment of healing tissue comparable with histological analysis of biopsy specimens. This noninvasive tool is highly suited to wound assessment and may represent a diagnostic alternative to punch biopsies. © 2013 British Association of Dermatologists.

  17. Prevalence and clinical characteristics of human respiratory syncytial virus in Chinese adults with acute respiratory tract infection.

    Science.gov (United States)

    Xiang, Zichun; Gonzalez, Richard; Ren, Lili; Xiao, Yan; Chen, Lan; Zhang, Jing; Wang, Wei; Yang, Qingqing; Li, Jianguo; Zhou, Hongli; Vernet, Guy; Paranhos-Baccalà, Gláucia; Wang, Zhong; Wang, Jianwei

    2013-02-01

    Respiratory syncytial virus (RSV) is a leading cause of respiratory tract illnesses worldwide. Although the prevalence and clinical manifestations of the two subtypes, RSV-A and RSV-B, have been studied in some detail in infants and young children, they have not been determined in adults. To evaluate the prevalence of the RSV subtypes and disease severity between RSV-A and RSV-B infections in adults, nasal and throat swabs that were collected from patients ≥15 years old who sought medical care for acute respiratory infections at the Fever Clinic of the Peking Union Medical College Hospital in Beijing, China between May 2005 and April 2010. The samples were tested for RSV infection using PCR and sequencing analysis. RSV was detected in 95 (1%) of the adult patients, of whom 53 (55.8%) were positive for RSV-A and 42 (44.2%) for RSV-B. The incidence of RSV infections increased with age (χ(2) = 37.17, P = 1.66E-07). Demographic data and clinical manifestations of RSV-A were similar to those of RSV-B. Although RSV-A and RSV-B co-circulated during the 2005-2006 and 2008-2009 seasons, RSV-A was predominant in the 2006-2008 seasons, whereas RSV-B was predominant in the 2009-2010 season. Upper respiratory tract infections were diagnosed in most RSV-infected patients (n = 80, 84.2%), and three patients suffered from pulmonary infection. This is the first study to provide data on the prevalence and clinical manifestations of RSV subgroups among Chinese adults with fever and acute illness, over five successive epidemic seasons. Copyright © 2012 Wiley Periodicals, Inc.

  18. Amino acid supplementation is anabolic during the acute phase of endotoxin-induced inflammation: A human randomized crossover trial.

    Science.gov (United States)

    Rittig, N; Bach, E; Thomsen, H H; Johannsen, M; Jørgensen, J O; Richelsen, B; Jessen, N; Møller, N

    2016-04-01

    Inflammation is catabolic and causes muscle loss. It is unknown if amino acid supplementation reverses these effects during the acute phase of inflammation. The aim was to test whether amino acid supplementation counteracts endotoxin-induced catabolism. Eight young, healthy, lean males were investigated three times in randomized order: (i) normal conditions (Placebo), (ii) endotoxemia (LPS), and (iii) endotoxemia with amino acid supplementation (LPS + A). Protein kinetics were determined using phenylalanine, tyrosine, and urea tracers. Each study day consisted of a four-hour non-insulin stimulated period and a two-hour hyperinsulinemic euglycemic clamp period. Muscle biopsies were collected once each period. Endotoxin administration created a significant inflammatory response (cytokines, hormones, and vital parameters) without significant differences between LPS and LPS + A. Whole body protein breakdown was elevated during LPS compared with Placebo and LPS + A (p translation factor 4E-binding protein 1 (4EBP1) phosphorylation (p = 0.007) without activating AMPK or affecting insulin signaling through Akt. During insulin stimulation net muscle phenylalanine release and protein degradation were further reduced. Amino acid supplementation in the acute phase of inflammation reduces whole body and muscle protein loss, and this effect is associated with activation of mTOR and downstream signaling to protein synthesis through mTORC1, suggesting a therapeutic role for intravenous amino acids in inflammatory states. The Central Denmark Region Ethics Commitee (1-10-71-410-12) www.clinicaltrials.gov (identification number NCT01705782). Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  19. Bronchitis - acute

    Science.gov (United States)

    ... sharing features on this page, please enable JavaScript. Acute bronchitis is swelling and inflamed tissue in the main ... present only for a short time. Causes When acute bronchitis occurs, it almost always comes after having a ...

  20. Acute cholecystitis

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000264.htm Acute cholecystitis To use the sharing features on this page, please enable JavaScript. Acute cholecystitis is sudden swelling and irritation of the gallbladder. ...

  1. Acute encephalopathy with concurrent respiratory and metabolic disturbances in first known parenteral human administration of flunixin meglumine and acepromazine maleate.

    Science.gov (United States)

    Kamali, Michael F; Wilson, Anwar C; Acquisto, Nicole M; Spillane, Linda; Schneider, Sandra M

    2013-08-01

    Flunexin is a nonsteroidal anti-inflammatory drug approved for veterinary use in horses and cattle. Acepromazine is a phenothiazine derivative used in horses, dogs, and cats. Human exposure to these substances is rare. We report a case of a human injection of two equine medications, flunixin and acepromazine, which resulted in altered mental status, respiratory alkalosis, gastrointestinal bleeding, and elevation of liver transaminases in a 43-year-old woman who worked as a horse trainer. The patient intentionally self-injected these medications and subsequently presented to the Emergency Department with altered mental status and lethargy. The patient required hospitalization for metabolic abnormalities, including respiratory alkalosis, and suffered a gastrointestinal bleed requiring blood transfusion. The patient ultimately recovered with supportive measures. We believe this to be the first case of concomitant injection of flunixin and acepromazine in a human. This report explains a case of parenteral administration of two equine medications and the subsequent complications in a patient that presented to the Emergency Department. Human exposure to veterinary medications cannot be predicted by their effect in animals due to variations in absorption, distribution, and metabolism. Physicians should be aware that individuals who work with animals may have access to large quantities of veterinary medicine. This case also exemplifies the challenges that Emergency Physicians face on a daily basis, and generates additional consideration for overdoses and intoxications from medications that are not considered commonplace in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. GB toxicity reassessed using newer techniques for estimation of human toxicity from animal inhalation toxicity data: new method for estimating acute human toxicity (GB).

    Science.gov (United States)

    Bide, R W; Armour, S J; Yee, E

    2005-01-01

    Estimated human inhalation toxicity values for Sarin (GB) were calculated using a new two independent (concentration, exposure time), one dependent (toxic response), non-linear dose response (toxicity) model combined with re-evaluated allometric equations relating to animal and human respiration. Historical animal studies of GB toxicity containing both exposure and fractional animal response data were used to test the new process. The final data set contained 6621 animals, 762 groups, 37 studies and 7 species. The toxicity of GB for each species was empirically related to exposure concentration (C; mg m(-3)) and exposure time (T; min) through the surface function Y = b0 + b1 Log10C + b2 Log10T or Y = b0 + b2 Log10C(n)T where Y is the Normit, b0, b1 and b2 are constants and n is the 'toxic load exponent' (Normit is PROBIT - 5). Between exposure times of 0.17 and 30 min, the average value for n in seven species was 1.35 +/- 0.15. The near parallel toxic load equations for each species and the linear relationship between minute volume/body weight ratio and the inhalation toxicity (LCt50) for GB were used to create a pseudo-human data set and then an exposure time/toxicity surface for the human. The calculated n for the human was 1.40. The pseudo-human data had much more variability at low exposure times. Raising the lower exposure limit to 1 min, did not change the LCt50 but did result in lower variability. Raising the lower value to 2 min was counterproductive. Based on the toxic load model for 1-30 min exposures, the human GB toxicities (LCt01, LCt05, LCt50 and LCt95) for 70 kg humans breathing 15 l min(-1) were estimated to be 11, 16, 36 and 83; 18, 25, 57 and 132 and 24, 34, 79 and 182 mg x min m(-3) for 2, 10 and 30 min exposures, respectively. These values are recommended for general use for the total human population. The empirical relationships employed in the calculations may not be valid for exposure times >30 min. 2005 John Wiley & Sons, Ltd.

  3. Cytogenetic evidence for recurrence of acute myelogenous leukemia after allogeneic bone marrow transplantation in donor hematopoietic cells

    Energy Technology Data Exchange (ETDEWEB)

    Elfenbein, G.J.; Brogaonkar, D.S.; Bias, W.B.

    1978-09-01

    A 22-yr-old man with acute myelocytic leukemia received a bone marrow transplant from a genotypically HLA-identical female sibling after cyclophosphamide preparation. He remained in complete remission for 18 mo, when he developed a chloroma in the perineum. The chloroma was treated with local radiotherapy. The chloroma recurred 8 mo later and was treated with radiotherapy followed by combination chemotherapy. At 34 mo after transplant, marrow relapse and chloroma were documented. The first chloroma contained host cells by fluorescent Y-chromatin body analyses of interphase nuclei. All metaphase cells and karyotypes from peripheral blood and marrow samples showed no evidence of host cells from 3 wk after transplant through the time of marrow relapse. Data from autosomal and sex chromosome studies indicate that the marrow relapse occurred in cells of donor origin. A new consistent chromosome abnormality (45, X, -X, t(8;21) (q22; q22)) was observed in a majority of donor cells. The patient received a second bone marrow transplant from the same donor after preparation with busulfan and cyclophosphamide and attained a complete remission with full hematologic engraftment.

  4. Functional recovery in acute traumatic spinal cord injury after transplantation of human umbilical cord mesenchymal stem cells.

    Science.gov (United States)

    Hu, Sheng-Li; Luo, Hai-Shui; Li, Jiang-Tao; Xia, Yong-Zhi; Li, Lan; Zhang, Li-Jun; Meng, Hui; Cui, Gao-Yu; Chen, Zhi; Wu, Nan; Lin, Jiang-Kai; Zhu, Gang; Feng, Hua

    2010-11-01

    Spinal cord injury results in loss of neurons, degeneration of axons, formation of glial scar, and severe functional impairment. Human umbilical cord mesenchymal stem cells can be induced to form neural cells in vitro. Thus, these cells have a potential therapeutic role for treating spinal cord injury. Rats were randomly divided into three groups: sham operation group, control group, and human umbilical cord mesenchymal stem cell group. All groups were subjected to spinal cord injury by weight drop device except for sham group. Thirty-six female Sprague-Dawley rats. The control group received Dulbecco's modified essential media/nutrient mixture F-12 injections, whereas the human umbilical cord mesenchymal stem cell group undertook cells transplantation at the dorsal spinal cord 2 mm rostrally and 2 mm caudally to the injury site at 24 hrs after spinal cord injury. Rats from each group were examined for neurologic function and contents of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and neurotrophin-3. Survival, migration, and differentiation of human umbilical cord mesenchymal stem cells, regeneration of axons, and formation of glial scar were also explored by using immunohistochemistry and immunofluorescence. Recovery of hindlimb locomotor function was significantly enhanced in the human umbilical cord mesenchymal stem cells grafted animals at 5 wks after transplantation. This recovery was accompanied by increased length of neurofilament-positive fibers and increased numbers of growth cone-like structures around the lesion site. Transplanted human umbilical cord-mesenchymal stem cells survived, migrated over short distances, and produced large amounts of glial cell line-derived neurotrophic factor and neurotrophin-3 in the host spinal cord. There were fewer reactive astrocytes in both the rostral and caudal stumps of the spinal cord in the human umbilical cord-mesenchymal stem cell group than in the control group. Treatment with

  5. Regulation of Lipolysis and Adipose Tissue Signaling during Acute Endotoxin-Induced Inflammation: A Human Randomized Crossover Trial.

    Directory of Open Access Journals (Sweden)

    Nikolaj Rittig

    Full Text Available Lipolysis is accelerated during the acute phase of inflammation, a process being regulated by pro-inflammatory cytokines (e.g. TNF-α, stress-hormones, and insulin. The intracellular mechanisms remain elusive and we therefore measured pro- and anti-lipolytic signaling pathways in adipocytes after in vivo endotoxin exposure.Eight healthy, lean, male subjects were investigated using a randomized cross over trial with two interventions: i bolus injection of saline (Placebo and ii bolus injection of lipopolysaccharide endotoxin (LPS. A 3H-palmitate tracer was used to measure palmitate rate of appearance (Rapalmitate and indirect calorimetry was performed to measure energy expenditures and lipid oxidation rates. A subcutaneous abdominal fat biopsy was obtained during both interventions and subjected to western blotting and qPCR quantifications.LPS caused a mean increase in serum free fatty acids (FFA concentrations of 90% (CI-95%: 37-142, p = 0.005, a median increase in Rapalmitate of 117% (CI-95%: 77-166, p<0.001, a mean increase in lipid oxidation of 49% (CI-95%: 1-96, p = 0.047, and a median increase in energy expenditure of 28% (CI-95%: 16-42, p = 0.001 compared with Placebo. These effects were associated with increased phosphorylation of hormone sensitive lipase (pHSL at ser650 in adipose tissue (p = 0.03, a trend towards elevated pHSL at ser552 (p = 0.09 and cAMP-dependent protein kinase A (PKA phosphorylation of perilipin 1 (PLIN1 (p = 0.09. Phosphatase and tensin homolog (PTEN also tended to increase (p = 0.08 while phosphorylation of Akt at Thr308 tended to decrease (p = 0.09 during LPS compared with Placebo. There was no difference between protein or mRNA expression of ATGL, G0S2, and CGI-58.LPS stimulated lipolysis in adipose tissue and is associated with increased pHSL and signs of increased PLIN1 phosphorylation combined with a trend toward decreased insulin signaling. The combination of these mechanisms appear to be the driving forces

  6. Effects of acute beta-adrenoceptor blockade with metoprolol on the renal response to dopamine in normal humans

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Lang-Jensen, T; Hansen, J M

    1994-01-01

    The present study investigated the contribution of adrenergic beta 1-receptor stimulation to the cardiovascular and renal effects of low-dose dopamine in eight normal, water-loaded humans. Metoprolol (100 mg) or placebo was administered orally at 08.00 h in a randomized, double-blind fashion on two...

  7. Imaging and modeling of acute pressure-induced changes of collagen and elastin microarchitectures in pig and human resistance arteries

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Leurgans, Thomas M; Spronck, Bart

    2017-01-01

    The impact of disease related changes in the extracellular matrix (ECM) on the mechanical properties of human resistance arteries largely remains to be established. Resistance arteries from both pig and human parietal pericardium (PRA) display a different ECM microarchitecture compared to frequen......The impact of disease related changes in the extracellular matrix (ECM) on the mechanical properties of human resistance arteries largely remains to be established. Resistance arteries from both pig and human parietal pericardium (PRA) display a different ECM microarchitecture compared...... to frequently used rodent mesenteric arteries. We hypothesized that the biaxial mechanics of PRA mirror pressure induced changes in the ECM microarchitecture. This was tested using isolated pig PRA as model system, integrating vital imaging, pressure myography and mathematical modeling. Collagenase and elastase...... digestions were applied to evaluate the loadbearing roles of collagen and elastin, respectively. The incremental elastic modulus linearly related to the straightness of adventitial collagen fibers circumferentially and longitudinally (both R(2)≥0.99), while there was a nonlinear relationship to the internal...

  8. EARLY SERODIAGNOSIS OF ACUTE HUMAN CYTOMEGALOVIRUS-INFECTION BY ENZYME-LINKED-IMMUNOSORBENT-ASSAY USING RECOMBINANT ANTIGENS

    NARCIS (Netherlands)

    VORNHAGEN, R; PLACHTER, B; HINDERER, W; THE, TH; VANZANTEN, J; MATTER, L; SCHMIDT, CA; SONNEBORN, HH; JAHN, G

    DNA fragments from eight different reading frames of human cytomegalovirus (HCMV) were generated by PCR and subsequently cloned and expressed in Escherichia coli in fusion with glutathione S-transferase. The recombinant viral antigens were evaluated in immunoblot analyses. The most reactive antigens

  9. Identification of hepatic niche harboring human acute lymphoblastic leukemic cells via the SDF-1/CXCR4 axis.

    Directory of Open Access Journals (Sweden)

    Itaru Kato

    Full Text Available In acute lymphoblastic leukemia (ALL patients, the bone marrow niche is widely known to be an important element of treatment response and relapse. Furthermore, a characteristic liver pathology observed in ALL patients implies that the hepatic microenvironment provides an extramedullary niche for leukemic cells. However, it remains unclear whether the liver actually provides a specific niche. The mechanism underlying this pathology is also poorly understood. Here, to answer these questions, we reconstituted the histopathology of leukemic liver by using patients-derived primary ALL cells into NOD/SCID/Yc (null mice. The liver pathology in this model was similar to that observed in the patients. By using this model, we clearly demonstrated that bile duct epithelial cells form a hepatic niche that supports infiltration and proliferation of ALL cells in the liver. Furthermore, we showed that functions of the niche are maintained by the SDF-1/CXCR4 axis, proposing a novel therapeutic approach targeting the extramedullary niche by inhibition of the SDF-1/CXCR4 axis. In conclusion, we demonstrated that the liver dissemination of leukemia is not due to nonselective infiltration, but rather systematic invasion and proliferation of leukemic cells in hepatic niche. Although the contribution of SDF-1/CXCR4 axis is reported in some cancer cells or leukemic niches such as bone marrow, we demonstrated that this axis works even in the extramedullary niche of leukemic cells. Our findings form the basis for therapeutic approaches that target the extramedullary niche by inhibiting the SDF-1/CXCR4 axis.

  10. CD90 and CD110 correlate with cancer stem cell potentials in human T-acute lymphoblastic leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Hiroto; Nishida, Hiroko; Iwata, Satoshi [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan); Dang, Nam H. [Department of Hematologic Malignancies, Nevada Cancer Institute, Las Vegas, NV (United States); Morimoto, Chikao, E-mail: morimoto@ims.u-tokyo.ac.jp [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan)

    2009-05-29

    Although cancer stem cells (CSCs) have been recently identified in myeloid leukemia, published data on lymphoid malignancy have been sparse. T-acute lymphoblastic leukemia (T-ALL) is characterized by the abnormal proliferation of T-cell precursors and is generally aggressive. As CD34 is the only positive-selection marker for CSCs in T-ALL, we performed extensive analysis of CD markers in T-ALL cell lines. We found that some of the tested lines consisted of heterogeneous populations of cells with various levels of surface marker expression. In particular, a small subpopulation of CD90 (Thy-1) and CD110 (c-Mpl) were shown to correlate with stem cell properties both in vitro and in transplantation experiments. As these markers are expressed on hematopoietic stem cells, our results suggest that stem cell-like population are enriched in CD90+/CD110+ fraction and they are useful positive-selection markers for the isolation of CSCs in some cases of T-ALL.

  11. The development of a three-dimensional scaffold for ex vivo biomimicry of human acute myeloid leukaemia.

    Science.gov (United States)

    Blanco, Teresa Mortera; Mantalaris, Athanasios; Bismarck, Alexander; Panoskaltsis, Nicki

    2010-03-01

    Acute myeloid leukaemia (AML) is a cancer of haematopoietic cells that develops in three-dimensional (3-D) bone marrow niches in vivo. The study of AML has been hampered by lack of appropriate ex vivo models that mimic this microenvironment. We hypothesised that fabrication and optimisation of suitable biomimetic scaffolds for culturing leukaemic cells ex vivo might facilitate the study of AML in its native 3-D niche. We evaluated the growth of three leukaemia subtype-specific cell lines, K-562, HL60 and Kasumi-6, on highly porous scaffolds fabricated from biodegradable and non-biodegradable polymeric materials, such as poly (L-lactic-co-glycolic acid) (PLGA), polyurethane (PU), poly (methyl-methacrylate), poly (D, L-lactade), poly (caprolactone), and polystyrene. Our results show that PLGA and PU supported the best seeding efficiency and leukaemic growth. Furthermore, the PLGA and PU scaffolds were coated with extracellular matrix (ECM) proteins, collagen type I (62.5 or 125 microg/ml) and fibronectin (25 or 50 microg/ml) to provide biorecognition signals. The 3 leukaemia subtype-specific lines grew best on PU scaffolds coated with 62.5 microg/ml collagen type I over 6 weeks in the absence of exogenous growth factors. In conclusion, PU-collagen scaffolds may provide a practical model to study the biology and treatment of primary AML in an ex vivo mimicry. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  12. Impact of acute malaria on pre-existing antibodies to viral and vaccine antigens in mice and humans.

    Directory of Open Access Journals (Sweden)

    Simran Banga

    Full Text Available Vaccine-induced immunity depends on long-lived plasma cells (LLPCs that maintain antibody levels. A recent mouse study showed that Plasmodium chaubaudi infection reduced pre-existing influenza-specific antibodies--raising concerns that malaria may compromise pre-existing vaccine responses. We extended these findings to P. yoelii infection, observing decreases in antibodies to model antigens in inbred mice and to influenza in outbred mice, associated with LLPC depletion and increased susceptibility to influenza rechallenge. We investigated the implications of these findings in Malian children by measuring vaccine-specific IgG (tetanus, measles, hepatitis B before and after the malaria-free 6-month dry season, 10 days after the first malaria episode of the malaria season, and after the subsequent dry season. On average, vaccine-specific IgG did not decrease following acute malaria. However, in some children malaria was associated with an accelerated decline in vaccine-specific IgG, underscoring the need to further investigate the impact of malaria on pre-existing vaccine-specific antibodies.

  13. A Review of the Cognitive Effects Observed in Humans Following Acute Supplementation with Flavonoids, and Their Associated Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Lynne Bell

    2015-12-01

    Full Text Available Flavonoids are polyphenolic compounds found in varying concentrations in many plant-based foods. Recent studies suggest that flavonoids can be beneficial to both cognitive and physiological health. Long term flavonoid supplementation over a period of weeks or months has been extensively investigated and reviewed, particularly with respect to cognitive ageing and neurodegenerative disease. Significantly less focus has been directed towards the short term effects of single doses of flavonoids on cognition. Here, we review 21 such studies with particular emphasis on the subclass and dose of flavonoids administered, the cognitive domains affected by flavonoid supplementation, and the effect size of the response. The emerging evidence suggests that flavonoids may be beneficial to attention, working memory, and psychomotor processing speed in a general population. Episodic memory effects are less well defined and may be restricted to child or older adult populations. The evidence also points towards a dose-dependent effect of flavonoids, but the physiological mechanisms of action remain unclear. Overall, there is encouraging evidence that flavonoid supplementation can benefit cognitive outcomes within an acute time frame of 0–6 h. But larger studies, combining cognitive and physiological measures, are needed to strengthen the evidence base.

  14. Metabolomics profiles delineate uridine deficiency contributes to mitochondria-mediated apoptosis induced by celastrol in human acute promyelocytic leukemia cells.

    Science.gov (United States)

    Zhang, Xiaoling; Yang, Jing; Chen, Minjian; Li, Lei; Huan, Fei; Li, Aiping; Liu, Yanqing; Xia, Yankai; Duan, Jin-Ao; Ma, Shiping

    2016-07-19

    Celastrol, extracted from "Thunder of God Vine", is a promising anti-cancer natural product. However, its effect on acute promyelocytic leukemia (APL) and underlying molecular mechanism are poorly understood. The purpose of this study was to explore its effect on APL and underlying mechanism based on metabolomics. Firstly, multiple assays indicated that celastrol could induce apoptosis of APL cells via p53-activated mitochondrial pathway. Secondly, unbiased metabolomics revealed that uridine was the most notable changed metabolite. Further study verified that uridine could reverse the apoptosis induced by celastrol. The decreased uridine was caused by suppressing the expression of gene encoding Dihydroorotate dehydrogenase, whose inhibitor could also induce apoptosis of APL cells. At last, mouse model confirmed that celastrol inhibited tumor growth through enhanced apoptosis. Celastrol could also decrease uridine and DHODH protein level in tumor tissues. Our in vivo study also indicated that celastrol had no systemic toxicity at pharmacological dose (2 mg/kg, i.p., 21 days). Altogether, our metabolomics study firstly reveals that uridine deficiency contributes to mitochondrial apoptosis induced by celastrol in APL cells. Celastrol shows great potential for the treatment of APL.

  15. Structural Basis of Neutralization by a Human Anti-severe Acute Respiratory Syndrome Spike Protein Antibody,80R.

    Energy Technology Data Exchange (ETDEWEB)

    Hwang,W.; Lin, Y.; Santelli, E.; Sui, J.; Jaroszewski, L.; Stec, B.; Farzan, M.; Marasco, W.; Liddington, R.

    2006-01-01

    Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease that caused pandemic spread in 2003. The etiological agent of SARS is a novel coronavirus (SARS-CoV). The coronaviral surface spike protein S is a type I transmembrane glycoprotein that mediates initial host binding via the cell surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the subsequent membrane fusion events required for cell entry. Here we report the crystal structure of the S1 receptor binding domain (RBD) in complex with a neutralizing antibody, 80R, at 2.3 {angstrom} resolution, as well as the structure of the uncomplexed S1 RBD at 2.2 {angstrom} resolution. We show that the 80R-binding epitope on the S1 RBD overlaps very closely with the ACE2-binding site, providing a rationale for the strong binding and broad neutralizing ability of the antibody. We provide a structural basis for the differential effects of certain mutations in the spike protein on 80R versus ACE2 binding, including escape mutants, which should facilitate the design of immunotherapeutics to treat a future SARS outbreak. We further show that the RBD of S1 forms dimers via an extensive interface that is disrupted in receptor- and antibody-bound crystal structures, and we propose a role for the dimer in virus stability and infectivity.

  16. Comparative Epidemiology of Human Infections with Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome Coronaviruses among Healthcare Personnel.

    Science.gov (United States)

    Liu, Shelan; Chan, Ta-Chien; Chu, Yu-Tseng; Wu, Joseph Tsung-Shu; Geng, Xingyi; Zhao, Na; Cheng, Wei; Chen, Enfu; King, Chwan-Chuen

    2016-01-01

    The largest nosocomial outbreak of Middle East respiratory syndrome (MERS) occurred in South Korea in 2015. Health Care Personnel (HCP) are at high risk of acquiring MERS-Coronavirus (MERS-CoV) infections, similar to the severe acute respiratory syndrome (SARS)-Coronavirus (SARS-CoV) infections first identified in 2003. This study described the similarities and differences in epidemiological and clinical characteristics of 183 confirmed global MERS cases and 98 SARS cases in Taiwan associated with HCP. The epidemiological findings showed that the mean age of MERS-HCP and total MERS cases were 40 (24~74) and 49 (2~90) years, respectively, much older than those in SARS [SARS-HCP: 35 (21~68) years, p = 0.006; total SARS: 42 (0~94) years, p = 0.0002]. The case fatality rates (CFR) was much lower in MERS-HCP [7.03% (9/128)] or SARS-HCP [12.24% (12/98)] than the MERS-non-HCP [36.96% (34/92), pinfections involving both novel Coronavirus is crucially important to protect HCP.

  17. The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Isabel Gonçalves Silva

    2017-08-01

    Full Text Available Acute myeloid leukemia (AML is a severe and often fatal systemic malignancy. Malignant cells are capable of escaping host immune surveillance by inactivating cytotoxic lymphoid cells. In this work we discovered a fundamental molecular pathway, which includes ligand-dependent activation of ectopically expressed latrophilin 1 and possibly other G-protein coupled receptors leading to increased translation and exocytosis of the immune receptor Tim-3 and its ligand galectin-9. This occurs in a protein kinase C and mTOR (mammalian target of rapamycin-dependent manner. Tim-3 participates in galectin-9 secretion and is also released in a free soluble form. Galectin-9 impairs the anti-cancer activity of cytotoxic lymphoid cells including natural killer (NK cells. Soluble Tim-3 prevents secretion of interleukin-2 (IL-2 required for the activation of cytotoxic lymphoid cells. These results were validated in ex vivo experiments using primary samples from AML patients. This pathway provides reliable targets for both highly specific diagnosis and immune therapy of AML.

  18. The Nasal Route as a Potential Pathway for Delivery of Erythropoietin in the Treatment of Acute Ischemic Stroke in Humans

    Directory of Open Access Journals (Sweden)

    Julio Cesar García-Rodríguez

    2009-01-01

    Full Text Available Intranasal delivery provides a practical, noninvasive method of bypassing the blood-brain barrier (BBB in order to deliver therapeutic agents to the brain. This method allows drugs that do not cross the BBB to be delivered to the central nervous system in a few minutes. With this technology, it will be possible to eliminate systemic administration and its potential side effects. Using the intranasal delivery system, researchers have demonstrated neuroprotective effects in different animal models of stroke using erythropoietin (EPO as a neuroprotector or other different types of EPO without erythropoiesis-stimulating activity. These new molecules retain their ability to protect neural tissue against injury and they include Asialoerythropoietin (asialoEPO carbamylated EPO (CEPO, and rHu-EPO with low sialic acid content (Neuro-EPO. Contrary to the other EPO variants, Neuro-EPO is not chemically modified, making it biologically similar to endogenous EPO, with the advantage of less adverse reactions when this molecule is applied chronically. This constitutes a potential benefit of Neuro-EPO over other variants of EPO for the chronic treatment of neurodegenerative illnesses. Nasal administration of EPO is a potential, novel, neurotherapeutic approach. However, it will be necessary to initiate clinical trials in stroke patients using intranasal delivery in order to obtain the clinical evidence of its neuroprotectant capacity in the treatment of patients with acute stroke and other neurodegenerative disorders. This new therapeutic approach could revolutionize the treatment of neurodegenerative disorders in the 21st century.

  19. Human resource management strategies for the retention of nurses in acute care settings in hospitals in Australia.

    Science.gov (United States)

    Hogan, Pamela; Moxham, Lorna; Dwyer, Trudy

    2007-04-01

    It is paramount that there is an adequate nursing workforce supply for now and in the future, to achieve equitable and quality health outcomes and consumer access to healthcare, regardless of geographic location. Nursing forms the largest body of employees in the health care system, spanning all segments of care. A shortage of nurses, particularly in the acute care settings in hospitals, jeopardizes the provision of quality health care to consumers. This article provides a literature review of Australian State and Federal Government reports into nurse retention. All reports discuss staff turnover rates; the average age of nurses; enrolment numbers in nursing courses; workloads; nursing workforce shortfalls and the effect on the work environment; leadership and management styles; organizational culture; change management; the mobility of nursing qualifications both locally and internationally and the critical need to value nurses. Then why has the situation of nurse retention not improved? Possible reasons for the continued nurse shortage and the promise of strategic HRM in addressing nurse retention are discussed.

  20. SIRT1 activation by a c-MYC oncogenic network promotes the maintenance and drug resistance of human FLT3-ITD acute myeloid leukemia stem cells.

    Science.gov (United States)

    Li, Ling; Osdal, Tereza; Ho, Yinwei; Chun, Sookhee; McDonald, Tinisha; Agarwal, Puneet; Lin, Allen; Chu, Su; Qi, Jing; Li, Liang; Hsieh, Yao-Te; Dos Santos, Cedric; Yuan, Hongfeng; Ha, Trung-Quang; Popa, Mihaela; Hovland, Randi; Bruserud, Øystein; Gjertsen, Bjørn Tore; Kuo, Ya-Huei; Chen, Wenyong; Lain, Sonia; McCormack, Emmet; Bhatia, Ravi

    2014-10-02

    The FLT3-ITD mutation is frequently observed in acute myeloid leukemia (AML) and is associated with poor prognosis. In such patients, FLT3 tyrosine kinase inhibitors (TKIs) are only partially effective and do not eliminate the leukemia stem cells (LSCs) that are assumed to be the source of treatment failure. Here, we show that the NAD-dependent SIRT1 deacetylase is selectively overexpressed in primary human FLT3-ITD AML LSCs. This SIRT1 overexpression is related to enhanced expression of the USP22 deubiquitinase induced by c-MYC, leading to reduced SIRT1 ubiquitination and enhanced stability. Inhibition of SIRT1 expression or activity reduced the growth of FLT3-ITD AML LSCs and significantly enhanced TKI-mediated killing of the cells. Therefore, these results identify a c-MYC-related network that enhances SIRT1 protein expression in human FLT3-ITD AML LSCs and contributes to their maintenance. Inhibition of this oncogenic network could be an attractive approach for targeting FLT3-ITD AML LSCs to improve treatment outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. A Descriptive Study of the Temporal Patterns of Volume and Contents Change in Human Acute Burn Edema: Application in Evidence-Based Intervention and Research Design.

    Science.gov (United States)

    Edgar, Dale W; Fear, Mark; Wood, Fiona M

    2016-01-01

    Edema after burn contributes significantly to burn wound depth conversion. In humans after burn injury, there is a lack of detailed understanding of the contents and temporal changes in volume of acute tissue edema. The novel findings of these studies relate to the collection of edema fluid after partial-thickness burn injury. Edema volume peaks on day 1 after burn without formal fluid resuscitation. The studies indicated that the peak was on day 2 for a resuscitated burn. In contrast, animal studies suggest that the peak of edema occurs by or before day 1 after injury. The findings confirm the pitfalls of evidence derived from animal models and assuming direct transference to humans. Postburn edema was demonstrated to be a high-protein fluid (ie, ≥10 g/L) for the duration of the inflammatory period. The presence of high-protein edema presents greater challenges to clinicians developing novel treatment options. The rate of volume change over time tapered to insignificant levels after day 4 following burn. Greater than 98% of the edema contents was fluid. However, the size of particulate matter did not preclude it passing through patent lymphatic collectors. The results indicate a necessity for urgent postburn intervention, which should incorporate the active stimulation of the lymphatic system to improve efficacy of edema removal.

  2. The pleiotropic effects of fisetin and hesperetin on human acute promyelocytic leukemia cells are mediated through apoptosis, cell cycle arrest, and alterations in signaling networks.

    Science.gov (United States)

    Adan, Aysun; Baran, Yusuf

    2015-11-01

    Fisetin and hesperetin, flavonoids from various plants, have several pharmaceutical activities including antioxidative, anti-inflammatory, and anticancer effects. However, studies elucidating the role and the mechanism(s) of action of fisetin and hesperetin in acute promyelocytic leukemia are absent. In this study, we investigated the mechanism of the antiproliferative and apoptotic actions exerted by fisetin and hesperetin on human HL60 acute promyelocytic leukemia cells. The viability of HL60 cells was evaluated using the MTT assay, apoptosis by annexin V/propidium iodide (PI) staining and cell cycle distribution using flow cytometry, and changes in caspase-3 enzyme activity and mitochondrial transmembrane potential. Moreover, we performed whole-genome microarray gene expression analysis to reveal genes affected by fisetin and hesperetin that can be important for developing of future targeted therapy. Based on data obtained from microarray analysis, we also described biological networks modulated after fisetin and hesperetin treatment by KEGG and IPA analysis. Fisetin and hesperetin treatment showed a concentration- and time-dependent inhibition of proliferation and induced G2/M arrest for both agents and G0/G1 arrest for hesperetin at only the highest concentrations. There was a disruption of mitochondrial membrane potential together with increased caspase-3 activity. Furthermore, fisetin- and hesperetin-triggered apoptosis was confirmed by annexin V/PI analysis. The microarray gene profiling analysis revealed some important biological pathways including mitogen-activated protein kinases (MAPK) and inhibitor of DNA binding (ID) signaling pathways altered by fisetin and hesperetin treatment as well as gave a list of genes modulated ≥2-fold involved in cell proliferation, cell division, and apoptosis. Altogether, data suggested that fisetin and hesperetin have anticancer properties and deserve further investigation.

  3. Proteomic Analysis of a Noninvasive Human Model of Acute Inflammation and Its Resolution: The Twenty-one Day Gingivitis Model

    Science.gov (United States)

    2010-01-01

    The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC−MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins. PMID:20662485

  4. Toward quantifying the usage costs of human immunity: Altered metabolic rates and hormone levels during acute immune activation in men.

    Science.gov (United States)

    Muehlenbein, Michael P; Hirschtick, Jana L; Bonner, Julia Z; Swartz, Ann M

    2010-01-01

    There is a paucity of data on the energetic demands of human immune functions, despite the fact that both clinical medicine and evolutionary biology would benefit from further clarification of these costs. To better understand the energetic requirements of mounting a mild immune response, as well as some of the major hormonal changes underlying these metabolic changes, we examined changes in resting metabolic rate (RMR) and hormones during and after respiratory tract infection in young adult men. An epidemiologic passive detection design was used to recruit 25 nonfebrile subjects naturally infected with respiratory tract pathogens. Symptomology, percent body fat, RMR, salivary testosterone and cortisol, and other information were collected at a minimum of three time points during and after convalescence. Comparisons of the differences in RMR, testosterone, and cortisol between sampling days within individual cases were made using paired t-tests. Participants experienced 8% higher RMR during illness, and a subset of these men experienced a mean increase greater than 14%. The participants also experienced 10% lower testosterone levels during illness, and a subset of these participants experienced a mean decrease of 30%, although cortisol levels did not change significantly. These results document elevated RMR following natural pathogen exposure in adult humans, demonstrating that even mild immune reactions can elicit significant increases in energy expenditure. Understanding the costs of immunity and the immunomodulatory actions of hormones are central to understanding the role of immunity in human life history evolution.

  5. Acute hypoxia diminishes the relationship between blood pressure and subarachnoid space width oscillations at the human cardiac frequency.

    Directory of Open Access Journals (Sweden)

    Magdalena Wszedybyl-Winklewska

    Full Text Available Acute hypoxia exerts strong effects on the cardiovascular system. Heart-generated pulsatile cerebrospinal fluid motion is recognised as a key factor ensuring brain homeostasis. We aimed to assess changes in heart-generated coupling between blood pressure (BP and subarachnoid space width (SAS oscillations during hypoxic exposure.Twenty participants were subjected to a controlled decrease in oxygen saturation (SaO2 = 80% for five minutes. BP and heart rate (HR were measured using continuous finger-pulse photoplethysmography, oxyhaemoglobin saturation with an ear-clip sensor, end-tidal CO2 with a gas analyser, and cerebral blood flow velocity (CBFV, pulsatility and resistive indices with Doppler ultrasound. Changes in SAS were recorded with a recently-developed method called near-infrared transillumination/backscattering sounding. Wavelet transform analysis was used to assess the relationship between BP and SAS oscillations.Gradual increases in systolic, diastolic BP and HR were observed immediately after the initiation of hypoxic challenge (at fifth minute +20.1%, +10.2%, +16.5% vs. baseline, respectively; all P<0.01, whereas SAS remained intact (P = NS. Concurrently, the CBFV was stable throughout the procedure, with the only increase observed in the last two minutes of deoxygenation (at the fifth minute +6.8% vs. baseline, P<0.05. The cardiac contribution to the relationship between BP and SAS oscillations diminished immediately after exposure to hypoxia (at the fifth minute, right hemisphere -27.7% and left hemisphere -26.3% vs. baseline; both P<0.05. Wavelet phase coherence did not change throughout the experiment (P = NS.Cerebral haemodynamics seem to be relatively stable during short exposure to normobaric hypoxia. Hypoxia attenuates heart-generated BP SAS coupling.

  6. High affinity complexes of pannexin channels and L-type calcium channel splice-variants in human lung: Possible role in clevidipine-induced dyspnea relief in acute heart failure

    Directory of Open Access Journals (Sweden)

    Gerhard P. Dahl

    2016-08-01

    Research in Context: Clevidipine lowers blood pressure by inhibiting calcium channels in vascular smooth muscle. In patients with acute heart failure, clevidipine was shown to relieve breathing problems. This was only partially related to the blood pressure lowering actions of clevidipine and not conferred by another calcium channel inhibitor. We here found calcium channel variants in human lung that are more selectively inhibited by clevidipine, especially when associated with pannexin channels. This study gives a possible mechanism for clevidipine's relief of breathing problems and supports future clinical trials testing the role of clevidipine in the treatment of acute heart failure.

  7. Acute Porphyrias.

    Science.gov (United States)

    Besur, Siddesh; Schmeltzer, Paul; Bonkovsky, Herbert L

    2015-09-01

    Porphyrias are a group of eight metabolic disorders characterized by defects in heme biosynthesis. Porphyrias are classified into two major categories: 1) the acute or inducible porphyrias and 2) the chronic cutaneous porphyrias. The acute hepatic porphyrias are further classified into acute intermittent porphyria (AIP), hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of delta-aminolevulinic acid (ALA) dehydratase (ALADP). AIP is the most common, and ALADP is the least common acute porphyria. The clinical presentations of acute porphyrias are nonspecific. There are no pathognomonic signs or symptoms. The most frequent presenting symptom is abdominal pain, but pain in the chest, back, or lower extremities may also occur. Hyponatremia is the most common electrolyte abnormality during acute attacks, and hypomagnesemia is also common. Both are risk factors for development of seizures, which occur in ∼ 20-30% of acute attacks. Once suspected, the diagnosis of porphyria can be rapidly established by checking random urinary porphobilinogen. Initial management of acute porphyria includes discontinuation of all potentially harmful drugs and management of symptoms. Acute attacks should be treated emergently with intravenous heme and glucose to avoid considerable morbidity and mortality. Acute attacks last a few days, and the majority of patients are asymptomatic between attacks. Prognosis is good if the condition is recognized early and treated aggressively. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    Energy Technology Data Exchange (ETDEWEB)

    Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  9. Rotavirus specific plasma secretory immunoglobulin in children with acute gastroenteritis and children vaccinated with an attenuated human rotavirus vaccine

    OpenAIRE

    Herrera Daniel; Vásquez Camilo; Corthésy Blaise E.; Franco M. A.; Angel Juana

    2013-01-01

    Rotavirus (RV)-specific secretory immunoglobulin (RV-sIg) has been previously detected in serum of naturally RV infected children and shown to reflect the intestinal Ig immune response. Total plasma sIga and plasma RV-sIg were evaluated by eLIsa in children with gastroenteritis due or not due to RV infection and in 50 children vaccinated with the attenuated RIX4414 human RV vaccine and 62 placebo recipients. RV-sIg was only detected in children with evidence of previous RV infection or with a...

  10. Imaging and modeling of acute pressure-induced changes of collagen and elastin microarchitectures in pig and human resistance arteries.

    Science.gov (United States)

    Bloksgaard, Maria; Leurgans, Thomas M; Spronck, Bart; Heusinkveld, Maarten H G; Thorsted, Bjarne; Rosenstand, Kristoffer; Nissen, Inger; Hansen, Ulla M; Brewer, Jonathan R; Bagatolli, Luis A; Rasmussen, Lars M; Irmukhamedov, Akhmadjon; Reesink, Koen D; De Mey, Jo G R

    2017-07-01

    The impact of disease-related changes in the extracellular matrix (ECM) on the mechanical properties of human resistance arteries largely remains to be established. Resistance arteries from both pig and human parietal pericardium (PRA) display a different ECM microarchitecture compared with frequently used rodent mesenteric arteries. We hypothesized that the biaxial mechanics of PRA mirror pressure-induced changes in the ECM microarchitecture. This was tested using isolated pig PRA as a model system, integrating vital imaging, pressure myography, and mathematical modeling. Collagenase and elastase digestions were applied to evaluate the load-bearing roles of collagen and elastin, respectively. The incremental elastic modulus linearly related to the straightness of adventitial collagen fibers circumferentially and longitudinally (both R2 ≥ 0.99), whereas there was a nonlinear relationship to the internal elastic lamina elastin fiber branching angles. Mathematical modeling suggested a collagen recruitment strain (means ± SE) of 1.1 ± 0.2 circumferentially and 0.20 ± 0.01 longitudinally, corresponding to a pressure of ~40 mmHg, a finding supported by the vital imaging. The integrated method was tested on human PRA to confirm its validity. These showed limited circumferential distensibility and elongation and a collagen recruitment strain of 0.8 ± 0.1 circumferentially and 0.06 ± 0.02 longitudinally, reached at a distending pressure below 20 mmHg. This was confirmed by vital imaging showing negligible microarchitectural changes of elastin and collagen upon pressurization. In conclusion, we show here, for the first time in resistance arteries, a quantitative relationship between pressure-induced changes in the extracellular matrix and the arterial wall mechanics. The strength of the integrated methods invites for future detailed studies of microvascular pathologies.NEW & NOTEWORTHY This is the first study to quantitatively relate pressure-induced microstructural

  11. Assessing Metabolism and Injury in Acute Human Traumatic Brain Injury with Magnetic Resonance Spectroscopy: Current and Future Applications

    Directory of Open Access Journals (Sweden)

    Matthew G. Stovell

    2017-09-01

    Full Text Available Traumatic brain injury (TBI triggers a series of complex pathophysiological processes. These include abnormalities in brain energy metabolism; consequent to reduced tissue pO2 arising from ischemia or abnormal tissue oxygen diffusion, or due to a failure of mitochondrial function. In vivo magnetic resonance spectroscopy (MRS allows non-invasive interrogation of brain tissue metabolism in patients with acute brain injury. Nuclei with “spin,” e.g., 1H, 31P, and 13C, are detectable using MRS and are found in metabolites at various stages of energy metabolism, possessing unique signatures due to their chemical shift or spin–spin interactions (J-coupling. The most commonly used clinical MRS technique, 1H MRS, uses the great abundance of hydrogen atoms within molecules in brain tissue. Spectra acquired with longer echo-times include N-acetylaspartate (NAA, creatine, and choline. NAA, a marker of neuronal mitochondrial activity related to adenosine triphosphate (ATP, is reported to be lower in patients with TBI than healthy controls, and the ratio of NAA/creatine at early time points may correlate with clinical outcome. 1H MRS acquired with shorter echo times produces a more complex spectrum, allowing detection of a wider range of metabolites.31 P MRS detects high-energy phosphate species, which are the end products of cellular respiration: ATP and phosphocreatine (PCr. ATP is the principal form of chemical energy in living organisms, and PCr is regarded as a readily mobilized reserve for its replenishment during periods of high utilization. The ratios of high-energy phosphates are thought to represent a balance between energy generation, reserve and use in the brain. In addition, the chemical shift difference between inorganic phosphate and PCr enables calculation of intracellular pH.13 C MRS detects the 13C isotope of carbon in brain metabolites. As the natural abundance of 13C is low (1.1%, 13C MRS is typically performed following

  12. A controlled trial of acute effects of human exposure to traffic particles on pulmonary oxidative stress and heart rate variability.

    Science.gov (United States)

    Laumbach, Robert J; Kipen, Howard M; Ko, Susan; Kelly-McNeil, Kathie; Cepeda, Clarimel; Pettit, Ashley; Ohman-Strickland, Pamela; Zhang, Lin; Zhang, Junfeng; Gong, Jicheng; Veleeparambil, Manoj; Gow, Andrew J

    2014-11-01

    For many individuals, daily commuting activities on roadways account for a substantial proportion of total exposure, as well as peak-level exposures, to traffic-related air pollutants (TRAPS) including ultrafine particles, but the health impacts of these exposures are not well-understood. We sought to determine if exposure to TRAPs particles during commuting causes acute oxidative stress in the respiratory tract or changes in heart rate variability (HRV), a measure of autonomic activity. We conducted a randomized, cross-over trial in which twenty-one young adults took two 1.5-hr rides in a passenger vehicle in morning rush-hour traffic. The subjects wore a powered-air-purifying respirator, and were blinded to high-efficiency particulate air (HEPA) filtration during one of the rides. At time points before and after the rides, we measured HRV and markers of oxidative stress in exhaled breath condensate (EBC) including nitrite, the sum of nitrite and nitrate, malondialdehyde, and 8-isoprostane. We used mixed linear models to evaluate the effect of exposure on EBC and HRV outcomes, adjusting for pre-exposure response levels. We used linear models to examine the effects of particle concentrations on EBC outcomes at post-exposure time points. Mean EBC nitrite and the sum of nitrite and nitrate were increased from baseline at immediately post-exposure comparing unfiltered to filtered rides (2.11 μM vs 1.70 μM, p = 0.02 and 19.1 μM vs 10.0 μM, p = 0.02, respectively). Mean EBC malondialdehyde (MDA) concentrations were about 10% greater following the unfiltered vs. filtered exposures, although this result was not statistically significant. We found no significant associations between exposure to traffic particles and HRV outcomes at any of the time points. At immediately post-exposure, an interquartile range increase in particle number concentration was associated with statistically significant increases in nitrite (99.4%, 95% CI 32.1% to 166.7%) and

  13. Effect of acute ozone induced airway inflammation on human sympathetic nerve traffic: a randomized, placebo controlled, crossover study.

    Directory of Open Access Journals (Sweden)

    Jens Tank

    Full Text Available BACKGROUND: Ozone concentrations in ambient air are related to cardiopulmonary perturbations in the aging population. Increased central sympathetic nerve activity induced by local airway inflammation may be one possible mechanism. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate this issue further, we performed a randomized, double-blind, cross-over study, including 14 healthy subjects (3 females, age 22-47 years, who underwent a 3 h exposure with intermittent exercise to either ozone (250 ppb or clean air. Induced sputum was collected 3 h after exposure. Nineteen to 22 hours after exposure, we recorded ECG, finger blood pressure, brachial blood pressure, respiration, cardiac output, and muscle sympathetic nerve activity (MSNA at rest, during deep breathing, maximum-inspiratory breath hold, and a Valsalva maneuver. While the ozone exposure induced the expected airway inflammation, as indicated by a significant increase in sputum neutrophils, we did not detect a significant estimated treatment effect adjusted for period on cardiovascular measurements. Resting heart rate (clean air: 59±2, ozone 60±2 bpm, blood pressure (clean air: 121±3/71±2 mmHg; ozone: 121±2/71±2 mmHg, cardiac output (clean air: 7.42±0.29 mmHg; ozone: 7.98±0.60 l/min, and plasma norepinephrine levels (clean air: 213±21 pg/ml; ozone: 202±16 pg/ml, were similar on both study days. No difference of resting MSNA was observed between ozone and air exposure (air: 23±2, ozone: 23±2 bursts/min. Maximum MSNA obtained at the end of apnea (air: 44±4, ozone: 48±4 bursts/min and during the phase II of the Valsalva maneuver (air: 64±5, ozone: 57±6 bursts/min was similar. CONCLUSIONS/SIGNIFICANCE: Our study suggests that acute ozone-induced airway inflammation does not increase resting sympathetic nerve traffic in healthy subjects, an observation that is relevant for environmental health. However, we can not exclude that chronic airway inflammation may contribute to sympathetic

  14. Comparative Epidemiology of Human Infections with Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome Coronaviruses among Healthcare Personnel.

    Directory of Open Access Journals (Sweden)

    Shelan Liu

    Full Text Available The largest nosocomial outbreak of Middle East respiratory syndrome (MERS occurred in South Korea in 2015. Health Care Personnel (HCP are at high risk of acquiring MERS-Coronavirus (MERS-CoV infections, similar to the severe acute respiratory syndrome (SARS-Coronavirus (SARS-CoV infections first identified in 2003. This study described the similarities and differences in epidemiological and clinical characteristics of 183 confirmed global MERS cases and 98 SARS cases in Taiwan associated with HCP. The epidemiological findings showed that the mean age of MERS-HCP and total MERS cases were 40 (24~74 and 49 (2~90 years, respectively, much older than those in SARS [SARS-HCP: 35 (21~68 years, p = 0.006; total SARS: 42 (0~94 years, p = 0.0002]. The case fatality rates (CFR was much lower in MERS-HCP [7.03% (9/128] or SARS-HCP [12.24% (12/98] than the MERS-non-HCP [36.96% (34/92, p<0.001] or SARS-non-HCP [24.50% (61/249, p<0.001], however, no difference was found between MERS-HCP and SARS-HCP [p = 0.181]. In terms of clinical period, the days from onset to death [13 (4~17 vs 14.5 (0~52, p = 0.045] and to discharge [11 (5~24 vs 24 (0~74, p = 0.010] and be hospitalized days [9.5 (3~22 vs 22 (0~69, p = 0.040] were much shorter in MERS-HCP than SARS-HCP. Similarly, days from onset to confirmation were shorter in MERS-HCP than MERS-non-HCP [6 (1~14 vs 10 (1~21, p = 0.044]. In conclusion, the severity of MERS-HCP and SARS-HCP was lower than that of MERS-non-HCP and SARS-non-HCP due to younger age and early confirmation in HCP groups. However, no statistical difference was found in MERS-HCP and SARS-HCP. Thus, prevention of nosocomial infections involving both novel Coronavirus is crucially important to protect HCP.

  15. Characterization of human coronavirus etiology in Chinese adults with acute upper respiratory tract infection by real-time RT-PCR assays.

    Directory of Open Access Journals (Sweden)

    Roujian Lu

    Full Text Available BACKGROUND: In addition to SARS associated coronaviruses, 4 non-SARS related human coronaviruses (HCoVs are recognized as common respiratory pathogens. The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. All specimens were also tested for the presence of other common respiratory viruses and newly identified viruses, human metapneumovirus (hMPV and human bocavirus (HBoV. 157 of the 981 (16.0% nasopharyngeal swabs were positive for HCoVs. The species detected were 229E (96 cases, 9.8%, OC43 (42 cases, 4.3%, HKU1 (16 cases, 1.6% and NL63 (11 cases, 1.1%. HCoV-229E was circulated in 21 of the 24 months of surveillance. The detection rates for both OC43 and NL63 were showed significantly year-to-year variation between 2009/10 and 2010/11, respectively (P<0.001 and P = 0.003, and there was a higher detection frequency of HKU1 in patients aged over 60 years (P = 0.03. 48 of 157(30.57% HCoV positive patients were co-infected. Undifferentiated human rhinoviruses and influenza (Flu A were the most common viruses detected (more than 35% in HCoV co-infections. Respiratory syncytial virus (RSV, human parainfluenza virus (PIV and HBoV were detected in very low rate (less than 1% among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. Our study also suggested that all non-SARS-associated HCoVs contribute significantly to URTI in adult patients in China.

  16. A protocol to isolate and qualify purified human preantral follicles in cases of acute leukemia, for future clinical applications.

    Science.gov (United States)

    Mouloungui, Elodie; Zver, Tristan; Roux, Christophe; Amiot, Clotilde

    2018-01-05

    Autotransplantation of cryopreserved ovarian cortex can be associated with a risk of cancer cell reseeding. This issue could be eliminated by grafting isolated preantral follicles. Collagenase NB6 is an enzyme produced under good manufacturing practices (GMP) in compliance with requirements for tissue engineering and transplantation in humans and thus can be used to isolate preantral follicles from ovarian tissue in the framework of further clinical applications. Multicolor flow cytometry is an effective tool to evaluate the potential contamination of follicular suspensions by leukemic cells. The efficiency of collagenase NB6 was evaluated in comparison to collagenase type IA and Liberase DH, in terms of yield, morphology and viability. A short-term in vitro culture of follicles isolated with collagenase NB6 was conducted for 3 days in a fibrin matrix. A modelization procedure was carried out to detect the presence of leukemic cells in follicular suspensions using multicolor flow cytometry (MFC). No statistical differences were found between collagenase NB6, Liberase DH (p = 0.386) and collagenase type IA (p = 0.171) regarding the number of human preantral follicles isolated. The mean diameter of isolated follicles was significantly lower with collagenase NB6 (p good manufacturing practices for cell therapy. Multicolor flow cytometry was able to confirm that final follicular suspensions were free from leukemic cells. This safe isolation technique using collagenase NB6 can be considered for future clinical applications.

  17. Expression of growth-related genes in young and older human skeletal muscle following an acute stimulation of protein synthesis.

    Science.gov (United States)

    Drummond, Micah J; Miyazaki, Mitsunori; Dreyer, Hans C; Pennings, Bart; Dhanani, Shaheen; Volpi, Elena; Esser, Karyn A; Rasmussen, Blake B

    2009-04-01

    Muscle growth is associated with an activation of the mTOR signaling pathway and satellite cell regulators. The purpose of this study was to determine whether 17 selected genes associated with mTOR/muscle protein synthesis and the satellite cells/myogenic program are differentially expressed in young and older human skeletal muscle at rest and in response to a potent anabolic stimulus [resistance exercise + essential amino acid ingestion (RE+EAA)]. Twelve male subjects (6 young, 6 old) completed a bout of heavy resistance exercise. Muscle biopsies were obtained before and at 3 and 6 h post RE+EAA. Subjects ingested leucine-enriched essential amino acids at 1 h postexercise. mRNA expression was determined using qRT-PCR. At rest, hVps34 mRNA was elevated in the older subjects (P muscle are more responsive in young men post RE+EAA. Our data provide new insights into the regulation of genes important for transcription and translation in young and old human skeletal muscle post RE+EAA.

  18. Acute effect of tea, wine, beer, and polyphenols on ecto-alkaline phosphatase activity in human vascular smooth muscle cells.

    Science.gov (United States)

    Negrão, Maria R; Keating, Elisa; Faria, Ana; Azevedo, Isabel; Martins, Maria J

    2006-07-12

    Alkaline phosphatase (ALP) is an ecto-enzyme widely distributed across species. It modulates a series of transmembranar transport systems, has an important role in bone mineralization, and can also be involved in vascular calcification. Polyphenol-rich diets seem to have protective effects on human health, namely, in the prevention of cardiovascular diseases. We aimed to investigate the effects of polyphenols and polyphenol-rich beverages upon membranar alkaline phosphatase (ecto-ALP) activity in intact human vascular smooth muscle cells (AALTR). The ecto-ALP activity was determined at pH 7.8, with p-nitrophenyl phosphate as the substrate, by absorbance spectrophotometry at 410 nm. Cell viability was assessed by the lactate dehydrogenase (LDH) method, and the polyphenol content of beverages was assessed using the Folin-Ciocalteu reagent. All polyphenols tested inhibited ecto-ALP activity, in a concentration-dependent way. Teas, wines, and beers also inhibited ecto-ALP activity, largely according to their polyphenol content. All tested compounds and beverages improved or did not change AALTR cell viability. Stout beer was an exception to the described behavior. Although more studies must be done, the inhibition of AALTR ecto-ALP activity by polyphenolic compounds and polyphenol-containing beverages may contribute to their cardiovascular protective effects.

  19. Underutilization of aspirin in people living with human immunodeficiency virus at increased risk for acute myocardial infarction: Systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Stella Pak

    2017-01-01

    Full Text Available Context: With the increased availability of potent combination antiretroviral therapies, the life expectancy of people living with human immunodeficiency virus (PLHIV has greatly increased. This rapid improvement in lifespan has served as a catalyst for a paradigm shift in human immunodeficiency virus (HIV care. The focus of HIV care models has transitioned from the sole treatment of acute opportunistic infections to comprehensive management of chronic diseases, such as cardiovascular disease (CVD. Multiple studies have demonstrated that PLHIV are 50% more likely to develop acute myocardial infarction (AMI, compared to the general population. Cardiovascular risk prevention is becoming an essential component of the overarching HIV treatment plan. Aims: This meta-analysis aims to compare the rate of aspirin use for AMI prevention in indicated patients between PLHIV and general population. Methods: PubMed, EMBASE, Web of Science, Cochrane Library, CINAHL, and MEDLINE databases were used to identify observational cohort trials. Studies were assessed by two reviewers for inclusion criteria. Two separate random-effects meta-analyses' models were performed using the DerSimonian and Laird method. Heterogeneity was assessed using the I2 value. Meta-regression with study level variables was used to explore potential sources of heterogeneity. The funnel-plot-based trim-and-fill method was applied to detect and adjust for potential publication bias. Statistical tests were two-sided and P< 0.05 was considered statistically significant. Results: A total of 13 studies were included for analysis. In these trials, 30.4% of PLHIV with increased risk for coronary heart disease (CHD used aspirin for AMI prevention, compared to 36.9% of patients at risk of CHD in the general population. Conclusions: The results of this meta-analysis provide evidence that aspirin is underutilized in both PLHIV and the general population across broad geographical zones. Aspirin use

  20. [Detection and clinical analysis of acute lower respiratory tract infection with human coronaviruses in children in Beijing area 2007-2015].

    Science.gov (United States)

    Qian, Yi; Xie, Zhengde; Ren, Lili; Liu, Chunyan; Xiao, Yan; Xu, Baoping; Yang, Yan; Qian, Suyun; Geng, Rong; Shen, Kunling

    2015-09-01

    To investigate human coronaviruses (HCoVs) infection in children with acute lower respiratory tract infection(ALRTI)and to explore the clinical features of ALRTI caused by HCoVs in children. Totally 4 371 children with clinical diagnosis of ALRTI during the period from March 2007 to February 2015 seen in Beijing Children's Hospital were recruited into this study. Patients were divided into 4 groups by age, including 1 890 cases in respiratory viruses including HCoVs (including HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1), respiratory syncytial virus (RSV) and so on. Clinical features of ALRTI with single HCoVs infection were analyzed and compared with hospitalized ALRTI cases with single RSV infection in the same period. (1) Totally 2 895 cases were positive for at least one virus in this study in 4 371 ALRTI patients (positive rate 66.23%), in which 147 cases were positive for HCoVs infection (positive rate 3.36%). (2) Positive rates of HCoVs in each year from 2007 to 2014 were 6.11%, 3.79%, 4.69%, 4.31%, 2.38% 2.10%, 0.77% and 2.65%, respectively. The mean positive rates of HCoVs for each month from January to December were 2.53%, 2.12%, 3.63%, 6.68%, 1.53%, 3.77%, 3.92%, 3.00%, 2.15%, 5.26%, 3.01% and 2.80%. (3) Detection results of each subtypes of HCoVs in total 4 371 pediatric ALRTI patients were: 48 cases positive for HCoV-OC43(1.10%), 32 cases positive for HCoV-229E(0.73%), 25 cases positive for HCoV-NL63 (0.57%), 27 cases positive for HCoV-HKU1 (0.62%). (4) Positive rates of HCoVs infection in infection of HCoVs in this study, of which 12 cases were diagnosed as bronchopneumonia, 3 cases developed acute laryngeal obstruction, 2 cases had acute bronchial asthma attack. Common clinical manifestations included cough (14 cases), gasping (13 cases), dyspnea (9 cases), fever (6 cases), hoarseness (4 cases), laryngeal stridor (4 cases) and abnormality on chest X-ray (including fuzzy lung texture, patchy shadow and consolidation) (12 cases). (6) There were no

  1. Analgesia for acute pain

    African Journals Online (AJOL)

    human right, and therefore the aim of acute pain management is adequate pain control to achieve ... the intervention causes unacceptable side-effects, it can lead to suboptimal pain relief and potentially dire outcomes. Knowledge .... it was found in a systematic review that music therapy reduces anxiety and analgesia ...

  2. Acute cholecystitis

    OpenAIRE

    Fialkowski, Elizabeth; Halpin, Valerie; Whinney, Robb R

    2008-01-01

    Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae. About 95% of people with acute cholecystitis have gallstones.It is thought that blockage of the bile duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.

  3. Acute cholecystitis

    OpenAIRE

    Halpin, Valerie

    2014-01-01

    Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae. About 95% of people with acute cholecystitis have gallstones.It is thought that blockage of the cystic duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.

  4. Acute cholecystitis

    OpenAIRE

    Halpin, Valerie; Gupta, Aditya

    2011-01-01

    Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae. About 95% of people with acute cholecystitis have gallstones.It is thought that blockage of the bile duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.

  5. Acute inactivation of the replicative helicase in human cells triggers MCM8-9-dependent DNA synthesis

    DEFF Research Database (Denmark)

    Natsume, Toyoaki; Nishimura, Kohei; Minocherhomji, Sheroy

    2017-01-01

    DNA replication fork progression can be disrupted at difficult to replicate loci in the human genome, which has the potential to challenge chromosome integrity. This replication fork disruption can lead to the dissociation of the replisome and the formation of DNA damage. To model the events....... This RAD51/MCM8-9 axis is distinct from the recently described RAD52-dependent DNA synthesis pathway that operates in early mitosis at common fragile sites. We propose that stalled replication forks can be restarted in S phase via homologous recombination using MCM8-9 as an alternative replicative helicase....... stemming from replisome dissociation during DNA replication perturbation, we used a degron-based system for inducible proteolysis of a subunit of the replicative helicase. We show that MCM2-depleted cells activate a DNA damage response pathway and generate replication-associated DNA double-strand breaks...

  6. Metabolically protective cytokines adiponectin and fibroblast growth factor-21 are increased by acute overfeeding in healthy humans.

    Directory of Open Access Journals (Sweden)

    Leonie K Heilbronn

    Full Text Available Circulating levels of metabolically protective and adverse cytokines are altered in obese humans and rodent models. However, it is not clear whether these cytokines are altered rapidly in response to over-nutrition, or as a later consequence of the obese state.Forty sedentary healthy individuals were examined prior to and at 3 and 28 days of high fat overfeeding (+1250 kCal/day, 45% fat. Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp, adiposity, serum levels of adiponectin and fibroblast growth factor-21 (FGF21, fatty acid binding protein-4 (FABP4, lipocalin-2 and plasminogen activator factor-1 (PAI1 were assessed. Statistics were performed by repeated measures ANOVA.Overfeeding increased weight, body fat and liver fat, fasting glucose, insulin and reduced insulin sensitivity by clamp (all P <0.05. Metabolically protective cytokines, adiponectin and FGF21 were increased at day 3 of overfeeding (P ≤0.001 and adiponectin was also elevated at day 28 (P=0.001. FABP4, lipocalin-2 and PAI-1 were not changed by overfeeding at either time point.Metabolically protective cytokines, adiponectin and FGF-21, were increased by over nutrition and weight gain in healthy humans, despite increases in insulin resistance. We speculate that this was in attempt to maintain glucose homeostasis in a state of nutritional excess. PAI-I, FABP4 and lipocalin 2 were not altered by overfeeding suggesting that changes in these cytokines may be a later consequence of the obese state.www.clinicaltrials.gov (NCT00562393.

  7. Idiotype vaccines against human T cell acute lymphoblastic leukemia. I. Generation and characterization of biologically active monoclonal anti-idiotopes.

    Science.gov (United States)

    Bhattacharya-Chatterjee, M; Pride, M W; Seon, B K; Kohler, H

    1987-08-15

    A murine monoclonal anti-tumor antibody termed SN2 (Ab1), isotype IgG1-kappa, that defines a unique human T cell leukemia-associated cell-surface glycoprotein, gp37 (m.w. 37,000), was used to generate monoclonal anti-idiotype antibodies (Ab2) in syngeneic BALB/c mice. The Ab2 were screened on the basis of their binding to the F(ab')2 fragments of SN2 and not to the F(ab')2 of pooled normal BALB/c mice sera IgG1 or to an unrelated BALB/c monoclonal antibody of the same isotype. Fifteen Ab2, obtained from two fusions, were specific for the SN2 idiotope and not against isotype or allotype determinants. To find out whether these Ab2 are directed against the paratope of SN2, the binding of radiolabeled SN2 to leukemic MOLT-4 and JM cells which contain gp37 as a surface constituent was studied in the presence of these anti-idiotopes. Clone 4EA2 inhibited the binding 100% at a concentration of 50 ng and 4DC6 inhibited 90% at a concentration of 250 ng. A third clone 4DD6 gave about 50% inhibition. Similar was the inhibition of SN2 binding to insolubilized MOLT-4 antigen or cell membrane preparation. The binding of SN2 (Ab1) to 4EA2 and 4DC6 was also inhibited by semipurified preparation of gp37 antigen. These results demonstrate that at least two of the anti-idiotope antibodies are binding either at or near the binding site idiotope of SN2. Next, the purified Ab2 was used to immunize syngeneic mice to induce antibody binding to MOLT-4 cells or gp37. Sera from mice immunized with 4EA2 and 4DC6 coupled to keyhole limpet hemocyanin contained antibodies which bind to semipurified gp37 antigen and MOLT-4 cells. Immune sera inhibited the binding of iodinated Ab2 and Ab1 indicating that an anti-anti-idiotopic antibody (Ab3) in mice shares idiotopes with Ab1 (SN2). Also, the binding of iodinated Ab2 to Ab1 was inhibited by rabbit antisera specific for gp37. Collectively, these data suggest that anti-idiotype antibodies 4EA2 and 4DC6 may be useful in the generation of idiotype

  8. Expression Levels of Human Equilibrative Nucleoside Transporter 1 and Deoxycytidine Kinase Enzyme as Prognostic Factors in Patients with Acute Myeloid Leukemia Treated with Cytarabine.

    Science.gov (United States)

    Candelaria, Myrna; Corrales-Alfaro, Carmen; Gutiérrez-Hernández, Olga; Díaz-Chavez, José; Labardini-Méndez, Juan; Vidal-Millán, Silvia; Herrera, Luis A

    2016-01-01

    Cytarabine (Ara-C) is the primary drug in different treatment schemas for acute myeloid leukemia (AML) and requires the human equilibrative nucleoside transporter (hENT1) to enter cells. The deoxycytidine kinase (dCK) enzyme limits its activation rate. Therefore, decreased expression levels of these genes may influence the response rate to this drug. AML patients without previous treatment were enrolled. The expression of hENT1 and dCK genes was analyzed using RT-PCR. Clinical parameters were registered. All patients received Ara-C + doxorubicin as an induction regimen (7 + 3 schema). Descriptive statistics were used to analyze data. Uni- and multivariate analyses were performed to determine factors that influenced response and survival. Twenty-eight patients were included from January 2011 until December 2012. Median age was 36.5 years. All patients had an adequate performance status (43% with ECOG 1 and 57% with ECOG 2). Cytogenetic risk was considered unfavorable in 54% of the patients. Complete response was achieved in 53.8%. Cox regression analysis showed that a higher hENT1 expression level was the only factor that influenced response and survival. These results highly suggest that the pharmacogenetic analyses of Ara-C influx may be decisive in AML patients. © 2016 S. Karger AG, Basel.

  9. [Effect of acute exposure to microwave from mobile phone on DNA damage and repair of cultured human lens epithelial cells in vitro].

    Science.gov (United States)

    Sun, Li-xia; Yao, Ke; He, Ji-liang; Lu, De-qiang; Wang, Kai-jun; Li, Hong-wu

    2006-08-01

    To investigate the DNA damage of human lens epithelial cells (LECs) caused by acute exposure to low-power 217 Hz modulated 1.8 GHz microwave radiation and DNA repair. Cultured LECs were exposed to 217 Hz modulated 1.8 GHz microwave radiation at SAR (specific absorption rate) of 0, 1, 2, 3 and 4 W/kg for 2 hours in an sXc-1800 incubator and irradiate system. The DNA single strand breaks were detected with comet assay in sham-irradiated cells and irradiated cells incubated for varying periods: 0, 30, 60, 120 and 240 min after irradiation. Images of comets were digitized and analyzed using an Imagine-pro plus software, and the indexes used in this study were tail length (TL) and tail moment (TM). The difference in DNA-breaks between the exposure and sham exposure groups induced by 1 and 2 W/kg irradiation was not significant at every detect time (P > 0.05). As for the dosage of 3 and 4 W/kg there was difference in both group immediately after irradiation (P 0.05), and existed in 4 W/kg group. No or repairable DNA damage was observed after 2 hour irradiation of 1.8 GHz microwave on LECs when SAR DNA damages caused by 4 W/kg irradiation were irreversible.

  10. Combined treatment with fenretinide and indomethacin induces AIF-mediated, non-classical cell death in human acute T-cell leukemia Jurkat cells

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    Hojka-Osinska, Anna, E-mail: hojka@immuno.iitd.pan.wroc.pl [Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, 53-114 Wroclaw (Poland); Ziolo, Ewa, E-mail: ziolo@immuno.iitd.pan.wroc.pl [Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, 53-114 Wroclaw (Poland); Rapak, Andrzej, E-mail: rapak@immuno.iitd.pan.wroc.pl [Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, 53-114 Wroclaw (Poland)

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer The combination of fenretinide and indomethacin induces a high level of cell death. Black-Right-Pointing-Pointer Apoptotic pathway is caspase-independent. Black-Right-Pointing-Pointer Jurkat cells undergo AIF-mediated cell death. -- Abstract: Currently used cytotoxic drugs in cancer therapy have a similar mechanism of action and low specificity. Applied simultaneously, they show an additive effect with strong side effects. Clinical trials with the use of different agents in cancer therapy show that the use of these compounds alone is not very effective in fighting cancer. An alternative solution could be to apply a combination of these agents, because their combination has a synergistic effect on some cancer cells. Therefore, in our investigations we examined the effects of a synthetic retinoid-fenretinide when combined with a non-steroidal anti-inflammatory drug-indomethacin on the process of apoptosis in the acute human T-cell leukemia cell line Jurkat. We demonstrate that treatment with the combination of the tested compounds induces the death of cells, that is peculiar and combines features of apoptosis as well as non-apoptotic cell death. In detail we observed, cell membrane permeabilization, phosphatydylserine exposure, no oligonucleosomal DNA fragmentation, no caspase-3 activation, but apoptosis inducing factor (AIF) nuclear translocation. Taken together these results indicate, that Jurkat cells after treatment with a combination of fenretinide and indomethacin undergo AIF-mediated programmed cell death.

  11. NOAEL-dose of a neonicotinoid pesticide, clothianidin, acutely induce anxiety-related behavior with human-audible vocalizations in male mice in a novel environment.

    Science.gov (United States)

    Hirano, Tetsushi; Yanai, Shogo; Takada, Tadashi; Yoneda, Naoki; Omotehara, Takuya; Kubota, Naoto; Minami, Kiichi; Yamamoto, Anzu; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2018-01-05

    Neonicotinoids are novel systemic pesticides acting as agonists on the nicotinic acetylcholine receptors (nAChRs) of insects. Experimental studies have revealed that neonicotinoids pose potential risks for the nervous systems of non-target species, but the brain regions responsible for their behavioral effects remain incompletely understood. This study aimed to assess the neurobehavioral effects of clothianidin (CTD), a later neonicotinoid developed in 2001 and widely used worldwide, and to explore the target regions of neonicotinoids in the mammalian brain. A single-administration of 5 or 50mg/kg CTD to male C57BL/6N mice at or below the no-observed-adverse-effect level (NOAEL) induced an acute increase in anxiety during the elevated plus-maze test. In addition, mice in the CTD-administered group spontaneously emitted human-audible vocalizations (4-16kHz), which are behavioral signs of aversive emotions, and showed increased numbers of c-fos immunoreactive cells in the paraventricular thalamic nucleus and dentate gyrus of the hippocampus. In conclusion, mice exposed to NOAEL-dose CTD would be rendered vulnerable to a novel environment via the activation of thalamic and hippocampal regions related to stress responses. These findings should provide critical insight into the neurobehavioral effects of neonicotinoids on mammals. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Human Coronaviruses HCoV-NL63 and HCoV-HKU1 in Hospitalized Children with Acute Respiratory Infections in Beijing, China

    Directory of Open Access Journals (Sweden)

    Li-Jin Cui

    2011-01-01

    Full Text Available The human coronaviruses (HCoVs HCoV-NL63 and HCoV-HKU1 are two recently discovered coronaviruses that circulate widely and are associated with acute respiratory infections (ARI. We detected HCoV-NL63 and HCoV-HKU1 in specimens collected from May 2008 to March 2010 from patients with ARI aged <7.75 years of age attending the Beijing Children's Hospital. Thirty-two (8.4% and 57 (14.9% of 382 specimens tested positive for HCoV-NL63 and HCoV-HKU1, respectively, by real-time RT-PCR. Use of a Luminex xTAG RVP Fast kit showed that coinfection with respiratory syncytial virus and parainfluenza 3 virus was common among patients infected with either virus type. In HCoV-HKU1-infected patients, the predominant clinical symptoms were cough, fever, and expectoration. In HCoV-NL63-infected patients they were cough, fever, and rhinorrhea. Phylogenetic studies showed that the HCoV-HKU1 nucleoprotein gene was relatively conserved compared to NCBI reference sequences, while the 1ab gene of HCoV-NL63 showed more variation.

  13. High frequency of cultivable human subgroup F adenoviruses in stool samples from a paediatric population admitted to hospital with acute gastroenteritis.

    Science.gov (United States)

    Arcangeletti, Maria-Cristina; Germini, Diego; Martorana, Davide; Rodighiero, Isabella; De Conto, Flora; Medici, Maria-Cristina; Chezzi, Carlo; Calderaro, Adriana

    2014-06-01

    The family Adenoviridae consists of five genera of which the genus Mastadenovirus includes human viruses classified into 57 serotypes clustered into seven subgroups (A-G). Serotypes 40 and 41 (subgroup F) are specifically associated with childhood gastroenteritis and are the most common cause of acute gastroenteritis in young children after rotaviruses and noroviruses. Standard methods for laboratory diagnosis of adenovirus infection include electron microscopy (EM) and conventional cell culture (CCC), although it is widely considered that adenoviruses 40 and 41 are difficult to cultivate, such that their circulation is most likely underestimated. One hundred and ten faecal specimens from paediatric patients with gastroenteritis were confirmed positive for adenovirus by EM and/or CCC at the Virology Unit of the University Hospital of Parma, Italy, during the period January 2010-December 2012. They were analysed to determine the actual prevalence of adenovirus 40 and 41 in these patients using PCR and restriction endonuclease analysis, and to evaluate their ability to be cultivated in standard cell lines. The results showed a high prevalence of subgroup F (62.7 %), with serotype 41 (89.8 %) predominating over serotype 40 (10.2 %). Surprisingly, among the 75 adenoviruses isolated by CCC, 37 (49 %) belonged to subgroup F, suggesting a higher capacity of adenovirus 40 and 41 to replicate in cell culture than previously thought. PCR and restriction enzyme techniques provide an efficient means of diagnosing enteric adenoviruses correctly, including subgroup F adenovirus strains in young children with gastroenteritis. © 2014 The Authors.

  14. High prevalence of human metapneumovirus subtype B in cases presenting as severe acute respiratory illness: an experience at tertiary care hospital.

    Science.gov (United States)

    Jain, Bhawana; Singh, Ajay Kr; Dangi, Tanushree; Agarwal, Anjali; Verma, Anil Kumar; Dwivedi, Mukesh; Singh, Kaleshwar P; Jain, Amita

    2014-04-01

    A comparatively newly discovered human metapneumovirus (HMPV) has emerged as an important cause of severe acute respiratory illness (SARI), second only to respiratory syncytial virus (RSV). RSV and HMPV taxonomically belong to same family and subfamily, and their clinical presentation and seasonal distribution are also seemed to be indistinguishable. Present study was planned to know the epidemiology and prevalence of HMPV and RSV in patients presented as SARI in a tertiary care hospital. Nasopharyngeal aspirate of 440 patients fulfilling World Health Organization criteria of SARI, enrolled during a 2-year study period, were collected and tested for the presence of RSV, HMPV and their subtypes A and B by real time polymerase chain reaction along with other respiratory viruses, viz influenza A, B, parainfluenza 1, 2, 3, 4, adenovirus, measles virus and bocavirus. The demographic details, clinical profile, underlying diseases, clinical diagnosis at the time of admission and seasonal distribution were studied and analyzed statistically. Overall positivity of RSV was 14.3% (24.68% in infections. RSV and HMPV positivity was restricted to winter season. We are reporting replacement of RSV with HMPV in this population. HMPV has emerged as an important cause of SARI in children <12 years of age. Alternative predominance of RSV and HMPV is an important observation. © 2013 John Wiley & Sons Ltd.

  15. AFM study shows prominent physical changes in elasticity and pericellular layer in human acute leukemic cells due to inadequate cell-cell communication

    Science.gov (United States)

    Guz, Nataliia V.; Patel, Sapan J.; Dokukin, Maxim E.; Clarkson, Bayard; Sokolov, Igor

    2016-12-01

    Biomechanical properties of single cells in vitro or ex vivo and their pericellular interfaces have recently attracted a lot of attention as a potential biophysical (and possibly prognostic) marker of various diseases and cell abnormalities. At the same time, the influence of the cell environment on the biomechanical properties of cells is not well studied. Here we use atomic force microscopy to demonstrate that cell-cell communication can have a profound effect on both cell elasticity and its pericellular coat. A human pre-B p190BCR/ABL acute lymphoblastic leukemia cell line (ALL3) was used in this study. Assuming that cell-cell communication is inversely proportional to the distance between cells, we study ALL3 cells in vitro growing at different cell densities. ALL3 cells demonstrate a clear density dependent behavior. These cells grow very well if started at a relatively high cell density (HD, >2 × 105 cells ml-1) and are poised to grow at low cell density (LD, pathologically transformed cells. Thus, cell-cell communication must be taken into account when studying biomechanics of cells, in particular, correlating cell phenotype and its biophysical properties.

  16. Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cell populations

    Science.gov (United States)

    Ye, Lei; Chang, Ying-Hua; Xiong, Qiang; Zhang, Pengyuan; Zhang, Liying; Somasundaram, Porur; Lepley, Mike; Swingen, Cory; Su, Liping; Wendel, Jacqueline S.; Guo, Jing; Jang, Albert; Rosenbush, Daniel; Greder, Lucas; Dutton, James R.; Zhang, Jianhua; Kamp, Timothy J.; Kaufman, Dan S.; Ge, Ying; Zhang, Jianyi

    2014-01-01

    Summary Human induced pluripotent stem cells (hiPSCs) hold promise for myocardial repair following injury, but preclinical studies in large animal models are required to determine optimal cell preparation and delivery strategies to maximize functional benefits and to evaluate safety. Here, we utilized a porcine model of acute myocardial infarction (MI) to investigate the functional impact of intramyocardial transplantation of hiPSC-derived cardiomyocytes, endothelial cells, and smooth muscle cells, in combination with a 3D fibrin patch loaded with insulin growth factor (IGF)-encapsulated microspheres. hiPSC-derived cardiomyocytes integrated into host myocardium and generated organized sarcomeric structures, and endothelial and smooth muscle cells contributed to host vasculature. Tri-lineage cell transplantation significantly improved left ventricular function, myocardial metabolism, and arteriole density, while reducing infarct size, ventricular wall stress and apoptosis without inducing ventricular arrhythmias. These findings in a large animal MI model highlight the potential of utilizing hiPSC-derived cells for cardiac repair. PMID:25479750

  17. Human mesenchymal precursor cells (Stro-1⁺) from spinal cord injury patients improve functional recovery and tissue sparing in an acute spinal cord injury rat model.

    Science.gov (United States)

    Hodgetts, Stuart I; Simmons, Paul J; Plant, Giles W

    2013-01-01

    This study aimed to determine the potential of purified (Stro-1(+)) human mesenchymal precursor cells (hMPCs) to repair the injured spinal cord (SC) after transplantation into T-cell-deficient athymic RNU nude rats following acute moderate contusive spinal cord injury (SCI). hMPCs were isolated from the bone marrow (BM) stroma of SCI patients and transplanted as a suspension graft in medium [with or without immunosuppression using cyclosporin A (CsA)]. Extensive anatomical analysis shows statistically significant improvement in functional recovery, tissue sparing, and cyst reduction. We provide quantitative assessment of supraspinal projections in combination with functional outcomes. hMPC-transplanted animals consistently achieved mean BBB scores of 15 at 8 weeks post injury. Quantitative histological staining revealed that graft-recipient animals possessed more intact spinal tissue and reduced cyst formation than controls. Fluorogold (FG) retrograde tracing revealed sparing/regeneration of supraspinal and local propriospinal axonal pathways, but no statistical differences were observed compared to controls. Immunohistochemical analysis revealed increased serotonergic (5-HT) and sensory (CGRP) axonal growth within and surrounding transplanted donor hMPCs 2 weeks posttransplantation, but no evidence of hMPC transdifferentiation was seen. Although hMPCs initially survive at 2 weeks posttransplantation, their numbers were dramatically reduced and no cells were detected at 8 weeks posttransplantation using retroviral/lentiviral GFP labeling and a human nuclear antigen (HNA) antibody. Additional immunosuppression with CsA did not improve hMPC survival or their ability to promote tissue sparing or functional recovery. We propose Stro-1(+)-selected hMPCs provide (i) a reproducible source for stem cell transplantation for SC therapy and (ii) a positive host microenvironment resulting in the promotion of tissue sparing/repair that subsequently improves behavioral outcomes

  18. The apoptotic mechanism of action of the sphingosine kinase 1 selective inhibitor SKI-178 in human acute myeloid leukemia cell lines.

    Science.gov (United States)

    Dick, Taryn E; Hengst, Jeremy A; Fox, Todd E; Colledge, Ashley L; Kale, Vijay P; Sung, Shen-Shu; Sharma, Arun; Amin, Shantu; Loughran, Thomas P; Kester, Mark; Wang, Hong-Gang; Yun, Jong K

    2015-03-01

    We previously developed SKI-178 (N'-[(1E)-1-(3,4-dimethoxyphenyl)ethylidene]-3-(4-methoxxyphenyl)-1H-pyrazole-5-carbohydrazide) as a novel sphingosine kinase-1 (SphK1) selective inhibitor and, herein, sought to determine the mechanism-of-action of SKI-178-induced cell death. Using human acute myeloid leukemia (AML) cell lines as a model, we present evidence that SKI-178 induces prolonged mitosis followed by apoptotic cell death through the intrinsic apoptotic cascade. Further examination of the mechanism of action of SKI-178 implicated c-Jun NH2-terminal kinase (JNK) and cyclin-dependent protein kinase 1 (CDK1) as critical factors required for SKI-178-induced apoptosis. In cell cycle synchronized human AML cell lines, we demonstrate that entry into mitosis is required for apoptotic induction by SKI-178 and that CDK1, not JNK, is required for SKI-178-induced apoptosis. We further demonstrate that the sustained activation of CDK1 during prolonged mitosis, mediated by SKI-178, leads to the simultaneous phosphorylation of the prosurvival Bcl-2 family members, Bcl-2 and Bcl-xl, as well as the phosphorylation and subsequent degradation of Mcl-1. Moreover, multidrug resistance mediated by multidrug-resistant protein1 and/or prosurvival Bcl-2 family member overexpression did not affect the sensitivity of AML cells to SKI-178. Taken together, these findings highlight the therapeutic potential of SKI-178 targeting SphK1 as a novel therapeutic agent for the treatment of AML, including multidrug-resistant/recurrent AML subtypes. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  19. Acute effects of hyperinsulinemia and hyperglycemia on vascular inflammatory biomarkers and endothelial function in overweight and obese humans

    Science.gov (United States)

    Perkins, Jennifer M.; Joy, Nino G.; Tate, Donna B.

    2015-01-01

    We investigated the separate and combined effects of hyperglycemia and hyperinsulinemia on markers of endothelial function, proinflammatory and proatherothrombotic responses in overweight/obese nondiabetic humans. Twenty-two individuals (13 F/9 M, BMI 30.1 ± 4.1 kg/m2) were studied during four randomized, single-blind protocols. The pancreatic clamp technique was combined with 4-h glucose clamps consisting of either 1) euinsulinemia-euglycemia, 2) euinsulinemia-hyperglycemia, 3) hyperinsulinemia-hyperglycemia, or 4) hyperinsulinemia-euglycemia. Insulin levels were higher (998 ± 66 vs. 194 ± 22 pmol/l) during hyperinsulinemia compared with euinsulinemia. Glucose levels were 11.1 mmol/l during hyperinsulinemia compared with 5.1 ± 0.1 mmol/l during euglycemia. VCAM, ICAM, P-selectin, E-selectin, IL-6, adiponectin, and PAI-1 responses were all increased (P hyperglycemia compared with other protocols. Hyperinsulinemia in the presence of hyperglycemia prevented the increase in proinflammatory and proatherothrombotic markers while also normalizing vascular endothelial function. We conclude that 4 h of moderate hyperglycemia can result in increases of proinflammatory markers (ICAM, VCAM, IL-6, E-selectin), platelet activation (P-selectin), reduced fibrinolytic balance (increased PAI-1), and disordered endothelial function in a group of obese and overweight individuals. Hyperinsulinemia prevents the actions of moderate hyperglycemia to reduce endothelial function and increase proinflammatory and proatherothrombotic markers. PMID:26015434

  20. Acute effects of exposure to vapours of standard and dearomatized white spirits in humans. 1. Dose-finding study.

    Science.gov (United States)

    Ernstgård, Lena; Lind, Birger; Johanson, Gunnar

    2009-04-01

    A move from 'standard' white spirit (stdWS, 15-20% aromatics) to low-aromatic or dearomatized white spirit (deWS) has been seen, as the latter are considered to carry a smaller risk of health effects. However, data on health risks of deWS on humans are sparse. The aim of this dose-finding study was to identify thresholds of irritation and central nervous system (CNS) effects of the two types of white spirit, as a basis for more detailed studies. Four female and four male healthy volunteers rated symptoms related to irritation, smell and CNS effects on a 0-100 mm visual analogue scale while exposed to increasing levels of deWS or stdWS in eight 10 min steps from 0.5 to 600 mg m(-3). Combined ratings of questions related to irritation revealed statistically significant increases compared with pre-exposure ratings at 50 mg m(-3) and higher exposures. The ratings increased in a dose-dependent fashion, the medians reaching 'somewhat' for stdWS and 'hardly at all' for deWS. Higher ratings of irritation were found during exposure to stdWS compared with deWS, reaching significance only at 500 mg m(-3). The combined ratings of CNS effects reached 'hardly at all', and were significantly increased only for stdWS at 500 and 600 mg m(-3).

  1. Effect of an acute consumption of a moderate amount of ethanol on plasma endocannabinoid levels in humans.

    Science.gov (United States)

    Feuerecker, Matthias; Hauer, Daniela; Gresset, Theresa; Lassas, Simone; Kaufmann, Ines; Vogeser, Michael; Briegel, Josef; Hornuss, Cyrill; Choukèr, Alexander; Schelling, Gustav

    2012-01-01

    Animal experiments have shown that the endocannabinoid system (ECS) plays an important role in the regulation of ethanol intake. We investigated these effects in healthy volunteers who consumed a moderate amount of ethanol (red wine) and measured plasma levels of the endocannabinoids (ECs) anandamide (AEA) and 2-arachidonoylglycerol (2-AG) to test whether alcohol consumption influences the ECS in humans. Grape juice or plain non-sparkling water served as non-alcoholic control liquids. In total, 55 adults were enrolled in this study and assigned to one of three groups drinking either 250 ml of red wine (28.0 g of ethanol, consumption. AEA had its maximal decline at 20 min (from 0.23 ± 0.12 to 0.18 ± 0.07 ng/ml, P consumption of a moderate amount of red wine reduces plasma AEA and 2-AG concentrations, whereas the volume and caloric equivalent of the sugar containing, non-alcoholic liquid grape juice does not affect plasma ECs. Plain water has a differential effect on the ECS by reducing 2-AG concentrations without affecting AEA.

  2. Rationale and Design of a Clinical Trial to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction: The Randomized Multicenter Double-Blind Controlled CAREMI Trial (Cardiac Stem Cells in Patients With Acute Myocardial Infarction).

    Science.gov (United States)

    Sanz-Ruiz, Ricardo; Casado Plasencia, Ana; Borlado, Luis R; Fernández-Santos, María Eugenia; Al-Daccak, Reem; Claus, Piet; Palacios, Itziar; Sádaba, Rafael; Charron, Dominique; Bogaert, Jan; Mulet, Miguel; Yotti, Raquel; Gilaberte, Immaculada; Bernad, Antonio; Bermejo, Javier; Janssens, Stefan; Fernández-Avilés, Franciso

    2017-06-23

    Stem cell therapy has increased the therapeutic armamentarium in the fight against ischemic heart disease and heart failure. The administration of exogenous stem cells has been investigated in patients suffering an acute myocardial infarction, with the final aim of salvaging jeopardized myocardium and preventing left ventricular adverse remodeling and functional deterioration. However, phase I and II clinical trials with autologous and first-generation stem cells have yielded inconsistent benefits and mixed results. In the search for new and more efficient cellular regenerative products, interesting cardioprotective, immunoregulatory, and cardioregenerative properties have been demonstrated for human cardiac stem cells. On the other hand, allogeneic cells show several advantages over autologous sources: they can be produced in large quantities, easily administered off-the-shelf early after an acute myocardial infarction, comply with stringent criteria for product homogeneity, potency, and quality control, and may exhibit a distinctive immunologic behavior. With a promising preclinical background, CAREMI (Cardiac Stem Cells in Patients With Acute Myocardial Infarction) has been designed as a double-blind, 2:1 randomized, controlled, and multicenter clinical trial that will evaluate the safety, feasibility, and efficacy of intracoronary delivery of allogeneic human cardiac stem cell in 55 patients with large acute myocardial infarction, left ventricular dysfunction, and at high risk of developing heart failure. This phase I/II clinical trial represents a novel experience in humans with allogeneic cardiac stem cell in a rigorously imaging-based selected group of acute myocardial infarction patients, with detailed safety immunologic assessments and magnetic resonance imaging-based efficacy end points. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02439398. © 2017 American Heart Association, Inc.

  3. Neuro-Epigenetic Indications of Acute Stress Response in Humans: The Case of MicroRNA-29c.

    Directory of Open Access Journals (Sweden)

    Sharon Vaisvaser

    Full Text Available Stress research has progressively become more integrative in nature, seeking to unfold crucial relations between the different phenotypic levels of stress manifestations. This study sought to unravel stress-induced variations in expression of human microRNAs sampled in peripheral blood mononuclear cells and further assess their relationship with neuronal and psychological indices. We obtained blood samples from 49 healthy male participants before and three hours after performing a social stress task, while undergoing functional magnetic resonance imaging (fMRI. A seed-based functional connectivity (FC analysis was conducted for the ventro-medial prefrontal cortex (vmPFC, a key area of stress regulation. Out of hundreds of microRNAs, a specific increase was identified in microRNA-29c (miR-29c expression, corresponding with both the experience of sustained stress via self-reports, and alterations in vmPFC functional connectivity. Explicitly, miR-29c expression levels corresponded with both increased connectivity of the vmPFC with the anterior insula (aIns, and decreased connectivity of the vmPFC with the left dorso-lateral prefrontal cortex (dlPFC. Our findings further revealed that miR-29c mediates an indirect path linking enhanced vmPFC-aIns connectivity during stress with subsequent experiences of sustained stress. The correlative patterns of miR-29c expression and vmPFC FC, along with the mediating effects on subjective stress sustainment and the presumed localization of miR-29c in astrocytes, together point to an intriguing assumption; miR-29c may serve as a biomarker in the blood for stress-induced functional neural alterations reflecting regulatory processes. Such a multi-level model may hold the key for future personalized intervention in stress psychopathology.

  4. The acute effect of fludrocortisone on basal and hCRH-stimulated hypothalamic--pituitary--adrenal (HPA) axis in humans.

    Science.gov (United States)

    Karamouzis, Ioannis; Berardelli, Rita; Marinazzo, Elisa; D'Angelo, Valentina; Zinnà, Domenico; Minetto, Marco Alessandro; Zichi, Clizia; Fussotto, Beatrice; Giordano, Roberta; Ghigo, Ezio; Arvat, Emanuela

    2013-09-01

    Mineralocorticoid receptors (MR) in the hippocampus display an important role in the control of hypothalamic-pituitary-adrenal (HPA)-axis, mediating the "proactive"-feedback of glucocorticoids. Fludrocortisone (FC), a potent MR agonist, has been shown to decrease HPA activity through a mechanism placed at hippocampal level. In order to clarify the effects of MR agonism on HPA function in humans, we studied the effects of FC, in a dose-related manner, on both basal and CRH-stimulated HPA axis during the quiescent phase. 8 young women were studied. ACTH, cortisol and aldosterone levels were evaluated every 15', from 1600 to 2000 hours, in randomized sessions: (1) placebo p.o. + placebo i.v., (2) 0.3 mg FC p.o. + placebo, (3) 0.1 mg FC. + placebo, (4) 0.075 mg FC + placebo, (5) 0.05 mg FC + placebo, (6) placebo + hCRH (2.0 μg/kg iv-bolus), (7) 0.3 mg FC + hCRH, (8) 0.1 mg FC + hCRH, (9) 0.075 mg FC + hCRH, (10) 0.05 mg FC + hCRH. FC induced a dose-related trend toward a further decrease of the ACTH and cortisol levels, while it showed a significant and dose-dependent inhibition of the hormonal response to hCRH (p HPA activity. These data suggest a possible hypophysial MR-mediated inhibiting effect of FC, although its pituitary glucocorticoid-mediated effect cannot be excluded. The interplay between fludrocortisone and hypophysial glucocorticoid receptors needs to be clarified in order to define better the clinical consequences of the hormonal replacement therapy of patients with primary adrenal insufficiency.

  5. Bronchitis (acute)

    OpenAIRE

    Wark, Peter

    2015-01-01

    Acute bronchitis affects more than 40 in 1000 adults per year in the UK. The causes are usually considered to be infective, but only around half of people have identifiable pathogens.The role of smoking or environmental tobacco smoke inhalation in predisposing to acute bronchitis is unclear.One third of people may have longer-term symptoms or recurrence.

  6. Acute nierschade

    NARCIS (Netherlands)

    Hageman, D.; Kooman, J.P.; Lance, M.D.; van Heurn, L.W.E.; Snoeijs, M.G.

    2012-01-01

    - 'Acute kidney injury' is modern terminology for a sudden decline in kidney function, and is defined by the RIFLE classification (RIFLE is an acronym for Risk, Injury, Failure, Loss and End-stage kidney disease).- Acute kidney injury occurs as a result of the combination of re