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Larval development, stages and an international comparison of husbandry parameters of the Vietnamese Mossy Frog Theloderma corticale (Boulenger, 1903) (Anura: Rhacophoridae)
A. Rauhaus,A. Gawor,R.G.B. Perl,S. Scheld
Asian Journal of Conservation Biology , 2012,
Abstract: We describe the larval development and stages of the locally threatened Vietnamese Mossy Frog Theloderma corticale, which is endemic to northern Vietnam. Diagnostic morphological characters are provided for Gosner (1960) larval stages 1-46. This is to our knowledge the first larval staging for the rhacophorid anuran genus Theloderma in general. As guideline for further breeding engagement with Theloderma representatives in an international scale, based on the species T. corticale as husbandry analogue, we further oppose larval development, captive reproduction and husbandry management both achieved under tropical conditions at the Amphibian breeding station of the Institute of Ecology and Biological Resources in Hanoi (Vietnam), and in Europe, at the amphibian breeding unit at Cologne Zoo (Germany). Observed ovipositions at Cologne Zoo took place from March to September and were initiated after increase of temperatures and humidity (increased spraying) subsequent to a hibernation phase in combination with raised water levels. The developmental time observed for T. corticale at 20°C was about 4.5 months. For providing a recent captive management overview, we furthermore compare our husbandry experiences and data on the reproductive biology of T. corticale with data from the literature.
Eficácia do moxalactam no tratamento de meningites purulentas causadas por Haemophilus infuenzae e Neisseria meningitidis
Silva, Hagamenon R. da;Costa, Yara Arag?o;Santos, Luiz Carlos S.;Costa, Everaldo;Freedman, John;Hoffman, Stephen;Scheld, Michael;Sand, Merle;Rocha, Heonir;
Memórias do Instituto Oswaldo Cruz , 1984, DOI: 10.1590/S0074-02761984000100002
Abstract: the clinical efficacy and safety of moxalactam in purulent bacterial meningitis in children caused by h. influenzae (27 patients) and n. meningitidis (6 patients) was tested in a randon uncontrolled study. clinical response was considered excelent, with cure of 32 of 33 patients. high levels of moxalactam were achieved in the blood and cerebro-spinal fluid, with concentrations largely exceeding the minimum bacterial concentration (mic) for the infecting organisms. tolerance was considered good, with only transient increases of transaminases and alkaline phosphatase in some patients; also, one patient developed a wound hematoma possibly related to moxalactam therapy.
Tratamiento de la meningitis bacteriana
Vincent J. Quagliarello,W. Michael Scheld
Revista Cubana de Medicina , 1998,
Abstract:
An A2A adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models
Christopher C Moore, Edward N Martin, Grace H Lee, Tom Obrig, Joel Linden, W Michael Scheld
BMC Infectious Diseases , 2008, DOI: 10.1186/1471-2334-8-141
Abstract: Sepsis was induced in mice by intraperitoneal inoculation of live bacteria (Escherichia coli or Staphylococcus aureus) or lipopolysaccharide (LPS). Mice inoculated with live bacteria were treated with an A2A AR agonist (ATL313) or phosphate buffered saline (PBS), with or without the addition of a dose of ceftriaxone. LPS inoculated mice were treated with ATL313 or PBS. Serum cytokines and chemokines were measured sequentially at 1, 2, 4, 8, and 24 hours after LPS was administered. In survival studies, mice were followed until death or for 7 days.There was a significant survival benefit in mice infected with live E. coli (100% vs. 20%, p = 0.013) or S. aureus (60% vs. 20%, p = 0.02) when treated with ATL313 in conjunction with an antibiotic versus antibiotic alone. ATL313 also improved survival from endotoxic shock when compared to PBS treatment (90% vs. 40%, p = 0.005). The serum concentrations of TNF-α, MIP-1α, MCP-1, IFN-γ, and IL-17 were decreased by ATL313 after LPS injection (p < 0.05). Additionally, ATL313 increased the concentration of IL-10 under the same conditions (p < 0.05). Circulating white blood cell concentrations were higher in ATL313 treated animals (p < 0.01).Further studies are warranted to determine the clinical utility of ATL313 as a novel treatment for sepsis.Approximately 900,000 cases of sepsis occur annually in the United States, causing roughly 210,000 deaths and costing almost 17 billion dollars [1]. The overwhelming inflammation that occurs along with infection during sepsis has been the target of several therapeutic interventions [2]. Unfortunately, despite successful treatment in animal models, antibody neutralization of individual components of this inflammation has not proved beneficial for the majority of patients in clinical sepsis trials [3].Tissue hypoxia, as occurs in sepsis, enhances breakdown of adenosine triphosphate (ATP) to adenosine monophosphate (AMP), which is then dephosphorylated by the cytosolic 5'nucloeotidase to aden
Toll-Like Receptor 4 Stimulation before or after Streptococcus pneumoniae Induced Sepsis Improves Survival and Is Dependent on T-Cells
Edgar Musie, Christopher C. Moore, Edward N. Martin, W. Michael Scheld
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0086015
Abstract: Introduction Endotoxin tolerance improves outcomes from gram negative sepsis but the underlying mechanism is not known. We determined if endotoxin tolerance before or after pneumococcal sepsis improved survival and the role of lymphocytes in this protection. Methods Mice received lipopolysaccharide (LPS) or vehicle before or after a lethal dose of Streptococcus pneumoniae. Survival, quantitative bacteriology, liver function, and cytokine concentrations were measured. We confirmed the necessity of Toll-like receptor 4 (TLR4) for endotoxin tolerance using C3H/HeN (TLR4 replete) and C3H/HeJ (TLR4 deficient) mice. The role of complement was investigated through A/J mice deficient in C5 complement. CBA/CaHN-Btkxid//J mice with dysfunctional B cells and Rag-1 knockout (KO) mice deficient in T and B cells delineated the role of lymphocytes. Results Endotoxin tolerance improved survival from pneumococcal sepsis in mice with TLR4 that received LPS pretreatment or posttreatment. Survival was associated with reduced bacterial burden and serum cytokine concentrations. Death was associated with abnormal liver function and blood glucose concentrations. Endotoxin tolerance improved survival in A/J and CBA/CaHN-Btkxid//J mice but not Rag-1 KO mice. Conclusions TLR4 stimulation before or after S. pneumoniae infection improved survival and was dependent on T-cells but did not require an intact complement cascade or functional B cells.
Cardiopulmonary Bypass during Cardiac Surgery Modulates Systemic Inflammation by Affecting Different Steps of the Leukocyte Recruitment Cascade
Jan Rossaint, Christian Berger, Hugo Van Aken, Hans H. Scheld, Peter K. Zahn, Andreas Rukosujew, Alexander Zarbock
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045738
Abstract: Background It is known that the use of a cardiopulmonary bypass (CPB) during cardiac surgery leads to leukocyte activation and may, among other causes, induce organ dysfunction due to increased leukocyte recruitment into different organs. Leukocyte extravasation occurs in a cascade-like fashion, including capturing, rolling, adhesion, and transmigration. However, the molecular mechanisms of increased leukocyte recruitment caused by CPB are not known. This clinical study was undertaken in order to investigate which steps of the leukocyte recruitment cascade are affected by the systemic inflammation during CPB. Methods We investigated the effects of CPB on the different steps of the leukocyte recruitment cascade in whole blood from healthy volunteers (n = 9) and patients undergoing cardiac surgery with the use of cardiopulmonary bypass (n = 7) or in off-pump coronary artery bypass-technique (OPCAB, n = 9) by using flow chamber experiments, transmigration assays, and biochemical analysis. Results CPB abrogated selectin-induced slow leukocyte rolling on E-selectin/ICAM-1 and P-selectin/ICAM-1. In contrast, chemokine-induced arrest and transmigration was significantly increased by CPB. Mechanistically, the abolishment of slow leukocyte rolling was due to disturbances in intracellular signaling with reduced phosphorylation of phospholipase C (PLC) γ2, Akt, and p38 MAP kinase. Furthermore, CPB induced an elevated transmigration which was caused by upregulation of Mac-1 on neutrophils. Conclusion These data suggest that CPB abrogates selectin-mediated slow leukocyte rolling by disturbing intracellular signaling, but that the clinically observed increased leukocyte recruitment caused by CPB is due to increased chemokine-induced arrest and transmigration. A better understanding of the underlying molecular mechanisms causing systemic inflammation after CPB may aid in the development of new therapeutic approaches.
Enrichment of HIV-1 Subtype AD Recombinants in a Ugandan Cohort of Severely Septic Patients
Najah I. Doka, Shevin T. Jacob, Patrick Banura, Christopher C. Moore, David Meya, Harriet Mayanja-Kizza, Steven J. Reynolds, W. Michael Scheld, Wen Yuan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048356
Abstract: Background Several population-wide HIV-1 subtype distribution studies in Uganda have evaluated relatively healthy clinic patients. Given the differences in HIV-1 disease progression based on subtype, we examined HIV-1 subtype distribution and disease outcomes among hospitalized patients with severe sepsis. Methods Patients with severe sepsis were enrolled at two hospitals in Uganda. Data collected included demographics, Karnofsky scores, highly active antiretroviral therapy (HAART) use, HIV-1 serostatus, CD4+ T cell concentration, whole blood lactate concentration, and blood cultures. HIV-1 subtypes were determined by sequencing parts of the gag and env genes, followed by phylogenetic analysis. Results Of the 267 patients evaluated, 228 (85.4%) were HIV infected. The predominant HIV-1 subtypes were A (46%), D (17%), and AD recombinants (30%). HIV-1 subtypes B, C, and other recombinants were uncommon. Patients infected with HIV-1 subtypes A, D and AD viruses were similar in demographics, CD4+ T cell concentration, HAART use, Karnofsky scores, whole blood lactate concentration, and positive blood cultures. There was no difference in 30-day mortality from severe sepsis between the 3 groups (p = 0.99). Conclusion A high proportion of HIV-1 subtypes A and AD recombinants was observed in this cohort of severely septic patients. The proportion of AD recombinants was higher in this cohort than in previous cohorts of Ugandan HIV-1 patients. No difference in baseline demographics, clinical factors or 30-day mortality was seen across HIV-subtypes.
Systematic Analysis of Gene Expression Differences between Left and Right Atria in Different Mouse Strains and in Human Atrial Tissue
Peter C. Kahr, Ilaria Piccini, Larissa Fabritz, Boris Greber, Hans Sch?ler, Hans H. Scheld, Andreas Hoffmeier, Nigel A. Brown, Paulus Kirchhof
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0026389
Abstract: Background Normal development of the atria requires left-right differentiation during embryonic development. Reduced expression of Pitx2c (paired-like homeodomain transcription factor 2, isoform c), a key regulator of left-right asymmetry, has recently been linked to atrial fibrillation. We therefore systematically studied the molecular composition of left and right atrial tissue in adult murine and human atria. Methods We compared left and right atrial gene expression in healthy, adult mice of different strains and ages by employing whole genome array analyses on freshly frozen atrial tissue. Selected genes with enriched expression in either atrium were validated by RT-qPCR and Western blot in further animals and in shock-frozen left and right atrial appendages of patients undergoing open heart surgery. Results We identified 77 genes with preferential expression in one atrium that were common in all strains and age groups analysed. Independent of strain and age, Pitx2c was the gene with the highest enrichment in left atrium, while Bmp10, a member of the TGFβ family, showed highest enrichment in right atrium. These differences were validated by RT-qPCR in murine and human tissue. Western blot showed a 2-fold left-right concentration gradient in PITX2 protein in adult human atria. Several of the genes and gene groups enriched in left atria have a known biological role for maintenance of healthy physiology, specifically the prevention of atrial pathologies involved in atrial fibrillation, including membrane electrophysiology, metabolic cellular function, and regulation of inflammatory processes. Comparison of the array datasets with published array analyses in heterozygous Pitx2c+/? atria suggested that approximately half of the genes with left-sided enrichment are regulated by Pitx2c. Conclusions Our study reveals systematic differences between left and right atrial gene expression and supports the hypothesis that Pitx2c has a functional role in maintaining “leftness” in the atrium in adult murine and human hearts.
Severe Sepsis in Two Ugandan Hospitals: a Prospective Observational Study of Management and Outcomes in a Predominantly HIV-1 Infected Population
Shevin T. Jacob,Christopher C. Moore,Patrick Banura,Relana Pinkerton,David Meya,Pius Opendi,Steven J. Reynolds,Nathan Kenya-Mugisha,Harriet Mayanja-Kizza,W. Michael Scheld
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0007782
Abstract: Sepsis likely contributes to the high burden of infectious disease morbidity and mortality in low income countries. Data regarding sepsis management in sub-Saharan Africa are limited. We conducted a prospective observational study reporting the management and outcomes of severely septic patients in two Ugandan hospitals. We describe their epidemiology, management, and clinical correlates for mortality.
Training needs assessment for clinicians at antiretroviral therapy clinics: evidence from a national survey in Uganda
Ibrahim M Lutalo, Gisela Schneider, Marcia R Weaver, Jessica H Oyugi, Lydia Sebuyira, Richard Kaye, Frank Lule, Elizabeth Namagala, W Scheld, Keith PWJ McAdam, Merle A Sande
Human Resources for Health , 2009, DOI: 10.1186/1478-4491-7-76
Abstract: The Infectious Diseases Institute, in collaboration with the Ugandan Ministry of Health, surveyed health professionals and heads of antiretroviral therapy clinics at a stratified random sample of 44 health facilities accredited to provide this therapy. A sample of 265 doctors, clinical officers, nurses and midwives reported on tasks they performed, previous human immunodeficiency virus training, and self-assessment of knowledge of human immunodeficiency virus and antiretroviral therapy. Heads of the antiretroviral therapy clinics reported on clinic characteristics.Thirty of 33 doctors (91%), 24 of 40 clinical officers (60%), 16 of 114 nurses (14%) and 13 of 54 midwives (24%) who worked in accredited antiretroviral therapy clinics reported that they prescribed this therapy (p < 0.001). Sixty-four percent of the people who prescribed antiretroviral therapy were not doctors. Among professionals who prescribed it, 76% of doctors, 62% of clinical officers, 62% of nurses and 51% of midwives were trained in initiating patients on antiretroviral therapy (p = 0.457); 73%, 46%, 50% and 23%, respectively, were trained in monitoring patients on the therapy (p = 0.017). Seven percent of doctors, 42% of clinical officers, 35% of nurses and 77% of midwives assessed that their overall knowledge of antiretroviral therapy was lower than good (p = 0.001).Training initiatives should be an integral part of the support for task shifting and ensure that antiretroviral therapy is used correctly and that toxicity or drug resistance do not reverse accomplishments to date.Considerable progress continues towards increasing access to anti-retroviral therapy (ART) in resource-limited settings. WHO, UNAIDS and UNICEF recently estimated that 2.12 million people have access to ART in sub-Saharan Africa, or 30% of people with HIV living there who need ART [1]. These accomplishments required training of health professionals, among other efforts to strengthen health systems. For example, the United St
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