Mechanisms controlling anaemia in Trypanosoma congolense infected mice.

Trypanosoma congolense are extracellular protozoan parasites of the blood stream of artiodactyls and are one of the main constraints on cattle production in Africa. In cattle, anaemia is the key feature of disease and persists after parasitaemia has declined to low or undetectable levels, but treatment to clear the parasites usually resolves the anaemia. The progress of anaemia after Trypanosoma congolense infection was followed in three mouse strains. Anaemia developed rapidly in all three strains until the peak of the first wave of parasitaemia. This was followed by a second phase, characterized by slower progress to severe anaemia in C57BL/6, by slow recovery in surviving A/J and a rapid recovery in BALB/c. There was no association between parasitaemia and severity of anaemia. Furthermore, functional T lymphocytes are not required for the induction of anaemia, since suppression of T cell activity with Cyclosporin A had neither an effect on the course of infection nor on anaemia. Expression of genes involved in erythropoiesis and iron metabolism was followed in spleen, liver and kidney tissues in the three strains of mice using microarrays. There was no evidence for a response to erythropoietin, consistent with anaemia of chronic disease, which is erythropoietin insensitive. However, the expression of transcription factors and genes involved in erythropoiesis and haemolysis did correlate with the expression of the inflammatory cytokines Il6 and Ifng. The innate immune response appears to be the major contributor to the inflammation associated with anaemia since suppression of T cells with CsA had no observable effect. Several transcription factors regulating haematopoiesis, Tal1, Gata1, Zfpm1 and Klf1 were expressed at consistently lower levels in C57BL/6 mice suggesting that these mice have a lower haematopoietic capacity and therefore less ability to recover from haemolysis induced anaemia after infection

Trypanosoma vivax Infections: Pushing Ahead with Mouse Models for the Study of Nagana. II. Immunobiological Dysfunctions

Trypanosoma vivax is the main species involved in trypanosomosis, but very little is known about the immunobiology of the infective process caused by this parasite. Recently we undertook to further characterize the main parasitological, haematological and pathological characteristics of mouse models of T. vivax infection and noted severe anemia and thrombocytopenia coincident with rising parasitemia. To gain more insight into the organism's immunobiology, we studied lymphocyte populations in central (bone marrow) and peripherical (spleen and blood) tissues following mouse infection with T. vivax and showed that the immune system apparatus is affected both quantitatively and qualitatively. More precisely, after an initial increase that primarily involves CD4+ T cells and macrophages, the number of splenic B cells decreases in a step-wise manner. Our results show that while infection triggers the activation and proliferation of Hematopoietic Stem Cells, Granulocyte-Monocyte, Common Myeloid and Megacaryocyte Erythrocyte progenitors decrease in number in the course of the infection. An in-depth analysis of B-cell progenitors also indicated that maturation of pro-B into pre-B precursors seems to be compromised. This interferes with the mature B cell dynamics and renewal in the periphery. Altogether, our results show that T. vivax induces profound immunological alterations in myeloid and lymphoid progenitors which may prevent adequate control of T. vivax trypanosomosis

Evaluation of clinical signs, parasitemia, hematologic and biochemical changes in cattle experimentally infected with Trypanosoma vivax

Abstract Infections by Trypanosoma vivax cause great losses to livestock in Africa and Central and South Americas. Outbreaks due this parasite have been occurred with increasing frequency in Brazil. Knowledge of changes caused byT. vivax during the course of this disease can be of great diagnostic value. Thus, clinical signs, parasitemia, hematologic and biochemical changes of cattle experimentally infected by this hemoparasite were evaluated. Two distinct phases were verified during the infection – an acute phase where circulating parasites were seen and then a chronic phase where fluctuations in parasitemia were detected including aparasitemic periods. A constant reduction in erythrocytes, hemoglobin and packed cell volume (PVC) were observed. White blood cells (WBC) showed pronounced changes such as severe neutropenia and lymphopenia during the acute phase of the illness. Decreases in cholesterol, albumin, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and increases in glucose, globulin, protein, and alkaline phosphatase (ALP) were observed. The “Lins” isolate of T. vivax showed pathogenicity for cattle, and intense parasitemia was detected in the early stages of infection. Circulating parasites were detected for about two months. The most evident laboratory abnormalities were found in WBC parameters, including thrombocytopenia

A Retrospective Analysis of Primary Tumour Histology and Survival in Breast Cancer Patients Developing Symptomatic Brain Metastases Treated with Whole Brain Radiotherapy (WBRT) at Mount Vernon Cancer Centre (MVCC).

Abstract Background: The purpose of this study was to determine the influence of primary tumour histology on survival following WBRT for brain metastases in patients with breast cancer.Methods: From treatment records we identified 294 patients with brain metastases and a diagnosis of primary breast cancer who were treated with WBRT at MVCC from January 2000 until December 2008. We obtained information from case notes and original pathology reports regarding TNM staging and receptor status: Estrogen (ER), progesterone (PR) and human epidermal growth factor receptor-2 (HER-2). Dates of diagnosis and death were sourced from records at MVCC, the Thames Cancer Registry and GP practices.Results: We obtained receptor status, TNM staging and dates of death for 294 patients; 19 were excluded as date of death could not be verified. The dates of primary diagnosis for the study cohort ranged from 1983 to 2008. The median age at diagnosis was 52 (range 24-81, interquartile range 42-62).Analysis of age at primary diagnosis expressed as &amp;lt; 50 or ≥ 50 demonstrated improved survival in the younger age group (HR 0.64 95% CI 0.50-0.83). Time to brain relapse amongst patients receiving WBRT was not related to initial tumour size (p=0.8) but was related to the number of affected nodes (reduced by 9 months per node, p=0.038) and women with (non-brain) metastatic disease at diagnosis had WBRT on average 2.4 years earlier than those that did not (p=0.004). TNM staging did not affect post WBRT survival. After adjusting for age at diagnosis (&amp;lt;,≥50), post WBRT survival was not affected by age at treatment. Controlling for the influence of age at diagnosis, Cox regression analysis of survival post WBRT demonstrated improved survival for ER positive patients (HR 0.66 95% CI 0.49-0.90). Survival post WBRT was not significantly influenced by HER-2 (HR 0.81 95% CI 0.55-1.19) or PR (HR 0.91 95% C.I. 0.63-1.33) status. Patients who experience late brain relapse (&amp;gt; 4 years post diagnosis) have slightly better survival post WBRT (HR 0.77, p=0.054). ER positive patients in this study developed brain metastases on average 1.8 years later than ER negative patients (95% CI 0.9-2.8).Conclusions: In this cohort ER positive patients who relapse in the brain do so later and live longer following WBRT (figure 1). Our data suggests that HER-2 status has little effect on post WBRT survival. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4110.</jats:p

7.5 Urea and Poultry Manure as Protein Supplement to Low Grade Grass for Sheep in the Accra Plains

The low protein content of dry season forage and its growth retarding effect on livestock has long been recognised as one of the main technical bottlenecks in ruminant livestock production in the tropics (Oyenuga, 1957; Lansbury, 1958; Rose-Innes, 1960). Such nutrient deficiency results in as much as 15% live-weight loss in grazing animals during the dry season, this delaying their maturity (Rose-Innes, 1960; Otchere, Dadzie, Erbynn and Abyebo, 1977). To help solve this problem, nitrogenous feedstuffs such as urea, poultry manure, groundnut cake and copra cake have been examined. Reported here is work on urea and poultry manure tested on West African Forest Type lambs at Legon, Ghana.</jats:p