Tracking intracavernously injected adipose-derived stem cells to bone marrow.

The intracavernous (i.c.) injection of stem cells (SCs) has been shown to improve erectile function in various erectile dysfunction (ED) animal models. However, the tissue distribution of the injected cells remains unknown. In this study we tracked i.c.-injected adipose-derived stem cells (ADSCs) in various tissues. Rat paratesticular fat was processed for ADSC isolation and culture. The animals were then subject to cavernous nerve (CN) crush injury or sham operation, followed by i.c. injection of 1 million autologous or allogeneic ADSCs that were labeled with 5-ethynyl-2-deoxyuridine (EdU). Another group of rats received i.c. injection of EdU-labeled allogeneic penile smooth muscle cells (PSMCs). At 2 and 7 days post injection, penises and femoral bone marrow were processed for histological analyses. Whole femoral bone marrows were also analyzed for EdU-positive cells by flow cytometry. The results show that ADSCs exited the penis within days of i.c. injection and migrated preferentially to bone marrow. Allogenicity did not affect the bone marrow appearance of ADSCs at either 2 or 7 days, whereas CN injury reduced the number of ADSCs in bone marrow significantly at 7 but not 2 days. The significance of these results in relation to SC therapy for ED is discussed

Pharmacologic modulation of RORγt translates to efficacy in preclinical and translational models of psoriasis and inflammatory arthritis.

The IL-23/IL-17 pathway is implicated in autoimmune diseases, particularly psoriasis, where biologics targeting IL-23 and IL-17 have shown significant clinical efficacy. Retinoid-related orphan nuclear receptor gamma t (RORγt) is required for Th17 differentiation and IL-17 production in adaptive and innate immune cells. We identified JNJ-54271074, a potent and highly-selective RORγt inverse agonist, which dose-dependently inhibited RORγt-driven transcription, decreased co-activator binding and promoted interaction with co-repressor protein. This compound selectively blocked Th17 differentiation, significantly reduced IL-17A production from memory T cells, and decreased IL-17A- and IL-22-producing human and murine γδ and NKT cells. In a murine collagen-induced arthritis model, JNJ-54271074 dose-dependently suppressed joint inflammation. Furthermore, JNJ-54271074 suppressed IL-17A production in human PBMC from rheumatoid arthritis patients. RORγt-deficient mice showed decreased IL-23-induced psoriasis-like skin inflammation and cytokine gene expression, consistent with dose-dependent inhibition in wild-type mice through oral dosing of JNJ-54271074. In a translational model of human psoriatic epidermal cells and skin-homing T cells, JNJ-54271074 selectively inhibited streptococcus extract-induced IL-17A and IL-17F. JNJ-54271074 is thus a potent, selective RORγt modulator with therapeutic potential in IL-23/IL-17 mediated autoimmune diseases

The impact of co-infections on the haematological profile of East African Short-horn Zebu calves

The cumulative effect of co-infections between pathogen pairs on the haematological response of East African Short-horn Zebu calves is described. Using a longitudinal study design a stratified clustered random sample of newborn calves were recruited into the Infectious Diseases of East African Livestock (IDEAL) study and monitored at 5-weekly intervals until 51 weeks of age. At each visit sampleswere collected and analysed to determine the infection status of each calf aswell as their haematological response. The haematological parameters investigated included packed cell volume (PCV), white blood cell count (WBC) and platelet count (Plt). The pathogens of interest included tick-borne protozoa and rickettsias, trypanosomes and intestinal parasites. Generalized additive mixed-effect models were used to model the infectious status of pathogens against each haematological parameter, including significant interactions between pathogens. These models were further used to predict the cumulative effect of co-infecting pathogen pairs on each haematological parameter. The most significant decrease in PCV was found with co-infections of trypanosomes and strongyles. Strongyle infections also resulted in a significant decrease in WBC at a high infectious load. Trypanosomes were the major cause of thrombocytopenia. Platelet counts were also affected by interactions between tick-borne pathogens. Interactions between concomitant pathogens were found to complicate the prognosis and clinical presentation of infected calves and should be taken into consideration in any study that investigates disease under field conditions.The work was done as part of the Infectious Diseases of East African Livestock (IDEAL) project, which is a collaboration between the University of Pretoria, University of Edinburgh, University of Nottingham and the International Livestock Research Institute (ILRI), Nairobi, Kenya.The IDEAL project was generously funded by the Wellcome Trust (project no. 079445). The pocH-100iV Diff automated blood analyser was kindly sponsored by Sysmex© Europe GMBH.http://journals.cambridge.org/action/displayJournal?jid=PARam201

Babesiosis of wild carnivores and ungulates

Abstract Although large and small piroplasms have been reported from various wild carnivore and ungulate species, relatively few have been named. In the past, mere presence of a piroplasm in a specific host frequently prompted naming of a new species. Descriptions were often inadequate or lacking altogether. Currently, demarcation of species relies heavily on molecular characterisation. Even serological evidence is deemed insufficient. Experimental transmission of Babesia spp. from domestic to wild animals is usually only successful in closely related species, or after splenectomy. There are indications that endemic stability, similar to the situation in livestock, is the general pattern in Babesia sp. infections in wildlife. All lions in Kruger National Park were found to be infected with B. leo, which did not lead to clinical disease manifestation in artificially infected lions. Under stressful conditions, infections could flare up and be fatal, as purportedly happened to the famous lioness ''Elsa''. Similarly black rhinos, which can harbour Babesia bicornis without ill effects, may develop clinical babesiosis during confinement after capture. Zoo-bred animals, which were not exposed to Babesia spp. at a young age, may be fully susceptible when released into a natural environment where other members of their species occur. This could have major implications for ex situ conservation programmes aimed at bolstering natural wildlife populations.

Identification of a Novel Babesia sp. from a Sable Antelope (Hippotragus niger Harris, 1838)▿

Babesiosis in a sable antelope (Hippotragus niger Harris, 1838) was first reported in 1930; the parasite was named Babesia irvinesmithi. Recently, specimens from an adult sable that presented with a sudden onset of disease and that subsequently died during immobilization were submitted for molecular characterization. Microscopic examination of thin blood smears revealed the presence of small piroplasms. DNA was extracted from blood samples; the V4 variable region of the 18S rRNA gene was amplified and analyzed using the reverse line blot (RLB) assay. Amplicons did not hybridize with any of the Babesia or Theileria species-specific probes present on the blot and hybridized only with a Babesia or Theileria genus-specific probe, suggesting the presence of a novel species. The full-length 18S rRNA gene sequence was obtained and aligned with published sequences of related genera, and phylogenetic trees were constructed. Sequence similarity analyses indicated that a Babesia species, designated Babesia sp. (sable), was present. The sequence showed its highest similarity to B. orientalis and to an unnamed Babesia species previously detected in bovine samples. The latter was later established to be Babesia occultans. A Babesia sp. (sable)-specific RLB oligonucleotide probe was designed and used to screen 200 South African sable samples, but so far, no other sample has been found to be positive for the presence of Babesia sp. (sable) DNA. In summary, we identified a novel piroplasm parasite from a sable antelope that died from an unknown illness. While the parasite was observed in blood smears, there is no direct evidence that it was the cause of death

Tracking intracavernously injected adipose-derived stem cells to bone marrow.

The intracavernous (i.c.) injection of stem cells (SCs) has been shown to improve erectile function in various erectile dysfunction (ED) animal models. However, the tissue distribution of the injected cells remains unknown. In this study we tracked i.c.-injected adipose-derived stem cells (ADSCs) in various tissues. Rat paratesticular fat was processed for ADSC isolation and culture. The animals were then subject to cavernous nerve (CN) crush injury or sham operation, followed by i.c. injection of 1 million autologous or allogeneic ADSCs that were labeled with 5-ethynyl-2-deoxyuridine (EdU). Another group of rats received i.c. injection of EdU-labeled allogeneic penile smooth muscle cells (PSMCs). At 2 and 7 days post injection, penises and femoral bone marrow were processed for histological analyses. Whole femoral bone marrows were also analyzed for EdU-positive cells by flow cytometry. The results show that ADSCs exited the penis within days of i.c. injection and migrated preferentially to bone marrow. Allogenicity did not affect the bone marrow appearance of ADSCs at either 2 or 7 days, whereas CN injury reduced the number of ADSCs in bone marrow significantly at 7 but not 2 days. The significance of these results in relation to SC therapy for ED is discussed