Pseudiverticulosis múltiple en intestino delgado en un caballo

This paper reports one case of a horse with acute colic syndrome that was referred to the Teaching Hospital Complutense of Madrid. Based on the history, clinical signs and complementary diagnostic tests, a colon displacement was diagnosed. In the exploratory celiotomy, a right dorsal displacement of the large colon and generalized enteritis were found. During the surgery, adhesions all along the small intestine and multiple diverticula of different size in the mesenteric border in portions of the jejunum were also found. Due to these findings and the poor condition of the patient, euthanasia was performed on human grounds. This case report concludes that attending veterinarian should include this uncommon pathology in their differential diagnosis when chronic signs of colic, weight loss or diarrheas are a feature.Describimos el caso clínico de un caballo con síndrome cólico agudo que fue remitido al Hospital Clínico Veterinario Complutense. En base a los datos de la historia clínica, la sintomatología y las pruebas complementarias realizadas, se le diagnosticó un desplazamiento de colon por lo que se decidió proceder a una laparotomía exploratoria en la que se observó un desplazamiento dorsal derecho de la flexura pelviana, una severa enteritis generalizada y una peritonitis séptica. Durante la cirugía también se hallaron adherencias a lo largo de todo el intestino delgado y divertículos de diversas dimensiones en el borde mesentérico en diferentes porciones del yeyuno. Debido a estos hallazgos y a la peritonitis séptica, se decidió llevar a cabo la eutanasia humanitaria intraoperatoria del caballo. Aunque la diverticulosis es una patología infrecuente, debe ser incluida en el diagnóstico diferencial de caballos que presentan cuadros cólicos recurrentes, pérdida de peso o cuadros diarreicos

Influence of dose and route of administration on the outcome of infection with the virulent Neospora caninum isolate Nc-Spain7 in pregnant sheep at mid-gestation

Experimental infections in pregnant sheep have been focused on studying the effect of the time of challenge on the outcome of N. caninum infection, whereas the impact of the dose and route of challenge has not been studied in depth. Therefore, clinical outcome, immune responses, parasite detection and burden, and lesion severity in placental tissues and foetal brains were investigated in 90-day-pregnant sheep inoculated intravenously with 105 (G1), 104 (G2), 103 (G3), or 102 (G4) tachyzoites or subcutaneously with 104 (G5) tachyzoites of the virulent Nc-Spain7 isolate and an uninfected group (G6). Comparing challenge doses, G1 was the only group that had 100% abortion. Likewise, IFN¿ levels in G1 increased earlier than those in other intravenously infected groups, and IgG levels on day 21 post-infection (pi) were higher in G1 than those in other intravenously infected groups. Concerning vertical transmission, G1 shows a higher parasite burden in the foetal brain than did G2 and G3. Comparing routes of administration, no differences in foetal survival rate or parasite load in the foetal brain were found. Although G2 had higher IFN¿ levels than G5 on day 10 pi, no differences were found in humoral immune responses. Because the outcome after intravenous infection with 105 tachyzoites was similar to that observed after intravenous infection with 106 tachyzoites used in a previous work (100% abortion and vertical transmission), we conclude that it may be reasonable to use 105 tachyzoites administered by the intravenous route in further experiments when assessing drugs or vaccine candidates

Influence of dose and route of administration on the outcome of infection with the virulent Neospora caninum isolate Nc-Spain7 in pregnant sheep at mid-gestation

15 páginas, 2 tablas, 7 figuras.Experimental infections in pregnant sheep have been focused on studying the effect of the time of challenge on the outcome of N. caninum infection, whereas the impact of the dose and route of challenge has not been studied in depth. Therefore, clinical outcome, immune responses, parasite detection and burden, and lesion severity in placental tissues and foetal brains were investigated in 90-day-pregnant sheep inoculated intravenously with 10(5) (G1), 10(4) (G2), 10(3) (G3), or 10(2) (G4) tachyzoites or subcutaneously with 10(4) (G5) tachyzoites of the virulent Nc-Spain7 isolate and an uninfected group (G6). Comparing challenge doses, G1 was the only group that had 100% abortion. Likewise, IFN gamma levels in G1 increased earlier than those in other intravenously infected groups, and IgG levels on day 21 post-infection (pi) were higher in G1 than those in other intravenously infected groups. Concerning vertical transmission, G1 shows a higher parasite burden in the foetal brain than did G2 and G3. Comparing routes of administration, no differences in foetal survival rate or parasite load in the foetal brain were found. Although G2 had higher IFN gamma levels than G5 on day 10 pi, no differences were found in humoral immune responses. Because the outcome after intravenous infection with 10(5) tachyzoites was similar to that observed after intravenous infection with 10(6) tachyzoites used in a previous work (100% abortion and vertical transmission), we conclude that it may be reasonable to use 10(5) tachyzoites administered by the intravenous route in further experiments when assessing drugs or vaccine candidates.We gratefully acknowledge Neus Callizo Esteve from Clinical Veterinary Hospital (Complutense University of Madrid, Spain) and Jose Maria Gonzalez (University of Zaragoza, Spain) for their excellent technical assistance. The Animal Experimentation Service (SEA) at the University of Zaragoza is acknowledged for using their facilities to carry out the reproduction programme. Roberto Sanchez Sanchez is supported by a fellowship from the Spanish Ministry of Education, Culture and Sports (MECD) as a part of the Programme of Training of University Teaching Staff (FPU, Grant Number FPU13/03438). This work was supported by the Ministry of Economy and Competitiveness (AGL2016-75935-C2) and Community of Madrid, Spain (PLATESA, S2013/ABI2906).Peer reviewe

Safety and efficacy of the bumped kinase inhibitor BKI-1553 in pregnant sheep experimentally infected with Neospora caninum tachyzoites

Neospora caninum is one of the main causes of abortion in cattle, and recent studies have highlighted its relevance as an abortifacient in small ruminants. Vaccines or drugs for the control of neosporosis are lacking. Bumped kinase inhibitors (BKIs), which are ATP-competitive inhibitors of calcium dependent protein kinase 1 (CDPK1), were shown to be highly efficacious against several apicomplexan parasites in vitro and in laboratory animal models. We here present the pharmacokinetics, safety and efficacy of BKI-1553 in pregnant ewes and foetuses using a pregnant sheep model of N. caninum infection. BKI-1553 showed exposure in pregnant ewes with trough concentrations of approximately 4 µM, and of 1 µM in foetuses. Subcutaneous BKI-1553 administration increased rectal temperatures shortly after treatment, and resulted in dermal nodules triggering a slight monocytosis after repeated doses at short intervals. BKI-1553 treatment decreased fever in infected pregnant ewes already after two applications, resulted in a 37–50% reduction in foetal mortality, and modulated immune responses; IFN¿ levels were increased early after infection and IgG levels were reduced subsequently. N. caninum was abundantly found in placental tissues; however, parasite detection in foetal brain tissue decreased from 94% in the infected/untreated group to 69–71% in the treated groups. In summary, BKI-1553 confers partial protection against abortion in a ruminant experimental model of N. caninum infection during pregnancy. In addition, reduced parasite detection, parasite load and lesions in foetal brains were observed

Ulcerative enteritis (quail disease) in lories

Ulcerative enteritis is found in a wide range of avian hosts but has not been described in psittacine birds. This case report describes ulcerative enteritis in four lories (two Trichoglossus sp. and two Eos sp.) that were found dead without any previous sign of disease. Macroscopically, all four birds showed good body condition. The only remarkable finding was a moderate dilatation of the small intestine with the presence of multiple yellow foci. Histologically, multiple ulcers extended into the submucosa and were filled with necrotic debris; bacteria and fibrin were observed in the intestinal mucosa. The liver and spleen exhibited a multifocal fibrinoid necrosis associated with a very moderate inflammatory reaction. Microbiological isolation revealed colonies of Clostridium colinum and Clostridium perfringens in die intestinal tract of the investigated birds.Peer Reviewe

The crystal structure of human XPG, the xeroderma pigmentosum group G endonuclease, provides insight into nucleotide excision DNA repair

16 p.-7 fig.-1 tab.Nucleotide excision repair (NER) is an essential pathway to remove bulky lesions affecting one strand of DNA. Defects in components of this repair system are at the ground of genetic diseases such as xeroderma pigmentosum (XP) and Cockayne syndrome (CS). The XP complementation group G (XPG) endonuclease cleaves the damaged DNA strand on the 3' side of the lesion coordinated with DNA re-synthesis. Here, we determined crystal structures of the XPG nuclease domain in the absence and presence of DNA. The overall fold exhibits similarities to other flap endonucleases but XPG harbors a dynamic helical arch that is uniquely oriented and defines a gateway. DNA binding through a helix-2-turn-helix motif, assisted by one flanking alpha-helix on each side, shows high plasticity, which is likely relevant for DNA scanning. A positively-charged canyon defined by the hydrophobic wedge and beta-pin motifs provides an additional DNA-binding surface. Mutational analysis identifies helical arch residues that play critical roles in XPG function. A model for XPG participation in NER is proposed. Our structures and biochemical data represent a valuable tool to understand the atomic ground of XP and CS, and constitute a starting point for potential therapeutic applications.Spanish Ministry of Science [BFU2017-87397-P,BFU2013-48374-P to C.F.T.]; PharmaMar partly funded this project. Funding for open access charge: The CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI)Peer reviewe

Biological activity in metal-contaminated calcareous agricultural soils The role of the organic matter composition and the particle size distribution

Organic matter (OM) plays a key role in microbial response to soil metal contamination, yet little is known about how the composition of the OM affects this response in Mediterranean calcareous agricultural soils. A set of Mediterranean soils, with different contents and compositions of OM and carbonate and fine mineral fractions, was spiked with a mixture of Cd, Cu, Pb, and Zn and incubated for 12 months for aging. Microbial (Biolog Ecoplates) and enzyme activities (dehydrogenase, DHA; β-galactosidase, BGAL; phosphatase, PHOS; and urease, URE) were assessed and related to metal availability and soil physicochemical parameters. All enzyme activities decreased significantly with metal contamination 36-68 % (DHA), 24-85 % (BGAL), 22-72 % (PHOS), and 14-84 % (URE) inhibitions. Similarly, catabolic activity was negatively affected, especially phenol catabolism (~86 % compared to 25-55 % inhibition for the rest of the substrates). Catabolic and DHA activities were negatively correlated with ethylenediaminetetraacetic acid (EDTA)-extractable Cd and Pb, but positively with CaCl2, NaNO3, and DTPA-extractable Cu and Zn. Soluble OM (water- and hot-water-soluble organic C) was positively related to enzyme and catabolic activities. Recalcitrant OM and fine mineral fractions were positively related to BGAL and PHOS. Conversely, catabolic activity was negatively related to clay and positively to silt and labile OM. Results indicate that the microbial response to metal contamination is highly affected by texture and OM composition. © 2014 Springer-Verlag Berlin Heidelberg

Biological activity in metal-contaminated calcareous agricultural soils: the role of the organic matter composition and the particle size distribution

Organic matter (OM) plays a key role in microbial response to soil metal contamination, yet little is known about how the composition of the OM affects this response in Mediterranean calcareous agricultural soils. A set of Mediterranean soils, with different contents and compositions of OM and carbonate and fine mineral fractions, was spiked with a mixture of Cd, Cu, Pb, and Zn and incubated for 12 months for aging. Microbial (Biolog Ecoplates) and enzyme activities (dehydrogenase, DHA; β-galactosidase, BGAL; phosphatase, PHOS; and urease, URE) were assessed and related to metal availability and soil physicochemical parameters. All enzyme activities decreased significantly with metal contamination: 36–68 % (DHA), 24–85 % (BGAL), 22–72 % (PHOS), and 14–84 % (URE) inhibitions. Similarly, catabolic activity was negatively affected, especially phenol catabolism (∼86 % compared to 25–55% inhibition for the rest of the substrates). Catabolic and DHA activities were negatively correlated with ethylenediaminetetraacetic acid (EDTA)-extractable Cd and Pb, but positively with CaCl2, NaNO3, and DTPA-extractable Cu and Zn. Soluble OM (water- and hot-water-soluble organic C) was positively related to enzyme and catabolic activities. Recalcitrant OM and fine mineral fractions were positively related to BGAL and PHOS. Conversely, catabolic activity was negatively related to clay and positively to silt and labile OM. Results indicate that the microbial response to metal contamination is highly affected by texture and OM composition.Universidad Complutense de Madrid (Santander-UCM)Comunidad de MadridDepto. de Química en Ciencias FarmacéuticasTRUEpubAPC financiada por la UC

Pharmacokinetics, safety and efficacy of Bumped Kinase Inhibitor (BKI) 1553 in a pregnant sheep model of neosporosis

1 página.-- Trabajo presentado al: 4th International Meeting on Apicomplexa in Farm Animals. (Madrid, Spain. 11-14 October ,2017).Funded by NIH (4180015), USDA (4180014) and Community of Madrid (S2013/ABI2906) research projects.Peer Reviewe

Treatment with Bumped Kinase Inhibitor 1294 Is Safe and Leads to Significant Protection against Abortion and Vertical Transmission in Sheep Experimentally Infected with Toxoplasma gondii during Pregnancy

16 páginas, 3 tablas, 6 figuras.Previous studies on drug efficacy showed low protection against abortion and vertical transmission of Toxoplasma gondii in pregnant sheep. Bumped kinase inhibitors (BKIs), which are ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1), were shown to be highly efficacious against several apicomplexan parasites in vitro and in laboratory animal models. Here, we present the safety and efficacy of BKI-1294 treatment (dosed orally at 100 mg/kg of body weight 5 times every 48 h) initiated 48 h after oral infection of sheep at midpregnancy with 1,000 TgShSp1 oocysts. BKI-1294 demonstrated systemic exposure in pregnant ewes, with maximum plasma concentrations of 2 to 3 M and trough concentrations of 0.4 M at 48 h after each dose. Oral administration of BKI-1294 in uninfected sheep at midpregnancy was deemed safe, since there were no changes in behavior, fecal consistency, rectal temperatures, hematological and biochemical parameters, or fetal mortality/morbidity. In ewes infected with a T. gondii oocyst dose lethal for fetuses, BKI-1294 treatment led to a minor rectal temperature increase after infection and a decrease in fetal/lamb mortality of 71%. None of the lambs born alive in the treated group exhibited congenital encephalitis lesions, and vertical transmission was prevented in 53% of them. BKI-1294 treatment during infection led to strong interferon gamma production after cell stimulation in vitro and a low humoral immune response to soluble tachyzoite antigens but high levels of anti-SAG1 antibodies. The results demonstrate a proof of concept for the therapeutic use of BKI-1294 to protect ovine fetuses from T. gondii infection during pregnancy.We gratefully acknowledge the SALUVET group (Complutense University of Madrid, Spain), Luis Miguel Ferrer, Jose Ventura, José Calasanz Jiménez, Francisco Saura, Teresa Navarro, and José María González from the University of Zaragoza (Spain), and Victor Herrero and Javier Blanco from Clinical Veterinary Hospital (Complutense University of Madrid, Spain) for their excellent technical assistance, Dale Kempf and Kennan Marsh, from AbbVie, Inc., for their suggestion of the Phosal vehicle used in the experiments reported here, Rama S. R. Vidadala and Dustin J. Maly, Department of Chemistry, University of Washington, for characterization and further purification of BKI-1294, and advice from Robert Choy and Eugenio L. de Hostos from the PATH Drug Development Program. The Animal Experimentation Service (SEA) at the University of Zaragoza is acknowledged for providing their facilities to carry out the reproduction program. R.S.-S. is supported by a fellowship from the Spanish Ministry of Education, Culture and Sports (MECD), as a part of the Program of Training of University Teaching Staff (FPU; grant number FPU13/03438). A.H. is supported by a Swiss National Science Foundation grant (no. 310030-165782). This work was supported by the Public Health Service, National Institutes of Health, Bethesda, MD (grants R01 AI 111341 and R01 HD 080670), the U.S. Department of Agriculture (grant 2014-67015-22106), and the Community of Madrid, Spain (PLATESA2, P2018/BAA-4370). I.F., A.H., K.K.O., W.C.V.V., and L.M.O.-M. conceived the study and participated in its design. R.S.-S. wrote the manuscript, with results interpretation and discussion inputs from I.F., J.R.-C., A.H., M.A.H., L.K.B., W.C.V.V., and L.M.O.-M. J.J.R. selected the animals and executed the reproductive program. R.S.-S., I.F., and M.R. carried out oocyst infection and drug administration. R.S.-S., I.F., M.R., M.P.D., M.G.-H., E.T., and J.B. participated in clinical examination and sampling of animals and performed necropsies and hematological, biochemical, and histopathological analyses. M.H., L.K.B., R.C., G.R.W., and K.K.O. determined the pharmacokinetics of the compound. R.S.-S. performed peripheral blood stimulation assay, serological assays, PCR analyses, statistical analysis, and interpretation of the results. All authors read and approved the final manuscript. W.C.V.V. is the president and co-owner of ParaTheraTech, Inc., a company that is developing BKIs for animal health. W.C.V.V. did not perform the experiments or interpret the results of the experiments, but he did edit the paper and helped plan the experiments. The other authors have no competing interests to declare