Jasonia glutinosa (L.) DC., a traditional herbal medicine, reduces inflammation, oxidative stress and protects the intestinal barrier in a murine model of colitis.

Jasonia glutinosa (L.) DC., known as rock tea (RT), is traditionally used in Spain as a digestive due to its beneficial properties in bowel disorders. The pharmacological nature of these properties has not been established yet. The aim of this work was to evaluate the therapeutic utility of RT in experimental colitis and to identify chemical constituents with anti-inflammatory and/or anti-oxidative properties. RT extract was prepared with ethanol in a Soxhlet apparatus and analysed by HPLC-DAD. Superoxide radical scavenging properties, xanthine oxidase and lipoxygenase (5-LOX) inhibitory activity, and capability to lower nitric oxide (NO) and tumor necrosis factor α (TNF-α) levels were measured in cell-free and cell-based assays. In the 2.5%-dextran-sodium sulphate (DSS) injury-repair model of ulcerative colitis (UC), mice were daily treated with sulfasalazine (SSZ, as reference drug, 100 mg/kg bw), RT (5, 25 and 50 mg/kg bw, p.o.), or vehicle over 20 days. Colitis was scored daily. Colon samples were examined macroscopically and histopathologically. Protein levels of myeloperoxidase (MPO), interleukins 6, and 10 (IL-6, IL-10), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) were studied as markers of oxidative stress and inflammatory activity. The integrity of the apical epithelial layer was assessed by immunofluorescence staining of zonula ocludens-1 (ZO-1). Finally, intestinal contractility was also evaluated by isometric myography. Fifteen phenolic compounds and three pigments were identified and quantified, of which caffeoylquinic acids, and the flavonoid, quercetin-3-O-galactoside, were the most abundant. RT extract significantly scavenged superoxide radicals, inhibited 5-LOX activity, and lowered NO and TNF-α levels. DSS-treated mice receiving RT scored clinically lower than controls during the first 3 days of DSS treatment and during the recovery period. SSZ was less effective than RT. Anatomical and histological examination of colon samples revealed that RT significantly prevented colon shortening, increased colon thickness, and lowered the macroscopic damage score. RT also significantly prevented the increase of MPO activity, IL-6 levels, iNOS and COX-2 expression, the loss of ZO-1 apical expression, and normalized contractility disturbances. In conclusion, daily administration of RT showed therapeutic properties in the DSS-model of UC. The benefits of RT can likely be attributed to its anti-inflammatory and antioxidant phenolic and flavonoid constituents.

Cystathionine ß-synthase deficiency causes infertility by impairing decidualization and gene expression networks in uterus implantation sites.

Hyperhomocysteinemia has been reported in human reproduction as a risk factor for early pregnancy loss, preeclampsia, and congenital birth defects like spina bifida. Female infertility was also observed in cystathionine beta synthase-deficient mice (Cbs-KO) as an animal model for severe hyperhomocysteinemia. The aim for the present research was to elucidate the time-point of pregnancy loss and to pinpoint gene and cellular changes involved in the underlying pathological mechanism. By mating 90-day-old wild-type and Cbs-KO female mice with their homologous male partners, we found that pregnancy loss in Cbs-KO occurred between the 8th and 12th gestation day during placenta formation. DNA microarrays were carried out on uterus from implantation and interimplantation samples obtained on day 8. The results allowed us to select genes potentially involved in embryo death; these were individually confirmed by RT-qPCR, and their expressions were also followed throughout pregnancy. We found that changes in expression of Calb1, Ttr, Expi, Inmt, Spink3, Rpgrip1, Krt15, Mt-4, Gzmc, Gzmb, Tdo2, and Afp were important for pregnancy success, since a different regulation in Cbs-KO mice was found. Also, differences in relationships among selected genes were observed, indicating a dysregulation of these genes in Cbs-KO females. In conclusion, our data provide more information on the gene expression cascade and its timely regulated process required for a successful pregnancy. In addition, we unveil new potential avenues to explore further investigations in pregnancy loss.

[Research study on renal targeted chemotherapy with magnetic harpoons and intravenous administration of ferro-carbon nanoparticles]. / Estudio experimental sobre quimioterapia focalizada en riñón mediante arpón magnético y administración intravenosa de nanopartículas ferrocarbonosas.

OBJECTIVES: The use of nanoparticules for drug transport is one of the topics with priority interest within the field of biomedical research. Our objective is to show the initial results of an innovative method to focalize drug carrier ferro-carbon nanoparticules to solid organs. We obtained and characterized various types of ferrous magnetic nanoparticules and studied their behaviour in vitro and in vivo in laboratory animals with intrarenal magnetic targets laparoscopically implanted. METHODS: Using a plasma arch we obtained ferro-carbon nanoparticules with the ability to absorb and deliver doxorubicin, showing an excellent behaviour in in vitro rheological studies. Under general anesthesia and control we inserted a gold covered magnetic microharpoon in the left kidney of New Zealand rabbits. At the same time we injected intravenously different doses of various types of nanoparticules. The animals were sacrified ofter pre-established times and pathologic studies of their kidneys, spleens, livers, lungs and bone marrow were carried out. RESULTS: After selection of the most adequafe nanoparticules for our purposes, we ascertained significant differences in the distribution of nanoparticules in postmortem studies, with accumulation in the magnetic target and surrounding renal parenchyma. Nevertheless, the reticuloendothelial system retains a great amount of the injected dose. CONCLUSIONS: Although our magnetic focalization system is effective, nanoparticule temporary protection systems should be tested to allow us avoid the action of the immune system.

Estudio experimental sobre quimioterapia focalizada en riñón mediante arpón magnético y administración intravenosa de nanopartículas ferrocarbonosas / Research study on renal targeted chemotherapy with magnetic harpoons and intravenous administration of ferro-carbon nanoparticles

OBJETIVOS: El empleo de nanopartículas en el transporte de fármacos es actualmente uno de los temas de interés prioritario dentro del campo de la investigación biomédica. Nuestro objetivo es mostrar los resultados iniciales de un método inédito para focalizar en órganos sólidos nanopartículas ferro carbonosas quimioportadoras. Hemos obtenido y caracterizado diversos tipos de nanopartículas ferromagnéticas, y hemos estudiado su comportamiento in vitro e in vivo en animales de experimentación con dianas magnéticas intrarrenales implantadas laparoscópicamente. METODOS: Obtenemos mediante arco de plasma nanopartículas ferro carbonosas capaces de absorber y desorber doxorrubicina y mostrar excelente comportamiento en estudios reológicos in vitro. Bajo anestesia general insertamos mediante control laparoscópico en el riñón izquierdo de conejos de raza neozelandesa un microarpón magnético encapsulado en oro. En el mismo acto inyectamos por vía intravenosa diferentes dosis de distintos tipos de nanopartículas. Los diversos lotes de animales se sacrifican tras diferentes tiempos y se analizan histológicamente ambos riñones, bazo, hígado, pulmones y médula ósea. RESULTADOS: Tras haber seleccionado las nanopartículas más adecuadas para nuestros fines, hemos constatado en los estudios post-mortem diferencias significativas en la distribución de las nanopartículas, con cúmulos de las mismas en la diana magnética y en el parénquima renal circundante. No obstante, el sistema retículoendotelial retiene gran parte de la carga inyectada. CONCLUSIONES: Aunque nuestro sistema de focalización magnética resulta efectivo, deben ensayarse sistemas de blindaje temporal de las nanopartículas que les permita eludir la acción del sistema inmune (AU)

OBJECTIVES: The use of nanoparticules for drug transport is one of the topics with priority interest within the field of biomedical research. Our objective is to show the initial results of an innovative method to focalize drug carrier ferro-carbon nanoparticules to solid organs. We obtained and characterized various types of ferrous magnetic nanoparticules and studied their behaviour in vitro and in vivo in laboratory animals with intrarenal magnetic targets laparoscopically implanted. METHODS: Using a plasma arch we obtained ferro-carbon nanoparticules with the ability to absorb and deliver doxorubicin, showing an excellent behaviour in in vitro rheological studies. Under general anesthesia and control we inserted a gold covered magnetic microharpoon in the left kidney of New Zealand rabbits. At the same time we injected intravenously different doses of various types of nanoparticules. The animals were sacrified ofter pre-established times and pathologic studies of their kidneys, spleens, livers, lungs and bone marrow were carried out. RESULTS: After selection of the most adequafe nanoparticules for our purposes, we ascertained significant differences in the distribution of nanoparticules in postmortem studies, with accumulation in the magnetic target and surrounding renal parenchyma. Nevertheless, the reticuloendothelial system retains a great amount of the injected dose. CONCLUSIONS: Although our magnetic focalization system is effective, nanoparticule temporary protection systems should be tested to allow us avoid the action of the immune system (AU)

A PCR technique for the detection of Jaagsiekte sheep retrovirus in the blood suitable for the screening of ovine pulmonary adenocarcinoma in field conditions.

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring contagious lung neoplasia caused by jaagsiekte sheep retrovirus (JSRV). Although no specific circulating antibodies against the virus can be detected in infected sheep, JSRV proviral DNA sequences can be found in peripheral blood leukocytes (PBLs) in clinically affected and in a proportion of in contact animals. In this study, existing hemi-nested PCR procedure is compared with a new one-step PCR technique that was developed to minimise potential DNA contamination and reduce sample and reagent handling. Different blood preparations were assessed and the best results were achieved on DNA prepared from buffy coat. The sensitivity of this PCR was lower in JSRV infected sheep without lesions of OPA than in clinically affected sheep, which indicate that this PCR may not be not fully appropriate for screening of individual sheep, but rather to provide results at flock level. This PCR is the only currently available blood test for detection of JSRV infected sheep and may be useful in epidemiological studies and in control programmes of OPA.