Characterisation of a refined rat model of respiratory infection with Pseudomonas aeruginosa and the effect of ciprofloxacin

AbstractBackgroundWe sought to characterise a refined rat model of respiratory infection with P. aeruginosa over an acute time course and test the antibiotic ciprofloxacin.MethodsAgar beads were prepared±SPAN®80. Rats were inoculated with sterile agar beads or those containing 105 colony forming units (cfu) P. aeruginosa via intra-tracheal dosing. Bacterial load and inflammatory parameters were measured.ResultsDiffering concentrations of SPAN® 80 modified median agar bead diameter and reduced particle size distribution. Beads prepared with 0.01% v/v SPAN®80 were evaluated in vivo. A stable lung infection up to 7days post infection was achieved and induced BALF neutrophilia 2 and 5days post infection. Ciprofloxacin (50mg/kg) significantly attenuated infection without affecting the inflammatory parameters measured.ConclusionSPAN® 80 can control the particle size and lung distribution of agar beads and P. aeruginosa-embedded beads prepared with 0.01%v/v SPAN®80 can induce infection and inflammation over 7days

The French child protection system

SIGLEAvailable from British Library Document Supply Centre- DSC:q94/22862 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Leishmaniosis due to Leishmania infantum in a FIV and FeIV positive cat with a squamous cell carcinoma diagnosed with histological, serological and isoenzymatic methods

Leishmaniosis caused by Leishmania infantum is an endemic zoonosis present in the Mediterranean area. Canidae (dog and fox) constitute the main reservoir hosts for the parasite, whilst wild rodents or the cat can be carriers of the protozoan and are considered as secondary potential reservoirs. This paper describes a case of disseminated feline leishmaniosis with cutaneous (ulcerative), visceral (spleen and lymph nodes) and blood involvement in a FIV-FelV positive cat. The microscopic identification of the Leishmania infection was initially made on a skin biopsy of the temporal area, where a squamous cell carcinoma was diagnosed. The diagnosis of the disease was achieved by several serological techniques (ELISA, IFAT and Western-blot). The strain was obtained by blood culture, characterized by electrophoresis of isoenzymes and identified as Leishmania infantum zymodeme MON-1. Since the infection due to L. infantum is a zoonosis, the potential feline reservoir should be more investigated. Serological analysis by Western blot on domestic cats provides a useful tool. In veterinary practice, feline leishmaniosis should be systematically included in the differential diagnosis when compatible cutaneous lesions are present, especially in the endemic areas of canine leishmaniosis

Leishmaniosis due to

Leishmaniosis caused by Leishmania infantum is an endemic zoonosis present in the Mediterranean area. Canidae (dog and fox) constitute the main reservoir hosts for the parasite, whilst wild rodents or the cat can be carriers of the protozoan and are considered as secondary potential reservoirs. This paper describes a case of disseminated feline leishmaniosis with cutaneous (ulcerative), visceral (spleen and lymph nodes) and blood involvement in a FIV-FelV positive cat. The microscopic identification of the Leishmania infection was initially made on a skin biopsy of the temporal area, where a squamous cell carcinoma was diagnosed. The diagnosis of the disease was achieved by several serological techniques (ELISA, IFAT and Western-blot). The strain was obtained by blood culture, characterized by electrophoresis of isoenzymes and identified as Leishmania infantum zymodeme MON-1. Since the infection due to L. infantum is a zoonosis, the potential feline reservoir should be more investigated. Serological analysis by Western blot on domestic cats provides a useful tool. In veterinary practice, feline leishmaniosis should be systematically included in the differential diagnosis when compatible cutaneous lesions are present, especially in the endemic areas of canine leishmaniosis

Child maltreatment in the family: a European perspective.

Child maltreatment is generally referred to under the global categories of physical, sexual, emotional/psychological abuse and neglect. The Concerted Action on the Prevention of Child Abuse in Europe (CAPCAE) reports on the specific forms of harm and injury, actions and persons believed responsible in eight European countries. The most common actions across all participating countries responsible for harm were those of violent parenting or absent parenting. A review of prevention strategies found that few programmes focused on specific behaviours or included measures to indicate whether their actions were successful in preventing further harm to children. It is recommended that fathers need to be targeted in prevention as well as mothers and that specific data collection of actual harms, actions, persons responsible and outcomes needs to be implemented as a priority in all European countries. Such specificity avoids a focus on risk which is unacceptable in some countries, over inclusive of parents and resource intensive

Resistance mechanisms to TP53-MDM2 inhibition identified by in vivo piggyBac transposon mutagenesis screen in an Arf-/-mouse model

Inhibitors of double minute 2 protein (MDM2)-tumor protein 53 (TP53) interaction are predicted to be effective in tumors in which the TP53 gene is wild type, by preventing TP53 protein degradation. One such setting is represented by the frequent CDKN2A deletion in human cancer that, through inactivation of p14ARF, activates MDM2 protein, which in turn degrades TP53 tumor suppressor. Here we used piggyBac (PB) transposon insertional mutagenesis to anticipate resistance mechanisms occurring during treatment with the MDM2- TP53 inhibitor HDM201. Constitutive PB mutagenesis in Arf-/- mice provided a collection of spontaneous tumors with characterized insertional genetic landscapes. Tumors were allografted in large cohorts of mice to assess the pharmacologic effects of HDM201. Sixteen out of 21 allograft models were sensitive to HDM201 but ultimately relapsed under treatment. A comparison of tumors with acquired resistance to HDM201 and untreated tumors identified 87 genes that were differentially and significantly targeted by the PB transposon. Resistant tumors displayed a complex clonality pattern suggesting the emergence of several resistant subclones. Among the most frequent alterations conferring resistance, we observed somatic and insertional loss-of-function mutations in transformation- related protein 53 (Trp53) in 54% of tumors and transposonmediated gain-of-function alterations in B-cell lymphoma-extra large (Bcl-xL), Mdm4, and two TP53 family members, resulting in expression of the TP53 dominant negative truncations δNTrp63 and δNTrp73. Enhanced BCL-xL and MDM4 protein expression was confirmed in resistant tumors, as well as in HDM201-resistant patient-derived tumor xenografts. Interestingly, concomitant inhibition of MDM2 and BCL-xL demonstrated significant synergy in p53 wild-type cell lines invitro. Collectively, our findings identify several potential mechanisms by which TP53 wild-type tumors may escape MDM2-targeted therapy