Einsatz von pflanzlichen Futterzusätzen zur Prophylaxe von E.coli - bedingten Durchfällen bei Absetzferkeln

The aim of this investigation was to examine the effect of different feed additives on prophylaxis of weaning diarrhoea.184 piglets were divided into 3 experimental groups and one control group by compensating randomisation. Feed additives were either herbs (“Herbenterosan”), oligogalacturonides (“Enteronid”) or lignocellulosis (“Agrocell”). Piglets were reared according to Council Regulation EC Nr. 889/2008 and weaned at 40 days of age. From day 4 after weaning until day 8 faeces of the piglets were examined every day to create a faecal score of each group (= group sum). Firm faeces were characterised as “0”, pasty faeces as “1” and liquid faeces as “2”. Live weight was examined regularly. Blood samples were collected twice for the analysis of haptoglobin and electrolytes. The Herbenterosan group showed the lowest group sum in faecal scoring. It was followed by the Enteronid group, the control group and the Agrocell group. No difference between groups was found in haptoglobin values. Electrolyte values (sodium, potassium and chloride) coincided with faecal scores: lower faecal score meant better values of electrolytes and conversely. The three different phytogenic feed additives were not able to prevent piglets from diarrhoea. The Herbenterosan group showed best values in faecal score and live weight gain

Einsatz von Kräutern, Tonmineralien und Effektiven Mikroorganismen zur Prophylaxe des Absetzdurchfalles

The effect of an herbal blend (Flos Chamomillae, Fruct. Myrtilli, Rad. Taraxaci, Herba Rhapontici Carthamoides, Rad. Dauci Carotae, Bulbus Allii Sativi) in combination with zeolite and Effective Microorganisms on diarrhea incidence of weaning pigs was studied. 82 healthy piglets were divided into four groups by compensating randomization: treatment and control and for both light and heavy. The animals of the experimental group were administered the herbal blend orally. The piglets were weighed regularly. Faeces were appraised with a faecal score on a scale from 0 (formed faeces) to 2 (fluid faeces). Diarrhea occurred in all groups. Blood sample collections were performed for analysis of haptoglobin and nonesterified fatty acids. The results showed no significant difference between experimental and control group. Considering the piglets of the light group a significant higher daily weight gain in the experimental group was found (327 g vs. 241 g, p = 0.0126). There was also a clear trend (p = 0.0603) toward faecal scores being lower in the light treatment group. Heavy piglets were not affected by eating the herbs. Our results showed that, while this particular herbal blend did not prevent diarrhea in piglets after weaning, it lessened the severity of diarrhea and significantly improved weight gains in the light treated piglets compared with the light untreated piglets

A systematic review of progranulin concentrations in biofluids in over 7,000 people—assessing the pathogenicity of GRN mutations and other influencing factors

Background: Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. Methods: Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. Results: We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. Conclusions: These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.</p

A systematic review of progranulin concentrations in biofluids in over 7,000 people—assessing the pathogenicity of GRN mutations and other influencing factors

Background: Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. Methods: Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. Results: We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. Conclusions: These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.</p

Risk factors for recurrent venous thromboembolism in the European collaborative paediatric database on cerebral venous thrombosis: a multicentre cohort study

Background The relative importance of previous diagnosis and hereditary prothrombotic risk factors for cerebral venous thrombosis (CVT) in children in determining risk of a second cerebral or systemic venous thrombosis (VT), compared with other clinical, neuroimaging, and treatment variables, is unknown. Methods We followed up the survivors of 396 consecutively enrolled patients with CVT, aged newborn to 18 years (median 5.2 years) for a median of 36 months (maximum 85 months). In accordance with international treatment guidelines, 250 children (65%) received acute anticoagulation. with unfractionated heparin or low-molecular weight heparin, followed by secondary anticoaguilation prophylaxis with low-molecular weight heparin or warfarin in 165 (43%). Results of 396 children enrolled, 12 died immediately and 22 (6%) had recurrent VT (13 cerebral; 3%) at a median of 6 months (range 0.1-85). Repeat venous imaging was available in 266 children. Recurrent VT only occurred in children whose first CVT was diagnosed after age 2 years; the underlying medical condition had no effect. In Cox regression analyses, non-administration of anticoagulant before relapse (hazard ratio [HR] 11 (.) 2 95% CI 3(.)4-37 (.) 0; p < 0.0001), persistent occlusion on repeat venous imaging (4(.)1, 1(.)1-14(.)8; p=0(.)032), and heterozygosity for the G20210A mutation in factor II (4(.)3, 1(.)1-16(.)2; p=0(.)034) were independently associated with recurrent VT. Among patients who had recurrent VT, 70% (15) occurred within the 6 months after onset. Conclusion Age at CVT onset, non-administration of anticoagulation, persistent venous occlusion, and presence of G20210A mutation in factor 11 predict recurrent VT in children. Secondary prophylactic anticoagulation should be given on a patient-to-patient basis in children with newly identified CVT and at high risk of recurrent VT. Factors that affect recanalisation need further research

Production and characterization of monoclonal anti-sphingosine-1-phosphate antibodies1

Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid involved in multiple physiological processes. Importantly, dysregulated S1P levels are associated with several pathologies, including cardiovascular and inflammatory diseases and cancer. This report describes the successful production and characterization of a murine monoclonal antibody, LT1002, directed against S1P, using novel immunization and screening methods applied to bioactive lipids. We also report the successful generation of LT1009, the humanized variant of LT1002, for potential clinical use. Both LT1002 and LT1009 have high affinity and specificity for S1P and do not cross-react with structurally related lipids. Using an in vitro bioassay, LT1002 and LT1009 were effective in blocking S1P-mediated release of the pro-angiogenic and prometastatic cytokine, interleukin-8, from human ovarian carcinoma cells, showing that both antibodies can out-compete S1P receptors in binding to S1P. In vivo anti-angiogenic activity of all antibody variants was demonstrated using the murine choroidal neovascularization model. Importantly, intravenous administration of the antibodies showed a marked effect on lymphocyte trafficking. The resulting lead candidate, LT1009, has been formulated for Phase 1 clinical trials in cancer and age-related macular degeneration. The anti-S1P antibody shows promise as a novel, first-in-class therapeutic acting as a “molecular sponge” to selectively deplete S1P from blood and other compartments where pathological S1P levels have been implicated in disease progression or in disorders where immune modulation may be beneficial