Intestinal transplantation under tacrolimus monotherapy after perioperative lymphoid depletion with rabbit anti-thymocyte globulin (thymoglobulin®)

Modifications in the timing and dosage of immunosuppression can ameliorate the morbidity and mortality that has prevented widespread use of intestinal transplantation (ITx) in children. Thirty-six patients receiving ITx, aged 5 months to 20 years were given 2-3 mg(kg of rabbit anti-thymocyte globulin (rATG, thymoglobulin®) just before ITx, and 2-3 mg(kg post-operatively (total 5 mg(kg). Twice daily doses of tacrolimus (TAC) were begun enterally within 24 h after graft reperfusion with reduction of dose quantity or frequency after 3 months. Prednisone or other agents were given to treat breakthrough rejection. After 8-28 months follow-up (mean 15.8 ± 5.3), 1- and 2-year patient and graft survival is 100% and 94%, respectively. Despite a 44% incidence of acute rejection in the first month, 16 of the 34 (47%) survivors are on TAC (n = 14) or sirolimus (n = 2) monotherapy; 15 receive TAC plus low dose prednisone; one each receive TAC plus sirolimus, TAC plus azathioprine and TAC plus sirolimus and prednisone. There was a low incidence of immunosuppression-related complications. This strategy of immunosuppression minimized maintenance TAC exposure, facilitated the long-term control of rejection, decreased the incidence of opportunistic infections, and resulted in a high rate of patient and graft survival. Copyright © Blackwell Munksgaard 2005

Pancreatic transplantation at the University of Pittsburgh.

Campath-1H preconditioning with tacrolimus monotherapy is an effective immunosuppressive regimen for pancreas transplantation, with acceptable patient and graft survival rates early after transplantation. Rejection rates are low under this protocol if the tacrolimus level is kept consistently >10 ng/ml. This immunosuppressive protocol, combined with recent technical refinements, has resulted in lower rates of thrombosis and overall complications. Pancreatic transplantation en-bloc with visceral grafts has the following unique features: Diabetes is a rare indication, and HLA matching is not required. The gland is immunologically protected by the simultaneously transplanted visceral organs. Disease gravity, surgical complexity and gut alloimmunity influence the overall pancreatic allograft survival. The current UNOS listing criteria and data registry should be modified for obvious logistic and scientific reasons

Evaluation of lateral flow assay as a field test for sero-diagnosis of bovine brucellosis

Indirect-ELISA offers a significant advantage over conventional serological methods in the diagnosis of brucellosis in endemic geographical region. Considering iELISA as a gold standard test, RBPT was more sensitive than LFA and the concordance of iELISA with LFA was comparable. The Lateral flow assay is a rapid point-of - care diagnostic test which makes it ideal for use in resource pour countries. It is an immuno-assay and is used also for diagnosis of bovine brucellosis. It is a highly sensitive and specific test which does not require expensive equipment, electricity and or refrigeration or special training. The LFA has shown good PPV (positive predictive value) and NPV (negative predictive value) greater than RBPT in the current study suggest that the test is a simple, cost-effective and rapid that provides accurate detection of antibodies to B. abortus in bovine serum samples, thereby saving time and eliminating the need for special training. It could be used conveniently on the field even in farms located in remote areas. However, evaluation on large sample size would be required for future use. Hence, looking to the results obtained in the present study and by other workers, it is recommended that this rapid test can therefore be practically implemented in serological screening for bovine brucellosis, although evaluation on a larger scale with various sera, and blood samples is still necessary

Health promoting potential of herbal teas and tinctures from Artemisia campestris subsp maritima: from traditional remedies to prospective products

This work explored the biotechnological potential of the medicinal halophyte Artemisia campestris subsp. maritima (dune wormwood) as a source of health promoting commodities. For that purpose, infusions, decoctions and tinctures were prepared from roots and aerial-organs and evaluated for in vitro antioxidant, anti-diabetic and tyrosinase-inhibitory potential, and also for polyphenolic and mineral contents and toxicity. The dune wormwood extracts had high polyphenolic content and several phenolics were identified by ultra-high performance liquid chromatography-photodiode array-mass-spectrometry (UHPLC-PDA-MS). The main compounds were quinic, chlorogenic and caffeic acids, coumarin sulfates and dicaffeoylquinic acids; several of the identified phytoconstituents are here firstly reported in this A. campestris subspecies. Results obtained with this plant's extracts point to nutritional applications as mineral supplementary source, safe for human consumption, as suggested by the moderate to low toxicity of the extracts towards mammalian cell lines. The dune wormwood extracts had in general high antioxidant activity and also the capacity to inhibit a-glucosidase and tyrosinase. In summary, dune wormwood extracts are a significant source of polyphenolic and mineral constituents, antioxidants and a-glucosidase and tyrosinase inhibitors, and thus, relevant for different commercial segments like the pharmaceutical, cosmetic and/or food industries.FCT - Foundation for Science and Technology [CCMAR/Multi/04326/2013]; Portuguese National Budget; FCT [IF/00049/2012, SFRH/BD/94407/2013]; Research Foundation - Flanders (FWO) [12M8315N]info:eu-repo/semantics/publishedVersio

The role of ARF6 in biliary atresia

Background & Aims: Altered extrahepatic bile ducts, gut, and cardiovascular anomalies constitute the variable phenotype of biliary atresia (BA). Methods: To identify potential susceptibility loci, Caucasian children, normal (controls) and with BA (cases) at two US centers were compared at >550000 SNP loci. Systems biology analysis was carried out on the data. In order to validate a key gene identified in the analysis, biliary morphogenesis was evaluated in 2-5-day post-fertilization zebrafish embryos after morpholino-antisense oligonucleotide knockdown of the candidate gene ADP ribosylation factor-6 (ARF6, Mo-arf6). Results: Among 39 and 24 cases at centers 1 and 2, respectively, and 1907 controls, which clustered together on principal component analysis, the SNPs rs3126184 and rs10140366 in a 3' flanking enhancer region for ARF6 demonstrated higher minor allele frequencies (MAF) in each cohort, and 63 combined cases, compared with controls (0.286 vs. 0.131, P = 5.94 x 10-7, OR 2.66; 0.286 vs. 0.13, P = 5.57 x 10-7, OR 2.66). Significance was enhanced in 77 total cases, which included 14 additional BA genotyped at rs3126184 only (p = 1.58 x 10-2, OR = 2.66). Pathway analysis of the 1000 top-ranked SNPs in CHP cases revealed enrichment of genes for EGF regulators (p<1 x 10-7), ERK/MAPK and CREB canonical pathways (p<1 x 10-34), and functional networks for cellular development and proliferation (p<1 x 10-45), further supporting the role of EGFR-ARF6 signaling in BA. In zebrafish embryos, Mo-arf6 injection resulted in a sparse intrahepatic biliary network, several biliary epithelial cell defects, and poor bile excretion to the gall bladder compared with uninjected embryos. Biliary defects were reproduced with the EGFR-blocker AG1478 alone or with Mo-arf6 at lower doses of each agent and rescued with arf6 mRNA. Conclusions: The BA-associated SNPs identify a chromosome 14q21.3 susceptibility locus encompassing the ARF6 gene. arf6 knockdown in zebrafish implicates early biliary dysgenesis as a basis for BA, and also suggests a role for EGFR signaling in BA pathogenesis