To expand the potential of pseudopterosins and seco-pseudopterosins isolated from the octocoral Pseudopterogorgia elisabethae of San Andrés and Providencia islands (southwest Caribbean Sea), we report the anti-microbial profile against four pathogenic microorganisms (Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Candida albicans) and report a more complete cytotoxic profile against five human cells lines (HeLa, PC-3, HCT116, MCF-7 and BJ) for the compounds PsG, PsP, PsQ, PsS, PsT, PsU, 3-O-acetyl-PsU, seco-PsJ, seco-PsK and IMNGD. For the cytotoxic profiles, all compounds evaluated showed moderate and non-selective activity against both tumor and normal cell lines, where PsQ and PsG were the most active compounds (GI50 values between 5.8 μM to 12.0 μM). With respect to their anti-microbial activity the compounds showed good and selective activity against the Gram-positive bacteria, while they did not show activity against the Gram-negative bacterium or yeast. PsU, PsQ, PsS, seco-PsK and PsG were the most active compounds (IC50 2.9–4.5 μM) against S. aureus and PsG, PsU and seco-PsK showed good activity (IC50 3.1–3.8 μM) against E. faecalis, comparable to the reference drug vancomycin (4.2 μM).
BackgroundIt is currently unknown if the intrathecal administration of a high dose of allogeneic mesenchymal stem cells (MSCs) is safe, how MSCs migrate throughout the vertebral canal after intrathecal administration, and whether MSCs are able to home to a site of injury. The aims of the study were: 1) to evaluate the safety of intrathecal injection of 100 million allogeneic adipose-derived MSCs (ASCs); 2) to assess the distribution of ASCs after atlanto-occipital (AO) and lumbosacral (LS) injection in healthy horses; and 3) to determine if ASCs homed to the site of injury in neurologically diseased horses.MethodsSix healthy horses received 100 × 106 allogeneic ASCs via AO (n = 3) or LS injection (n = 3). For two of these horses, ASCs were radiolabeled with technetium and injected AO (n = 1) or LS (n = 1). Neurological examinations were performed daily, and blood and cerebrospinal fluid (CSF) were evaluated prior to and at 30 days after injection. Scintigraphic images were obtained immediately postinjection and at 30 mins, 1 h, 5 h, and 24 h after injection. Three horses with cervical vertebral compressive myelopathy (CVCM) received 100 × 106 allogeneic ASCs labeled with green fluorescent protein (GFP) via AO injection and were euthanized 1–2 weeks after injection for a full nervous system necropsy. CSF parameters were compared using a paired student’s t test.ResultsThere were no significant alterations in blood, CSF, or neurological examinations at any point after either AO or LS ASC injections into healthy horses. The radioactive signal could be identified all the way to the lumbar area after AO ASC injection. After LS injection, the signal extended caudally but only a minimal radioactive signal extended further cranially. GFP-labeled ASCs were not present at the site of disease at either 1 or 2 weeks following intrathecal administration.ConclusionsThe intrathecal injection of allogeneic ASCs was safe and easy to perform in horses. The AO administration of ASCs resulted in better distribution within the entire subarachnoid space in healthy horses. ASCs could not be found after 7 or 15 days of injection at the site of injury in horses with CVCM.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0849-6) contains supplementary material, which is available to authorized users.
Plant-endoparasitic root-knot nematodes feed on specialized giant cells that they induce in the vascular cylinder of susceptible plants. Although it has been established that a number of plant genes change their expression pattern during giant cell differentiation, virtually no data are available about the mechanisms involved in that change. One possibility is differential promoter recognition by the transcription factor(s) responsible for the expression of specific genes. We have isolated and characterized a genomic clone from tomato containing the promoter region of LEMMI9, one of the few plant genes that have been reported to be highly expressed in galls (predominantly in giant cells). The analysis of transgenic potato plants carrying a LEMMI9 promoter-beta glucuronidase (GUS) fusion has demonstrated that the tomato promoter was activated in Meloidogyne incognita-induced galls in a heterologous system. We have located putative regulatory sequences in the promoter and have found that nuclear proteins from the galls formed specific DNA-protein complexes with the proximal region of the LEMMI9 promoter. The nuclear protein-binding sequence mapped to a region of 111 bp immediately upstream from the TATA box. This region contains a 12-bp repeat possibly involved in the formation of DNA-protein complexes, which might be related to the LEMMI9 transcriptional activation in the giant cells.
This study searched for mutations in the MLH1 and MSH2 genes in 23 unrelated Colombian families with suspected hereditary nonpolyposis colorectal cancer (HNPCC). The families were grouped according to the fulfillment of the Amsterdam II criteria or the Bethesda guidelines. We screened all probands by single-strand conformational polymorphism (SSCP) and direct DNA sequencing. Eleven families fulfilled the Amsterdam criteria II and 12 families the Bethesda guidelines. Germline mutations were detected in 11 families, which corresponds to a mutation detection rate of 48%. When only families fulfilling the Amsterdam II criteria were analyzed, the mutation detection rate rose to 82%. Only 8% of the mutation detection rate was found in families following the Bethesda guidelines. Three mutations were shared by two different families, which corresponds to a total of eight different mutations, seven of them found in the MLH1 gene and one in the MSH2 gene. We have identified four mutations that have not been previously reported to the International Collaborative Group of HNPCC. Three of these are pathogenic, a single base substitution (C > T) at codon 640, exon 17, a G deletion at codon 619, exon 16 and in the MLH1 gene and a two-nucleotide deletion (TG) at codon 184, exon 3 in the MSH2. Also, an unclassified variant, a substitution (C > G) at the codon 141, exon 5 of the MLH1, was detected.
Emptying the vasculature with an Esmarch bandage before IV-RLP can improve amikacin concentrations in the metacarpophalangeal joint of horses with no effect on the levels of amikacin in the radiocarpal joint.
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