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Cooperia oncophora is one of the most common intestinal parasitic nematodes in cattle worldwide. To date, C. oncophora infections are treated using broad-spectrum anthelmintics. However, during the past decade, reports of anthelmintic resistance in this parasite species have emerged worldwide, necessitating new avenues for its control, possibly through vaccination. In this frame, we analyzed the adult-stage C. oncophora excretome/secretome (ES), covering both the protein and glycan components, since this fraction constitutes the primary interface between parasite and host and may hold potential vaccine candidates. Two-dimensional gel electrophoretic separation of the ES material enabled the MALDI-TOF mass spectrometry (MS)-directed identification of 12 distinct proteins, grouped in three separate molecular weight fractions: (i) a high molecular weight fraction consisting of a double-domain activation-associated secreted protein (ASP), (ii) a midmolecular weight fraction predominantly containing a single-domain ASP, a thioredoxin peroxidase and innexin, and (iii) a low molecular weight protein pool essentially holding two distinct low molecular weight antigens. Further MS-driven glycan analysis mapped a variety of N-glycans to the midmolecular weight single-domain ASP, with Man6GlcNAc2 oligomannosyl glycans as the major species. The predominance of the nonglycosylated double-domain ASP in the high-molecular weight fraction renders it ideal for advancement toward vaccine trials and development.

Resistance against macrocyclic lactones such as ivermectin is widespread among parasitic gastrointestinal nematodes of small ruminants and is rapidly increasing in cattle parasites. ABC transporters of the subfamily B, the so-called P-glycoproteins (Pgps) have been frequently implicated in ivermectin resistance and are a major cause of multi-drug resistance in protozoa and helminths. The Pgp inhibitor verapamil (VPL) dramatically enhanced susceptibility of the cattle parasitic nematode Cooperia oncophora to ivermectin in vitro as measured in a larval developmental assay and a larval migration inhibition assay using third stage larvae. Moreover, VPL completely restored susceptibility to ivermectin in a resistant isolate resulting in virtually identical dose-response curves of susceptible and resistant isolates in the presence of VPL. Further characterisation of the molecular mechanisms resulting in Pgp-mediated ivermectin resistance is still hampered by the lack of molecular and biochemical information for Pgps of parasitic nematodes. Using PCR with degenerate primers, fragments of four different C. oncophora Pgps could be amplified and the Conpgp-2, previously implicated in macrocyclic lactone resistance in Haemonchus contortus, and Conpgp-3 full-length cDNAs were obtained by RACE PCR. The pgp sequences presented here contribute important data required to systematically screen resistant C. oncophora isolates for up- or down-regulation of Pgps and for the detection of single nucleotide polymorphisms in Pgps to detect selection of specific Pgp alleles by anthelmintics as early as possible., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Cooperia oncophora and Ostertagia ostertagi are among the most important gastrointestinal nematodes of cattle worldwide. The economic losses caused by these parasites are on the order of hundreds of millions of dollars per year. Conventional treatment of these parasites is through anthelmintic drugs; however, as resistance to anthelmintics increases, overall effectiveness has begun decreasing. New methods of control and alternative drug targets are necessary. In-depth analysis of transcriptomic data can help provide these targets., Results: The assembly of 8.7 million and 11 million sequences from C. oncophora and O. ostertagi, respectively, resulted in 29,900 and 34,792 transcripts. Among these, 69% and 73% of the predicted peptides encoded by C. oncophora and O. ostertagi had homologues in other nematodes. Approximately 21% and 24% were constitutively expressed in both species, respectively; however, the numbers of transcripts that were stage specific were much smaller (~1% of the transcripts expressed in a stage). Approximately 21% of the transcripts in C. oncophora and 22% in O. ostertagi were up-regulated in a particular stage. Functional molecular signatures were detected for 46% and 35% of the transcripts in C. oncophora and O. ostertagi, respectively. More in-depth examinations of the most prevalent domains led to knowledge of gene expression changes between the free-living (egg, L1, L2 and L3 sheathed) and parasitic (L3 exsheathed, L4, and adult) stages. Domains previously implicated in growth and development such as chromo domains and the MADF domain tended to dominate in the free-living stages. In contrast, domains potentially involved in feeding such as the zinc finger and CAP domains dominated in the parasitic stages. Pathway analyses showed significant associations between life-cycle stages and peptides involved in energy metabolism in O. ostertagi whereas metabolism of cofactors and vitamins were specifically up-regulated in the parasitic stages of C. oncophora. Substantial differences were observed also between Gene Ontology terms associated with free-living and parasitic stages., Conclusions: This study characterized transcriptomes from multiple life stages from both C. oncophora and O. ostertagi. These data represent an important resource for studying these parasites. The results of this study show distinct differences in the genes involved in the free-living and parasitic life cycle stages. The data produced will enable better annotation of the upcoming genome sequences and will allow future comparative analyses of the biology, evolution and adaptation to parasitism in nematodes.

Two patients with high-output gastrocutaneous fistulas were treated with total parenteral nutrition and gastric antisecretory drugs. IV administration of omeprazole decreased acid output in one patient in a rapid and significant way, resulting in the spontaneous healing of the fistula after eight days of treatment. In the second patient, omeprazole caused a marked reduction in the acidity of the fluid in the fistula, which also closed without surgical operation. The long-standing decrease in acid output induced by intravenous omeprazole may be very useful for promoting spontaneous closure of high-output gastrocutaneous fistula.

Helodermin is a peptide from the venom of the lizard Heloderma suspectum (Gila Monster) showing a high degree of sequence similarity with VIP, PHI and secretin in its N-terminal moiety. The present data support the presence of peptide(s) closely related to helodermin in the brain, gut and salivary glands of rat. In our radioimmunoassays, we routinely used one of the three specific antisera obtained from rabbits that were immunized against lizard helodermin coupled to bovine serum albumin with carbodiimide. Heat- and acid-stable immunoreactive helodermin-like material was more abundant in striatum, hippocampus and anterior pituitary than in cerebral cortex and hypothalamus. High levels of helodermin-like material were also present in salivary glands, duodenum and jejunum. When submitted to gel permeation chromatography on a TSK-G 2000 SW column, the apparent molecular radius of most of the immunoreactive material ranged from 6 to 12 KDa.

In 4 conscious dogs with gastric fistulas the somatostatin responses to a meal were measured and compared to the responses seen after i.v. infusion of atropine sulfate (20 and 50 micrograms.kg-1.h-1) or cimetidine (8 mg.kg-1.h-1). The experiments were repeated after truncal vagotomy. The somatostatin responses to bombesin (0.5 micrograms.kg-1.h-1) were also measured before and after vagotomy. Vagotomy decreased basal and postprandial somatostatin levels and reduced the somatostatin responses to feeding during the first 30-min period following the ingestion of the meal but not during subsequent periods. Bombesin-induced somatostatin release was increased after vagotomy. Atropine decreased the somatostatin responses to the meal before and after vagotomy. Cimetidine had no significant effect. These studies suggest that, in conscious dogs, somatostatin released into the circulation is partly under vagal control and that, as for gastrin release, vagal pathways for stimulation and inhibition are present. Our studies also suggest that cholinergic mechanisms are involved in the control of postprandial somatostatin release.

The results of 631 cancers of the stomach treated by gastrectomy between 1970 and 1983 were closely reviewed in six departments of surgery. This review showed that the prognostic factors determined by resectability, extension of the tumor and lymph node involvement are considered to be reliable following the various pre- and postoperative examinations. In addition, it was shown that most of the gastrectomies were performed following conventional procedures and that the widespread lymph node dissections are not applied in a systematic manner. The postoperative mortality is very low (4.4%) for all the gastrectomies and even lower for the radical gastrectomies (3%). The 5 year survival rate for all the gastrectomies is 15%; this rate amounts to 36% for the gastrectomies performed with a curative aim. In the discussion, the adjuvant radiotherapy and chemotherapy are discussed and their timeliness is shown.

The pharmacological treatment of alimentary tract fistulas was for a long time limited to the use of atropine and related substances. More recently H2 blockers, pirenzepine, omeprazole and loperamide have been used. It is likely that in the coming years specific and long acting derivatives of somatostatin and enkephalins inhibiting digestive secretions will be synthetized.