Trypanocidal Activity of Marine Natural Products

Marine natural products are a diverse, unique collection of compounds with immense therapeutic potential. This has resulted in these molecules being evaluated for a number of different disease indications including the neglected protozoan diseases, human African trypanosomiasis and Chagas disease, for which very few drugs are currently available. This article will review the marine natural products for which activity against the kinetoplastid parasites; Trypanosoma brucei brucei, T.b. rhodesiense and T. cruzi has been reported. As it is important to know the selectivity of a compound when evaluating its trypanocidal activity, this article will only cover molecules which have simultaneously been tested for cytotoxicity against a mammalian cell line. Compounds have been grouped according to their chemical structure and representative examples from each class were selected for detailed discussion.     

Genome‐wide association analysis of salmon lice (Lepeophtheirus salmonis) resistance in a North American Atlantic salmon population

Our objective was to detect single nucleotide polymorphisms (SNPs) associated with resistance to the salmon louse in the Saint John River aquacultural population of North American Atlantic salmon using estimated breeding values (EBVs) and 6K genotypes from the parent‐generation and lice count phenotypes from the challenged, but ungenotyped, offspring‐generation. In 2011 and 2012, we challenged recent smolts with approximately 100 copepodids each. Fish were euthanized once the lice reached the chalimus stages and lice count, sex, tank and salt water weight were recorded. We used a multiple trait model to estimate breeding values for the parent‐generation using their own fresh water weights and the salt water weights and lice counts of the offspring‐generation. Salmon lice count heritability for untransformed and transformed data was 0.17 and 0.29 respectively. Two different genome‐wide association study methods were compared: (i) forward multiple linear regression and (ii) a mixed linear model using principal components to correct for population stratification as implemented in the egscore function of GenABEL. The two methods detected different SNPs located on different chromosomes. The multiple regression method incorporated 70 SNPs found on chromosomes 2, 7, 9, 12, 14, 15, 21, 22, 1p/23, 24. Many SNPs entered into the forward multiple regression are likely to be false positives from not correcting for the observed population stratification and cryptic relatedness. In contrast, the mixed linear model identified only two SNPs, one on chromosome 1p/23 (6.9%) and one on chromosome 1q (6.1%) consistent with louse‐resistance being a quantitative trait.     

A single IGF1 allele is a major determinant of small size in dogs

The domestic dog exhibits greater diversity in body size than any other terrestrial vertebrate. We used a strategy that exploits the breed structure of dogs to investigate the genetic basis of size. First, through a genome-wide scan, we identified a major quantitative trait locus (QTL) on chromosome 15 influencing size variation within a single breed. Second, we examined genetic variation in the 15-megabase interval surrounding the QTL in small and giant breeds and found marked evidence for a selective sweep spanning a single gene (IGF1), encoding insulin-like growth factor 1. A single IGF1 single-nucleotide polymorphism haplotype is common to all small breeds and nearly absent from giant breeds, suggesting that the same causal sequence variant is a major contributor to body size in all small dogs.     

Evaluation of laparoscopic-assisted placement of jejunostomy feeding tubes in dogs

OBJECTIVE: To evaluate feasibility of performing laparoscopic-assisted placement of a jejunostomy feeding tube (J-tube) and compare complications associated with placement, short-term feedings, and medium-term healing with surgically placed tubes in dogs. DESIGN: Prospective study. ANIMALS: 15 healthy mixed-breed dogs. PROCEDURES: Dogs were randomly allocated to undergo open surgical or laparoscopic-assisted J-tube placement. Required nutrients were administered by a combination of enteric and oral feeding while monitoring for complications. Radiographic contrast studies documented tube direction and location, altered motility, or evidence of stricture. RESULTS: Jejunostomy tubes were successfully placed in the correct location and direction in all dogs. In the laparoscopic group, the ileum was initially selected in 2 dogs, 2 dogs developed moderate hemorrhage at a portal site, and 2 J-tubes kinked during placement but were successfully readjusted postoperatively. All dogs tolerated postoperative feedings. All dogs developed minor ostomy site inflammation, and 1 dog developed bile-induced dermatitis at the ostomy site. Despite mild, transient neutrophilia, no significant difference was noted in WBC counts between groups. No dog had altered gastric motility or evidence of stricture, although the jejunopexy site remained identifiable in several dogs at 30 days. CONCLUSIONS AND CLINICAL RELEVANCE: Requirements for successful J-tube placement were met by use of a laparoscopic-assisted technique, and postoperative complications were mild and comparable to those seen with surgical placement. Laparoscopic-assisted J-tube placement compares favorably to surgical placement in healthy dogs and should be considered as an option for dogs requiring enterostomy feeding but not requiring a celiotomy for other reasons.     

Pulmonary thromboembolism associated with Blastomyces dermatitidis in a dog

An 8-year-old, male castrated golden retriever presented for cough and increased respiratory effort. Radiographs revealed an alveolar pattern in the right caudal lung lobe and an opacity at the carina suspected to be enlarged tracheobronchial lymph nodes. The disease progressed to involve the right middle lung lobe. Cytopathology of a fine-needle aspirate and bronchoalveolar lavage fluid were nondiagnostic. Surgical removal of the right caudal lung lobe and biopsy of the perihilar lymph nodes revealed pulmonary thromboembolism and reactive lymph nodes. The dog died several days postoperatively, and necropsy revealed diffuse pulmonary thromboembolism. Additionally, Blastomyces dermatitis organisms were identified in a pyogranulomatous mass surrounding the trachea near the carina. In an extensive literature search, no reports of pulmonary thromboembolism associated with blastomycosis were identified. It is suspected that the inflammation secondary to blastomycosis caused the thromboembolism.     

Effects of Cocoa-Derived Polyphenols on Cognitive Function in Humans. Systematic Review and Analysis of Methodological Aspects

Plant Foods for Human Nutrition - The effects of cocoa-derived polyphenols on cognitive functions have been analyzed through numerous studies using different interventions (doses, vehicles, time...     

Effect of dosing and sampling time on serum thyroxine, free thyroxine, and thyrotropin concentrations in dogs following multidose etodolac administration

Thirty-eight dogs with orthopedic disorders received etodolac, an NSAID, at 10.0 to 13.3 mg/kg PO once daily for 14 to 19 days. Mean total thyroxine (T4), free thyroxine (fT4), and canine thyrotropin (cTSH) values before and after etodolac administration were compared using paired t-tests. A significant (P <.05) decrease in T4 values occurred after etodolac administration with 21% of these values falling below the reference range. A significant (P <.05) increase in cTSH following etodolac administration, but none of the values was above the reference range. No significant changes occurred in mean fT4 values; however, 10% of the values fell below the reference range. In conclusion, T4 and fT4 test results should be interpreted with caution in dogs receiving etodolac.     

The expression of histamine H4 receptor mRNA in the skin and other tissues of normal dogs

The histamine 4 (H₄) receptor was first cloned and characterized in 2000 using the human H₃ receptor DNA sequence. The H₄ receptor has been shown to participate in various aspects of inflammation, such as chemotaxis, upregulation of adhesion molecule expression and modulation of cytokine secretion. The primary goal of this study was to determine whether H₄ receptor mRNA is expressed in normal canine skin by performing an RT‐PCR. An additional goal was to determine the expression of this receptor in the colon, liver, spleen and kidney. Tissues were collected from five healthy, young‐adult pit bull dogs. Samples were immediately placed in RNAlater^® solution and stored at ?20°C until processed. The amplified products in all skin samples in addition to the colon, liver, spleen and kidney (variable expression) had the expected size of 400–500 bp. The sequenced amplicons matched the National Center for Biotechnology Information published sequence for the canine H₄ receptor. The study results showed that canine normal skin expresses the H₄ receptor mRNA. Further studies using immunohistochemistry should be conducted to demonstrate the expression of the H₄ receptor at the protein level and to localize the expression of this receptor in the skin.     

Evaluation of head-out constant volume body plethysmography for measurement of specific airway resistance in conscious, sedated sheep

OBJECTIVE: To evaluate the use of a modified whole body plethysmograph in awake sheep. ANIMALS: 10 healthy adult sheep. PROCEDURE: Concurrent measurements of specific airway resistance (sR(aw)) and pulmonary resistance (R(L)) were obtained using a novel noninvasive head-out constant-volume plethysmograph and esophageal balloon-pneumotachography, respectively. All data were collected before and after external resistive loading with 1 and 5.6 cm H2O/L/s. Functional residual capacity (FRC) was measured by helium dilution for computation of airway resistance (R(aw)) preloading (R(aw) = sR(aw)/FRC). RESULTS: The sR(aw) and R(L) were closely correlated in 10 adult sheep. Additionally, sR(aw), and R(L) accurately reflected the magnitude of added resistance. The mean FRC was 52 mL/kg and used to calculate R(aw). At baseline, the values for R(aw) were significantly correlated with sR(aw) and R(L). CONCLUSIONS AND CLINICAL RELEVANCE: Precise measurements of sR(aw) and R(aw) at baseline and sR(aw) after external resistive loading were obtained by use of this novel noninvasive plethysmographic technology. This method should have application to veterinary patients or animals used in research in which noninvasive rapid or serial measurements of sR(aw) in the conscious state are required.     

Identification of stable normalization genes for quantitative real-time PCP, in porcine articular cartilage

Background: Expression levels for genes of interest must be normalized with an appropriate reference, or housekeeping gene, to make accurate comparisons of quantitative real-time PCR results. The purpose of this study was to identify the most stable housekeeping genes in porcine articular cartilage subjected to a mechanical injury from a panel of 10 candidate genes. Results: Ten candidate housekeeping genes were evaluated in three different treatment groups of mechanically impacted porcine articular cartilage. The genes evaluated were: beta actin, beta-2-microglobulin, glyceraldehyde-3-phosphate dehydrogenase, hydroxymethylbilane synthase, hypoxanthine phosphoribosyl transferase, peptidylprolyl isomerase A (cyclophilin A), ribosomal protein L4, succinate dehydrogenase flavoprotein subunit A, TATA box binding protein, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein-zeta polypeptide. The stability of the genes was measured using geNorm, BestKeeper, and NormFinder software. The four most stable genes measured via geNorm were (most to least stable) succinate dehydrogenase flavoprotein, subunit A, peptidylprolyl isomerase A, glyceraldehyde-3-phosphate dehydrogenase, beta actin; the four most stable genes measured via BestKeeper were glyceraldehyde-3-phosphate dehydrogenase, peptidylprolyl isomerase A, beta actin, succinate dehydrogenase flavoprotein, subunit A; and the four most stable genes measured via NormFinder were peptidylprolyl isomerase A, succinate dehydrogenase flavoprotein, subunit A, glyceraldehyde-3-phosphate dehydrogenase, beta actin. Conclusions: BestKeeper, geNorm, and NormFinder all generated similar results for the most stable genes in porcine articular cartilage. The use of these appropriate reference genes will facilitate accurate gene expression studies of porcine articular cartilage and suggest appropriate housekeeping genes for articular cartilage studies in other species.