The effects of aspirin on gastric mucosal integrity, surface hydrophobicity, and prostaglandin metabolism in cyclooxygenase knockout mice

BACKGROUND & AIMS: Insight into the role of the different cyclooxygenase isoforms in prostaglandin biosynthesis, surface hydrophobicity, and gastric mucosal barrier integrity can be gained by comparing the effects of luminal damaging agents in wild-type and cyclooxygenase knockout mice. METHODS: Fasted wild-type, cyclooxygenase-1, and cyclooxygenase-2 knockout mice were intragastrically administered saline, 0.6N HCl, or aspirin (aspirin 20 mmol/L) in combination with 0.6N HCl and killed 1 hour later, at which time the gastric lesion score was assessed and biopsy samples were taken for surface, biochemical, and morphological analyses. RESULTS: The gastric mucosa of cyclooxygenase-1 knockout mice was more severely injured by both HCl alone and aspirin/HCl than that of wild-type and cyclooxygenase-2 knockout mice. HCl alone and aspirin/HCl also induced a more profound decrease in surface hydrophobicity in cyclooxygenase-1 knockout mice than in wild-type mice, whereas this surface property was unaffected in cyclooxygenase-2 knockout mice. The gastric injury induced by aspirin/HCl in cyclooxygenase-1 knockout mice could be prevented if the animals were treated with phosphatidylcholine-associated aspirin. Aspirin/HCl, in comparison to saline or HCl alone, induced a 4-6-fold increase in gastric mucosal prostaglandin E(2) concentration in the cyclooxygenase-1 knockout mice, whereas it decreased prostaglandin E(2) levels in wild-type and cyclooxygenase-2 knockout mice. This paradoxical aspirin-induced increase in gastric prostaglandin E(2) in cyclooxygenase-1 knockout mice seemed to correspond to an increase in cyclooxygenase-2 messenger RNA and protein expression. The gastric lesion score seemed to be significantly associated with alterations in surface hydrophobicity but not with mucosal prostaglandin E(2) concentration. CONCLUSIONS: Our evidence on cyclooxygenase knockout mice suggests that aspirin predominantly causes gastric injury by a non-prostaglandin mechanism, perhaps by attenuating surface hydrophobicity, a possibility supported by the low gastric toxicity of phosphatidylcholine/aspirin. However, prostaglandins generated by cyclooxygenase-1 may play an important permissive role in maintaining gastric mucosal barrier integrity. Aspirin seems to paradoxically increase the gastric mucosal prostaglandin E(2) concentration in cyclooxygenase-1 knockout mice, possibly by the induction of cyclooxygenase-2.     

Trichomonicidal activity of a new anthraquinone isolated from the roots of Morinda panamensis Seem

Trichomoniasis, caused by the protozoan parasite Trichomonas vaginalis, is the most common nonviral sexually transmitted infection worldwide. Although drug treatment is available, unpleasant side effects and increased resistance to the nitroimidazole family have been documented. Hence, there is a need for the identification of new and safe therapeutic agents against T. vaginalis. Antimicrobial activity of anthraquinone compounds has been reported by a number of authors. The genus Morinda is well known for the diversity of anthraquinones with numerous biological activities. A new anthraquinone, lucidin-ω-isopropyl ether, was isolated from the roots of Morinda panamensis Seem. The structure of the compound was determined by ¹H and ¹³C Nuclear Magnetic Resonance (NMR) analyses, in addition to comparison with literature reports. Using in vitro susceptibility assay, the half inhibitory concentration (IC₅₀) of lucidin-ω-isopropyl ether for T. vaginalis (1.32 μg/mL) was found similar to that of metronidazole concentration tested (6 μM = 1.03 μg/mL). In addition, this anthraquinone was capable of inhibiting the parasite's ability to kill HeLa cells and decreased proteolytic activity of the proteinase TvMP50 from T. vaginalis. This was associated with the decreased expression of the mp50 gene. These results demonstrate the trichomonicidal potential by lucidin-ω-isopropyl ether. Further action-mode studies are necessary to elucidate the antiparasitic mechanism of this new anthraquinone to develop a more potent antitrichomonal agent.     

Allee effect promotes diversity in traveling waves of colonization

Most mathematical studies on expanding populations have focused on the rate of range expansion of a population. However, the genetic consequences of population expansion remain an understudied body of theory. Describing an expanding population as a traveling wave solution derived from a classical reaction-diffusion model, we analyze the spatio-temporal evolution of its genetic structure. We show that the presence of an Allee effect (i.e., a lower per capita growth rate at low densities) drastically modifies genetic diversity, both in the colonization front and behind it. With an Allee effect (i.e., pushed colonization waves), all of the genetic diversity of a population is conserved in the colonization front. In the absence of an Allee effect (i.e., pulled waves), only the furthest forward members of the initial population persist in the colonization front, indicating a strong erosion of the diversity in this population. These results counteract commonly held notions that the Allee effect generally has adverse consequences. Our study contributes new knowledge to the surfing phenomenon in continuous models without random genetic drift. It also provides insight into the dynamics of traveling wave solutions and leads to a new interpretation of the mathematical notions of pulled and pushed waves.     

Laparoscopic-assisted versus open resection of right-sided colonic cancer—a prospective randomized controlled trial

Purposes  

This study aims to compare the perioperative outcomes and survival between laparoscopic-assisted right hemicolectomy (LARH) and open right hemicolectomy (ORH) for right-sided colon cancer.     

Developmental outcomes of children with congenital diaphragmatic hernia: A multicenter prospective study

Purpose

To determine developmental outcomes and associated factors in patients with congenital diaphragmatic hernia (CDH) at 2 years of age.

Methods

This is a multicenter prospective study of a CDH birth cohort. Clinical and socioeconomic data were collected. Bayley Scales of Infant Development (BSID-III) and Vineland Adaptive Behavior Scales (VABS-II) were performed at 2 years of age.

Results

BSID-III and VABS-II assessments were completed on 48 and 49 children, respectively. The BSID-III mean cognitive, language, and motor scores were significantly below the norm mean with average scores of 93 ± 15, 95 ± 16, and 95 ± 11. Ten percent (5/47) scored more than 2 standard deviations below the norm on one or more domains. VABS-II scores were similar to BSID-III scores with mean communication, daily living skills, social, motor, adaptive behavior scores of 97 ± 14, 94 ± 16, 93 ± 13, 97 ± 10, and 94 ± 14. For the BSID-III, supplemental oxygen at 28 days, a prenatal diagnosis, need for extracorporeal membrane oxygenation (ECMO) and exclusive tube feeds at time of discharge were associated with lower scores. At 2 years of age, history of hospital readmission and need for tube feeds were associated with lower scores. Lower socioeconomic status correlated with lower developmental scores when adjusted for significant health factors.

Conclusion

CDH patients on average have lower developmental scores at 2 years of age compared to the norm. A need for ECMO, oxygen at 28 days of life, ongoing health issues and lower socioeconomic status are factors associated with developmental delays.     

The diagnostic value of fine needle aspiration in parotid lumps

Introduction

Fine needle aspiration (FNA) is a safe and quick method of diagnosing superficial lumps, which aids preoperative planning. However, FNA of the parotid gland has not gained the widespread acceptance noted in other head and neck lumps. The aim of this study was to determine the ability of FNA of the parotid gland to differentiate benign and malignant disease, and to determine the impact on surgical outcome.

Methods

A retrospective analysis of 201 consecutive parotid operations with preoperative FNA in a large district hospital in the UK was performed. The diagnostic characteristics were calculated for benign and malignant disease, and the impact on surgical procedure was determined.

Results

In identifying benign disease, FNA has a sensitivity of 85% and a specificity of 76%. In detecting malignant disease, FNA has a sensitivity and specificity of 52% and 92% respectively. A false positive on FNA was associated with a higher incidence of neck dissection.

Conclusions

FNA is a useful diagnostic test. However, owing to low sensitivity, it is necessary to interpret it in the context of all other clinical information.