The proton pump inhibitors (PPIs) lansoprazole (LPZ) and omeprazole (OPZ) have been widely used for more than 20 years in the treatment of acid-related diseases such as gastro-duodenal ulcers and ...reflux esophagitis. Both LPZ and OPZ are derivatives of 2-(2- pyridylmethyl)sulfinyl-1H-benzimidazole, but LPZ has a trifluoroethoxy group in the molecule which seems to provide unique pharmacological properties in addition to its anti-secretory effect. For example, the anti-secretory effect of LPZ in rats was roughly 2 times greater than that of OPZ but the anti-ulcer effects were more than 10 times stronger than those of OPZ in rat models of reflux esophagitis, indomethacin-induced gastric antral ulcers and mepirizole-induced duodenal ulcers. It has also been reported that LPZ has acid-independent protective effects on the gastrointestinal mucosa, anti-inflammatory effects, and anti-bacterial effects on Helicobacter pylori. In contrast, recent advances in endoscopy have revealed that non-steroidal anti-inflammatory drugs (NSAIDs) often cause ulcers not only in the stomach and duodenum, but also in the small intestine in humans. Anti-secretory drugs such as PPIs and histamine H(2)-receptor antagonists (H(2)-RAs) are commonly used for the treatment of upper gastrointestinal mucosal lesions induced by NSAIDs. However, the effects of these drugs on NSAID-induced small intestinal lesions are still not fully understood. In this article, both a brief history of the discovery of LPZ and the unique pharmacological properties of LPZ independent from its anti-secretory action are reviewed, and the effects of PPIs and H(2)-RAs on NSAID-induced small intestinal lesions are discussed.
Background: The scientific discoveries of health risks resulting from methylmercury exposure began in 1865 describing ataxia, dysarthria, constriction of visual fields, impaired hearing, and sensory ...disturbance as symptoms of fatal methylmercury poisoning. Objective: Our aim was to examine how knowledge and consensus on methylmercury toxicity have developed in order to identify problems of wider concern in research. Data sources and extraction: We tracked key publications that reflected new insights into human methylmercury toxicity. From this evidence, we identified possible caveats of potential significance for environmental health research in general. Synthesis: At first, methylmercury research was impaired by inappropriate attention to narrow case definitions and uncertain chemical speciation. It also ignored the link between ecotoxicity and human toxicity. As a result, serious delays affected the recognition of methylmercury as a cause of serious human poisonings in Minamata, Japan. Developmental neurotoxicity was first reported in 1952, but despite accumulating evidence, the vulnerability of the developing nervous system was not taken into account in risk assessment internationally until approximately 50 years later. Imprecision in exposure assessment and other forms of uncertainty tended to cause an underestimation of methylmercury toxicity and repeatedly led to calls for more research rather than prevention. Conclusions: Coupled with legal and political rigidity that demanded convincing documentation before considering prevention and compensation, types of uncertainty that are common in environmental research delayed the scientific consensus and were used as an excuse for deferring corrective action. Symptoms of methylmercury toxicity, such as tunnel vision, forgetfulness, and lack of coordination, also seemed to affect environmental health research and its interpretation.
NSAID-induced enteropathy has been the focus of recent basic and clinical research subsequent to the development of the capsule endoscope and double-balloon endoscope. We review the possible ...pathogenic mechanisms underlying NSAID-induced enteropathy and discuss the role of the inhibition of COX-1/COX-2 and the influences of food as well as various prophylactic treatments on these lesions.
Studies were performed in experimental animals.
Multiple factors, such as intestinal hypermotility, decreased mucus secretion, enterobacteria, and upregulation of iNOS/NO expression, are involved in the pathogenesis of NSAID-induced enteropathy, in addition to the decreased production of PGs due to the inhibition of COX. Enterobacterial invasion is the most important pathogenic event, and intestinal hypermotility, which was associated with this event, is essential for the development of these lesions. NSAIDs also upregulate the expression of COX-2, and the inhibition of both COX-1 and COX-2 is required for the intestinal ulcerogenic properties of NSAIDs to manifest. NSAID-induced enteropathy is prevented by PGE2, atropine, ampicillin, and aminoguanidine as well as soluble dietary fiber, and exacerbated by antisecretory drugs such as proton pump inhibitors.
These findings on the pathogenesis of NSAID-induced enteropathy will be useful for the future development of intestinal-sparing alternatives to standard NSAIDs.
Evidence for a link between long-term exposure to air pollution and lung cancer is limited to Western populations. In this prospective cohort study, we examined this association in a Japanese ...population.
The study comprised 63 520 participants living in 6 areas in 3 Japanese prefectures who were enrolled between 1983 and 1985. Exposure to particulate matter less than 2.5 µm in aerodynamic diameter (PM(2.5)), sulfur dioxide (SO(2)), and nitrogen dioxide (NO(2)) was assessed using data from monitoring stations located in or nearby each area. The Cox proportional hazards model was used to calculate the hazard ratios associated with the average concentrations of these air pollutants.
The 10-year average concentrations of PM(2.5), SO(2), and NO(2) before recruitment (1974-1983) were 16.8 to 41.9 µg/m(3), 2.4 to 19.0 ppb, and 1.2 to 33.7 ppb, respectively (inter-area range). During an average follow-up of 8.7 years, there were 6687 deaths, including 518 deaths from lung cancer. The hazard ratios for lung cancer mortality associated with a 10-unit increase in PM(2.5) (µg/m(3)), SO(2) (ppb), and NO(2) (ppb) were 1.24 (95% confidence interval: 1.12-1.37), 1.26 (1.07-1.48), and 1.17 (1.10-1.26), respectively, after adjustment for tobacco smoking and other confounding factors. In addition, a significant increase in risk was observed for male smokers and female never smokers. Respiratory diseases, particularly pneumonia, were also significantly associated with all the air pollutants.
Long-term exposure to air pollution is associated with lung cancer and respiratory diseases in Japan.
ABSTRACT
Young barley leaves (Hordeum vulgare L.) have various health effects and are employed as an ingredient in the production of health-promoting foods. Promoting antiobesity is one such health ...effect; however, the mechanism and bioactive compounds are unclear. In this research, young barley leaf extract (YB) was demonstrated to possess pancreatic lipase inhibitory activity. The addition of YB to a high-fat diet in mice increased fecal lipid content, indicating reduced absorption of lipids as the mechanism underlying antiobesity effect. The investigation of bioactive compounds in YB resulted in the identification of fructose–bisphosphate aldolase as a proteinous lipase inhibitor. Maximum inhibition of the protein was 45%, but inhibition was displayed at a concentration as low as 16 ng/mL, which is a characteristic inhibition compared with other reported proteinous lipase inhibitors.
Rabbits are frequently used in studies assessing the toxicity of ophthalmic drugs; however, the postnatal histological changes that occur in the rabbit eye have not been fully described. To ...characterize postnatal ocular development in white rabbits, a histological investigation of the eyes and eyelids was sequentially performed between postnatal days (PNDs) 1 and 42. The eyes opened during PNDs10 to 12. Significant changes prior to eyelid opening included the proliferation of uveal and optic nerve cells, regression of the lenticular vasculature, and thinning of the retina with a decreasing number of retinal cells. After eyelid opening, several significant changes occurred in the anterior segment, including thickening of the cornea and the development of lacrimation-related tissues in the eyelid and conjunctiva. Additionally, the differentiation of retinal layer-derived cells and optic nerve thickening occurred. The lens size continued to increase throughout the postnatal period. The histological structure of the eyes and eyelids was nearly mature by PNDs28 to 42. This study characterizes the postnatal changes in the histological features of the eyes in juvenile white rabbits, providing fundamental knowledge on the appropriate design of histological studies of the eyes in juvenile rabbits, particularly ophthalmic drug evaluations.
Recent advances in endoscopic techniques such as capsule endoscopy have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the small intestine in humans, but there are ...few effective agents for treatment of small intestinal ulcers. Although the pathogenesis of NSAID-induced intestinal ulcer has been widely studied, dietary factors have seldom been considered. In the present review, the role of dietary fiber (DF) in the formation of NSAID-induced intestinal ulcers is discussed. In previous studies, small intestinal lesions were not observed when NSAIDs were administered to fasted rats, dogs, and cats, but were observed in conventionally-fed animals, suggesting the importance of feeding in the formation of intestinal lesions induced by NSAIDs. However, in animals fed diets containing low or no DF, indomethacin (IND) did not produce lesions in the small intestine, but did produce lesions in animals fed diets supplemented with insoluble dietary fiber (IDF, cellulose). The results suggest that IDF in the diet plays an important role in the formation of NSAID-induced intestinal lesions. On the other hand, addition of soluble dietary fibers (SDFs) such as pectin or mucin to regular diet markedly decreased NSAID-induced intestinal lesions. Thus, IDF and SDF have opposing effects on IND-induced intestinal lesions, i.e., IDF is harmful while SDF is protective. SDFs potentially represent a novel and safe means for protecting the small intestine against NSAID-induced intestinal lesions.
The effects of prenatal exposure to toxic elements on birth outcomes and child development have been an area of concern. This study aimed to assess the profile of prenatal exposure to toxic elements, ...arsenic (As), bismuth (Bi), cadmium (Cd), mercury (total mercury (THg), methylmercury (MHg), inorganic mercury (IHg)), lead (Pb), antimony (Sb) and tin (Sn), and essential trace elements, copper (Cu), selenium (Se) and zinc (Zn), using the maternal blood, cord blood and placenta in the Tohoku Study of Child Development of Japan (N = 594-650).
Inductively coupled plasma mass spectrometry was used to determine the concentrations of these elements (except mercury). Levels of THg and MeHg were measured using cold vapour atomic absorption spectrophotometry and a gas chromatograph-electron capture detector, respectively.
Median concentrations (25th-75th) of As, Cd, Pb, Sb, Sn and THg in the maternal blood were 4.06 (2.68-6.81), 1.18 (0.74-1.79), 10.8 (8.65-13.5), 0.2 (0.06-0.40) and 0.2 (0.1-0.38) ng mL
and 5.42 (3.89-7.59) ng g
, respectively. Median concentrations (25th-75th) of As, Cd, Pb, Sb, Sn and THg in the cord blood were 3.68 (2.58-5.25), 0.53 (0.10-1.25), 9.89 (8.02-12.5), 0.39 (0.06-0.92) and 0.2 (0.2-0.38) ng mL
and 9.96 (7.05-13.8) ng g
, respectively.
THg and Sb levels in the cord blood were twofold higher than those in the maternal blood. Cord blood to maternal blood ratios for As, Cd and Sb widely varied between individuals. To understand the effects of prenatal exposure, further research regarding the variations of placental transfer of elements is necessary.
Subclinical endometritis affects reproductive outcomes and causes economic losses in dairy cows, thus, it is important to understand disease progression mechanisms and develop diagnostic procedures ...for better disease management. We measured the levels of 146 lipid mediators in uterine flush samples using lipid chromatography-mass spectrometry. We detected 25 lipid mediators in the uterine flush of both the control and subclinical endometritis cows; 15 of the 25 lipid mediators were AA-derived metabolites. Among the AA-derived metabolites, cyclooxygenase (COX)-generated mediators were the most abundant. Specifically, levels of 11β-13,14-dihydro-15-keto prostaglandin (PG) F2α, PGE2, PGA2, 13-hydroxyoctadecadienoic acid, and PGD1 were elevated in all the cows with subclinical endometritis. This study may provide new insights for the management of subclinical bovine endometritis.
Antisecretory drugs such as histamine H2-receptor antagonists (H2-RAs) and proton pump inhibitors (PPIs) are commonly used for the treatment of gastric and duodenal ulcers induced by nonsteroidal ...anti-inflammatory drugs (NSAIDs). However, the effects of these drugs on NSAID-induced small intestinal ulcers are not fully understood. The effects of H2-RAs and PPIs on NSAID-induced gastrointestinal lesions and small intestinal motility were examined in rats. Male Wistar rats (180-220 g) were used. Indomethacin (10 mg/kg) was administered orally in fasted or fed rats, and gastrointestinal lesions were examined 24 h after indomethacin administration. Intestinal motility was measured by using a balloon method under urethane anesthesia. Indomethacin produced multiple lesions in the gastric corpus in fasted rats and in the small intestine in fed rats: 1) H2-RAs (cimetidine, ranitidine, and famotidine) and PPIs (omeprazole, lansoprazole, and rabeprazole) markedly inhibited the formation of gastric lesions. 2) The drugs, except for lansoprazole, increased intestinal lesions. 3) H2-RAs augmented the increase in intestinal motility caused by indomethacin, and the effects of H2-RAs on motility and intestinal lesions were markedly inhibited by atropine. 4) Lansoprazole inhibited the formation of intestinal lesions, and the effect was prevented by both pharmacological ablation of capsaicin-sensitive sensory neurons and pretreatment with N-nitro-l-arginine methyl ester, a selective inhibitor of nitric-oxide synthesis. The results suggest that: 1) inhibition of acid secretion by antisecretory drugs may exacerbate NSAID-induced intestinal lesions, 2) H2-RAs further aggravate lesions by increasing intestinal motility via the activation of cholinergic pathways, and 3) lansoprazole protects the intestinal mucosa against NSAID-related ulcerative stimuli.
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