Sepsis, as a severe systemic inflammatory response to bacterial infection, represents a major clinical problem. It is characterized by the excessive production of reactive oxygen species (ROS) both in the circulation and in the affected organs. The excessive generation of ROS inevitably leads to oxidative stress in the microvasculature and has been implicated as a causative event in a number of pathologies including sepsis. In this review, we focus on the role of oxidative and nitrosative stress during the early onset of sepsis. Changes in microvascular endothelial cells, the cell type that occurs in all organs, are discussed. The mechanisms underlying septic induction of oxidative and nitrosative stresses, the functional consequences of these stresses, and potential adjunct therapies for microvascular dysfunction in sepsis are identified.
We reviewed the recent literature concerning investigations of esophageal peristaltic function. The gold standard for the assessment of esophageal peristaltic function is manometry with pH monitoring. Even with this investigation modality, however, we are in fact doing no more than estimating esophageal peristaltic function from the manometry and pH results. With esophageal fluoroscopy and scintigraphy, where we observe esophageal motility, there are problems with radiation exposure and handling of radioactive agents that make widespread use difficult. In recent years, the development of multichannel intraluminal impedance (MII) manometry has allowed simultaneous measurement of intraesophageal pressure and assessment of esophageal peristalsis. Using MII it is also possible to distinguish whether gas or liquid is passing down the esophagus. When manometry is performed in conjunction with transnasal esophagogastroduodenoscopy, with this unique combination it is possible to measure the intraesophageal pressure while actually observing the swallowing motion at the same time. Assessment of esophageal peristaltic function is now moving from simple measurement of intraesophageal pressure to simultaneous impedance manometry and endoscopic observation of esophageal peristalsis itself.
Proton pump inhibitors (PPIs) are now commonly used for the treatment of acid related diseases such as peptic ulcer and reflux esophagitis. Because of their ability to produce direct inhibition of the proton pump, PPIs provide more sustained increase of the gastric pH than H2-receptor (H2R) antagonists. Diverse reports have been published on gastric epithelial cell modality associated with PPI treatment both in animal models and clinical settings. The present review summarizes the recent accumulated evidence on gastric epithelial cell modality associated with PPI treatment, including the formation of gastric carcinoid tumors and fundic gland polyps, and the development of gastric mucosal atrophy. Long-term PPI treatment has been reported to cause enlargement of the parietal cells and enterochromaffin-like cells, and to decrease the number of chief cells without affecting A-like cell. Although the development of gastric carcinoid tumors after chronic PPI treatment has been reported in animal studies, no such occurrences have been demonstrated in humans. The effect of PPIs on the formation of fundic gland polyps and the development of atrophic gastritis should be investigated in future studies.
Heme oxygenase (HO) catalyzes the rate-limiting step in heme degradation to produce carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently converted to bilirubin by its reductase, and iron is recycled for heme synthesis. The inducible HO isoform, HO-1, is involved in the protection of multiple tissues and organs. The mechanism of protective actions of HO-1 has not been completely elucidated, but recent evidence suggests that one or more of heme metabolites can mediate the protective effects of HO-1. Particularly, CO mimics the antioxidant, anti-inflammatory, anti-apoptotic and antiproliferative actions of HO-1. Many of these effects of CO depend on the production of cyclic guanosine monophosphate (cGMP), and the modulation of mitogen-activated protein kinase (MAPK) pathways. The transcription factors, including nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases, including MAPK pathway, play an important regulatory role in HO-1 expression by dietary antioxidants and drugs. This review attempts to concisely summarize the molecular and biochemical characteristics of HO-1, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by dietary antioxidants and drugs. In addition, the cytoprotective roles of HO-1 shall be discussed from the perspective of each of the metabolic by-products.
Quality of ulcer healing (QOUH) is defined as ideal ulcer healing featuring with the fine granular ulcer scar, high functional restoration and the resistance to recurrence. This study was designed to compare the rates of QOUH achievement in rat gastric ulcer model between acid suppressant treated group and gastroprotectant treated group accompanied with elucidations of molecular mechanisms. Serosal injection of acetic acids for generating gastric ulcer and intraperitoneal (ip) injection of recombinant interleukin 1-beta (IL-1β) for recurring healed ulcer was done in SD rats. The 72 rats were divided into three groups according to treatment as follows; Group I, no further treatment, Group II, 8 weeks treatment of omeprazole, and Group III, 8 weeks of gastroprotectant treatment. IL-1β was administered for ulcer recurrence after 28 weeks of acetic acid injection. At four weeks after gastric ulcerogenesis, 58.3% (7/12) of active gastric ulcer were converted to healing stage in Group III, but 16.7% (2/12) in Group II and none in Group I, for which significant levels of epidermal growth factor, mucin, and pS2/trefoil peptide1 were contributive to these accelerated healings of Group III. ip injections of rIL-1β (200 μg/kg) at 28 weeks after acetic acid injection led to 100% of ulcer recurrence in Group I and 75.0% in Group II, but only 16.7% of Group III rats showed ulcer recurrence. Significantly attenuated levels of inflammatory cytokines including IL-2, transforming growth factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), nitrotyrosine were responsible for the resistance to ulcer recurrence in Group III. Conclusively, gastroprotectant might be prerequisite in order to achieve ideal QOUH through significant inductions of remodeling.
The aging of society and ongoing health care cost-control policy set the trend for the self-medication which leads to the growing interest in health promotion and prolongation of healthy life expectancy through self-health management. We developed a self-medication support system to provide comprehensive support to consumers at pharmacies and drug stores. This system facilitates the effective use of information and knowledge based on medicine and health. This self-medication support system comprised a set of two terminals connected network server in the data center: a user terminal for consumers use and an advisor terminals for specialized advisor, pharmacists, registered dieticians, and etc. This system enables specialized sales people to provide the appropriate advice based on the factors of consumer’s problem, and to make suggestions for improving his/her lifestyle: eating habit, doing exercise, and having relaxation time. As a result of the trial use of this system at pharmacy stores, a certain degree of correlation between the results of a questionnaire on unidentified complaints and dietary patterns causing potential micronutrient deficiency was demonstrated.
The liver is one of the major target organs affected in sepsis that are usually accompanied with free radical formation. The use of minus charge for the prevention and cure of various radical related diseases is gaining wide importance in the medicinal field. Here, we investigate whether minus charge stimulation (MCS) inhibits nitric oxide (NO) production induced by lipopolysaccharide (LPS) in the mice liver. The survival rate was compared in LPS-treated group with MCS group. The liver NO radical was measured using electron spin resonance technique. Serum alanine transaminase (ALT) was estimated for liver injury. MCS significantly improved the survival rate of LPS-treated mice and inhibited increase of ALT in serum levels. MCS also reduced NO radical production significantly in the LPS-treated mice liver tissue. In conclusion, our results indicate that MCS prevents LPS-induced liver injury, which may be through the inhibition of liver NO radical production.
Detection of resistance to drugs for Mycobacterium tuberculosis takes about two months from the sample collection using culture-based methods. To test a rapid method for detection of resistance for five antituberculosis drugs using DNA microarray and to examine its potential for clinical use, we employed a DNA microarray for detection of seven mutations genes related to resistance of five kinds of antituberculous drugs using Mycobacterium tuberculosis DNA isolated from sputum. The results of microarray analysis were compared with the results of a standard culture method of Lowenstein-jensen drug sensitivity testing system. DNA microarray analysis showed a high sensitivity (>90%) for all five drugs. Specificity of rifampicin and ethambutol were nearly 90%, however specificity of isoniazid (60%) and kanamycin (67%) were not enough. The amount of Mycobacterium tuberculosis DNA required for microarray analysis corresponded to at least 1–9 Acid-Fast Bacilli per 10 fields by carbolfuchsin staining. DNA microarray analysis appears to be useful for estimation of drug resistances, nevertheless its limitations. To minimize misunderstanding, it is necessary to confirm the number of bacilli in the sputum, and culture method is needed for comparison when use the PCR-based array system.