Development of isolated perfused whole stomach for motility study in rat and cat

An isolatedex vivo perfused mammalian stomach preparation is an ideal model for the study of motility avoiding central nervous influence and circulating humoral factors. In this paper, we describe the technique of such preparation in two different species: rat and cat, and its implication for motility study. While the isolated stomach was perfused with Krebs-Ringer solution via celiac artery, motility of the antrum was recorded using an open-tip tube in rats and a bipolar platinum electrode and a strain gauge in cats. The spontaneous antral motility and its response to drugs, such as dopamine and domperidone proved that the preparation would be a useful model to study motility devoid of influences of the central nervous system and circulating humoral agents.Dr. S.K. Odaibo was supported by a special postdoctoral clinical research fellowship award PG/256/168 from the University of Ilorin, Ilorin, Nigeria.Presented in part at the American Gastroenterological Association Meeting, Washington, DC, May 1983.     

Thrombomodulin accelerates activated protein C production and inhibits thrombin generation in the plasma of disseminated intravascular coagulation patients.

Thrombomodulin (TM) has been under development as a medicine for disseminated intravascular coagulation (DIC), and is expected to exhibit strong anticoagulant activity by inhibiting thrombin generation via the acceleration of protein C activation. In the present study, we examined the pharmacological action of TM in plasma obtained from DIC patients. TM was found to inhibit thrombin generation and accelerate activated protein C (APC) production at 0.3-30 TM units/ml in plasma obtained from DIC patients irrespective of their underlying disorders. In addition, there was a positive correlation between the inhibition of thrombin generation and the amount of APC produced. Thrombin generation was inhibited by over 50% when the plasma level of APC was increased by more than 0.2 microg/ml. These results indicate that TM inhibits thrombin generation in plasma obtained from DIC patients by accelerating APC production. Moreover, the results imply that the thrombin generation test may be a good method to speculate the efficacy of TM on every patient before the administration of TM.     

Adoptive immunotherapy with lymphokine-activated killer cells plus recombinant interleukin 2 in patients with unresectable hepatocellular carcinoma

Ten patients with hepatocellular carcinoma, three of whom had pulmonary metastasis, were treated with adoptive immunotherapy using autologous lymphokine-activated killer cells plus recombinant interleukin 2. Patients received 15 micrograms per day of recombinant interleukin 2 consecutively (for 14 to 64 days), from Day 7 prior to the first leukapheresis, and received 10(9) to 10(10) lymphokine-activated killer cells once or twice per week intravenously; the lymphokine-activated killer cells had been generated from mononuclear cells obtained through leukapheresis. Preadministration of recombinant interleukin 2 prior to the first leukapheresis resulted in a remarkable increase of lymphokine-activated killer activity in seven of nine cases in whom lymphokine-activated killer activity had been poorly inducible even at high concentrations of recombinant interleukin 2. At the end of the treatment, liver tumor regression (34 and 63%, respectively, of two-dimensional size) was observed in two of two patients with a solitary tumor; no increase of liver tumor size was observed in seven patients with massive or multiple tumors, and no changes in the size or number of pulmonary metastatic tumors in any patients were observed. More than a 35% decrease in serum alpha-fetoprotein level was noted in four of nine alpha-fetoprotein-positive patients. However, Child's grades, performance status and lymphokine-activated killer activity on entry into the study could not be used as parameters to predict therapy responsiveness. Neither serious side effects nor significant changes of serum bilirubin, ALT and creatinine were noted. Thus, this treatment seems to be well tolerated even in advanced hepatocellular carcinoma with poor liver function reserve, and tumor regression could be expected in small-burden hepatocellular carcinoma. The assessment of the therapeutic effects and application in hepatocellular carcinoma awaits the development of this trial.     

Differences in the risk factors of reflux esophagitis according to age in Korea

The prevalence of gastroesophageal reflux disease in Korea has been believed to be low, but the incidence of gastroesophageal reflux disease in Korea is expected to increase because of the longer life expectancy and more ingestion of westernized food. The aim of this study was to report differences in the risk factors of reflux esophagitis (RE) according to age in Korea. We prospectively recruited the subjects who had RE among those who visited a health promotion center for upper gastrointestinal cancer surveillance at Hallym Medical Center (five institutions) between January 2008 and February 2009. The enrolled study participants comprised 742 subjects with RE and 1484 healthy controls. The independent risk factors of RE in young and adult group were male sex, smoking, coffee, body mass index ≥ 25, hiatal hernia, and Helicobacter pylori negativity. The risk factors of RE in elderly group were smoking, coffee, and hiatal hernia. The risk factors for RE according to age group were found to differ. In elderly group, Helicobacter pylori infection was not a significant protective factor contrary to young and adult groups.     

Assessment of Effects of Air Pollution on Daily Outpatient Visits using the Air Quality Index

Background

The air quality index (AQI) is widely used to characterize the quality of ambient air. Chinese cities officially report the AQI on a daily basis. To assess the possible effects of air pollution on daily outpatient visits, we examined the association between AQI and the daily outpatient count.

Methods

Daily data on outpatient visits to each clinical department were collected from the Z county hospital of Datong City, China. The collection period was between 5 April and 30 June, 2012. Daily AQI data and meteorological information were simultaneously recorded. We compared outpatient counts between the index days and comparison days, and calculated Pearson’s product moment correlation coefficient between outpatient counts and AQI levels.

Results

The average AQI level for index days was significantly higher than that for comparison days. No significant difference was observed in temperature or relative humidity between index days and comparison days. The outpatient counts for pediatrics were significantly higher on index days than on comparison days, and no significant difference was noted in other clinical departments. The outpatient counts for pediatrics positively correlated with the AQI level, and no correlation was noted in other clinical departments.

Conclusion

The present study assessed the association between daily outpatient visits and air pollution using AQI. The results obtained suggest that air pollution could increase the outpatient count for pediatrics.     

Continuous illumination through larval development suppresses dopamine synthesis in the suprachiasmatic nucleus, causing activation of α-MSH synthesis in the pituitary and abnormal metamorphic skin pigmentation in flounder

In order to better understand the endocrine aberrations related to abnormal metamorphic pigmentation that appear in flounder larvae reared in tanks, this study examined the effects of continuous 24-h illumination (LL) through larval development on the expression of tyrosine hydroxylase-1 (th1), proopiomelanocortin (pomc), α-melanophore-stimulating hormone (α-MSH) and melanin concentrating hormone (MCH), which are known to participate in the control of background adaptation of body color. We observed two conspicuous deviations in the endocrine system under LL when compared with natural light conditions (LD). First, LL severely suppressed th1 expression in the dopaminergic neurons in the anterior diencephalon, including the suprachiasmatic nucleus (SCN). Second, pomc and α-MSH expression in the pars intermedia melanotrophs was enhanced by LL. Skin color was paler under LL than LD before metamorphic pigmentation, and abnormal metamorphic pigmentation occurred at a higher ratio in LL. We therefore hypothesize that continuous LL inhibited dopamine synthesis in the SCN, which resulted in up-regulation of pomc mRNA expression in the melanotrophs. In spite of the up-regulation of pomc in the melanotrophs, larval skin was adjusted to be pale by MCH which was not affected by LL. Accumulation of α-MSH in the melanotrophs is caused by uncoupling of α-MSH synthesis and secretion due to inhibitory role of MCH on α-MSH secretion, which results in abnormal metamorphic pigmentation by affecting differentiation of adult-type melanophores. Our data demonstrate that continuous illumination at the post-embryonic stage has negative effects on the neuroendocrine system and pituitary in flounder.     

Sulfatide accumulation in the dystrophic terminals of gracile axonal dystrophy mice: lipid analysis using matrix-assisted laser desorption/ionization imaging mass spectrometry

The gracile axonal dystrophy (gad) mutation in Uch-l1, the gene encoding the ubiquitin carboxy-terminal hydrolase isozyme L1 (UCH-L1), causes selective dying back degeneration of dorsal root ganglion neuron in the medulla oblongata along with progressive sensory-motor ataxia. Axonal spheroids are observed within degenerating axons, and their contents may illuminate the pathogenic mechanisms leading to neurodegeneration in gad mice. To analyze changes in negatively charged lipid molecules in dystrophic axons of gad mice, we performed matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS), electron microscopy, and fluorescence immunohistochemistry on tissue sections from gad and wild-type mouse medulla. MALDI-IMS revealed that m/z 806.68 and 822.68 molecules, assigned to sulfatide (ST) C18:0 and ST C18:0(OH), respectively, were concentrated in the dorsomedial medulla. This spatial distribution overlapped significantly with that of axonal spheroids. Immunostaining revealed that spheroids accumulated myelin and lymphocyte protein, a known ST binding protein. Sulfatides with short-chain fatty acids (C16–C20) are generally localized in intracellular vesicles; therefore, ST C18:0 accumulation may reflect intracellular vesicle aggregation within spheroids. Ubiquitin system disruption apparently alters lipid metabolism, membrane organization, protein turnover, and axonal transport. Changes in membrane organization, particularly STs within lipid rafts, may disrupt cellular signaling pathways necessary for neuronal viability.