Indomethacin treatment during initial period of acetic acid-induced rat gastric ulcer healing promotes persistent polymorphonuclear cell-infiltration and increases future ulcer recurrence

The study was performed to examine whether indomethacin administered during the initial period of acetic acid-induced gastric ulcer healing affects future ulcer recurrence. Gastric ulcers were produced in rats by subserosal injection of acetic acid. Indomethacin (1 mg/kg/day, orally) administered either alone or concomitant with ornoprostil (50µg/kg/day, orally) was started on the fourth day and continued for 56 days. In rats whose ulcer healed at the 90th day after production of ulcer, endoscopy was done every 30 days to examine recurrence of ulcer. Gastric specimens were obtained 10, 30, 60, 90, and 240 days after ulcer production for histology, to quantitate the height of regenerated mucosa, thickness of fibrous tissue, degree of polymorphonuclear cell infiltration, and PAS-positive cells. Cumulative ulcer recurrence rate was significantly higher in rats initially treated with indomethacin than in controls. Increased polymorphonuclear cell infiltration was the major histologic abnormality persisting after cessation of indomethacin. Ornoprostil reversed these abnormalities caused by indomethacin. In conclusion, the administration of indomethacin during the initial period of the ulcer healing promoted persistent polymorphonuclear cell infiltration and increased ulcer recurrence rates, possibly via a prostaglandin-dependent mechanism.The work was supported by The Ministry of Education, Science and Culture of Grant-in-Aid for General Scientific Research 02454236 and by the DVA Medical Research Service.     

New Method of Evaluating Sublethal Damage to Erythrocytes by Blood Pumps

Abstract We recently proposed a new concept, the total destruction time of erythrocytes, to indicate sublethal damage to erythrocytes by blood pumps. In this article, results of additional experiments concerning this new concept are reported. Five paired in vitro hemolysis tests with bovine blood were conducted using a cone-type centrifugal pump (Group A) and an impeller-type pump (Group B). A total pressure head of 100 mm Hg was applied. The factors evaluated were the normalized index of hemolysis and the total destruction time, or the pumping duration, required to raise the level of the plasma-free hemoglobin to 50% of the total hemoglobin. The morphologic change of the erythrocytes also was analyzed. The percentage of crenated cells was calculated from blood smear specimens 1 min after starting the pumps and 2 h before the total destruction time of Group A in each experiment. Although there was no statistical difference in the normalized index of hemolysis between the two groups, the total destruction time of Group A erythrocytes was significantly shorter than that of Group B (18.9 ± 4.5 h and 33.7 ± 9.9 h in Group A and group B, respectively; p < 2). The rate of crenated erythrocytes was higher in Group A than in Group B at a point 2 h before the total destruction time of Group A. The total destruction time values seem to define a good method for establishing sublethal traumatic damage to erythrocytes in blood pumps.     

Human blastocysts and endometrial epithelial cells express activated leukocyte cell adhesion molecule (ALCAM/CD166)

Activated leukocyte cell adhesion molecule (ALCAM)/cluster of differentiation (CD166) is a type I transmembrane cell adhesion molecule belonging to the Ig superfamily and a ligand for CD6 that is expressed on T lymphocytes. Recently, homophilic (ALCAM-ALCAM) adhesion was shown to play important roles in tight cell-to-cell interaction and regulation of stem cell differentiation. To investigate the involvement of ALCAM in embryo implantation, the expression of ALCAM was examined in human blastocysts and endometrium. Immunohistochemical study showed that ALCAM was expressed on endometrial luminal and glandular epithelial cells but not on the endometrial stromal cells in either the proliferative or secretory phase. Northern blot analysis of isolated endometrial epithelial cells and stromal cells showed that ALCAM mRNA was expressed in endometrial epithelial cells. Flow cytometry confirmed cell surface expression of ALCAM on endometrial epithelial cells. On the other hand, nested RT-PCR analysis demonstrated that ALCAM mRNA was expressed in human blastocysts but not in the embryos in the 8-cell or morula stages, which were obtained from patients undergoing in vitro fertilization treatment. These findings indicate that ALCAM is expressed on human endometrial epithelial cells and blastocysts. The developing stage-specific expression on the embryo suggests that the ALCAM-ALCAM cell adhesion system is involved in an initial interaction of the embryo with maternal endometrium.     

Relationship between diabetic retinopathy and vascular endothelial function in elderly type 2 diabetic Japanese patients without cardiovascular disease

Background:   Many recent studies point to the importance, in diabetic patients, of vascular endothelial function as an early marker of not only macrovascular complications but also of microangiopathy. The aim of this study is to investigate the relationship between diabetic retinopathy and endothelial function in elderly diabetic patients by using brachial artery flow-mediated dilation (FMD).
Methods:   We studied 71 type 2 diabetic patients aged 65 years or older without cardiovascular diseases. The subjects were categorized as three groups: (i) without diabetic retinopathy ( n  = 49); (ii) with non-proliferative diabetic retinopathy group ( n  = 15); and (iii) those with preproliferative or proliferative diabetic retinopathy ( n  = 7). Brachial artery FMD measurement was performed by high-resolution ultrasonography. The Kruskal–Wallis test, the χ² test and multivariate logistic regression analysis were used to identify associations between both retinopathy and clinical characteristics and FMD.
Results:   There were no differences in clinical characteristics between the three groups. FMD of the three groups were significantly decreased correlating with the severity of retinopathy (8.03% vs 5.40% vs 2.30%; P  = 0.003). Multivariate logistic regression analysis showed that there was a significant correlation between diabetic retinopathy and FMD (odds ratio 0.801; P  = 0.009).
Conclusion:   Our study suggests that FMD has a relation to microangiopathy in elderly diabetic subjects. Prospective studies will be required to determine whether this test has any clinical use for identifying elderly diabetic patients who are likely to develop diabetic retinopathy.     

Two cases of nemaline myopathy diagnosed after episodes of respiratory failure]

Here we report two cases of congenital myopathy visited our hospital with respiratory failure. Case 1 was a 31-year-old woman, who had muscular weakness from birth but had never been diagnosed. She had an onset of pneumonia followed by severe type 2 respiratory failure. Even after the healing of pneumonia, hypercapnia remained. A diagnosis of nemaline myopathy was made after muscle biopsy. Case 2 is a 62-year-old man, who had slowly progressing respiratory failure accompanied with severe hypercapnea. His respiratory failure was improved by NIPPV. He also under went muscle biopsy and nemaline myopathy was diagnosed. Nemaline myopathy is one of congenital myopathy and is known to be a nonprogressive or slowly progressive disorder. However, some patients are diagnosed appropriately only when adult onset acute respiratory failure occurs.     

Glucose Metabolism of the Isolated Eccrine Sweat Gland: II. THE RELATION BETWEEN GLUCOSE METABOLISM AND SODIUM TRANSPORT

This paper attempts to further clarify the characteristics of Mecholyl- or epinephrine-stimulated glucose metabolism in the isolated monkey eccrine sweat gland with special emphasis on its relationship to increased sodium transport. The Mecholyl- or epinephrine-stimulated glucose metabolism (as estimated by either lactate or (14)CO(2) production or both) is seen only in the secretory coil and not in the duct. It is markedly suppressed in the absence of glucose, Na(+), or K(+). It is inhibited by ouabain (10(-3) M) and partially suppressed in a low-sodium (40 mM), high-potassium (100 mM) medium.2,4-dinitrophenol (10(-4) M) reverses ouabain-induced inhibition of lactate and (14)CO(2) production but only partially reverses inhibition induced by Na(+) + K(+) deprivation, indicating that metabolic inhibition by ouabain is secondary to the inhibition of sodium transport. There is no synergism between Mecholyl and epinephrine. The absence of any significant inhibitory effects by acetazolamide (Diamox) or HCO(3) (-)-free media suggests that H(+) transport may not be important in sweat gland function. In contrast to a report by Wolfe et al., human eccrine sweat glands show considerable oxidative activity ((14)CO(2) production of 0.42-0.72 nmol/gland/h). These observations are discussed in terms of the linkage between sweat gland energy metabolism and sodium transport.     

Effectiveness of the proximal optimization technique for longitudinal stent elongation caused by post‐balloon dilatation

Objectives

To evaluate the effectiveness of the proximal optimization technique (POT) to prevent longitudinal stent elongation.

Background

The mechanism of stent elongation, which occurs after post‐balloon dilation, is still unclear.

Methods

A total of 103 lesions treated with optical coherence tomography guided coronary intervention between May 2013 and November 2017 were retrospectively analyzed. Lesions were divided according to the circumferential degree of malapposition at the stent edge immediately after deployment into well‐apposed group (<180°) and malapposed group (≥180°). Post‐dilation was performed from distal to proximal within the stent until August 2016 (non‐POT cohort), and POT was applied thereafter (POT cohort). In the POT cohort, post‐dilation was done at the proximal portion of the stent with sufficiently large balloon to minimize malapposition followed by distal dilatations. Stent elongation length was defined as the change in stent length from stent deployment to after post‐dilatation.

Results

In the non‐POT cohort, 72 lesions, including 54 lesions in the well‐apposed group and 18 in the malapposed group were analyzed. Stent elongation length was significantly longer in the malapposed group than in the well‐apposed group (1.51 ± 1.34 mm vs 0.13 ± 0.84 mm, P < 0.01). In the POT cohort, 31 lesions including 21 in the well‐apposed group and 10 in the malapposed group were analyzed. Stent elongation length was not significantly different between the groups (?0.09 ± 0.91 mm vs 0.30 ± 0.99 mm, P = 0.29).

Conclusions

Malapposition of the stent edge is responsible for longitudinal stent elongation caused by post‐dilatation. POT appeared to effectively prevent longitudinal stent elongation.

     

Low well-being, cognitive impairment and visual impairment associated with functional disabilities in elderly Japanese patients with diabetes mellitus

Background:   The objective of this study is to examine the important factors associated with functional disabilities in elderly patients with diabetes mellitus.
Methods:   This was a multicenter cross-sectional study. A total of 1135 elderly diabetic outpatients aged over 65 years in 10 hospitals participated in our study. Functional disabilities were assessed with questionnaires on the instrumental activity of daily livings (IADL), intellectual activity and social role using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Cognitive function and well-being were assessed by the mini-mental state examination and morale scale, respectively.
Results:   The patients were divided into three age groups. The oldest (≥ 80 years) group reported significant high prevalence of functional disabilities (10% to 36%) compared to the youngest (65–69 years) group (4% to 20%). The number of vascular complications (≥ 4) was associated with a 5.5–8.8 fold increased risk of disabilities relating to the tasks on IADL (using public transportation, shopping, preparing meals and paying bills). Using multiple logistic regression analyses, low scores of morale scales (≤ 7) and mini-mental state examination (≤ 23) were significantly associated with disabilities on the IADL, intellectual activity and social role after adjustment for age, gender, BMI, duration of diabetes, HbA1c, insulin treatment, microangiopathy and macroangiopathy. Insulin treatment and low visual acuity were also associated with the IADL after adjustment for the other variables.
Conclusions:   Older age, insulin treatment, low well-being, cognitive impairment, and visual impairment were independently associated with the functional disabilities of elderly patients with diabetes mellitus.