Ectopic gastric mucosa and glandular tissue of a salivary type in the anal canal concomitant with a diverticulum in hemorrhoidal tissue: Report of a case

Summary This is believed to be the first report of aberrant gastric and salivary glands in the anal epithelium. An anal diverticulum and scoliosis of the lower spine were concomitant findings.     

Relationships between matrix metalloproteinases and tissue inhibitor of metalloproteinases in the wall of abdominal aortic aneurysms.

AIM: The pathologic feature of aortic aneurysm is considered to be the remodeling of the aortic wall, involving fragmentation and decrease of elastic fibers in the tunica media. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, have been implicated in collagen and elastin degeneration within the aortic wall. The precise relationship among MMPs and tissue inhibitor of metalloproteinases (TIMPs) is still unclear. We have studied the expression of MMP-2, MMP-9 tissue inhibitor of metalloprotein-1 (TIMP-1), TIMP-2 and membrane type 1-MMP (MT-1-MMP) in the wall of small AAAs (30-45 mm), large AAAs (>45 mm) and controls (<25 mm). We investigated the relationship among expressions of MMP-2, TIMP-2 and MT1-MMP in the walls. METHODS: The aortic walls in the patients with AAA were harvested from the maximum diameter, while the aortic walls in autopsy cases were harvested as controls. We analyzed tissue distribution of cell types by immunochemistry, protein expression by Western blotting and mRNA expression by competitive polymerase chain reaction. RESULTS: They consisted of 11 in controls, 8 in small AAAs and 26 in large AAAs. Among the MMPs-positive-cells, mainly macrophage, MMP-2-positive cells were in the intima, but MMP-9-positive cells in the intima and adventitia. In the small size, MMP-2 and MMP-9 mRNA were higher than those of control. In the large size, MT1-MMP and MMP-9 mRNA were higher than those of the controls. In the mRNA level of the whole AAA, significant correlations were present between MMP-2 and MMP-9, between MMP-2 and TIMP-1, and between MMP-9 and TIMP-1. These expressions were confirmed by Western blotting. CONCLUSION: We concluded as follows: 1) MMP-2 and MMP-9 may play an important role in the developmental process of AAA. 2) TIMP-1 plays an important role of interacting MMP-2 and/or MMP-9. 3) MMP-2 and MT1-MMP may play an important role in the early stages of AAAs.     

Acute hepatitis E of a man who consumed wild boar meat prior to the onset of illness in Nagasaki, Japan.

Zoonotic infection of hepatitis E virus (HEV) has been suggested. To date, pigs, deer, and wild boar have been implicated as reservoirs of HEV in Japan. However, it is not known to what extent zoonotic transmission of HEV play roles of causing HEV transmission. In the present report, we describe a case of acute hepatitis E in which a transmission of HEV by a zoonotic transmission is strongly suggested. The patient had eaten grilled wild boar meat 59 days prior to onset of acute hepatitis. Although the meat was not stored, one of the two people who ate boar meat with the patient at the same time showed high levels of HEV-IgM and -IgG and normal levels of liver enzymes, suggesting a subclinical infection of HEV. Accumulating evidence suggests that eating wild boars is associated with a high risk of acquiring hepatitis E infection.     

High glucose induces plasminogen activator inhibitor-1 expression through Rho/Rho-kinase-mediated NF-kappaB activation in bovine aortic endothelial cells

Recently, it has become evident that elevated levels of plasminogen activator inhibitor-1 (PAI-1) are associated with myocardial infarction and stroke, especially in patients with diabetes. The molecular mechanisms involved in hyperglycemia-induced PAI-1 expression in bovine aortic endothelial cells (BAEC) were investigated. PAI-1 expression in BAEC was significantly increased in accordance with the concentration of glucose in media from 5.7 mM to 23 mM. Stimulation with high glucose (23 mM) significantly increased small GTPase Rho A activation. Pretreatment with a Rho-kinase inhibitor, Y-27632 (1-10 microM), significantly blocked high glucose-induced PAI-1 expression. NF-kappaB activity determined using the luciferase reporter gene assay was significantly enhanced by high glucose, and pretreatment with Y-27632 inhibited high glucose-induced PAI-1 expression at the basal level. An inhibitor of NF-kappaB action, namely parthenolide (0.1 microM), BAY 11-7082 (5 microM) and SN50 (1 microM), significantly blocked high glucose-mediated PAI-1 expression to a level with low glucose (5.7 mM). These data suggested that high glucose-induced PAI-1 expression in endothelial cells is mediated by NF-kappaB activation through the Rho/Rho-kinase pathway. Inhibition of Rho/Rho-kinase signaling might be a novel target for diabetes and metabolic syndrome.     

IgA class antibodies to 2-oxo-acid dehydrogenase complex are not predictive markers of histopathological progression in primary biliary cirrhosis

Although antimitochondrial antibody (AMA) is the characteristic serological feature of primary biliary cirrhosis (PBC), its pathogenic role remains unclear. In our previous study, we reported a positive correlation between immunoglobulin (Ig) A class anti-2-oxo-acid dehydrogenase complex (2-OADC) and histopathological stage. To determine whether the appearance of IgA class anti-2-OADC by immunoblotting represents an early marker of more aggressive disease or whether it is late finding during the disease course of PBC, we tested not only the entire IgA class but also IgA1, IgA2 and secretory IgA class anti-2-OADC in serial serum samples from 15 patients with PBC. During the median observation period of 51 months, four cases showed histopathological progression (from stage 1 to 2, stage 1 to 3, stage 1 to 4 and stage 2 to 4). There was no statistically significant correlation between the above IgA class anti-2-OADCs and histopathological progression. There was no significant correlation between histopathological stages and IgA2 class anti-2-OADC or secretory IgA class anti-2-OADC by immunoblotting. IgA class anti-2-OADC was more frequent in stages 3–4 than in stages 1–2 (p = 0.0049), but IgA1 class anti-2-OADC was more frequent in stages 1–2 than in stages 3–4 (p = 0.0232). Our present study demonstrated that serum IgA class 2-OADC was not a predictive marker of histopathological progression but was associated with the histopathological stage of PBC. Although the IgA class AMA may have a specific pathogenic role for PBC, the discrepant results between IgA and IgA1 class anti-2-OADC should be further assessed to investigate different functional activities depending on their molecular form.     

Mechanical properties of nerve roots and rami radiculares isolated from fresh pig spinal cords

No reports have described experiments designed to determine the strength characteristics of spinal nerve roots and rami radiculares for the purpose of explaining the complexity of symptoms of medullary cone lesions and cauda equina syndrome. In this study, to explain the pathogenesis of cauda equina syndrome, monoaxial tensile tests were performed to determine the strength characteristics of spinal nerve roots and rami radiculares, and analysis was conducted to evaluate the stress-strain relationship and strength characteristics. Using the same tensile test device, the nerve root and ramus radiculares isolated from the spinal cords of pigs were subjected to the tensile test and stress relaxation test at load strain rates of 0.1, 1, 10, and 100 s^-1 under identical settings. The tensile strength of the nerve root was not rate dependent, while the ramus radiculares tensile strength tended to decrease as the strain rate increased. These findings provide important insights into cauda equina symptoms, radiculopathy, and clinical symptoms of the medullary cone.     

Clinical study of repaglinide efficacy and safety in type 2 diabetes mellitus patients with blood glucose levels inadequately controlled by sitagliptin

Aims/Introduction

The aim of the present study was to evaluate the long‐term efficacy and safety of adding repaglinide in patients with type 2 diabetes mellitus whose blood glucose levels were not sufficiently controlled by treatment with a dipeptidyl peptidase‐4 inhibitor, sitagliptin, in addition to diet and exercise therapies.

Materials and Methods

This was a multicenter, uncontrolled, dose‐titration study with a treatment period of 52 weeks. The primary end‐point was the change in glycated hemoglobin levels from baseline.

Results

The glycated hemoglobin level was 7.43 ± 0.57% (mean ± standard deviation) at baseline, and decreased to 6.93 ± 0.91% at the end of the study. The mean changes in glycated hemoglobin levels at 4 weeks and at the end of the study were −0.44 ± 0.28% and −0.50 ± 0.82%, respectively. The glycated hemoglobin‐lowering effect was maintained for 52 weeks. The rate of adverse events was 86.0% (86/100), and there were 352 adverse events. The rate of adverse drug reactions was 21.0% (21/100). Hypoglycemia was reported in 5.0% (5/100) of patients, but there was no incidence of ‘major hypoglycemia’.

Conclusions

Combination therapy with repaglinide and sitagliptin was considered effective for a long term without clinical safety problems in patients with type 2 diabetes mellitus.     

Craniofacial anatomical risk factors in men with obstructive sleep apnea and heart failure: a pilot study

Purpose

Obstructive sleep apnea (OSA) is complicated with heart failure (HF); however, the reason for this is not well understood. Craniofacial anatomic risk factors may contribute to OSA pathogenesis in HF patients. However, there are no data about cephalometric findings among OSA patients with HF.

Methods

Consecutive patients with HF and OSA (defined as total apnea–hypopnea index (AHI) ≥15/h) were enrolled. As controls, OSA patients without HF but matching the test group in age, BMI, and obstructive AHI were also enrolled.

Results

Overall, 17 OSA patients with HF and 34 OSA patients without HF were compared. There are no significant differences in the characteristics or polysomnographic parameters between 2 groups. In the cephalometric findings, compared with patients without HF, patients with HF showed a significantly greater angle between the line SN to point “A” (SNA) and a longer inferior airway space and greater airway area. However, the tongue area of patients with HF was more than those without HF.

Conclusions

The craniofacial structures of OSA patients with HF were different from those without HF. OSA patients with HF had an upper airway anatomy that is more likely to collapse when sleeping while recumbent, despite having a larger airway space.