Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal

N-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have protective effects against atherosclerosis. Monocyte chemotactic protein (MCP)-1 is a major inflammatory mediator in the progression of atherosclerosis. However, little is known about the regulation of Mcp-1 by DHA and EPA in vessels and vascular smooth muscle cells (VSMCs). In this study, we compared the effect of DHA and EPA on the expression of Mcp-1 in rat arterial strips and rat VSMCs. DHA, but not EPA, suppressed Mcp-1 expression in arterial strips. Furthermore, DHA generated 4-hydroxy hexenal (4-HHE), an end product of n-3 polyunsaturated fatty acids (PUFAs), in arterial strips as measured by liquid chromatography-tandem mass spectrometry. In addition, 4-HHE treatment suppressed Mcp-1 expression in arterial strips, suggesting 4-HHE derived from DHA may be involved in the mechanism of this phenomenon. In contrast, Mcp-1 expression was stimulated by DHA, EPA and 4-HHE through p38 kinase and the Keap1-Nuclear factor erythroid-derived 2-like 2 (Nrf2) pathway in VSMCs. In conclusion, there is a dual effect of n-3 PUFAs on the regulation of Mcp-1 expression. Further study is necessary to elucidate the pathological role of this phenomenon.     

Immunological response to interferon-gamma priming prior to interferon-alpha treatment in refractory chronic hepatitis C in relation to viral clearance

The aim of this study was to clarify the immunological and virological responses to pre-administration of interferon-γ prior to initiation of interferon-α treatment in patients with refractory chronic hepatitis C. Twenty-two nonresponders to 6-months of IFN-α treatment were enrolled. The hepatitis C virus (HCV) genotype was Ib in all. Natural IFN-γ (1 MIU/day) was administered daily for 14 days followed by natural IFN-α (5 MIU/day) daily for 14 days and then three times weekly for 22 weeks. Serum immunological parameters (IL-10, neopterin, BMG, sCD8, sCD4, IL-6, IL-12) were measured as were the levels of several cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-5, IL-6, IL-10). Three patients dropped out; two because of the occurrence of other diseases and one because of an adverse effect. At the end of the period of IFN-α treatment, HCV-RNA had become negative in six of 19 patients (end-of treatment response; ETR). Six months after the completion of IFN administration, a virological sustained response (SR) was seen in two of 19 patients. The mean serum levels of IL-10 were significantly decreased 6 weeks after the start of treatment. Other immunological parameter levels increased significantly during the period of IFN-γ administration, and tended to return to the pretreatment level after the start of IFN-α administration. Univariate logistic regression analysis showed that the initial change in the levels of these parameters or the change in the ratios of Th1/Th2 parameter levels are useful factors indicative of the end of the treatment response. These findings suggest that priming with IFN-γ prior to the initiation of IFN-α treatment in patients with refractory chronic hepatitis C can modulate the host immune response and this might contribute to viral clearance.     

Voxel-based analysis of age and gender effects on striatal [123I] FP-CIT binding in healthy Japanese adults

Annals of Nuclear Medicine - Although previous studies have investigated age and gender effects on striatal subregional dopamine transporter (DaT) binding, these studies were mostly based on a...     

Carotid atherosclerosis and cardiovascular risk factors: a comparison of residents of a rural area of Okinawa with residents of a typical suburban area of Fukuoka, Japan

Areas of Japan are known worldwide for the longevity of their residents. Okinawa has the highest longevity in Japan and a low rate of death due to cardiovascular disease. We investigated carotid atherosclerotic (CA) risk factors in islands of I city in Okinawa prefecture and compared them with K town, a suburban area of Fukuoka prefecture in Kyushu, to determine the relationship between cardiovascular risk factors and carotid atherosclerosis. We investigated conventional cardiovascular risk factors in 1078 I city residents (375 men, mean age 63.7 and 703 women, mean age 60.0) in 2000 and 2364 K town residents (676 men, mean age 57.1 and 1688 women, mean age 53.0) in 1999. Carotid atherosclerosis was assessed by mean intima-media thickness (IMT) by B-mode ultrasound. The mean IMT was significantly lower in the residents of I city than in those of K town (P < 0.05). Total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels and smoking rate were also lower in I city than in K town. Body mass index (BMI) and triglyceride (TG) level were higher in I city than in K town. In I city, multiple regression analysis found independent relationships between carotid atherosclerosis and age, sex (male), hypertension, LDL cholesterol, high-density-lipoprotein cholesterol (HDL-C), and diabetes. The lower mean IMT is probably related to a lower lifetime burden of atherosclerotic risk factors, which may in turn be related to the longevity of Okinawa residents. BMI was not a cardiovascular risk factor, although LDL cholesterol was a common important risk factor.     

Impact of reflux esophagitis on the esophageal function before and after laparoscopic fundoplication

Background

High-resolution manometry (HRM), which is breakthrough testing equipment to evaluate esophageal motor function, was developed in Europe and United State and has garnered attention. Moreover, multichannel intraluminal impedance pH (MII-pH) testing has allowed us to grasp all liquid/gas reflux including not only acid but also non-acid reflux. We examined the impact of the presence of reflux esophagitis (RE) on esophageal motor function before and after laparoscopic fundoplication.

Materials and methods

The subjects included 100 patients (male: 63 patients, mean age: 54.1?±?15.8) among 145 patients who underwent laparoscopic fundoplication for GERD associated diseases during a 4-year period from October 2012 to September 2016, excluding 6 patients who underwent further surgery, 32 patients on whom HRM was not performed, 3 patients who had technical errors during testing, and 4 patients for whom the status of RE was unknown. Regarding HRM, Mano Scan from Given Imaging Ltd. was used, and for the analysis, Mano View version 3.0 from the same company was used, after which data was calculated based on the Chicago Classification advocated by Pandolfino et al. Moreover, for the MII-pH testing, Sleuth manufactured by Sandhill Scientific. Inc. was used and automatic analysis was conducted by a computer. Postoperative assessments were conducted 3 months following surgery for all. Data was described in the median value and inter-quartile range, with a statistically significant difference defined as p?<?0.05 by Chi square, Mann–Whitney, and Wilcoxon tests.

Results

RE+?group (Los Angeles classification A:B:C:D?=?7:9:16:12 patients) included 44 patients (44%), of older age compared to the RE? group (62 vs. 50 years, p?=?0.012) and a higher Body Mass Index value (24.0 vs. 22.5, p?=?0.045); however, no differences were observed in terms of gender and duration of symptoms. In the preoperative findings on MII-pH, the RE+?group demonstrated significantly longer acid reflux time (4.7 vs. 1.3%, p?=?0.005), while in the HRM findings, the RE? group demonstrated a significantly longer abdominal esophagus (0 vs. 0.4 cm, p?=?0.049) and maintained esophageal body motor function (DCI: 1054 vs. 1407 mmHg s cm, p?=?0.021, Intact peristalsis ratio: 90 vs. 100%, p?=?0.037). As to the comparison of the treatment effect before and after laparoscopic fundoplication (Toupet fundoplication for all), significant improvements were observed in both groups in various parameters regarding reflux including acid reflux time, total number of liquid reflux episodes and total number of reflux episodes. Moreover, for both groups, the total length of the lower esophageal sphincter (LES) (RE+?group: 2.7 vs. 3.2 cm, p?=?0.001, RE? group: 3.0 vs. 3.4 cm, p?=?0.003) and the total length of the abdominal esophagus (RE+?group: 0 vs. 1.6 cm, p?<?0.001, RE? group: 0 vs. 1.8 cm, p?=?0.001) were significantly extended following surgery; however, no change was observed in DCI before and after surgery.

Conclusions

Regardless of the presence of RE, cardiac function and LES function were improved following laparoscopic Toupet fundoplication, but no changes were observed in esophageal body motor function.

     

Metastatic hypopharyngeal and esophageal cancer to a percutaneous endoscopic gastrostomy site

The patient was a 63-year-old man who underwent percutaneous endoscopic gastrostomy (PEG) for nutritional management while undergoing radiochemotherapy for hypopharyngeal and esophageal cancer. At about 6 months after PEG, redness and swelling were seen around the gastrostomy site, and pathological testing confirmed the same poorly differentiated squamous cell carcinoma as the hypopharyngeal and esophageal cancer. The tumor caused symptoms associated with buried bumper syndrome to increase significantly.     

Attenuation of canine cerebral vasospasm after subarachnoid hemorrhage by protein kinase C inhibitors despite augmented phosphorylation of myosin light chain

The purpose of the present study is to assess the roles of protein kinase C (PKC) isoforms, especially PKC delta and alpha, and 20-kD myosin light chain (MLC(20)) phosphorylation in the mechanism of cerebral vasospasm following subarachnoid hemorrhage (SAH). We had shown that those PKC isoforms are involved in the development of cerebral vasospasm. Using PKC isoform-specific inhibitors in a 'two- hemorrhage' canine model, we examined changes in the development of cerebral vasospasm, translocation of PKC isoforms and MLC(20) phosphorylation level in canine basilar arteries. A PKC inhibitor (5 microM rottlerin for PKC delta or chelerythrine for PKC alpha) was injected into the cisterna magna on day 4 before the second hemorrhage. The treatment was continued daily until day 7. Rottlerin inhibited the initial phase of vasospasm and PKC delta translocation, but did not significantly inhibit PKC alpha translocation. Chelerythrine inhibited cerebral vasospasm, and the translocation of both PKC delta and alpha throughout the entire course of the study. Although cerebral vasospasm after SAH was inhibited by each PKC inhibitor, the MLC(20) phosphorylation level remained elevated as in the untreated hemorrhage-control study. We conclude that cerebral vasospasm following SAH depends on PKC delta and alpha, while the enhancement of MLC(20) phosphorylation contributes little to this form of vasospasm.     

Delayed esophageal perforation after laparoscopic fundoplication in a patient with diabetes mellitus: a case report

A 55-year-old man on hemodialysis for diabetic nephropathy suffered from vomiting and hematoemesis. He was diagnosed to have reflux esophagitis with Los Angeles classification grade D, which was accompanied by a shortened esophagus and stricture. His reflux esophagitis was proton pump inhibitor resistant. Therefore, we performed laparoscopic Toupet fundoplication. Delayed esophageal perforation occurred on the ninth day postoperatively, for which he had to be reoperated. To our knowledge, there is no previous report of delayed esophageal perforation after laparoscopic fundoplication. Esophageal perforation might have been caused by denudation or attenuation of the abdominal esophagus.