The effects of acute exercise-induced cortisol on CCR2 expression on human monocytes

CC-chemokine receptor 2 (CCR2) and its ligand, monocyte chemotactic protein-1 (MCP-1, also known as CCL2), are crucial for the recruitment of monocytes/macrophages to sites of inflammation. We conducted a series of experiments to investigate the relationship between stress, monocyte CCR2 expression and migration activity. First, we collected peripheral blood mononuclear cells (PBMC) from untrained subjects (n=8) and measured CCR2 expression on CD14(+) monocytes cultured with cortisol, epinephrine and norepinephrine. Second, we collected PBMC from the subjects before and after they cycled for 60 min at 70% peak O(2) uptake (VO2(peak)), and measured alterations in CCR2 expression on monocytes following exercise. Third, we cultured PBMC with serum obtained before and after exercise and the glucocorticoid antagonist RU-486 to determine the effect of cortisol on CCR2 expression in vitro. Last, we measured the ability of PBMC treated with serum or cortisol to migrate through membrane filters in response to CCL2. Cortisol (but not epinephrine or norepinephrine) increased CCR2 expression on monocytes in a dose- and time-dependent manner. Exercise did not influence CCR2 expression on PBMC, whereas incubation of PBMC with post-exercise serum significantly increased CCR2 expression. Both cortisol and post-exercise serum increased the migration of PBMC toward CCL2. The increase in CCR2 expression on PBMC following stimulation with cortisol and serum was blocked by the glucocorticoid receptor antagonist RU-486. In conclusion, cortisol released during exercise increased monocyte CCR2 expression and migration activity in vitro. These alterations may influence inflammation and regeneration of damaged tissue after acute stress.     

Oxytocin receptor-deficient mice developed late-onset obesity

The oxytocin receptor has been suggested to be involved in energy metabolism, such as food intake and energy consumption. Here, we demonstrate that oxytocin receptor-deficient (Oxtr-/-) male mice exhibited late-onset obesity with increases in abdominal fat pads and fasting plasma triglycerides. Daily food intake and spontaneous motor activity of Oxtr-/- mice were not significantly different as compared with wild-type mice. In contrast, brown adipose tissue in Oxtr-/- mice contained large lipid droplets and cold-induced thermogenesis was impaired. This study demonstrates that oxytocin receptor plays essential roles in the regulation of energy homeostasis.     

Reduction of angiotensin II in the cerebrospinal fluid of patients with multiple sclerosis

We previously demonstrated that angiotensin II acts as a crucial neuroprotective factor after neural injury through angiotensin II type-2 (AT2) receptor signaling. Although the pathway is known to play an important role in the development of experimental autoimmune encephalomyelitis, cerebrospinal fluid (CSF) angiotensin II levels in patients with multiple sclerosis (MS) have never been studied. To clarify the significance of angiotensin II in MS, we assayed angiotensin II concentrations using an established enzyme-linked immunoabsorbent assay in CSF samples from patients with MS (n = 21), patients with inflammatory neuropathies (IN) (n = 23) and control individuals who did not have either of the neurological diseases or any other disease that might affect the angiotensin II levels in the CSF (control) (n = 24). Angiotensin II levels in the CSF were 3.79 +/- 1.54 pg/ml in the MS group, 5.13 +/- 2.27 pg/ml in the IN group and 6.71 +/- 2.65 pg/ml in the control group. The angiotensin II levels in the CSF of the MS group were significantly lower than in the control group (p = 0.00057). Angiotensin II concentration in the CSF tended to have a negative correlation with the Kurtzke's Expanded Disability Status Scale scores during MS relapse (p = 0.0847). These findings suggest that reduced levels of intrathecal angiotensin II may be related to the abnormal neural damage and repair processes in MS.     

IFCC guideline for sampling, measuring and reporting ionized magnesium in plasma.

Analyzers with ion-selective electrodes (ISEs) for ionized magnesium (iMg) should yield comparable and unbiased results for iMg. This IFCC guideline on sampling, measuring and reporting iMg in plasma provides a prerequisite to achieve this goal [in this document, "plasma" refers to circulating plasma and the forms in which it is sampled, namely the plasma phase of anticoagulated whole blood (or "blood"), plasma separated from blood cells, or serum]. The guideline recommends measuring and reporting ionized magnesium as a substance concentration relative to the substance concentration of magnesium in primary aqueous calibrants with magnesium, sodium, and calcium chloride of physiological ionic strength. The recommended name is "the concentration of ionized magnesium in plasma". Based on this guideline, results will be approximately 3% higher than the true substance concentration and 4% lower than the true molality in plasma. Calcium ions interfere with all current magnesium ion-selective electrodes (Mg-ISEs), and thus it is necessary to determine both ions simultaneously in each sample and correct the result for Ca2+ interference. Binding of Mg in plasma is pH-dependent. Therefore, pH should be measured simultaneously with iMg to allow adjustment of the result to pH 7.4. The concentration of iMg in plasma may be physiologically and clinically more relevant than the concentration of total magnesium. Furthermore, blood-gas analyzers or instruments for point-of-care testing are able to measure plasma iMg using whole blood (with intact blood cells) as the sample, minimizing turn-around time compared to serum and plasma, which require removal of blood cells.     

Sentinel node micrometastases have high proliferative potential in gastric cancer

BACKGROUND: The 6th edition of the TNM classification has recently defined "sentinel nodes (SN)," "micrometastasis," and "isolated tumor cells (ITC)." The present study examines the frequency and proliferative activity of such metastases with focus on the SNs of gastric cancer. METHODS: We enrolled 133 patients with cT1-2 tumors (cT1: 104, cT2: 29) and mapped SNs. Lymph node metastases were examined by routine histology and by immunohistochemistry with anti-cytokeratin. We used the Ki-67 antibody to detect the primary tumor and lymph node metastases to evaluate proliferative activity. RESULTS: The number of patients with SNs metastases and metastatic SNs was 19 and 52, respectively. The frequencies of macrometastasis, micrometastasis, and ITC were 48%, 25%, and 27%, respectively. Ki-67 expression in the tumor closely correlated with lymphatic invasion (P = 0.0001), venous invasion (P < 0.0001), and lymph node metastasis (P < 0.0001). Cells in 96% of macrometastases, 92% of micrometastases, and 29% of ITCs were Ki-67 positive. CONCLUSIONS: We showed that micrometastasis and some ITCs in SNs had proliferative activity. We suggest that micrometastasis and ITCs should be removed, especially during SN navigation surgery, until their clinical significance is clarified.     

Inositol 1,4,5-trisphosphate receptors are autoantibody target antigens in patients with Sjögren's syndrome and other systemic rheumatic diseases

IP₃R2 and IP₃R3 double knock-out mice present with exocrine dysfunctions such as secretion deficits of saliva and pancreatic juice. Therefore, we investigated whether the presence of antibodies to IP₃Rs could be found in patients with Sjögren's syndrome, and the location of the epitopes. Subjects included 35 primary Sjögren's syndrome, 39 secondary Sjögren's syndrome, 144 rheumatoid arthritis, and 96 other connective tissue disease patients. As controls, 33 healthy subjects were included. Immunoblot was conducted using recombinant proteins IP₃R1, IP₃R2, and IP₃R3 made from full-length cDNA, and core, T604, and EL for epitope mapping. Antibodies to IP₃R1 in sera from patients with primary Sjögren's syndrome, secondary Sjögren's syndrome, and rheumatoid arthritis were found to be positive in 17 of 35 (48.6%), 13 of 39 (33%), and 34 of 124 (27.4%) cases, respectively. These frequencies were significantly higher than the 1 of 33 (3.0%) found in normal healthy subjects. The frequency of anti-IP₃R2 antibodies in rheumatoid arthritis was found to be higher than those found in Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Anti-IP₃R2 antibodies found in rheumatoid arthritis primarily recognized residues 578–2171 of the internal coupling and regulatory domain. On the other hand, anti-IP₃R1 found in Sjögren's syndrome recognized residues 224–604 of the core protein IP₃R1. Anti-IP₃R1 antibodies were present in 48.6% of primary Sjögren's syndrome and in 3.0% of normal healthy subjects. Anti-IP₃R2 antibodies were detected most frequently in rheumatoid arthritis. Locations of the antigenic epitopes were found to differ among the disease conditions.     

Association between reflux esophagitis and/or hiatus hernia and gastric mucosal atrophy level in Japan

BACKGROUND AND AIMS: The mechanisms involved in reflux esophagitis (RE) are mainly esophageal motor dysfunction and abnormal esophageal acid exposure. Therefore the extent of gastric mucosal atrophy (GMA), which is related to gastric acid secretion, is an important factor in the development of RE. The aim of this study was to evaluate the prevalence of RE and hiatus hernia (HH) according to level of GMA. METHODS: A total of 1897 prospective, consecutive endoscopic examinations were performed by the same endoscopist to investigate the prevalence of RE and HH in patients with closed or open-type GMA. The patients were divided into four age groups: under 44, 45-54, 55-64 and over 65 years. RESULTS: The prevalence of RE and HH in patients with closed-type GMA was significantly higher than that of open-type GMA in the 45-54, 55-64 and over 65 age groups. In patients with open-type GMA, the prevalence of RE in each age group was similar at 5.0-7.4%, and the prevalence of HH in the over 65 age group was significantly higher than that of the 55-64 age group. In patients with closed-type GMA, the prevalence of RE and HH in the over 65 age group was significantly higher than that of other age groups. CONCLUSIONS: The existence of closed-type GMA and age over 65 years were important factors in the development of RE and HH.     

Pneumoperitoneum caused by ruptured gas-containing liver abscess

An 84-year-old woman was admitted to our hospital with high fever, and she suddenly complained of severe abdominal pain the next day. Computed tomography revealed a gas-containing abscess in the lateral segment of the liver, with spontaneous pneumoperitoneum. An emergency lateral segmentectomy was performed, and Klebsiella pneumoniae was cultured from the liver tissue, abscess, and blood. The patient made a satisfactory recovery and was discharged on the thirty-first postoperative day. Pneumoperitoneum caused by the rupture of a gas-containing liver abscess is rare, and to our best knowledge, this is the first report, in the English-language literature, of a patient who has undergone successful hepatectomy for such a condition.     

Effects of copper supplementation on lipid profiles in elderly patients with copper deficiency

AIM: The purpose of this study was to examine the effects of copper supplementation on lipid profiles in elderly patients with copper deficiency. METHODS: Nine long-term bed-ridden, patients (5 men and 4 women, mean age 83.3+/-8.7 years old) with severe copper deficiency, who had a serum copper of 15 microg/dL or less (normal range 70-140 microg/dL), had their diets supplemented with copper sulfate (3 mg/day) over 12 weeks in addition to their diet of only one kind of enteral food with a low concentration of copper. Copper, ceruloplasmin, total cholesterol (TC), triacylglycerides (TG), HDL-cholesterol (HDL-C), c-reactive protein (CRP), creatinine (Cr), zinc (Zn) and albumin (Alb) in the serum were measured before, 4 weeks and 12 weeks after copper supplementation. RESULTS: Serum copper and ceruloplasmin were significantly increased at 4 weeks after copper supplementation. TG was significantly increased at 4 weeks after copper supplementation, but at 12 weeks the increase of TG was not significant. TC, HDL-C, CRP, Cr, Zn and Alb were not changed by copper supplementation. CONCLUSION: TG was transiently increased by copper supplementation in elderly patients with copper deficiency. TC and HDL-C were not changed by copper supplementation.