Hiroya Akabori

A Possible Role of GLP-1 in the Pathophysiology of Early Dumping Syndrome

Exaggerated plasma concentrations of GLP-1 precede reactive hypoglycemia after oral glucose in gastrectomy patients, resulting in late dumping syndrome. Recently, we showed that GLP-1 elicits the activation of sympathetic outflow. Because sympathetic activation is thought to be a cause of early dumping, we hypothesized that exaggerated GLP-1 may contribute to the pathophysiology of early dumping syndrome. In 11 patients after gastrectomy and 14 controls, blood pressure, heart rate, and plasma concentrations of norepinephrine, epinephrine, GLP-1, glucagon, insulin, and glucose were measured after oral glucose. In gastrectomy patients, GLP-1, norepinephrine, and heart rate peaked 15 to 30 min after oral glucose. Significant positive correlations were found among GLP-1, norepinephrine, and heart rate at 30 min, and these parameters at 30 min were significantly higher in patients with early dumping syndrome. These results suggest that GLP-1 is involved in the pathophysiology of early dumping syndrome.

Adiponectin Deficiency Promotes the Production of Inflammatory Mediators While Severely Exacerbating Hepatic Injury in Mice with Polymicrobial Sepsis

BACKGROUND Adiponectin (APN), which is an adipose tissue-derived hormone, is known as an anti-inflammatory cytokine. The effects of APN on the production of inflammatory mediators and hepatic injury during polymicrobial sepsis were evaluated using APN-knockout (KO) mice that had undergone a cecal ligation and puncture (CLP) and rosiglitazone, a selective peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, which increases the plasma APN concentration. MATERIALS AND METHODS Wild type (WT) and APN-KO mice were underwent CLP. The plasma and hepatic levels of inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1), were measured before, at 24, and 48 h after CLP. A histological analysis of the liver and the plasma alanine aminotransferase (ALT) levels were examined to evaluate hepatic injury. The plasma levels of inflammatory mediators after CLP with pretreatment of rosiglitazone were compared with those without rosiglitazone. RESULTS APN deficiency resulted in significant increases in the plasma levels of TNF-alpha, IL-6, and MCP-1 at 24 h after CLP. Hepatic MCP-1 and plasma AST levels in APN-KO mice were significantly higher than those in WT mice at 48 h after CLP. A steatosis change and MCP-1 expressions in hepatocytes were induced in APN-KO mice during sepsis. The administration of rosiglitazone significantly lowered the plasma levels of inflammatory mediators, including TNF-alpha, IL-6, and MCP-1, in WT mice but not in APN-KO mice during sepsis. CONCLUSION These results suggest that an APN deficiency induces an excessive systemic inflammatory status and exacerbates hepatic injury during polymicrobial sepsis.

Transient receptor potential vanilloid 1 antagonist, capsazepine, improves survival in a rat hemorrhagic shock model.

Objective:To evaluate the role of transient receptor potential vanilloid 1 (TRPV1) in a rat hemorrhagic shock (HS) model using the TRPV1 antagonist, capsazepine (CPZ). Summary Background Data:TRPV1, distributed within the sensory nerve, plays a role in the regulation of cardiovascular functions. TRPV1 may be involved in the cardiovascular responses to HS. Methods:Male rats were anesthetized and HS was induced with the mean arterial pressure (MAP) at 30 mm Hg for 90 minutes. CPZ (5.0 μmol/kg) was administered at 30 minutes after the shock induction, and the 24-hour survival rates were assessed. The MAP, heart rate, and shed blood volume (SBV) were recorded throughout the experiment. Arterial blood gas analysis and the plasma catecholamines levels were measured before and after HS. Double-immunohistochemistry for Fos and tyrosine hydroxylase (TH) was performed in the rostral ventrolateral medulla (RVLM) of the brain. Results:CPZ significantly improved the 24-hour survival rates, which was accompanied by the increase in the MAP and the SBV, a decrease of the plasma catecholamines levels, and attenuation of the severe metabolic acidosis. Furthermore, CPZ reduced the percentage of double-labeled neurons for Fos and TH in the RVLM of the rat brain. Conclusions:TRPV1 may be involved in the regulation of the cardiovascular responses to HS, at least in part, by recruiting catecholaminergic neurons in the RVLM. CPZ appears to induce metabolic compensations, which may be potentially useful in HS.

MECHANISM OF THE ANTI-INFLAMMATORY EFFECT OF 17β-ESTRADIOL ON BRAIN FOLLOWING TRAUMA-HEMORRHAGE

ABSTRACT Although 17&bgr;-estradiol (E2) is reported to improve the inflammatory response after trauma-hemorrhage (T-H), it remains unknown whether E2 plays any role in the central nervous system after T-H. Microglial cells, resident central macrophages, are thought to play a central role in exacerbating cell-mediated inflammation. We hypothesized that T-H up-regulates microglial cell-mediated inflammatory response in the brain, and E2 produces central anti-inflammatory effects via negative regulation of microglial cells. Male Sprague-Dawley rats were subjected to sham operation (cannulation plus laparotomy) or T-H (midline laparotomy; mean blood pressure, 35 ± 5 mmHg for 90 min followed by resuscitation) and immediately killed after resuscitation. Rats received vehicle or E2 (1 mg/kg body weight i.v.) at the onset of resuscitation. In other experiments, minocycline (40 mg/kg body weight i.p.), microglia inhibitor, was administered 1 h before T-H to prevent inflammatory response in the microglia after T-H. The plasma and hypothalamic tumor necrosis factor (TNF-&agr;) levels were increased, along with the activation of microglial cells in T-H rats compared with shams. Furthermore, T-H increased microglial TNF-&agr; productive capacity in vitro. 17&bgr; administration after T-H prevented these inflammatory responses. In rats pretreated with minocycline, decreased microglial TNF-&agr; production and hypothalamic TNF-&agr; levels were observed, but plasma TNF-&agr; levels were not altered after T-H. Thus, T-H induces inflammatory responses even in the hypothalamus, and E2 seems to be a useful adjunct for down-regulating microglial cell-mediated inflammatory response after T-H.

Diagnostic potential of endotoxin scattering photometry for sepsis and septic shock.

ABSTRACT Endotoxin scattering photometry (ESP) is a novel Limulus amebocyte lysate (LAL) assay that uses a laser light-scattering particle-counting method. In the present study, we compared ESP, standard turbidimetric LAL assay, and procalcitonin assay for the evaluation of sepsis after emergency gastrointestinal surgery. A total of 174 samples were collected from 40 adult patients undergoing emergency gastrointestinal surgery and 10 patients with colorectal cancer undergoing elective surgery as nonseptic controls. Plasma endotoxin levels were measured with ESP and turbidimetric LAL assay, and plasma procalcitonin levels were assessed with a standard procalcitonin assay. Plasma endotoxin and procalcitonin levels increased corresponding to the degree of sepsis. Endotoxin scattering photometry significantly discriminated between patients with or without septic shock: sensitivity, 81.1%; specificity, 76.6%; positive predictive value, 48.4%; negative predictive value, 93.8%; and accuracy, 77.6%. The area under the receiver operating characteristic curve for septic shock with the ESP assay (endotoxin cutoff value, 23.8 pg/mL) was 0.8532 ± 0.0301 (95% confidence interval, 0.7841–0.9030; P < 0.0001). The predictive power of ESP was superior to that of turbidimetric assay (difference, 0.1965 ± 0.0588; 95% confidence interval, 0.0812–0.3117; P = 0.0008). There was no significant difference in predictive power between ESP and procalcitonin assay. Endotoxin scattering photometry also discriminated between patients with and without sepsis. Area under the receiver operating characteristic curve analysis showed that ESP had the best predictive power for diagnosing sepsis. In conclusion, compared with turbidimetric LAL assay, ESP more sensitively detected plasma endotoxin and significantly discriminated between sepsis and septic shock in patients undergoing gastrointestinal emergency surgery.

Postprandial hyperglycemia after a gastrectomy and the prediabetic state: A comparison between a distal and total gastrectomy

PurposePostprandial hyperglycemia is recognized as an important risk factor for developing type 2 diabetes; it is also common in patients after a gastrectomy and is likely to become exacerbated after a total gastrectomy rather than after a distal gastrectomy. In this study, we investigated the glucose and insulin responses after oral glucose tolerance test (OGTT), and compared the incidence of postchallenge hyperglycemia after OGTT in patients after a distal and total gastrectomy.MethodsForty-six patients, including 18 patients after a distal gastrectomy and 28 after a total gastrectomy, underwent a 75-g OGTT, and the plasma concentrations of glucose and insulin were measured after OGTT.ResultsGlucose peaked at 30 min in the distal gastrectomy patients and 60 min in the total gastrectomy patients, and there were significant differences in the 1-h plasma glucose (PG) and 1.5-h PG levels between the distal and total gastrectomy patients. Insulin peaked at 60 min in both the distal and total gastrectomy patients, and there were significant differences in insulin levels at 60 min between the distal and total gastrectomy patients. The incidence of postchallenge hyperglycemia in the patients after a total gastrectomy (57.1%) was higher than in those after distal gastrectomy (27.8%). Moreover, significant positive correlations were found between 1-h PG and hemoglobin antigen HbA1c after a total gastrectomy but not after a distal gastrectomy.ConclusionsThese results suggest that postchallenge hyperglycemia after OGTT may become more exacerbated after a total gastrectomy than after a distal gastrectomy. Postprandial hyperglycemia, especially after a total gastrectomy, may therefore be involved in the development of diabetes.

Edaravone improves the survival of rats subjected to hemorrhagic shock without resuscitation

Our aim in this study was to find out whether edaravone (3-methyl-1-phenyl-pyrazolin-5-one, MCI-186), a novel free radical scavenger, improved the survival rate in a rat hemorrhagic shock (HS) model. Fifty male Sprague-Dawley rats were divided randomly into an edaravone group and a saline group. Both groups were subjected to HS by inducing a mean arterial pressure of 30 mmHg for 60 min without resuscitation. The edaravone group was divided into four subgroups based on when edaravone was given: 0, 15, 30, or 60 min after HS. The saline group was given saline immediately after HS. We evaluated the 24-h survival rate in each group. The survival rate of the edaravone subgroup given edaravone immediately after HS was significantly better than that of the saline group. Edaravone improved the survival rate in a rat HS without resuscitation model. Edaravone was most effective when given immediately after HS.

Effect of sleeve gastrectomy on body weight, food intake, glucose tolerance, and metabolic hormone level in two different rat models: Goto-Kakizaki and diet-induced obese rat

BACKGROUND It is still an important question whether sleeve gastrectomy (SG) is appropriate only in the context of obesity-the condition for which it was originally developed-or whether lean people with insulin-deficient diabetes might also benefit. The aim of this study is to evaluate the effects of SG in Goto-Kakizaki (GK) and diet-induced obese (DIO) rats that have distinct characteristics in beta-cell function and fat mass. MATERIALS AND METHODS SG was performed in GK and DIO rats. Body weight, food intake, and fasting blood glucose were monitored after surgery. Des-acyl ghrelin in fasting condition and blood glucose, insulin, and glucagon-like peptide-1 levels during meal test were measured. Homeostatic model assessment and insulinogenic index were examined. RESULTS In both GK and DIO rats, SG improved glucose tolerance with increased glucagon-like peptide-1 and insulin secretion during meal test, and reduced fasting des-acyl ghrelin levels. Insulin sensitivity was enhanced after SG in DIO rats. The improvement in glucose tolerance after SG was shown earlier in DIO rats than in GK rats and weight regain after SG occurred faster and was more prominent in GK rats than in DIO rats. CONCLUSIONS In both DIO and GK rats, SG could improve glucose tolerance with increased insulin secretion and/or action. The improvement in glucose tolerance was shown earlier in DIO rats than in GK rats.

Utility of a microwave surgical instrument in sealing lymphatic vessels.

BACKGROUND This study assessed the ability of a novel microwave coagulation surgical instrument (MWCX) to seal lymphatic vessels when compared with LigaSure (Valleylab, Boulder, CO), the Harmonic Scalpel (HS; Ethicon Endo-Surgery, Cincinnati, OH), and electric cautery. METHODS The burst pressure of pig inguinal lymphatic vessels was assessed after the sealing of vessels with each surgical instrument. The rate of lymphorrhea from pig mesenteric lymphatic vessels was also investigated using indocyanine green and visualized with the Photodynamic Eye system (Hamamatsu Hotoniks, Hamamatsu, Japan). RESULTS Burst pressures were higher with MWCX (average, 300 mm Hg), LigaSure (average, 290 mm Hg), and HS (average, 253 mm Hg) when compared with electric cautery (average, 152.3 mm Hg; vs MWCX: P = .002, vs LigaSure: P = .002, vs HS: P = .004). The rate of lymphorrhea was significantly lower with LigaSure (13.3%), HS (18.8%), and MWCX (13.3%) when compared with electric cautery (77.3%; vs LigaSure: P < .001, vs HS: P < .001, vs MWCX: P < .001). CONCLUSIONS MWCX was equivalent to LigaSure and HS in terms of the ability to seal lymphatic vessels.

Lymphoepithelial cyst with sebaceous glands of the pancreas: a case report

BackgroundLymphoepithelial cyst (LEC) of the pancreas is a rare benign tumor. LEC with sebaceous glands of the pancreas is extremely rare, and its histogenesis remains unclear.Case presentationWe present a 66-year-old man with an incidental finding of a cystic lesion at the neck of the pancreas. Pancreatic juice cytology results and elevated serum carbohydrate antigen 19-9 and Dupan-2 levels indicated that the cyst was a potential adenocarcinoma. Therefore, a pancreaticoduodenectomy was performed. Macroscopically, the tumor was a unilocular cyst with a thin transparent wall, filled with soft yellow material. Pathological findings showed that the cyst was lined with squamous epithelium, accompanied by dense lymphoid tissue with scattered germinal centers. There were no hair follicles, but sebaceous glands were present in the lymphoid tissue just beneath the squamous epithelium. Therefore, the histopathological diagnosis was an LEC with sebaceous glands of the pancreas. Furthermore, the squamous epithelium surrounding the cyst was pathologically continuous with the tubular structure, indicating that the tubular structure transitioned into the squamous epithelium.ConclusionsWe report an extremely rare case of LEC with sebaceous glands of the pancreas. Moreover, the pathological findings, which showed that the tubular structure transitioned into the squamous epithelium, suggested that this was squamous metaplasia. In order to investigate the histogenesis of LEC of the pancreas, the pathological findings must be evaluated.