[show abstract][hide abstract] ABSTRACT: Male breast carcinoma is an uncommon neoplasm, accounting for 0.6% of all breast carcinomas. Invasive ductal carcinoma of no special type is the most common type of male breast carcinoma, and mucinous carcinoma occurring in the male breast is extremely rare. In the present study, we report a case of mucinous carcinoma of the male breast and discuss the clinicopathological features of this type of tumor. A 63-year-old Japanese male presented with a gradually enlarged nodule in the right breast. The resected breast specimen revealed pure mucinous carcinoma and immunohistochemical analyses demonstrated that tumor cells were positive for estrogen receptor (ER), but negative for progesterone receptor (PgR). In addition, HER2 expression was not amplified. Pure mucinous carcinoma is generally associated with a low incidence of lymph node or distant metastases, and excellent disease-free survival in females. However, certain cases of this type of tumor with axillary lymph node metastasis in the male breast have been reported. In addition, the immunoprofiles of mucinous carcinoma in males are fundamentally the same as those in females. More than 90% of cases show positive immunoreactivity for ER and/or PgR, and HER2 expression is not amplified. However, it has been reported that breast cancer in males is more frequently positive for ER than in females, and has less HER2 overexpression. The high rate of hormone receptor-positive breast cancer in males is considered to be due to similar conditions as those in breast cancer in postmenopausal women. The pathogenesis of male breast carcinoma, including mucinous carcinoma, remains unclear; therefore, additional clinicopathological studies are required.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Early diagnosis and treatment for breast cancers has greatly improved in recent years, however, subset of this disease with early recurrence have remained to be unpredictable. Several studies has addressed that strong CD10 expression in tumor stroma is associated with poor survival rate of breast cancers, but no correlation between CD10 expression and disease-free survival has been elucidated yet. For these reasons, this study with modified immunohistochemical (IHC) staining evaluated the expression of CD10 in invasive breast carcinomas (IBCs) and analyzed correlations between CD10 expression on tumor cells, stromal cells and myeloid-like cells with clinicopathological parameters and recurrence status. METHOD: IHC staining method was performed on formalin-fixed paraffin-embedded sections of 73 cases of primary IBCs, with record of pathological characteristics of subjects followed up from 1998 to 2007. RESULTS: Stromal CD10 expression was observed in 39/73 cases (53.4 %) with strong expression in 41.0 %. Three cases stained positive for myeloid-like cells and five for carcinomatous cells, of which 6 cases had recurrence and/or regional LN status. Stromal CD10 expression was significantly higher in the unfavorable group (69.6 %; 16/23 cases) compared with the favorable group (32.1 %; 9/28 cases) (p = 0.048). The levels of CD10 expression showed significant difference among clinical outcomes (recurrence or non-recurrence), independent of regional LN status (p = 0.034), histology type (p = 0.044), ER status (p = 0.042), PgR status (p = 0.039), Her2 status (p = 0.038) and Ki67 index (p = 0.036) (partial Pearson correlations). Cox proportional-hazards regression showed that risk factors for disease-free survival were stromal CD10 expression [CD10±, CD10+ versus CD10++; p = 0.003; HR 2.824 (1.427-5.591)]; regional LN status [N0, N1, N2, versus N3; p = 0.004; HR 2.107 (1.262-3.517)] and PgR status [negative versus positive, p = 0.006, HR 0.172 (0.049-0.596)]. CONCLUSION: CD10 expression on stroma with or without other positive tumor cells and/or myeloid-like cells may function as a powerful prognostic factor for IBC disease-free survival rates, predicting of potential recurrence. It can be determined by a simple modified IHC staining method, which is independent of other prognostic morphologic markers and biomarkers in IBC.
[show abstract][hide abstract] ABSTRACT: Infections are important causes of postoperative morbidity after gastric surgery; currently, no factors have been identified that can predict postoperative infection. Adiponectin (ADN) mediates energy metabolism and functions as an immunomodulator. Perioperative ADN levels and perioperative immune functioning could be mutually related. Here we evaluated a potential biological marker to reliably predict the incidence of postoperative infections to prevent such comorbidities.
We analyzed 150 consecutive patients who underwent elective gastric cancer surgery at the Shiga University of Medical Science Hospital (Shiga, Japan) from 1997 to 2009; of these, most surgeries (n = 100) were performed 2008 onwards. The patient characteristics and surgery-related factors between two groups (with and without infection) were compared by the paired t-test and χ(2) test, including preoperative ADN levels, postoperative day 1 ADN levels, and ADN ratio (postoperative ADN levels/preoperative ADN levels) as baseline factors. Logistic regression analysis was performed to access the independent association between ADN ratio and postoperative infection. Finally, receiver operating curves (ROCs) were constructed to examine its clinical utility.
Sixty patients (40%) experienced postoperative infections. The baseline values of age, American Society of Anesthesiologists physical status, total operating time, blood loss, surgical procedure, C-reactive protein (CRP) levels, preoperative ADN levels, and ADN ratio were significantly different between groups. Logistic regression analysis using these factors indicated that type 2 diabetes mellitus (T2DM) and ADN ratio were significantly independent variables (*p<0.05, ** p<0.01, respectively). ROC analysis revealed that the useful cutoff values (sensitivity/specificity) for preoperative ADN levels, ADN ratio, blood loss, operating time, and CRP levels were 8.81(0.567/0.568), 0.76 (0.767/0.761), 405 g (0.717/0.693), 342 min (0.617/0.614), and 8.94 mg/dl (0.583/0.591), respectively.
T2DM and ADN ratio were independent predictors of postoperative infection and ADN ratio was the most useful predictor for postoperative infection.
PLoS ONE 01/2013; 8(3):e56129. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: We compared treatment completion rates and safety of docetaxel and cyclophosphamide six- cycle therapy (TC6) with docetaxel followed by 5FU, epirubicin and cyclophosphamide (T-FEC) therapy in Japanese patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Materials and Methods: We administered TC6 q3w or T-FEC q3w to HER2-negative breast cancer patients. The primary endpoint of this trial was toxicity. As second endpoints, the treatment completion rate and relative dose intensity were evaluated. Results: The TC6 and T-FEC group consisted of 22 and 21 patients, respectively. Concerning hematological toxicity, grade 3 or higher adverse reactions included neutropenia and febrile neutropenia. As non-hematological adverse events, exanthema and peripheral neuropathy were frequently reported in the TC6 group, whereas more patients of the T-FEC group reported nausea and vomiting. In TC6, the treatment completion rate was 86.4% and the relative dose intensity of docetaxel was 93.2%. In T-FEC, the values were 95.2% and 98.9%, respectively. Conclusions: These results suggest that TC6 is tolerable in Japanese, and that this regimen can also be performed in outpatient clinics. However, with the TC6 regimen, the compliance was slightly lower than with the T-FEC regimen, and supportive therapy needs to be managed appropriately.
Asian Pacific journal of cancer prevention: APJCP 01/2013; 14(8):4835-4838. · 1.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: Goshajinkigan (GJG) is used for the treatment of several neurological symptoms. We investigated the efficacy of GJG and mecobalamin (B12) against neurotoxicity associated with docetaxel (DOC) in breast cancer patients. Materials and Methods: Sixty breast cancer patients were treated with DOC. Thirty-three patients (GJG group) received oral administration of 7.5 g/day GJG and 27 patients (B12 group) received oral administration of 1500 μg/day B12. Neuropathy was evaluated according to DEB-NTC (Neurotoxicity Criteria of Debiopharm), Common Terminology Criteria for Adverse Events (NCI-CTC) ver. 3.0, and a visual analogue scale (VAS). This study employed a randomized open design. Results: The incidence of neuropathy was 39.3% in the GJG group, and 88.9% in the B12 group (p<0.01). In the GJG group, grade 1 DEB-NTC was observed in 2 cases, grade 2 in 5 cases and grade 3 in 5 cases. Grade 1 NCI-CTC was observed in 7 cases, grade 2 in 6 cases, and VAS was 2.7±2.2. In the B12 group, grades 1, 2 and 3 DEB-NTC were observed in one case, 12 cases and 12 cases, respectively; and grades 1, 2 and 3 NCI-CTC were observed in 11 cases, 12 cases and one case, and VAS was 4.9±2.4. Conclusions: Concomitant administration of GJG is useful in preventing neuropathy in breast cancer patients treated with a DOC regimen.
Asian Pacific journal of cancer prevention: APJCP 01/2013; 14(11):6351-6. · 1.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: The infusion rate is considered to affect incidence and severity of infusion reactions (IRs) caused by protein formulations. Trastuzumab (TRS) is approved for 90-minute infusion as the initial dose followed by 30-minute infusion with 250 ml saline. In the study, we evaluated the safety of TRS intravenously administered over 30 minutes with 100 ml saline to reduce burden of patients, safety of infusion with 250 ml saline already being established. Materials and Methods: Women with HER2 positive breast cancer, ≥18 years and ≥55% left ventricular ejection fraction (LVEF), were registered in the study. Patients received 8mg/kg of TRS 250 ml over 90 minutes followed by 6mg/kg of TRS 100ml over 30 minutes in a three-week cycle. Results: A total of 31 patients were recruited, 24 for adjuvant therapy and seven with metastases. The median age was 59 years (range 39 to 82). The total number of TRS doses ranged from 5 to 17 with the median of 15. Mild IR occurred in two patients at the first dose. However, no IR was observed after reducing to 100 ml saline. No decrease of LVEF, increase of serum brain natriuretic peptide or any other adverse events were reported. Conclusions: Intravenous infusion of TRS with 100 ml saline over 30 minutes in breast cancer patients can be considered safe based on results from the study. It can be given on an outpatient basis as with the currently recommended dilution in 250 ml saline.
Asian Pacific journal of cancer prevention: APJCP 01/2013; 14(8):4843-4846. · 1.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Invasive lobular carcinoma (ILC) is a distinct type of breast carcinoma and represents 5-15% of invasive breast carcinomas in female. However, the occurrence of ILC is exceptional in male breast, and the incidence is 1.5-1.9% of male breast carcinomas. Herein, we report a case of pleomorphic lobular carcinoma in a male breast. A 76-year-old Japanese male with a history of treatment with a progestational agent for prostate cancer presented with a right breast tumor. Magnetic resonance imaging showed gynecomastia of bilateral breasts and an irregular-shaped nodule in his right breast. Histopathological study revealed infiltrative neoplastic growth of discohesive tumor cells arranged in single-filed linear cords or trabeculae. These neoplastic cells had variable-sized large nuclei containing occasional nucleoli. Immunohistochemically, these tumor cells lacked E-cadherin expression. Accordingly, an ultimate diagnosis of pleomorphic lobular carcinoma was made. This is the third documented case of pleomorphic lobular carcinoma of male breast. Our analyses of the clinicopathological features of this type of tumor revealed that patients were middle-aged or elderly men, and all cases were free from lymph node metastases or recurrence. Gynecomastia and a history of hormonal agent intake were present only in the current case. The most commonly proposed risk factor for the development of male breast cancer is elevated level of estrogen, and a possible link between the development of male breast cancer and estrogen therapy for prostate cancer has been suggested. The clinicopathological features of ILC of male breast remains unclear; therefore, additional studies are needed to clarify them.
International journal of clinical and experimental pathology 01/2013; 6(7):1441-4. · 2.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: TC (docetaxel 75 mg/m(2) and cyclophosphamide 600 mg/m(2) q3w) combination is used for neoadjuvant/adjuvant chemotherapy in primary breast cancer. The incidence of allergic reaction is reportedly more common in patients who receive docetaxel before cyclophosphamide. This study aims to determine the significance of cyclophosphamide and docetaxel administration sequence. METHODS: Prospective analysis was performed of 49 consecutive patients treated with TC for stage I-IIB breast cancer from March 2010 to June 2011. Premedication was administered with granisetron, dexamethasone, and chlorpheniramine. Patient charts were reviewed for completion rate and adverse events. Two-tailed Fisher exact test was used to evaluate adverse events between prior cyclophosphamide and prior docetaxel. RESULTS: Of 49 patients, 26 received docetaxel prior to cyclophosphamide and 23 received cyclophosphamide before docetaxel. There were no differences in patient characteristics between the two groups. Completion rates were 95.6 % in the prior cyclophosphamide group, and 100 % in the prior docetaxel group. The relative dose intensities of docetaxel and cyclophosphamide were 94.5 and 94.8 % in the prior cyclophosphamide group, and 98.5 and 98.7 % in the prior docetaxel group (p < 0.01). In the prior cyclophosphamide group, severe neutropenia occurred in 96 % of patients, but in only 46 % of patients in the prior docetaxel group (p < 0.01). Significantly fewer cases of skin eczema (27 versus 61 %), nausea (8 versus 48 %), stomatitis (23 versus 61 %), and diarrhea (4 versus 30 %) were observed in the prior docetaxel group as compared with the prior cyclophosphamide group (p < 0.01). Decreased incidences of fatigue (50 versus 65 %) and edema (19 versus 35 %) were found in the prior docetaxel group (p < 0.05). No difference was observed in allergic reaction or neuropathy between the two groups. CONCLUSION: Patients receiving cyclophosphamide prior to docetaxel were at increased risk of several toxicities as compared with patients receiving docetaxel prior to cyclophosphamide in TC combination therapy.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: The tolerance and safety associated with the administration order of the anthracycline and taxane drugs have not been evaluated. PATIENTS AND METHODS: Breast cancer patients with node-positive or high-risk patients with node-negative were eligible. The feasibility and toxicity were evaluated in the following regimens-arm A, 3 courses of fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) followed by 3 courses of docetaxel 100 mg/m(2) (DOC); arm B, 3 courses of DOC followed by 3 courses of FEC. RESULTS: Forty-two patients were registered. The relative dose intensity was 94.2 % for FEC and 97.8 % for DOC in arm A, and 98.9 % for DOC and 95.2 % for FEC in arm B. In arm A, grade 3 or higher hematological toxicity was observed in nine patients, and febrile neutropenia developed in three patients with FEC. In arm B, grade 3 or higher hematological toxicity was observed in seven patients, but febrile neutropenia was not noted in any patient. CONCLUSION: The regimens in both arms A and B were safe regarding adjuvant chemotherapy for early breast cancer. However, DOC followed by FEC might be more tolerable. Further studies will maximize the results obtained with DOC followed by FEC.
International Journal of Clinical Oncology 04/2012; · 1.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: A carcinoma displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as a lymphoepithelioma-like carcinoma (LEC), and some of LEC is associated with Epstein-Barr virus (EBV). All of the 13 previously reported cases of LEC of the biliary system were intrahepatic in location. Herein, we describe the first case of LEC of the inferior common bile duct. A 68-year-old Japanese man, who had been previously treated for hepatocellular carcinoma using microwave coagulation therapy, was found to have tumors of the common bile duct and pancreas head. Histopathological study of the resected tumor showed solid or cohesive nests of large undifferentiated cells with irregular large vesicular nuclei and nucleoli. Around the tumor cell nests, dense lymphoplasmacytic infiltration was observed. Focal glandular differentiation (approximately 5%) was also present. These histopathological features corresponded morphologically to LEC. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7, CK 19 and CA19-9, but negative for CK 20 and Hep Par 1. In situ hybridization for Epstein Barr virus early small RNAs disclosed no nuclear signal in tumor cells. Therefore, a diagnosis of non-EBV-associated LEC of the inferior common bile duct was made. Although the prognosis of the biliary LEC is thought to be better than that of conventional cholangiocarcinoma, the differences in prognosis between EBV-positive and -negative cases have not yet been established. Therefore, additional case studies will be needed to clarify the clinicopathological features of LEC of the biliary tract.
World journal of gastrointestinal oncology. 07/2011; 3(7):111-5.
[show abstract][hide abstract] ABSTRACT: This study presents a new method that enables the detection of sentinel lymph nodes (SLN) with high sensitivity using indocyanine green (ICG) fluorescence imaging.
This study enrolled 128 patients with clinically node-negative breast cancer. Fluorescence imaging was obtained after ICG was injected into the areola. Subcutaneous lymphatic channels were immediately visible.
Lymphatic channels and SLN were successfully visualized in all patients. One lymphatic channel was 60%, two channels were 24%, and three channels were 16%. The number of fluorescence SLN ranged from 1 to 6, and blue-dyed SLN ranged from 0 to 3. In the latter, SLN were not identified in 44 patients. Nineteen patients had pathologically identified lymph node metastases. All of them were recognized by fluorescence imaging, but 8 patients had lymph nodes with metastases were not identified by dye method.
This ICG fluorescence imaging technique is feasible and safe for detecting SLN in a less invasive manner than conventional mapping, with real-time observations.
Surgery Today 02/2011; 41(2):197-202. · 0.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: It has been thought that there is a possibility that infusion speed generally affects the manifested frequency of infusion reaction and its strength. The infusion prescription time of trastuzumab should be over 90 minutes according to the package insert. In the infusion US, is possible over 30 minutes after the second time. We sought to evaluate the safety and tolerability of trastuzumab administered as a 30-minute infusion. Patients: Eighteen patients of HER2-positive breast cancer were treated, and their age ranged from 37 to 65 years old(median, 54 years old). Method: Patients were infused with 8 mg/kg of trastuzumab over 90 minutes and, if tolerated, all subsequent maintenance doses of 6 mg/kg are over 30 minutes. Result: The infusion times for 30 minutes were twice to 17 times(16 times the median). Mild infusion reactions were seen in 2 cases at the time of the initial prescription, but the infusion reaction was not judged from the prescription for 30 minutes. Mild eczema was admitted by 3 cases after prescription. No decline in cardiac function was seen. Conclusion: Our data strongly suggest that trastuzumab can be safely infused over 30 minutes for 6 mg/kg maintenance doses. However, it is thought that the number of cases will increase in future, and confirmation is necessary.
Gan to kagaku ryoho. Cancer & chemotherapy 10/2010; 37(10):1887-91.
[show abstract][hide abstract] ABSTRACT: As adjuvant chemotherapy for breast cancer, the addition of taxane to regimens containing anthracycline has been shown to be effective. However, in Japan, it is not probability yet as for safety. We examined the feasibility of FEC 100 followed by DOC 100 as adjuvant chemotherapy for breast cancer.
Node-positive breast cancer patients or node-negative high-risk patients were eligible. The treatment completion rate and toxicity were evaluated in 3 courses of FEC 100 mg/m2 followed by 3 courses of DOC 100 mg/m2.
Twenty-one patients were registered and completion rate was 100%. The relative dose intensity (RDI) was 94.2% for FEC 100 and 97.8% for DOC 100. Grade 3 or higher neutropenia observed in 38% and febrile neutropenia developed in 14%. Non-hematological toxicities were slight.
The regimen of FEC 100 followed by DOC 100 was safe in adjuvant chemotherapy for breast cancer in our country.
Gan to kagaku ryoho. Cancer & chemotherapy 08/2010; 37(8):1483-7.
[show abstract][hide abstract] ABSTRACT: Capecitabine + docetaxel combination therapy proves highly effective against the advanced or recurrent breast cancer. Therefore, it has been investigated as a first-line treatment for metastatic breast cancer. Hand-foot syndrome (HFS), a typical side effect of capecitabine, decreases the QOL of patients and sometimes prevents further medication using capecitabine. A 56-year-old woman who had liver, bone and local skin metastases two years after her left breast cancer operation, was treated with capecitabine + docetaxel combination therapy. Severe HFS disturbed the continuation of the therapy. Some other chemo-therapies were attempted after discontinuing the therapy; however, the metastases progressed. Finally, we tried to prevent HFS with vitamin B6 and started the capecitabine + docetaxel combination therapy. HFS was controlled completely. The liver tumor disappeared in MRI and CT images after 18 courses. In this case, vitamin B6 seemed to be effective to control HSF and allow continuation of capecitabine + docetaxel combination therapy.
Gan to kagaku ryoho. Cancer & chemotherapy 04/2010; 37(4):687-9.
[show abstract][hide abstract] ABSTRACT: Acute renal failure (ARF) is the rapid loss of the renal filtration function, which is characterized by metabolic acidosis, high potassium levels, a body fluid imbalance, and so on. The overall mortality rate of ARF is about 45%; however, the mortality rate of sepsis-induced ARF is about 70%. In addition, sepsis is the most common trigger of ARF. Little is known about the pathogenesis of septic ARF, although renal hypoperfusion and ischemia have been proposed as being central. Blood purification therapies for septic ARF include the elimination of pathogenesis, such as endotoxin or mediators that contribute to ARF, and renal replacement therapy (RRT). The adsorption of endotoxin with direct hemoperfusion using polymyxin-B immobilized fiber makes the urinary output increase, while also improving renal function. It would seem logical to initiate RRT earlier rather than later, especially in rapidly developing symptomatic oliguric renal failure with metabolic derangement. Continuous RRT (CRRT) has an advantage over intermittent RRT in that it provides greater hemodynamic stability, easier fluid removal and greater flexibility in providing parenteral nutrition as a result of a greater control over the fluid balance. CRRT may be able to reduce chronic dialysis dependence. Patients with sepsis and ARF are hyper-catabolic. Some studies have suggested that increased doses of dialysis improve survival in patients who are hypercatabolic and have ARF. The increase in the ultrafiltration rate may, however, be associated with some difficulties, namely cost and labor. The mechanisms of septic ARF therefore need to be further elucidated and the potential of RRT in improving the mortality associated with ARF needs to be established.
Contributions to nephrology 01/2010; 166:40-6. · 1.49 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Surgery Today 02/2008; 38(5):476-7. · 0.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the role of transient receptor potential vanilloid 1 (TRPV1) in a rat hemorrhagic shock (HS) model using the TRPV1 antagonist, capsazepine (CPZ).
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.
Male rats were anesthetized and HS was induced with the mean arterial pressure (MAP) at 30 mm Hg for 90 minutes. CPZ (5.0 micromol/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.
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.
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.
Annals of Surgery 07/2007; 245(6):964-70. · 6.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Adiponectin is an anti-inflammatory cytokine that is specifically and abundantly produced by adipocytes as a secretory protein. A direct interaction between adiponectin and lipopolysaccharide (LPS) is not fully understood. To elucidate the effects of adiponectin on LPS, we first investigated interactions between recombinant adiponectin and LPS.
Various concentrations of LPS (50, 500, and 5000 pg/ml) and recombinant adiponectin (1, 10, and 100 microg/ml) were incubated for 1 h. The limulus amoebocyte lysate (LAL) activities in the mixture were measured. Interactions between adiponectin (100 microg/ml) and LPS (100 and 300 microg/ml) were also analyzed in Western blotting. Next, we determined plasma adiponectin, tumor necrosis factor-alpha (TNF-alpha), and endotoxin levels at 1.5, 3, and 24 h after onsets of rodent polymicrobial sepsis induced by cecal ligation and puncture (CLP).
The incubation with adiponectin significantly and dose-dependently suppressed LAL activity in the mixture compared to control. Western blotting revealed that adiponectin incubated with LPS shifted to a higher mass. In the animal model of sepsis, both plasma endotoxin and TNF-alpha levels after CLP gradually increased and were significantly higher at 3, 24 h compared to those after sham operation. On the contrary, plasma adiponectin levels after CLP gradually decreased and were significantly lower at 3, 24 h compared to those after sham operation. Plasma adiponectin levels were negatively correlated with plasma endotoxin levels (r = -0.77, P < 0.01).
Our results indicate that adiponectin might neutralize LPS in vitro and diminish LPS activity in rats with polymicrobial sepsis. These findings suggest that the anti-inflammatory effects of adiponectin are in part likely because of neutralization of LPS activity.
Journal of Surgical Research 08/2006; 134(2):348-53. · 2.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Digestive Diseases and Sciences 01/2006; 50(12):2263-7. · 2.26 Impact Factor