The incidence of rectal carcinoids is rising because of the widespread use of screening colonoscopy. Rectal carcinoids detected incidentally are usually in earlier stages at diagnosis. Rectal carcinoids estimated endoscopically as < 10 mm in diameter without atypical features and confined to the submucosal layer can be removed endoscopically. Here, we review the efficacy and safety of various endoscopic treatments for small rectal carcinoid tumors, including conventional polypectomy, endoscopic mucosal resection (EMR), cap-assisted EMR (or aspiration lumpectomy), endoscopic submucosal resection with ligating device, endoscopic submucosal dissection, and transanal endoscopic microsurgery. It is necessary to carefully choose an effective and safe primary resection method for complete histological resection.
Carcinoid tumor; Rectum; Polypectomy; Endoscopic mucosal resection; Endoscopic submucosal dissection
Endoscopic band ligation (EBL) is the preferred endoscopic technique for the endoscopic treatment of acute esophageal variceal bleeding. EBL has also been used to treat nonvariceal bleeding. Recently, Han et al demonstrated that EBL can be a feasible and safe alternate technique for the management of iatrogenic gastric perforation especially in cases in which closure with endoclips is difficult. EBL is technically simpler to perform than other methods and provides a good view of the lesions under direct pressure and suction from the transparent ligation cap. EBL can be used even if the diameter of the perforation is greater than 10 mm or if there is a severe tangential angle. In this commentary, we discuss the efficacy and safety of EBL for the closure of iatrogenic gastrointestinal perforation. We also discuss the advantages and disadvantages of EBL for the treatment of nonvariceal bleeding.
Band ligation; Endoscopy; Intestinal perforation; Gastrointestinal hemorrhage
RNA interference (RNAi) is a gene regulation mechanism initiated by RNA molecules that enables sequence-specific gene silencing by promoting degradation of specific mRNAs. Molecular therapy using small interfering RNA (siRNA) has shown great therapeutic potential for diseases caused by abnormal gene overexpression or mutation. The major challenges to application of siRNA therapeutics include the stability and effective delivery of siRNA in vivo. Important progress in nanotechnology has led to the development of efficient siRNA delivery systems. In this review, the authors discuss recent advances in nanoparticle-mediated siRNA delivery and the application of siRNA in clinical trials for cancer therapy. This review will also offer perspectives on future applications of siRNA therapeutics.
Boerhaave’s syndrome is spontaneous rupture of the esophagus, a rare condition with high mortality that occurs most often after forceful vomiting. Polyethylene glycol (PEG) solution is the most common preparation used for colonoscopy. Since large volumes have to be ingested, PEG may induce severe vomiting or retching. However, Boerhaave’s syndrome has rarely been reported as a potential problem related to PEG solution. We report a case of spontaneous esophageal rupture due to violent vomiting during bowel preparation with PEG solution in a patient with postpolypectomy bleeding.
Esophageal perforation; Colonoscopy; Polyethylene glycols
Background/Aim. Hepcidin, an iron regulatory hormone, is increased in response to inflammation and some infections. We investigated the relationships among serum prohepcidin, iron status, Helicobacter pylori infection status, and the presence of gastric mucosal atrophy. Methods. Seventy subjects undergoing esophagogastroduodenoscopy underwent multiple gastric biopsies, and the possibility of H. pylori infection and the degree of endoscopic and histologic gastritis were investigated. In all subjects, serum prohepcidin and iron parameters were evaluated. Results. No correlations were observed between serum prohepcidin levels and the other markers of anemia, such as hemoglobin, serum iron, ferritin, and total iron binding capacity. Serum prohepcidin levels were not significantly different between the H. pylori-positive group and the H. pylori-negative group. Serum prohepcidin levels in atrophic gastritis patients were significantly lower than those in subjects without atrophic gastritis irrespective of H. pylori infection. Conclusion. Serum prohepcidin levels were not altered by H. pylori infection. Serum prohepcidin levels decrease in patients with atrophic gastritis, irrespective of H. pylori infection. It suggests that hepcidin may decrease due to gastric atrophy, a condition that causes a loss of hepcidin-producing parietal cells. Further investigations with a larger number of patients are necessary to substantiate this point.
Air in the main pancreatic duct has been reported only rarely and might be associated with either a spontaneous or a surgically induced alteration of the anatomy of the biliary tract. We report a case of “innocent” air found incidentally in the main pancreatic duct. To our knowledge, this is only the third such case reported. A 54-year-old woman presented with hemoptysis that had lasted for 3 d. She underwent a chest computed tomography scan, which revealed not only focal bronchiectasis in the left lower lobe, but also air in the main pancreatic duct and dilatation of the common bile duct. She was managed conservatively for the hemoptysis and no further problems developed. She had no specific gastrointestinal symptoms and had no history of surgery or medication. Her laboratory parameters were normal. Magnetic resonance cholangiopancreatography also demonstrated air in the main pancreatic duct and a dilated common bile duct (CBD). Duodenoscopy revealed separate biliary and pancreatic orifices with patulous openings and some air bubbles appearing in the pancreatic orifice. Endoscopic retrograde cholangiopancreatography (ERCP) showed the dilated CBD and pancreatic duct with some air bubbles, but no other abnormal lesions. She was discharged with no further problems. Most patients with air in the main pancreatic duct have had a pancreatobiliary disease, or a history of pancreatobiliary disease, pancreatobiliary surgery or sphincterotomy. If the air is innocent, as in our case, ERCP should be performed to evaluate any altered sphincteric function or anatomy such as patulous openings.
Air; Main pancreatic duct; Endoscopic retrograde cholangiopancreatography
Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that is important in many physiological and pathological processes, such as lipid metabolism, insulin sensitivity, inflammation, cell proliferation, and carcinogenesis. Several studies have shown that PPARγ plays an important role in gastric mucosal injury due to Helicobacter pylori (H. pylori). As H. pylori infection is the main etiologic factor in chronic gastritis and gastric cancer, understanding of the potential roles of PPARγ in H. pylori infection may lead to the development of a therapeutic target. In this paper, the authors discuss the current knowledge on the role of PPARγ in H. pylori infection and its related gastric carcinogenesis.
Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy. This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecular signature of individual cells. Molecular imaging has several advantages including minimal damage to tissues, repetitive visualization, and utility for conducting quantitative analyses. Advancements in basic science coupled with endoscopy have made early detection of gastrointestinal cancer possible. Molecular imaging during gastrointestinal endoscopy requires the development of safe biomarkers and exogenous probes to detect molecular changes in cells with high specificity anda high signal-to-background ratio. Additionally, a high-resolution endoscope with an accurate wide-field viewing capability must be developed. Targeted endoscopic imaging is expected to improve early diagnosis and individual therapy of gastrointestinal cancer.
Autofluorescence endoscopy; Confocal endomicroscopy; Endoscopy; Molecular imaging; Molecular probes, Near-infrared fluorescence imaging; Targeted endoscopic imaging
Lymphangioma of the colon is a relatively rare non-epithelial tumor and usually presents as a submucosal polypoid lesion. Many cases incidentally discovered are usually asymptomatic. However, they may present as abdominal pain or bleeding, and their resection is normally required. Lymphangioma itself is generally recognized as a benign tumor and no cases of malignant transformation have yet been reported, although its natural history is currently unknown. To the best of our knowledge, this study is the first to describe a case of spontaneous resolution in multiple colonic lymphangiomas without any specific treatment.
Lymphangioma; Colon; Natural history
AIM: To evaluate duodenal polyps, divided into non-neoplastic and neoplastic lesions. In addition, the clinical characteristics of duodenal hyperplastic polyps are determined.
METHODS: We analyzed medical records of 50 114 consecutive patients submitted to for first diagnostic esophago-gastroduodenoscopy between January 2004 and December 2009. We excluded lesions on the ampulla of Vater and submucosal tumors. We studied 510 cases that were diagnosed endoscopically with duodenal polyps and enrolled a total of 221 cases that had undergone tissue biopsy. We analyzed the differences between non-neoplastic and neoplastic lesions, and determined the clinical features of duodenal hyperplastic polyps.
RESULTS: Non-neoplastic lesions were found in 196 patients and neoplastic lesions in 25 patients. On univariate analysis, there were significant differences in shape, location, and size. Polyps more than 10 mm in diameter or polyps in the second portion had independent risk factors for being neoplastic lesions, as identified by multivariate analysis. In 23 cases of hyperplastic polyps (79.3%), they were accompanied by gastro-duodenal pathology, which was possibly associated with Helicobacter pylori.
CONCLUSION: Polyps of more than 10 mm or polyps in the second portion of the duodenum should be evaluated by histological examination.
Duodenum; Polyp; Helicobacter pylori
Endoscopic resection has proven to be a safe and effective alternative to surgery for duodenal adenomas. However, few data are available on the adequacy of resection and long-term outcomes. This study evaluated the efficacy and longterm endoscopic findings in a cohort of Korean patients who underwent endoscopic mucosal resection (EMR) of sporadic duodenal adenomas.
Seventeen patients with nonampullary duodenal adenomas without familial polyposis syndrome and who were treated by EMR between January 2001 and December 2007 were evaluated retrospectively. Their management, follow-up, and outcomes were reviewed.
In total, seventeen lesions were removed from EMR in 17 patients (mean age, 59.3 years; 6 women, 11 men). The mean size of the tumors was 15.1 mm (median, 13 mm, range, 8-27 mm). Of these 17 adenomas, 16 adenomas were tubulous and 1 was tubulovillous. The EMR was performed successfully in all 17 patients in a single session. After a median follow-up period of 29 months (range, 13-72 months), all patients remained in remission. One patient had bleeding at the site of the EMR. There were no perforations after the EMR.
EMR for sporadic duodenal adenomas seemed to be a safe and effective treatment modality.
Duodenal neoplasm; Adenoma; Endoscopic mucosal resection; Treatment efficacy
AIM: To investigate whether percutaneous endoscopic gastrostomy (PEG) tube placement is safe in patients with ventriculoperitoneal (VP) shunts.
METHODS: This was a retrospective study of all patients undergoing PEG insertion at our institution between June 1999 and June 2006. Post-PEG complications were compared between two groups according to the presence or absence of VP shunts. VP shunt infection rates, the interval between PEG placement and VP shunt catheter insertion, and long-term follow-up were also investigated.
RESULTS: Fifty-five patients qualified for the study. Seven patients (12.7%) had pre-existing VP shunts. All patients received prophylactic antibiotics. The complication rate did not differ between VP shunt patients undergoing PEG (PEG/VP group) and non-VP shunt patients undergoing PEG (control group) [1 (14.3%) vs 6 (12.5%), P = 1.000]. All patients in the PEG/VP group had undergone VP shunt insertion prior to PEG placement. The mean interval between VP shunt insertion and PEG placement was 308.7 d (range, 65-831 d). The mean follow-up duration in the PEG/VP group was 6.4 mo (range, 1-15 mo). There were no VP shunt infections, although one patient in the PEG/VP group developed a minor peristomal infection during follow-up.
CONCLUSION: Complications following PEG placement in patients with VP shunts were infrequent in this study.
Percutaneous endoscopic gastrostomy; Ventriculoperitoneal shunt; Complication; Ventriculoperitoneal shunt infection; Prophylactic antibiotic
AIM: To evaluate the prevalence of chronic gastrointestinal symptoms and their impact on health-related quality of life (HRQOL) in the Korean population.
METHODS: A cross-sectional survey, using a reliable and valid Rome II based questionnaire, was performed on randomly selected residents, between 18 and 69 years in age. All respondents were interviewed at their homes or offices by a team of interviewers. The impact of chronic gastrointestinal symptoms on HRQOL was assessed using the Korean version of the 36-item Short-Form general health survey (SF-36).
RESULTS: Of the 1807 eligible subjects, 1417 (78.4%: male 762; female 655) were surveyed. Out of the respondents, 18.6% exhibited at least one chronic gastrointestinal symptom. The prevalence of gastroesophageal reflux disease (GERD), defined as heartburn and/or acid regurgitation experienced at least weekly, was 3.5% (95% CI, 2.6-4.5). The prevalence of uninvestigated dyspepsia, irritable bowel syndrome (IBS) and chronic constipation based on Rome II criteria were 11.7% (95% CI, 10.1-13.5), 2.2% (95% CI, 1.5-3.1), and 2.6% (95% CI, 1.8-3.5) respectively. Compared with subjects without chronic gastrointestinal symptoms (n = 1153), those with GERD (n = 50), uninvestigated dyspepsia (n = 166) and IBS (n = 31) had significantly worse scores on most domains of the SF-36 scales.
CONCLUSION: The prevalence of GERD, uninvestigated dyspepsia and IBS were 3.5%, 11.7% and 2.2% respectively, in the Korean population. The health-related quality of life was significantly impaired in subjects with GERD, uninvestigated dyspepsia and IBS in this community.
Chronic gastrointestinal symptom; Gastroesophageal reflux disease; Dyspepsia; Irritable bowel syndrome; Qaulity of life
AIM: To assess the occurrence of gastric acid reflux into the esophagus in endoscopically confirmed prolapse gastropathy syndrome (PGS).
METHODS: Using ambulatory esophageal pH measurement (BRAVOTM wireless esophageal pH monitoring system), twenty-six patients with PGS were compared with twenty-one patients with erosive esophagitis (EE) as controls. We assessed several reflux parameters, including the percentage of total time at pH < 4, and the DeMeester score.
RESULTS: There were no statistical differences between the PGS group and the EE group as to mean age, sex ratio and pH recording time. The EE group showed more severe reflux than the PGS group, as evaluated in terms of the longest duration of reflux, the number of reflux episodes, the number of reflux episodes lasting > 5 min, the total time with pH < 4 during acid reflux episodes, and the DeMeester score, but none of these parameters showed statistically significant difference. Although 53.8% (14/26) of the PGS group and 76.2% (16/21) of the EE group demonstrated pathologic acid reflux (DeMeester score > 14.72), there was no statistically significant difference between the two groups in the incidence of pathologic acid reflux (P = 0.11).
CONCLUSION: There was no statistically significant difference in pathologic acid reflux between the PGS and EE group. These data suggest that endoscopically diagnosed PGS might be a predictor of pathologic acid reflux.
Prolapse gastropathy syndrome; Pathologic acid reflux; Erosive esophagitis; Ambulatory esophageal pH monitoring; Retching
AIM: To determine whether thalidomide prevents microvascular injury in acute radiation proctitis in white rats.
METHODS: Fourteen female Wistar rats were used: six in the radiation group, six in the thalidomide group, and two in normal controls. The radiation and thalidomide groups were irradiated at the pelvic area using a single 30 Gy exposure. The thalidomide (150 mg/kg) was injected into the peritoneum for 7 d from the day of irradiation. All animals were sacrificed and the rectums were removed on day 8 after irradiation. The microvessels of resected specimens were immunohistochemically stained with thrombomodulin (TM), von Willebrand Factor (vWF), and vascular endothelial growth factor (VEGF).
RESULTS: The microscopic scores did not differ significantly between the radiation and thalidomide groups, but both were higher than in the control group. Expression of TM was significantly lower in the endothelial cells (EC) of the radiation group than in the control and thalidomide groups (P < 0.001). The number of capillaries expressing vWF in the EC was higher in the radiation group (15.3 ± 6.8) than in the control group (3.7 ± 1.7), and the number of capillaries expressing vWF was attenuated by thalidomide (10.8 ± 3.5, P < 0.001). The intensity of VEGF expression in capillaries was greater in the radiation group than in the control group and was also attenuated by thalidomide (P = 0.003).
CONCLUSION: The mechanisms of acute radiation-induced proctitis in the rats are related to endothelial cell injury of microvessel, which may be attenuated with thalidomide.
Radiation proctitis; Von Willebrand factor; Thrombomodulin; Vascular endothelial growth factor; Thalidomide
AIM: To compare the hemostatic efficacy and safety of two mechanical endoscopic methods: endoscopic band ligation (EBL) and endoscopic hemoclip placement (EHP) in patients with actively bleeding Mallory-Weiss syndrome (MWS).
METHODS: A prospective randomized study to compare the efficacy and safety of EHP with EBL was performed from January 2002 to August 2005. Forty-one patients with active bleeding from MWS were treated with EHP (n = 21) or EBL (n = 20).
RESULTS: There were no significant differences between groups with respect to clinical and endoscopic characteristics. The mean number of hemoclips applied was 3.2 ± 1.5 and the mean number of bands applied was 1.2 ± 0.4. Primary hemostasis was achieved in all patients. Recurrent bleeding was observed in one patient from the EHP group and two from the EBL group. Patients with recurrent bleeding were treated by the same modality as at randomization and secondary hemostasis was achieved in all. There were no significant differences between the two groups in total transfusion amount or duration of hospital stay. No complications or bleeding-related death resulted.
CONCLUSION: EHP and EBL are equally effective and safe for the management of active bleeding in patients with Mallory-Weiss syndrome, even in those with shock or comorbid diseases.
Mallory-Weiss syndrome; Hemostasis; Endoscopic band ligation; Endoscopic clipping
We report a case of gastric penetration caused by accidental ingestion of a chicken bone in a 42-year old woman with a partially wearing denture. Three days ago, she accidentally swallowed several lumps of poorly-chewed chicken. Physical examination disclosed mild tenderness in the periumbilical area. Abdominal Computed tomography (CT) showed a suspicious penetration or perforation of the stomach wall measuring about 3 cm, by a linear radiopaque material at the lesser curvature of the antrum. The end of a chicken bone was very close to but did not penetrate the liver. Endoscopic examination revealed a chicken bone that penetrated into the prepyloric antrum. The penetrating chicken bone was removed with grasping forceps. Five endoscopic clips were applied immediately at the removal site and the periumbilical pain resolved promptly. After removal of the chicken bone, the patient was treated with conservative care for three days, after which she was completely asymptomatic and discharged without complication. To treat gastric penetration by a foreign body, endoclipping can be a useful method in patients with no signs or symptoms of peritoneal irritation.
Gastric penetration; Chicken bone; Hemoclip
An 81-year-old man presented with epigastric pain and weight loss for one month. He had a past history of pulmonary tuberculosis, 10 years ago. We performed a gastroscopy, which showed a linear depressed whitish gastric ulcer scar (0.8 cm in length) in the posterior wall of the prepyloric antrum. The result of biopsy was reported as squamous epithelium. Immunohistochemical staining using an antibody to high molecular weight cytokeratin (HMC) revealed positive staining in the squamous epithelium. Two years later, the lesion was followed up. The lesion remained at same site endoscopically, but no squamous epithelium could be seen microscopically.
Squamous metaplasia; Gastric ulcer scar; High molecular weight cytokeratin
Background and Objectives
Non-calcified plaque (NCP) identified by coronary CT angiography (CCTA) has been reported in up to 10% of individuals with coronary artery calcium score (CACS) of zero. However, clinical risk factors and the prognostic value of NCP in asymptomatic subjects with CACS of zero are unknown.
Subjects and Methods
The study population consisted of consecutive asymptomatic subjects (48±8 years, 57% men) who underwent CCTA from December 2005 to January 2008 as part of a general health evaluation.
Among 4491 of overall asymptomatic individuals with CACS of zero, 313 subjects (7%) had NCP: 279 patients (6%) with non-obstructive and 34 (1%) with obstructive. In multivariable analyses, age, male gender, diabetes, hypertension, and dyslipidemia were significantly associated with presence of NCP (all p<0.05). During the median follow-up duration of 22 months (interquartile percentile: 18 to 28 months) of subjects with NCP (n=313) and age, gender, and CCTA date matched individuals without NCP (n=313), there was no clinical event including all-cause death nor composite outcome of cardiac death, myocardial infarct, unstable angina requiring hospitalization, and revascularization after 90 days from index CCTA in both groups.
In the largest series of asymptomatic individuals with CACS of zero undergoing CCTA, age, male gender, diabetes, hypertension, and dyslipidemia were independently associated with NCP. However, a future risk of exclusive NCP in asymptomatic subjects with CACS of zero was negligible.
Coronary; Atherosclerotic plaque; Calcium; Computed tomography
To evaluate the in vivo magnetic resonance (MR) imaging efficacy of manganese (Mn(II)) molecular imaging probes targeted to oxidation-specific epitopes (OSE).
OSE are critical in the initiation, progression and de-stabilization of atherosclerotic plaques. Gadolinium (Gd(III)) based MR imaging agents can be associated with systemic toxicity. Mn is an endogenous, bio-compatible, paramagnetic metal ion that has poor MR efficacy when chelated, but strong efficacy when released within cells.
Multimodal Mn-micelles were generated to contain rhodamine for confocal microscopy and conjugated with either the murine monoclonal IgG antibody MDA2 targeted to malondialdehyde (MDA)-lysine epitopes or the human single-chain Fv antibody fragment IK17 targeted to MDA-like epitopes (‘targeted micelles”). Micelle formulations were characterized in vitro and in vivo and their MR efficacy (9.4 Tesla) evaluated in apoE−/− and LDLR−/− mice (0.05 mmol Mn/Kg dose) (total of 120 mice for all experiments). In vivo competitive inhibition studies were performed to evaluate target specificity. Untargeted, MDA2-Gd and IK17-Gd micelles (0.075 mmol Gd/Kg) were included as controls.
In vitro studies demonstrated that targeted Mn-micelles accumulate in macrophages when pre-exposed to MDA-LDL with ~10X increase in longitudinal relativity. Following intravenous injection, strong MR signal enhancement was observed 48–72 hours after administration of targeted Mn-micelles, with co-localization within intraplaque macrophages. Co-injection of free MDA2 with the MDA2-Mn micelles resulted in full suppression of MR signal in the arterial wall confirming target specificity. Similar MR efficacy was noted in apoE−/− and LDLR−/− mice with aortic atherosclerosis. No significant differences in MR efficacy were noted between targeted Mn and Gd micelles.
This study demonstrates that bio-compatible multimodal Mn-based molecular imaging probes detect OSE within atherosclerotic plaques and may facilitate clinical translation of non-invasive imaging of human atherosclerosis.
Atherosclerosis; MRI; oxidation; molecular imaging; inflammation
To investigate gastric juice nitrate/nitrite concentration according to mucosal surface pH extent (area) of gastric corpus intimately contacting the gastric juice.
Materials and Methods
We included ninety-nine patients with dyspepsia. To evaluate gastric mucosal surface pH and its extent, gastric chromosocpy was performed by spraying phenol red dye on the corpus mucosa and estimating the extent of area with color changed. Nitrate/nitrite concentrations and pH of gastric juice were measured by ELISA and pH meter, respectively. Silver staining was done to histologically confirm the presence of Helicobacter pylori.
Intragastric nitrate/nitrite concentrations in patients, showing phenol red staining mucosa were higher than those of unstaining mucosa (p=0.001): the more extensive in the area of phenol red staining area of corpus, the higher gastric juice pH found (r=0.692, p<0.001). Furthermore, the intragastric nitrate/nitrite concentrations correlated positively with gastric juice pH (r=0.481, p<0.001).
The changes of mucosal surface pH and its extent in gastric corpus might affect either pH or nitrate/nitrite level of gastric juice.
Nitrate/nitrite; gastric mucosa surface pH; gastric juice pH; chromoscopy; Helicobacter pylori
Background. The aim of this study was to compare the effect of high-dose oral rabeprazole versus high-dose IV PPI on rebleeding after endoscopic treatment of bleeding peptic ulcers. Methods. This was a two-center, prospective, randomized, controlled trial. Patients with a high-risk bleeding peptic ulcer had endoscopic hemostasis and were randomly assigned to the high-dose oral rabeprazole group (20 mg twice daily for 72 hours) or the high-dose IV omeprazole group (80 mg as a bolus injection followed by continuous infusion at 8 mg/h for 72 hours). Results. The study was stopped because of slow enrollment (total n = 106). The rebleeding rates within 3 days were 3.7% (2 of 54 patients) given oral rabeprazole and 1.9% (1 of 52 patients) given IV omeprazole (P = 1.000). The rebleeding rates after 3 days were 1.9% and 0% (P = 1.000), respectively. The surgical intervention rates were 3.7% and 0% (P = 0.495), and the mortality rates were 1.9% and 0% (P = 1.000), respectively. Conclusions. The effect of high-dose oral rabeprazole did not differ significantly from that of high-dose IV omeprazole on rebleeding, surgical intervention, or mortality after endoscopic treatment of bleeding peptic ulcers, but this requires further evaluation.
A common side effect of oxaliplatin is peripheral neurotoxicity. Oxidative stress to dorsal root ganglion (DRG) may be one of important pathogenic mechanisms. Green tea contains four polyphenol catechins, which are known to be potent antioxidants. The present work is aimed to determine whether green tea extracts have neuroproective or palliative effects on neurotoxicity symptoms induced by oxaliplatin.
We conducted behavioral tests including sensory and thermal thresholds, an electrophysiological study, and TUNEL staining to assess neurotoxicity during the experimental period using animal models.
A total of 14 adult rats were randomly allocated into two groups. Oxaliplatin (4 mg/kg) with or without green tea (300 mg/kg orally once daily) was administered intraperitoneally twice per week for 6 weeks. At 4 and 6 weeks after oxaliplatin administration, sensory threshold values were significantly decreased and at 6 weeks after oxaliplatin administration, thermal threshold values were significantly increased in oxaliplatin-treated rats compared with those in rat treated with oxaliplatin and green tea extracts. The electrophysiological assessment, including sensory nerve conduction and H-reflex-related sensory nerve conduction velocity, revealed no significant changes in the two groups. TUNEL staining showed no significant difference in the number of apoptotic-featured cells between the two experimental groups in the DRG or peripheral nerves, but the number of apoptotic-featured cells in DRG was higher than that in sciatic nerves within each group.
Green tea extracts may be a useful adjuvant to alleviate sensory symptoms after oxaliplatin administration, such as allodynia, but did not prevent morphometric or electrophysiological alterations induced by oxaliplatin.
Oxaliplatin; Peripheral neuropathy; Green tea extract; Antioxidant
The aim of this study was to determine whether iron oxide particles targeted to oxidation-specific epitopes image atherosclerotic lesions.
Oxidized low-density lipoprotein plays a major role in atherosclerotic plaque progression and destabilization. Prior studies indicate that gadolinium micelles labeled with oxidation-specific antibodies allow for in vivo detection of vulnerable plaques with magnetic resonance imaging (MRI). However, issues related to biotransformation/retention of gadolinium might limit clinical translation. Iron oxides are recognized as safe and effective contrast agents for MRI. Because the efficacy of passively targeted iron particles remains variable, it was hypothesized that iron particles targeted to oxidation-specific epitopes might increase the utility of this platform.
Lipid-coated ultra-small superparamagnetic iron particles (LUSPIOs) (<20 nm) and superparamagnetic iron particles (<40 nm) were conjugated with antibodies targeted to either malondialdehyde-lysine or oxidized phospholipid epitopes. All formulations were characterized, and their in vivo efficacy evaluated in apolipoprotein E deficient mice 24 h after bolus administration of a 3.9-mg Fe/kg dose with MRI. In vivo imaging data were correlated with the presence of oxidation-specific epitopes with immunohistochemistry.
MRI of atherosclerotic lesions, as manifested by signal loss, was observed after administration of targeted LUSPIOs. Immunohistochemistry confirmed the presence of malondialdehyde-epitopes and iron particles. Limited signal attenuation was observed for untargeted LUSPIOs. Additionally, no significant arterial wall uptake was observed for targeted or untargeted lipid-coated superparamagnetic iron oxide particles, due to their limited ability to penetrate the vessel wall.
This study demonstrates that LUSPIOs targeted to oxidation-specific epitopes image atherosclerotic lesions and suggests a clinically translatable platform for the detection of atherosclerotic plaque.
atherosclerosis; inflammation; molecular imaging; MRI