Antioxidant activity of chito-oligosaccharides on pancreatic islet cells in streptozotocin-induced diabetes in rats

AIM:To investigate the antioxidant activity of chitooligosaccharides(COSs)on pancreatic islet cells in diabetic rats induced by streptozotocin. METHODS:The antioxidant effect of COSs on pancreatic islet cells was detected under optical microscopy and with colorimetric assay and gel electrophoresis.The activities of glutathione peroxidase and superoxide dismutase,total antioxidant capacity,and content of malondialdehyde in serum and tissue slices of pancreas were examined after 60 d to determine the effect of COSs in streptozotocin-induced diabetes in rats. RESULTS:COSs can prohibit the apoptosis of pancreatic islet cells.All concentrations of COSs can improve the capability of total antioxidant capacity and activity of superoxide dismutase and decrease the content of malondialdehyde drastically.Morphological investigation in the pancreas showed that COSs have resulted in the reduction of islets,loss of pancreatic cells,and nuclear pyknosis of pancreatic cells. CONCLUSION:COSs possess various biological activities and can be used in the treatment of diabetes mellitus.

Antidiabetic effects of chitooligosaccharides on pancreatic islet cells in streptozotocin-induced diabetic rats

AIM: To investigate the effect of chitooligosaccharides on proliferation of pancreatic islet cells, release of insulin and 2 h plasma glucose in streptozotocin-induced diabetic rats.METHODS: In vitro, the effect of chitooligosaccharides on proliferation of pancreatic islet cells and release of insulin was detected with optical microscopy, colorimetric assay, and radioimmunoassay respectively. In vivo, the general clinical symptoms, 2 h plasma glucose, urine glucose, oral glucose tolerance were examined after sixty days of feeding study to determine the effect of chitooligosaccharides in streptozotocin-induced diabetic rats. RESULTS: Chitooligosaccharides could effectively accelerate the proliferation of pancreatic islet cells. Chitooligosaccharides (100 mg/L) had direct and prominent effect on pancreastic β cells and insulin release from islet cells. All concentrations of chitooligosaccharides could improve the general clinical symptoms of diabetic rats, decrease the 2 h plasma glucose and urine glucose, and normalize the disorders of glucose tolerance.CONCLUSION: Chitooligosaccharides possess various biological activities and can be used in the treatment of diabetes mellitus.

Liver cell adenoma:A case report with clonal analysis and literature review

We report a case of liver cell adenoma （LCA） in a 33-year-old female patient with special respect to its clonality status, pathogenic factors and differential diagnosis. The case was examined by histopathology, immunohistochemistry and a clonality assay based on X-chromosomal inactivation mosaicism in female somatic tissues and polymorphism at androgen receptor focus. The clinicopathological features of the reported cases from China and other countries were compared. The lesion was spherical, sizing 2 cm in its maximal dimension. Histologically, it was composed of cells arranged in cords, most of which were two-cell-thick and separated by sinusoids. Focal fatty change and excessive glycogen storage were observed. The tumor cells were round or polygonal in shape, resembling the surrounding parenchymal cells. Mitosis was not found. No portal tract, central vein or ductule was found within the lesion. The tumor tissue showed a positive reaction for cytokeratin （CK） 18, but not for CK19, vimentin, estrogen and progesterone receptors. Monoclonality was demonstrated for the lesion, confirming the diagnosis of an LCA. Clonality analysis is helpful for its distinction from focal nodular hyperplasia.K

Liver cell adenoma with malignant transformation:A case report

A 57-year-old woman was referred to our hospital because of a liver mass detected by computed tomography.She had taken oral contraceptives for only one month at the age of thirty.Physical examination revealed no abnormalities,and laboratory data,including hepatic function tests,were within the normal range,with the exception of elevated levels of those serum proteins induced by the absence of vitamin K or by raised levels of the antagonist (PIVKA)-Ⅱ (3 502 AU/ml). Abdominal ultrasonography revealed a hyperechoic mass measuring 10×10 cm in the left posterior segment of the liver.Because hepatocellular carcinoma could not be completely excluded,this mass was resected.The tumor consisted of sheets of uniform cells with clear cytoplasm, perinuclear eosinophilic granules and round nuclei.These histological findings were consistent with liver cell adenoma. Background hepatic tissue appeared normal.After resection of the tumor,serum PIVKA-Ⅱ fell to within the normal range. An area of hepatocellular carcinoma (HCC) with a mid- trabecular pattern was immunohistochemically found,which was positive for PIVKA-Ⅱ.Sinusoidal endothelial cells were CD34-positive,containing scattered PIVKA-Ⅱ positive cells. This tumor was therefore finally diagnosed as liver cell adenoma with focal malignant transformation to HCC.

Coexistence of small cell neuroendocrine carcinoma and villous adenoma in the ampulla of Vater

Small cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare and different from the common ampullary adenocarcinoma. The ampullary adenoma is also a rare neoplasm and has the potential to develop an adenocarcinoma. Their coexistence has been rarely reported in the literature. We herein describe an unusual case of a small cell neuroendocrine carcinoma associated with a villous adenoma in the ampulla of Vater with emphasis on computed tomography (CT) and histopathological findings. We also discuss their clinical, histopathological and radiological features as well as possible histogenesis.

CLINICOPATHOLOGIC FEATURES AND SURGICAL TREATMENT OF NONFUNCTIONING ISLET CELL TUMORS

Objective.To in vestigate clinicopathologic characteristics and surgical results of nonfunctiona l islet cell tumors.Methods.We performed retrospective analysis of50patient s with nonfunctional islet cell tumor treat-ed at Peking Union Medical College Hospital from July1968to July1999,and summarized clinical symptoms and signs,primary diagnosis before surgery,surgical treatments,pathologic and im munohisto-logical characteristics.Results.Of the50cases examined from July 1968to July1999,12were found during physical examinations. The most common symptoms were upper abdominal pain and upper abdominal dis-com fort,which appeared in20casesand17casesrespectively,an d the most common sign was abdominal masses.B-ultrasound and CT are the most commonly used means for preoperative examination,with posit ive rates of97.8%and100%respectively.Op-e rative mortality was2%.Five-year survival rate of radical surgery of maligna nt cases was75%.Immuno-histological examinations showed that tumors rich i n multi-peptide linked hormones,neuron-specific eno-lase and chromaffin were in65%cases,90.6%and73.3% respectively.The positive rates of insulin,glucagons,somatostatin,pancreat ic polypeptide,gastrin and vasoactive intestinal peptide were68.2% ,51.2%,42.9%,40% ,25%and15.8%respectively.Conclusion.Nonfuncti onal islet cell tumors lack diagnostic specificity.Ultrasound and CT are primar y examination methods.Immunohistological analysis indicates different hormones ,but lacks the presence of related clinical symptoms.Surgery is an effective treatment for nonfunctional islet cell tumors,and even for those with distal m etastasis,immediate surgical removal and treatment can improve prognosis.

Pleomorphic Adenoma with Exuberant Squamous Metaplasia and Keratin Cysts Mimicking Squamous Cell Carcinoma in Minor Salivary Gland

Salivary gland tumors, the second most common neoplasm of the mouth after squamous cell carcinoma, account for a significant proportion of tumors of the oral and perioral regions. An unusual case of adenoma presented as a solitary intraoral palatine mass in a 32-year-old woman is reported here. The tumor was interpreted as an unusual pleomorphic adenoma because of the presence of exuberant squamous metaplasia, clinically mimicking squamous cell carcinoma. Moreover, the presence of cystic structures filled with keratinized material was also salient feature. Pleomorphic adenomas may occasionally display focal squamous metaplastic changes;when extensive, it presents the potential for misinterpretation of the histology as indicative of well-differentiated squamous cell carcinoma.

Preparation of Recombinant Islet Cell Autoantigen 69 kD Fusion Protein

To get recombinant antigen (Is/et Cell Autoantigen 69)ICA69 which was expressed in Escherichia coli strains (E.coli) by means of the gene engineering technique so that it can be used for early diagnosis of and screening in type Ⅰ diabetes mellitus, the cDNA fragment of human ICA69 was amplified by PCR, and then cloned into pSPORT 1 vector. After DNA sequencing, it was inserted into pGEX-2T between the sites of EcoR Ⅰ and Sma Ⅰ, then recombinant plasmid p2T-ICA69 was constructed and introduced into E.coli. The GST-ICA69 fusion protein was expressed by the induction of IPTG. The recombinant ICA69 proteins were used to detect the antibodies against hICA69 in 100 healthy subjects and type Ⅰ diabetic serum by the use of indirect ELISA. The sequence analysis showed that the amplified fragments contained 1449 bp, encoded 483 amino acids, and had been correctly inserted into pGEX-2T vector. The recombinant proteins expressed in the prokaryotic cells had immunogenicity and could be used to detect antibodies against ICA69 in type Ⅰ diabetic serum. Finally it can be concluded in this paper that the expression products obtained by the method of gene engineering are recombinant ICA69 antigen and may be used to improve the forecast rate and the diagnostic rate of type Ⅰ diabetes in combination with other tests.

PANETH CELL ADENOMA OF THE STOMACH

Two cases of Paneth cell adenoma of the stomach are reported and the histological, ultrastructural, immunohistochemical and immunocytochemical features are described. The surgical specimens showed varied pictures of dysplasia with severe atrophic gastritis and Intestinal metaplasia. 60%-70% of the tumor cells contained coarse cytoplasmic granules stained red with eosin or PAS but remained unstained with aician blue pH2. 5 and exhibited positive immunostaining for lysozyme. The nature of these granules was confirmed by electron microscopy and immunoelectron microscopy. In addition, some enldocrine cells were detected in the neoplastic glands. The characteristics of Paneth cell adenoma of the stomach are discussed. There might be a close relation in the histogenesis with intestinal metaplasia suggested.

A large basal cell adenoma extending to the ipsilateral skull base and mastoid in the right parotid gland: A case report

BACKGROUND Basal cell adenoma (BCA) is a rare benign tumour that has unique histological characteristics and primarily arises in the parotid glands. According to published reports, nearby tissue destruction by BCA seems impossible. CASE SUMMARY We presented a case of a 54-year-old woman with a mass in the deep lobe of the right parotid gland involving the ipsilateral skull base and mastoid. The patient exhibited gradual right facial swelling but no other obvious symptoms. Combined resection of the total right parotid gland and partial skull base excision were performed. The biopsy conducted before the surgery and sections cut from intraoperatively obtained tissues were not definitive for identifying the character of the neoplasm. A final diagnosis of tubular BCA without malignant elements was established based on postoperative pathology results and immunohistochemical analysis. The tumour did not recur during the 12-mo follow-up period. CONCLUSION A diagnosis of BCA can only be established based on a histopathological examination after an excisional biopsy, and tubular BCA should carefully be considered as a destructive type.

Liver cell adenoma showing sequential alteration of radiological findings suggestive of well-differentiated hepatocellular carcinoma

A liver tumor 35 mm in diameter was found incidentally in a 40-year-old woman who had no history of liver diseases or the use of oral contraceptives.Radiological diagnostics showed the typical findings of liver cell adenoma(LCA).Dynamic computed tomography revealed that the tumor showed a homogenous enhancement in the arterial phase and almost the same enhancement as the surrounding liver parenchyma in the delayed phase.The tumor was found to contain fat on magnetic resonance imaging.A benign fat containing liver tumor was suggested.However,radiological findings altered,which caused us to suspect that a welldifferentiated hepatocellular carcinoma(HCC)containing fat was becoming dedifferentiated.Partial hepatectomy was performed and the pathological findings showed the typical findings of LCA.This case was an extremely rare LCA,which had no background of risk for LCA and developed the sequential alteration of the radiological findings to suspect well-differentiated HCC.

Experimental study of piperlongumine inducing apoptosis of human breast adenoma MDA-MB-231 cells

Objective： The aim of the study was to investigate the apoptosis induced by piperlongumine on human breast adenoma MDA-MB-231 cells and the mechanism involved. Methods： Human breast adenoma MDA-MB-231 cells line was cultured in vitro. The inhibitory effect of piperlongumine on the proliferation of human breast adenoma MDA-MB-231 cells was measured by CCK-8 assay. Distribution of cell cycle was analyzed by flow cytometry. The apoptosis rates of MDA-MB- 231 cells were measured using Annexin V/PI staining. The flow cytometry with the probe of DCFH-DA was used to detect the intracellular reactive oxygen species levels. Western blot was used to explore the protein expression of Bcl-2 and Bax. Results： The CCK-8 assay showed that piperlongumine had an inhibiting effect on the proliferation of MDA-MB-231 cells in a concentrationand time-dependent manner. MDA-MB-231 cells were markedly arrested at G0/G1 phase after treatment of piperlongumine. Piperlongumine induced apoptosis of MDA-MB-231 cells obviously. The level of intracellular reactive oxygen species was increased in a dose-dependent manner. The antioxidant N-acetyI-L-cystein inhibited the apoptosis of cells and the level of intracellular reactive oxygen species was also decreased. By Western blot analysis, we found the expression of Bax was up-regulated whereas that of Bcl-2 was down-regulated in a concentration-dependent manner. Conclusion： PiperIongumine possesses a significant function for inhibiting proliferation, arresting cells at G0/G1 phase and inducing apoptosis of MDA-MB-231 cells, which seems to be associated with the increased generation of intracellular reactive oxygen species as well as the down-regulation of Bcl-2 and up-regulation of Bax.

Surgical treatment of nonfunctioning islet cell tumor: report of 41 cases

BACKGROUND: Nonfunctioning islet cell tumor (NIT)as a rare pancreatic endocrine neoplasm is characterized byunspecific clinical symptoms and is hard to diagnose. InChina, NIT accounts for 15%-41% in pancreatic endocrineneoplasms just next to insulinoma. In this study, weevaluated the surgical modalities of NIT.METHODS: From January 1978 through February 2002, 41patients with NIT were treated at the Department of Sur-gery of the First Affiliated Hospital, China Medical Univer-sity, Shenyang, China. Tumors in the head of the pancreaswere noted in 28 patients, and in the body or in the tail in13 patients. The mean diameter of the tumors was 10. 7cm. Fifteen patients underwent enucleation and 21 receivedpancreatectomy. Tumors were unresectable in 5 patientsbecause of extensive infiltration. The mean diameter was9.6 cm in patients treated by enucleation, 13.1 cm in thoseby pancreaticoduodenectomy, 9.9 cm in those by distalpancreatectomy, and 11.6 cm in those with unresectabletumors.RESULTS: The curative resection rate was 88% (n =36),and the complication rate after enucleation and pancreatec-tomy was 33% ( n = 5 ) and 14% (n=3), respectively. Nolocal recurrence was found after both enucleation and pan-createctomy. Liver metastases occurred in 3 patients treatedby enucleation.CONCLUSIONS: Both enucleation and pancreatectomy areeffective for NIT of the pancreas. No local recurrence hasbeen found in patients treated by the two surgical proce-dures. The complication rates of the two modalities arecomparable.

Spiral CT localization of pancreatic function-ing islet cell tumors

BACKGROUND: Surgeons are always concerned about the localization of pancreatic functioning islet cell tumor. If the tumor is accurately localized before operation, resection of the pancreatic body and tail without intention can be avoided. The purpose of this study was to evaluate spiral CT localization of pancreatic functioning islet cell tumors and CT techniques. METHODS: CT manifestations in 6 patients with clinically and pathologically proved pancreatic functioning islet cell tumors ware analyzed retrospectively. RESULTS: In 4 patients with insulinomas and 2 patients with glucagonomas, 5 were localized accurately by CT be- fore surgery and 1 was detected retrospectively. The en- hancement of tumors was greater than that of normal pan- creas in arterial phase and pancreatic parenchymal phase. Four patients showed mild high-density and 2, iso-density in the portal venous phase. CONCLUSION: Spiral CT multi-phase enhanced scan with 1.5 ml/kg contrast agent and 2-5 mm slice width can loca- lize functioning islet cell tumors accurately.

Effects of High Concentration Glucose on the Expression of NF-κB,Bax and Cytochrome C and Apoptosis of Islet Cells in Mice

The roles of NF-kappaB （NF-κB） expression, Bax activity and cytochrome C （Cyt C） release, apoptosis of islet cells induced by high concentration glucose were explored in vitro. Pancreatic islet cells, which were isolated from Kunming mice, were cultured with different concentrations of glucose in DMEM, and divided into the following groups： G1, G2, G3, G4, G5, and G6 groups, corresponding to the glucose concentrations of 5.6, 7.8, 11.1, 16.7, 22.5, and 27.6 mmol/L, respectively. After culture for 120 h, insulin secretion was evaluated by radioimmunoassay, and the NF-rd3 expression was detected by immunocytochemistry. Bax activity and Cyt C release were measured by immunofluorescence, and apoptosis was examined by Hoechst33342 assay. The results showed that in GI, G2 and G3 groups, insulin secretion was enhanced with the increase of glucose concentration, and the NF-κB expression was also increased （P〈0.05）, but Bax activity, Cyt C release and apoptosis rate showed no significant difference among them. However, in G4, G5, and G6 groups, apoptosis rate of islet cells, NF-rd3 expression, Bax activity, and Cyt C release were all significantly increased, and insulin secretion was impaired as compared with G1, G2, and G3 groups （P〈0.05）. It was concluded that the exposure of islet cells to high glucose could induce islet cells apoptosis as well as impaired insulin secretion. The NF-κB signaling pathway and mitochondria pathway in islet cells might play some roles in the progressive loss of islet cells in diabetes. The inhibition of the NF-κB expression could be an effective strategy for protecting pancreatic islet cells.

SPECTRUM OF FUNCTIONING ISLET CELL TUMOR ON MULTISLICE COMPUTED TOMOGRAPHY:EXPERIENCE ON 70 PATIENTS

Objective To review experience in preoperative detection of islet cell tumors using multislice computed tomography （MSCT） and summarize various imaging features of functioning islet cell tumors on enhanced MSCT. Methods Seventy patients with clinical or pathological diagnosis of functioning pancreatic islet cell tumor between October 2003 and February 2007 were included in this retrospective study. Seventy-four enhanced MSCT scans in these patients were identified. All MSCT scans were interpreted by two experienced radiologists by consensus interpretation. Surgery and pathology reports were used to confirm the diagnosis, localization, and size of tumors. Results Totally, 73 functioning islet cell tumors including 65 benign insulinomas, 2 benign glucagonomas, 3 malignant insulinomas, and 3 malignant glucagonomas were pathologically diagnosed. Tumors in only two cases were not found by MSCT. In 67 benign lesions, 32 showed typical enhancement style, 21 showed prolonged enhancement in portal venous phase, 4 showed delayed enhancement, 4 had iso-dense enhancement with normal pancreatic parenchyma, 2 had no enhancement at all in arterial phase and portal venous phase, and 4 had inhomogeneous enhancement with necrosis or cyst-formation. Patchy or spotty calcifications were found in 3 of the 67 tumors. In 6 malignant islet cell tumors, vessel invasion （2/6） and bowel invasion （1/6） were seen. Different enhancement patterns were shown. All hepatic metastases showed hyper-enhancement during their arterial phase. Conelttsions Pancreatic islet cell tumor may display a wide spectrum of presentations in MSCT. Tumors with unusual appearances often present as diagnostic challenges. Non-contrast and post-contrast multiphase scans are recommended for the localization of functioning islet cell tumors.

Intra-islet endothelial cell and β-cell crosstalk: Implication for islet cell transplantation

The intra-islet microvasculature is a critical interface between the blood and islet endocrine cells governing a number of cellular and pathophysiological processes associated with the pancreatic tissue. A growing body of evidence indicates a strong functional and physical interdependency of β-cells with endothelial cells(ECs), the building blocks of islet microvasculature. Intra-islet ECs, actively regulate vascular permeability and appear to play a role in fine-tuning blood glucose sensing and regulation. These cells also tend to behave as "guardians", controlling the expression and movement of a number of important immune mediators, thereby strongly contributing to the physiology of islets. This review will focus on the molecular signalling and crosstalk between the intra-islet ECs and β-cells and how their relationship can be a potential target for intervention strategies in islet pathology and islet transplantation.

Imaging pancreatic islet cells by positron emission tomography

It was estimated that every year more than 30000 persons in the United States- approximately 80 people per day- are diagnosed with type 1 diabetes(T1D). T1 D is caused by autoimmune destruction of the pancreatic islet(β cells) cells. Islet transplantation has become a promising therapy option for T1 D patients, while the lack of suitable tools is difficult to directly evaluate of the viability of the grafted islet over time. Positron emission tomography(PET) as an important non-invasive methodology providing high sensitivity and good resolution, is able to accurate detection of the disturbed biochemical processes and physiological abnormality in living organism. The successful PET imaging of islets would be able to localize the specific site where transplanted islets engraft in the liver, and to quantify the level of islets remain alive and functional over time. This information would be vital to establishing and evaluating the efficiency of pancreatic islet transplantation. Many novel imaging agents have been developed to improve the sensitivity and specificity of PET islet imaging. In this article, we summarize the latest developments in carbon-11, fluorine-18, copper-64, and gallium-68 labeled radioligands for the PET imaging of pancreatic islet cells.

Total pancreatectomy with islet cell transplantation vs intrathecal narcotic pump infusion for pain control in chronic pancreatitis

AIM: To evaluate pain control in chronic pancreatitis patients who underwent total pancreatectomy with islet cell transplantation or intrathecal narcotic pump infusion.METHODS: We recognized 13 patients who underwent intrathecal narcotic pump(ITNP) infusion and 57 patients who underwent total pancreatectomy with autologous islet cell transplantation(TP + ICT) for chronic pancreatitis(CP) pain control between 1998 and 2008 at Indiana University Hospital. All patients had already failed multiple other modalities for pain control and the decision to proceed with either intervention was made at the discretion of the patients and their treating physicians. All patients were evaluated retrospectively using a questionnaire inquiring about their pain control(using a 0-10 pain scale), daily narcotic dose usage, and hospital admission days for pain control before each intervention and during their last follow-up. RESULTS: All 13 ITNP patients and 30 available TP + ICT patients were evaluated. The mean age was approximately 40 years in both groups. The median duration of pain before intervention was 6 years and 7 years in the ITNP and TP + ICT groups, respectively. The median pain score dropped from 8 to 2.5(on a scale of 0-10) in both groups on their last follow up. The median daily dose of narcotics also decreased from 393 mg equivalent of morphine sulfate to 8 mg in the ITNP group and from 300 mg to 40 mg in the TP + ICT group. No patient had diabetes mellitus(DM) before either procedure whereas 85% of those who underwent pancreatectomy were insulin dependent on their last evaluation despite ICT. CONCLUSION: ITNP and TP + ICT are comparable for pain control in patients with CP however with high incidence of DM among those who underwent TP + ICT. Prospective comparative studies and longer follow up are needed to better define treatment outcomes.