ErbB2 growth factor receptor, a marker for neuroendocrine cells?

BACKGROUND/AIMS: The overexpression of ErbB2 in pancreatic cancer has been reported with a varying incidence ranging between 1 and 80%. Our routine examination, however, revealed a consistently strong immunoreactivity of three anti-ErbB2 growth factor receptor antibodies in pancreatic islets and intrapancreatic ganglia. To validate our findings and to understand the reasons for the reported differences in the frequency of ErbB2 overexpression in pancreatic cancer, the following studies were performed. MATERIALS AND METHODS: Tissue samples from 12 normal pancreata, 7 surgical chronic pancreatitis cases, 21 primary pancreatic adenocarcinomas, 9 metastatic pancreatic adenocarcinomas, and 4 islet cell tumors were subjected to immunohistochemical examination using antibodies from three manufacturers. Cultured human islet cells and pancreatic cancer cell lines, as well as samples from the gastrointestinal tract, the CNS, and the adrenal gland were included in the study. For comparison, mammary cancer tissue and mammary cancer cells, as well as selected tissues from Syrian golden hamsters, were used. To verify the results, Western blot and Northern slot-blot analyses were performed. RESULTS: Pancreatic cancer cells, in vitro and in vivo, showed a remarkable heterogeneity in the immunostaining of ErbB2, ranging from very faintly to strongly stained. On the other hand, in both humans and hamsters, a consistently strong immunostaining was found in the Langerhans' islets, in the ganglia of intrapancreatic and extrapancreatic nerves, as well as in the CNS, spinal cord and adrenal gland. CONCLUSIONS: ErbB2 appears to play an important role in neuroendocrine tissues and is probably involved in the development and functional regulation of these cells. The concomitant expression of these factors and islet cell hormones very likely results in the activation of multiple growth-promoting pathways in pancreatic cancer and its aggressive behavior.     

Plasma ghrelin,obesity, and the polycystic ovary syndrome: correlation with insulin resistance and androgen levels

In addition to its orexigenic properties, ghrelin has been shown to modulate the secretory pattern of pituitary hormones, and it may exert direct effects on peripheral organs such as the gonads and endocrine pancreas. To study possible interactions among ghrelin, glucose homeostasis, and the reproductive system, we investigated 10 obese women with polycystic ovary syndrome (OB-PCOS) in comparison with 10 age- and body mass index-matched obese subjects (OB). Plasma levels of insulin, glucose, androgens, and ghrelin were measured at baseline condition and after 7 months of therapy (hypocaloric diet + metformin or placebo). Plasma ghrelin levels were lower in OB-PCOS than in OB (P < 0.05). A strong negative correlation between ghrelin and androstenedione levels was found in both populations at baseline (OB-PCOS: P < 0.01; OB: P < 0.001) and after therapy (OB-PCOS: P < 0.01; OB: P < 0.05), whereas no correlation was found between ghrelin and other androgens. In both groups, the markers of insulin resistance in fasting and stimulated conditions (glucose/insulin ratio, homeostasis model insulin resistance index, homeostasis model applied to the oral glucose tolerance test) demonstrated decreased insulin sensitivity. However, a negative correlation between plasma ghrelin and all these markers was observed only in the OB-PCOS group (P < 0.05). Accordingly, a negative correlation between ghrelin variation and treatment-induced changes of the glucose/insulin ratio, HOMA-R, and HOMA(OGTT) was observed only in the OB-PCOS group (P < 0.05). In conclusion, OB-PCOS women have lower ghrelin levels than those expected based on the presence of obesity. Only in OB-PCOS, ghrelin negatively correlates with insulin sensitivity. In addition, regardless of the presence of PCOS, a marked negative correlation exists between ghrelin and androstenedione levels, suggestive of an interaction between ghrelin and steroid synthesis or action.     

Effects of anti-ischaemic drug therapy in silent myocardial ischaemia type I: the Swiss Interventional Study on Silent Ischaemia type I (SWISSI I): a randomized, controlled pilot study.

AIMS: To determine the effect of anti-ischaemic drug therapy on long-term outcomes of asymptomatic patients without coronary artery disease (CAD) history but silent exercise ST-depression. METHODS AND RESULTS: In a randomized multicentre trial, 263 of 522 asymptomatic subjects without CAD but at least one CAD risk factor in whom silent ischaemia by exercise ECG was confirmed by stress imaging were asked to participate. The 54 (21%) consenting patients were randomized to anti-anginal drug therapy in addition to risk factor control (MED, n = 26) or risk factor control-only (RFC, n = 28). They were followed yearly for 11.2 +/- 2.2 years. During 483 patient-years, cardiac death, non-fatal myocardial infarction, or acute coronary syndrome requiring hospitalization or revascularization occurred in 3 (12%) of MED vs. 17 (61%) of RFC patients (P < 0.001). In addition, MED patients had consistently lower rates of exercise-induced ischaemia during follow-up, and left ventricular ejection fraction remained unchanged (-0.7%, P = 0.597) in contrast to RFC patients in whom it decreased over time (-6.0%, P = 0.006). CONCLUSION: Anti-ischaemic drug therapy and aspirin seem to reduce cardiac events in subjects with asymptomatic ischaemia type I. In such patients, exercise-induced ST-segment depression should be verified by stress imaging; if silent ischaemia is documented, anti-ischaemic drug therapy and aspirin should be considered.     

Pancreatic incidentalomas: a growing clinical challenge exemplified by an intrapancreatic accessory spleen

In part owing to an increasing use of high resolution imaging technologies a growing number of incidental pancreatic lesions are detected. A 40-year-old patient was admitted to our hospital to undergo resection for an unclear solid pancreatic tumor in the pancreatic tail. Preoperative imaging studies suspected an inactive neuroendocrine neoplasm. After distal pancreatectomy, the histopathological analysis revealed an intrapancreatic accessory spleen. Since reliable biomarkers are not established the clinical management of pancreatic incidentalomas is still challenging.     

Microsatellite GT polymorphism in intron 2 of human Toll-like receptor (TLR) 2 gene and susceptibility to periodontitis

As pattern recognition receptor, Toll-like receptor (TLR) 2 is a signal molecule essential for the cellular response to Porphyromonas gingivalis. A recently described guanine-thymine (GT) repeat microsatellite polymorphism of the human TLR2 gene leads to impaired promotor activity. A total of 380 patients with chronic periodontitis and 590 unrelated healthy control individuals of Caucasian descent were genotyped for the GT repeat microsatellite polymorphism of the TLR2 gene. The mutations were identified with polymerase chain reaction followed by sizing of GT repeat length. The number of GT repeats ranged from 13 to 29 in both study groups. There was no significant difference between periodontitis patients and healthy controls regarding the frequency of GT repeats (p = 0.365). Subclassification of alleles into three subclasses (S allele, M allele, and L allele) revealed no significant association (p = 0.810). Moreover, also the comparison of the summarized prevalence of S and L alleles (high promotor activity) with that of the M allele (low promotor activity) was not significantly different among study groups (p = 0.377). The susceptibility to chronic peridontitis was not associated with the functional effective GT repeat microsatellite polymorphism in the human TLR2 gene.     

Shear bond strength of orthodontic brackets to enamel after application of a caries infiltrant

Objective:To examine differences in the shear bond strength of orthodontic brackets on differently mineralized enamel surfaces after applying a caries infiltrant or conventional adhesive.Materials and Methods:A total of 320 bovine incisors were assigned to eight pretreated groups, and the shear force required for debonding was recorded. Residual adhesive was evaluated by light microscopy using the adhesive remnant index. Statistical analysis included Kolmogorov-Smirnov, analysis of variance (ANOVA), and Scheffé tests.Results:The highest bond strength (18.8 ± 4.4 MPa) was obtained after use of the caries infiltrant. More residual adhesive and fewer enamel defects were observed on infiltrated enamel surfaces. Brackets on demineralized enamel produced multiple enamel defects.Conclusions:Acceptable bond strengths were obtained with all material combinations. A caries-infiltrant applied before bracket fixation has a protective effect, especially on demineralized enamel.