A glucose-based molecular rotor inhibitor of glycogen phosphorylase as a probe of cellular enzymatic function.

Molecular rotors belong to a family of fluorescent compounds characterized as molecular switches, where a fluorescence on/off signal signifies a change in the molecule's microenvironment. Herein, the successful synthesis and detailed study of (E)-2-cyano-3-(p-(dimethylamino)phenyl)-N-(ß-D-glucopyranosyl)acrylamide (RotA), is reported. RotA was found to be a strong inhibitor of rabbit muscle glycogen phosphorylase (RMGPb), that binds at the catalytic site of the enzyme. RotA's interactions with the residues lining the catalytic site of RMGPb were determined by X-ray crystallography. Spectroscopic studies coupled with theoretical calculations proved that RotA is a molecular rotor. When bound in the catalytic channel of RMGPb, it behaved as a light switch, generating a strong fluorescence signal, allowing utilization of RotA as a probe that locates glycogen phosphorylase (GP). RotA, mono-, di- and per-acetylated derivatives, as well as nanoparticles with RotA encapsulated in polyethylene glycol-poly-L-histidine, were used in live cell fluorescence microscopy imaging to test the delivery of RotA through the plasma membrane of HepG2 and A431 cells, with the nanoparticles providing the best results. Once in the intracellular milieu, RotA exhibits remarkable colocalization with GP and significant biological effects, both in cell growth and inhibition of GP.

Development of an animal model of fibrous cholangitis in pigs.

INTRODUCTION: The aim of this study was to develop a model of fibrous cholangitis in the offspring of gravid domestic pigs through the administration of 1,4-phenylene diisothiocyanate (DITC). MATERIAL AND METHODS: Six young domestic pigs and two gravid pigs with their offspring (21 pigs) were used as experimental models and six wild-type animals were used as controls. All pigs were divided into five main groups and five subgroups, according to their developmental stage and time of exposure to DITC. The following histopathological characteristics were quantitatively evaluated on a scale of 0-5: ductal proliferation, periportal fibrosis, inflammatory infiltration, periductal fibrosis and edema, intraluminal fibrosis, duct wall thickening, epithelial apoptosis, and arterial hyperplasia/hypertrophy. RESULTS: Statistically significant differences were observed for most of the histopathological markers between the group of pigs' offspring that received DITC at early gestation and their control group. Moreover, the group of animals that were exposed to the agent at early gestation exhibited significant differences for all histopathological characteristics compared to the animals that were exposed at late gestation. On the other hand, no statistically significant differences were observed between the group of animals that received the agent at late gestation and their healthy controls. CONCLUSIONS: Administration of DITC to domestic pigs in early pregnancy may induce histopathological patterns of fibrous cholangitis to their offspring imitating biliary atresia. This model may provide insight to the pathogenesis of the obstructive cholangitis in pigs.

Pulmonary aspergilloma: a potential cause of false positive fluorodeoxyglucose positron emission tomography scan.

Pulmonary aspergilloma is a fungus ball developed in a pre-existing lung cavity, generally in the superior lobes. Its size remains stable in most cases and it is usually asymptomatic. Herein, we present a case of a 64-year-old male with pulmonary aspergilloma, which was developed in an emphysematous cyst of the right inferior lobe, increased in size, and fluorodeoxyglucose positron emission tomography scan was positive. There are only a few reported cases of pulmonary aspergilloma with a false positive fluorodeoxyglucose positron emission tomography scan.

A pathological fracture and a solitary mass in the right clavicle: an unusual first presentation of HCC and the role of immunohistochemistry.

Hepatocellular carcinoma (HCC) is an aggressive malignant tumor that occurs throughout the world. Μetastases from hepatocellular carcinoma (HCC) were generally considered to be rare in the past, because the carcinoma had an aggressive clinical course. In our era, has been reported that extra-hepatic metastases occur in 13.5%-41.7% of HCC patients and this is considered as terminal-stage cancer. The prognosis for patients at this stage continues to be poor due to limited effective treatment. The common sites of extrahepatic metastases in patients with HCC are the lungs, regional lymph nodes, kidney, bone marrow and adrenals. We present here an extremely infrequent case of a patient, without known liver disease, in which the presenting symptom was a pathological-in retrospect-fracture of his right clavicle which wasn't properly evaluated, until he presented a bulky mass in the region 6 months later. For our patient, the added diagnostic difficulty alongside the unknown liver disease, has been that the clavicular metastases was the first presentation of any metastatic disease, rather than the more common sites of HCC spread to adjacent lung or lymph nodes.

Serum leptin levels in patients undergoing carotid endarterectomy: a pilot study.

INTRODUCTION: Elevated serum leptin levels are associated with cardiovascular events. We investigated the role of serum leptin in patients undergoing carotid endarterectomy (CEA). METHODS: A total of 74 patients (55 men; 38 symptomatic and 36 asymptomatic; mean age 66.9 +/- 8.2 years) undergoing CEA for >70% carotid artery stenosis were enrolled. RESULTS: Serum leptin levels were lower in symptomatic compared with asymptomatic patients (7.1 +/- 1.3 vs 14.4 +/- 4.7 ng/dL; P < .001). Interleukin-6 (IL-6) levels were higher in symptomatic compared with asymptomatic patients (4.3 +/- 1.7 vs 3.3 +/- 1.1 pg/dL; P = .017). Symptomatic patients had more intense macrophage accumulation (0.7% +/- 0.1% vs 0.3% +/- 0.1%; P < .001). Serum leptin and serum IL-6 levels were independently associated with the presence of symptoms in multivariate analysis. CONCLUSION: Serum leptin levels were decreased in symptomatic carotid artery disease. This finding requires further investigation in larger studies.

External validation of the modified Thoracoscore in a new thoracic surgery program: prediction of in-hospital mortality.

Informed consent prior to any surgical intervention should include in-hospital survival estimation after the procedure performed. The recently developed Thoracoscore predicts well the postoperative mortality possibility. The purpose of our study was to test the modified Thoracoscore performance in our new thoracic program. One hundred and fifty-five consecutive patients underwent thoracic surgery procedure within two years. The procedures performed were: 62 lung resections, 10 open tumor biopsies, 21 neck and mediastinal procedures, 33 chest wall and pleural procedures, 8 tracheal procedures, 3 esophageal procedures, 13 minor cardiac procedures, and 5 chest trauma cases. The modified Thoracoscore was calculated based on the following variables: age, gender, priority of the procedure, malignancy, type of procedure, Zubrod score, ASA class, and number of co-morbidities. The observed mortality was 5.2% (eight deaths) while the predicted one based on the modified Thoracoscore was 4.9%. The scoring system we used had excellent discriminatory ability with a C statistic (0.95, 95% CIs 0.91-0.99). The Hosmer-Lemeshow goodness-of-fit was not statistically significant (P=0.82), indicating acceptable calibration of the model for the present series. The modified Thoracoscore's ability to predict postoperative survival in the whole context of thoracic surgery performs well in our program. Application of any risk scoring system requires external validation and provides comparison of the actual outcomes with other programs.

Rapid development of an axillary mass in an adult: a case of cystic hygroma.

Cystic hygroma is a congenital anomaly of lymphatic origin, which mainly develops during childhood. Its development in adulthood, however, has been proposed to be related to several predisposing factors such as trauma, infection, tumor growth or iatrogenic stimuli. The development of cystic hygroma in the extremities of adults is extremely rare and moreover, its development in the axillary region has, to our knowledge, been reported only once in the literature. We describe an unusual case of a cystic hygroma which developed rapidly in the axillary region of a female patient in the absence of any predisposing factor. The diagnostic workup and the need for surgical excision of the mass to obtain an accurate, histologic diagnosis is presented.

Emergency helical CT scan in acute abdomen: a case of intestinal intussusception.

Surgeons are familiar to the nosological entity "partial intestinal obstruction". Intussusception constitutes a rare etiologic factor for this entity but usually remains undiagnosed preoperatively. Several imaging techniques have been proposed as useful in the diagnosis of intussusception but none of these has a remarkable sensitivity and specificity. In the following case of partial intestinal obstruction, we performed an helical CT scan of the abdomen. The method revealed with an excellent accuracy the nature (intussusception) and the location (ascending colon) of the partial intestinal obstruction. Having the extra advantage of the shorter examination time than the classical CT scan, we propose the helical CT as an alternative diagnostic modality for preoperative evaluation of patients with partial intestinal obstruction.

Alternative bi-pectoral muscle flaps for postoperative sternotomy mediastinitis.

Suppuration, mediastinitis, and disruption of median sternotomy are all rare, but nevertheless severe complications. We propose a simple mobilization of the two pectoralis major muscles for use as flaps to fill the sternal defect without the need for humeral detachment or a second cutaneous incision. These will be supplied from both the thoracoacromial vessels and the perforating arteries of the nongrafted internal mammary artery (IMA). Our technique is quick and easy, giving excellent results. Furthermore, by maintaining the perforating branches, we also preserve the nongrafted IMA.

Bile duct injuries associated with laparoscopic and open cholecystectomy: an 11-year experience in one institute.

PURPOSE: Bile duct injury (BDI) represents the most serious complication of laparoscopic cholecystectomy (LC). The aim of this retrospective single-institution study was to evaluate the real incidence of BDI during laparoscopic and open cholecystectomy (OC) in a tertiary academic center in Athens, Greece. METHODS: Between January 1991 and December 2001, 3637 patients underwent cholecystectomy in our department; as LC in 2079 patients (LC group) and as OC in 1558 patients (OC group). All the LCs were performed or supervised by five staff surgeons and all the OCs were performed or supervised by another five staff surgeons. RESULTS: There were 13 BDIs associated with LC (0.62%) and 6 associated with OC (0.38%) (P = 0.317). There was one death associated with BDI after LC. Only two (15.4%) of the BDIs associated with LC occurred within the proposed learning curve limit of 50 LCs per individual surgeon. CONCLUSION: Laparoscopic cholecystectomy is safe and is not associated with a higher incidence of BDI than OC. Moreover, we did not find that the learning curve for LC affected BDI occurrence.

Clinical significance of serum levels of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients.

OBJECTIVES: This study evaluated serum concentrations of soluble cell adhesion molecules in patients with gastric cancer and in healthy control subjects. Our objectives were to correlate these levels with clinicopathological features, established tumor markers, and patient survival, and to assess changes in serum levels of cell adhesion molecules after tumor surgery. METHODS: The serum concentrations of the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were investigated by ELISA in 57 gastric cancer patients, both before and 7 days after surgery, and in 47 healthy control subjects. RESULTS: Preoperative serum concentrations of ICAM-1 and VCAM-1 in gastric cancer patients were significantly higher when compared with those of healthy controls, whereas there were no differences regarding serum E-selectin levels. Serum levels of E-selectin, ICAM-1, and VCAM-1 correlated significantly with each other. There was a significant association between preoperative levels of all three adhesion molecules and disease stage, gastric wall invasion, lymph node involvement, and presence of distant metastases. Their concentrations decreased significantly after radical resection of the tumor, whereas they remained almost unchanged in patients with unresectable disease. Elevated preoperative serum levels of E-selectin, ICAM-1, and VCAM-1 levels were found in 24.6%, 33.3%, and 28.1% of patients, respectively. Elevated levels of all three molecules were significant prognostic factors for patient survival but not independent of disease stage. CONCLUSIONS: These findings suggest that serum concentrations of E-selectin, ICAM-1, and VCAM-1 may reflect tumor progression and metastasis, and may be clinically useful.