Exogenously imposed postprandial-like rises in systemic glucose and GLP-1 do not produce an incretin effect, suggesting an indirect mechanism of GLP-1 action

The insulinotropic intestinal hormone GLP-1 is thought to exert one of its effects by direct action on the pancreatic beta-cell receptors. GLP-1 is rapidly degraded in plasma, such that only a small amount of the active form reaches the pancreas, making it questionable whether this amount is sufficient to produce a direct incretin effect. The aim of our study was to assess, in a dog model, the putative incretin action of GLP-1 acting directly on the beta-cell in the context of postprandial rises in GLP-1 and glucose. Conscious dogs were fed a high-fat, high-carbohydrate meal, and insulin response was measured. We also infused systemic glucose plus GLP-1, or glucose alone, to simulate the meal test values of these variables and measured insulin response. The results were as follows: during the meal, we measured a robust insulin response (52 +/- 9 to 136 +/- 14 pmol/l, P < 0.05 vs. basal) with increases in portal glucose and GLP-1 but only limited increases in systemic glucose (5.3 +/- 0.1 to 5.7 +/- 0.1 mmol/l, P = 0.1 vs. basal) and GLP-1 (6 +/- 0 to 9 +/- 1 pmol/l, P = 0.5 vs. basal). Exogenous infusion of systemic glucose and GLP-1 produced a moderate increase in insulin (43 +/- 5 to 84 +/- 15 pmol/l, 43% of the meal insulin). However, infusion of glucose alone, without GLP-1, produced a similar insulin response (37 +/- 6 to 82 +/- 14 pmol, 53% of the meal insulin, P = 0.7 vs. glucose and GLP-1 infusion). In conclusion, in dogs with postprandial rises in systemic glucose and GLP-1, the hormone might not have a direct insulinotropic effect and could regulate glycemia via indirect, portohepatic-initiated neural mechanisms.     

Laparoscopic abdominal cysts fenestration using harmonic scalpel

The use of ultrasonically activated scalpel for tissue cutting and coagulation is a potential replacement for electrosurgery, which can be related to different complications. Its working principle is to transform the electric power into the mechanical longitudinal movement of the working part of the instrument, by a piezoelectric transducer situated in the hand piece. Between October 2000 and June 2004, six patients with abdominal cysts were treated by laparoscopy, using the harmonic scalpel. The average age was 40.8 (ranging from 15-60) years. Laparoscopic abdominal cyst fenestration was performed in five patients, and laparoscopic cholecystectomy and abdominal cyst fenestration were done in one patient during the same operation. The average duration of the operation was 40 (ranging from 25-70) minutes and hospital stay was 2.8 (ranging from 1-5) days. Laparoscopic abdominal cyst fenestration using the harmonic scalpel is a safe and successful operation, with good results including all the advantages of the minimally invasive surgery.     

Local recurrence of primary non-ampullary adenocarcinoma of duodenum after surgical treatment--a case report and a literature review

Worldwide there is no general attitude on optimal surgical procedure in treatment of primary non-ampullary adenocarcinoma of duodenum, especially for early stage of duodenal cancer. Some authors prefer local excision and segmental resection while others rather perform duodenopancreatic resection, even in the case of early stage of duodenal cancer with aim to avoid tumor recurrence. In this paper we present a rare clinical course of a 60-year-old male patient with an endoscopically and pathohistologically proven early stage duodenal cancer that was treated by wide local excision. Three years after operation, control endoscopy showed "flat" polyp in the duodenum and radical duodenopancreatic resection was performed. Pathohistological examination of resected specimen showed cancer that had spread throughout the duodenal wall with metastases in the regional lymph nodes. According to our findings and literature review we gave some direction concerning the optimal diagnostic and surgical procedure for this rare tumor.     

Biphasic Myopathic Phenotype of Mouse DUX,an ORF within Conserved FSHD-Related Repeats

Facioscapulohumeral muscular dystrophy (FSHD) is caused by contractions of D4Z4 repeats at 4q35.2 thought to induce misregulation of nearby genes, one of which, DUX4, is actually localized within each repeat. A conserved ORF (mDUX), embedded within D4Z4-like repeats, encoding a double-homeodomain protein, was recently identified on mouse chromosome 10. We show here that high level mDUX expression induces myoblast death, while low non-toxic levels block myogenic differentiation by down-regulating MyoD and Myf5. Toxicity and MyoD/Myf5 expression changes were competitively reversed by overexpression of Pax3 or Pax7, implying mechanistic similarities with the anti-myogenic activity of human DUX4. We tested the effect of mDUX expression on Xenopus development, and found that global overexpression led to abnormalities in gastrulation. When targeted unilaterally into blastomeres fated to become tail muscle in 16-cell embryos, mDUX caused markedly reduced tail myogenesis on the injected side. These novel cell and animal models highlight the myopathic nature of sequences within the FSHD-related repeat array.     

Merkel cell carcinoma: case report

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma of the skin. Although it is 40 times less common than malignant melanoma, its mortality is much higher compared to melanoma. From 1986 to 2001 there was rapidly increasing incidence in reported cases of MCC, with a tripling in the rate over this 15-year period. The vast majority of MCC presents on sun-exposed skin. The head and neck area is the most common site of tumor occurrence. We present 70-year old female patient with painless red-colored nodule, size 2 x 2 x 2 cm on the dorsal side of mid left forearm. The surgical excision with negative margins was performed, and pathohistological analysis confirmed Merkel cell carcinoma. Sentinel lymph node biopsy was negative. In conclusion, as MCC is a very aggressive rare skin carcinoma with lethal outcome, it should be mandatory to perform biopsies of any suspected skin lesion.     

Antioxidant and antimicrobial properties of the lichens <Emphasis Type="Italic">Anaptychya ciliaris,Nephroma parile,Ochrolechia tartarea</Emphasis> and <Emphasis Type="Italic">Parmelia centrifuga</Emphasis>

The aim of this study was to characterize the antioxidant and antimicrobial activity of the methanol extracts of: Anaptychya ciliaris, Nephroma parile, Ochrolechia tartarea and Parmelia centrifuga. The methanol extract of the P. centrifuga showed a strong antioxidant activity, in comparison to the extracts from A. ciliaris, O. tartarea and N. parile which were relatively weaker. Furthermore, the methanol extract of the lichen P. centrifuga was shown to contain the highest total phenol content (54.19 mg/g of the dry extract). Interestingly, a statistically significant positive relationship between the antioxidant activity and the total phenol content was observed. The minimum inhibitory concentration (MIC) against six bacterial and eleven fungi was established for the methanol extracts from each of species of lichens. The methanol extracts of the lichens P. centrifuga and O. tartarea showed the strongest both antibacterial and antifungal activity. Taken together, the results from this study suggest that the lichens P. centrifuga and O. tartarea may be used as a natural source of antioxidants in addition to providing certain antimicrobial features.     

Reduced activity of enzymes coupling ATP-generating with ATP-consuming processes in the failing myocardium

Adipocytes express two lipid-binding proteins; the major one termed the adipocyte lipid-binding protein or aP2 (ALBP/aP2) and a minor one referred to as the keratinocyte lipid-binding protein (KLBP). In order to evaluate the potential physiological roles for these proteins, their biochemical and biophysical properties have been analyzed and compared. ALBP/aP2 and KLBP exhibit similar binding affinities for most long-chain fatty acids; however, ALBP/aP2 exhibits a two to three-fold increased affinity for myristic, palmitic, oleic and linoleic acids, the predominant fatty acids of adipocytes. As measured by guanidinium hydrochloride denaturation, the stability of ALBP/aP2 is nearly 3 kcal/mol greater than that of KLBP. While the pI of ALBP/aP2 was determined to be 9.0, that of KLBP is 6.5 suggesting differing net charges at physiological pH. Analysis of surface electrostatic properties of ALBP/aP2 and KLBP revealed similar charge polarity, although differences in the detailed charge distribution exist between the proteins. The distribution of hydrophobic patches was also different between the proteins, ALBP/aP2 has only scattered hydrophobic surfaces while KLBP has a large hydrophobic patch near the ligand portal into the binding cavity. In sum, these results point out that despite the striking similarity between ALBP/aP2 and KLBP in tertiary structure, significant differences in ligand binding and surface properties exist between the two proteins. Hence, while it is tempting to speculate that ALBP/aP2 and KLBP are metabolically interchangeable, careful analysis suggests that the two proteins are quite distinct and likely to play unique metabolic roles.     

Knockout of Kir6.2 negates ischemic preconditioning-induced protection of myocardial energetics

Although ischemic preconditioning induces bioenergetic tolerance and thereby remodels energy metabolism that is crucial for postischemic recovery of the heart, the molecular components associated with preservation of cellular energy production, transfer, and utilization are not fully understood. Here myocardial bioenergetic dynamics were assessed by (18)O-assisted (31)P-NMR spectroscopy in control or preconditioned hearts from wild-type (WT) or Kir6.2-knockout (Kir6.2-KO) mice that lack metabolism-sensing sarcolemmal ATP-sensitive K(+) (K(ATP)) channels. In WT vs. Kir6.2-KO hearts, preconditioning induced a significantly higher total ATP turnover (232 +/- 20 vs. 155 +/- 15 nmol x mg protein(-1) x min(-1)), ATP synthesis rate (58 +/- 3 vs. 46 +/- 3% (18)O labeling of gamma-ATP), and ATP consumption rate (51 +/- 4 vs. 31 +/- 4% (18)O labeling of P(i)) after ischemia-reperfusion. Moreover, preconditioning preserved cardiac creatine kinase-catalyzed phosphotransfer in WT (234 +/- 26 nmol x mg protein(-1) x min(-1)) but not Kir6.2-KO (133 +/- 18 nmol x mg protein(-1) x min(-1)) hearts. In contrast with WT hearts, preconditioning failed to preserve contractile recovery in Kir6.2-KO hearts, as tight coupling between postischemic performance and high-energy phosphoryl transfer was compromised in the K(ATP)-channel-deficient myocardium. Thus intact K(ATP) channels are integral in ischemic preconditioning-induced protection of cellular energetic dynamics and associated cardiac performance.     

Chest radiography findings in primary pulmonary tuberculosis in children

Plain chest radiography plays a major role in the diagnosis and follow-up of pulmonary tuberculosis in childhood. The aim of our study was to investigate the distribution of characteristic chest radiographic findings at diagnosis in children with pulmonary tuberculosis. The age of the patients and the type and localization of radiographic changes at admission were retrospectively analyzed. We reviewed chest radiographs in 204 children admitted from January 1, 1991 until June 30, 1994 for newly diagnosed pulmonary tuberculosis. Mean age +/- SD was 6.4 +/- 4.2 years (range 0-14). The most common lesion was lymphadenopathy (found in 172 children, 84.3%). It was significantly more common in the youngest age group (0-4 years) and was more significantly present in the right hilo-mediastinal region. Parenchymal changes were found in 125 children (61.3%). They were also significantly more common in the young age group and in the right lung. Other less common lesions included pleuritis, atelectasis, destructive-cavitary lesions and miliary dissemination. In conclusion, the leading radiographic finding in pulmonary tuberculosis in childhood remains hilar lymphadenopathy, but parenchymal changes are clearly strongly present, and should be sought and appreciated in the diagnostic work-up for pulmonary tuberculosis in childhood.     

Biophysically Inspired Rational Design of Structured Chimeric Substrates for DNAzyme Cascade Engineering

The development of large-scale molecular computational networks is a promising approach to implementing logical decision making at the nanoscale, analogous to cellular signaling and regulatory cascades. DNA strands with catalytic activity (DNAzymes) are one means of systematically constructing molecular computation networks with inherent signal amplification. Linking multiple DNAzymes into a computational circuit requires the design of substrate molecules that allow a signal to be passed from one DNAzyme to another through programmed biochemical interactions. In this paper, we chronicle an iterative design process guided by biophysical and kinetic constraints on the desired reaction pathways and use the resulting substrate design to implement heterogeneous DNAzyme signaling cascades. A key aspect of our design process is the use of secondary structure in the substrate molecule to sequester a downstream effector sequence prior to cleavage by an upstream DNAzyme. Our goal was to develop a concrete substrate molecule design to achieve efficient signal propagation with maximal activation and minimal leakage. We have previously employed the resulting design to develop high-performance DNAzyme-based signaling systems with applications in pathogen detection and autonomous theranostics.