Repair of Bile Duct Injury Using Indocyanine Green Following Laparoscopic Cholecystectomy.

Bile duct injury (BDI) is a potential complication that may arise during cholecystectomy and continues to occur with a certain frequency in the present day. Numerous reports have been published regarding the utilization of indocyanine green (ICG) for the prevention of biliary injury, and we feel that the importance of ICG is being recognized. In this context, we present a case wherein a BDI occurred following cholecystectomy, and ICG was employed for the safe repair of the biliary tract.

A Case of Resection of Hepatocellular Carcinoma in a Patient With Fontan-Associated Liver Disease.

The Fontan procedure (FP) is an operation used in patients with congenital single ventricle disease. The long-term prognosis after surgery has improved due to technological advances. However, the hemodynamics after FP are complicated. There are some reports of Fontan-associated liver disease (FALD) after FP. We report a case of a young woman who developed hepatocellular carcinoma due to FALD.

Serum carnitine as a biomarker of sarcopenia and nutritional status in preoperative gastrointestinal cancer patients.

BACKGROUND: Sarcopenia is an important factor in the postoperative outcome of gastrointestinal cancer patients. However, little research has been carried out on potential biomarkers of sarcopenia. Carnitine is an amino acid derivative that is stored in skeletal muscle and is essential for muscle energy metabolism. The primary purpose of this study was to investigate whether serum carnitine level is a biomarker of sarcopenia in preoperative patients with gastrointestinal cancer. The secondary purposes were (i) to examine the associations between carnitine, nutritional status, and albumin level, and (ii) to determine whether carnitine is a prognostic factor for postoperative complications. METHODS: One hundred fourteen patients scheduled to undergo gastroenterological surgery between August 2016 and January 2017 were enrolled. Their mean age was 68.4 ± 10.5, and 64.9% were male. Serum carnitine fractions [total carnitine (TC), free l-carnitine (FC), and acylcarnitine (AC)] were measured prior to surgery. The correlation between carnitine level and a variety of clinical features was analysed, including skeletal muscle index (SMI), sarcopenia, prognostic nutritional index (PNI), and postoperative complications. RESULTS: Tumour locations included the oesophagus (n = 17), stomach (n = 16), pancreas (n = 20), bile duct (n = 9), liver [n = 33; primary liver cancer (n = 18), liver metastasis (n = 15)], and colorectal region (n = 19). TC and FC levels varied significantly by tumour location. TC and FC showed significant positive correlations with SMI [TC (r = 0.295, P = 0.0014), FC (r = 0.286, P = 0.0020)] and PNI [TC (P = 0.0178, r = 0.222), FC (P = 0.0067, r = 0.2526)]. These levels were significantly lower in the sarcopenia group (TC, P = 0.0124; FC, P = 0.0243). In addition, TC and FC showed significant positive correlations with ALB level [TC (P = 0.038 r = 0.19), FC (P = 0.016 r = 0.23)]. When patients were divided into high ALB (≥3.5 g/dL, 96 patients) and low ALB (<3.5 g/dL, 18 patients) groups, these correlations were no longer significant, but in the low ALB group there was a tendency towards a negative relationship between ALB level and both TC and FC. No significant relationship was found between postoperative complications and carnitine level. CONCLUSIONS: This study suggests that carnitine level is a biomarker of sarcopenia and nutritional status. However, it did not find an association between carnitine level and postoperative complications.

Pancreaticoduodenectomy preserving aberrant gastroduodenal artery utilized in a previous coronary artery bypass grafting: A case report and review of literature.

RATIONALE: Pancreaticoduodenectomy (PD) is a technically demanding procedure with high rates of morbidity and mortality. Therefore, preoperative evaluation of anatomy is indispensable. Multi-detector row computed tomography (CT) enables us to precisely understand arterial anatomy. It is a well-known fact that anatomical variants are often present in the hepatic artery (HA) but rarely in the gastroduodenal artery (GDA). We present the case of a patient with ampullary cancer with a rare anatomical anomaly, "replaced GDA (rGDA) " arising from the superior mesenteric artery, along with a history of coronary artery bypass grafting (CABG) using right gastroepiploic artery (RGEA). PATIENT CONCERNS: A 69-year-old male patient was referred to our department for further investigation of elevated hepatobiliary enzymes. He presented with no symptoms besides intermittent fever of 38°C. He had an operative history of CABG using the RGEA. DIAGNOSIS: Abdominal CT and esophagogastroduodenoscopy showed an ampullary tumor and biopsy specimen from the lesion revealed adenocarcinoma. CT angiography revealed the rGDA instead of a normal common HA. INTERVENTION: We performed a safe PD, preserving the rGDA and the RGEA to maintain hepatic and cardiac perfusion. OUTCOMES: Owing to the presence of a refractory pancreatic fistula, the length-of-hospital stay was extended, and he was discharged on postoperative day 72 without vascular complications. At present, the patient is in good physical condition and does not present with cardiovascular complications as well as tumor recurrence at 6 months after surgery. LESSONS: This is possibly the first case of a patient who underwent PD and has a proper HA following a GDA arising from a superior mesenteric artery (rGDA) and has a previous operative history of CABG using the gastroepiploic artery. The coexistence of the history of cardiovascular surgery made PD for this patient considerably more challenging.In the case of a rare anatomical anomaly, a coronary artery bypass via the RGEA should not be considered as an obstacle when R0 resection is achievable.

Emergency laparoscopic cholecystectomy for intraabdominal hemorrhage in a patient with a left ventricular assist device: a case report.

BACKGROUND: Continuous-flow left ventricular assist devices (LVADs), called "second generation LVADs," have significantly improved the survival and quality of life outcomes. Accordingly, non-cardiac surgery in a patient with LVADs has required for conditions not directly related to their LVADs. And the management of bleeding in non-cardiac site remains one of long-term critical topics. Laparoscopic approach is useful in a patient with LVADs; however, there have been only few clinical reports. This report describes the first case of laparoscopic cholecystectomy (LC) for intraabdominal hemorrhage from the gallbladder serosa in a patient with LVADs. CASE PRESENTATION: A 56-year-old man with an LVAD had undergone LVAD (Jarvik 2000™; Jarvik Heart, Inc., New York, NY, USA) implantation at 53 years of age. He was in shock, and contrast-enhanced computed tomography revealed abdominal hemorrhage from the gallbladder serosa. Emergency laparoscopic cholecystectomy was performed. We could avoid injury of the LVADs driveline, which was located across the upper abdominal midline, near the right hypochondriac region, by laparoscopic approach. LVADs (Jarvik 2000) did not disturb the operating field because of its smaller size. There were no intra- and postoperative complications. CONCLUSIONS: Laparoscopic approach is useful and safe in a patient with LVADs for abdominal surgery. We could perform LC for intraabdominal hemorrhage from gallbladder serosa safety.

Single molecular observation of DNA and DNA complexes by atomic force microscopy.

Atomic force microscopy (AFM) provides a novel way to understand the structure-function relationship of protein synthesis at a single-molecular level. High-resolution AFM imaging in air, liquid and vacuum allows for single DNA, RNA and proteins to be observed at the nano-scale in addition to their conformational transitions, bound states, temporal behavior, and assembly. The recent development of frequency modulation mode AFM has led to imaging hydration structures of DNA in water and molecular polarization of DNA complexes in vacuum. Real-time imaging in near-physiological environments captures transcriptional activation with characteristic conformation of DNA-protein complexes. We review current achievements and the future potential of methodological and biological AFM to reveal insights into DNA, RNA and their complexes.

Dynamic component of sports is an important determinant factor of heart rate recovery.

OBJECTIVE: It is usually suggested that life expectancy of top athletes especially in endurance sports is longer than that of sedentary people. On the other hand, heart rate recovery (HRR) after exercise is an independent risk factor for cardiovascular disease and mortality, but differences in HRR between various top athletes are unclear. We examined HRR in various top athletes to clarify a role of HRR that may affect their life expectancy. METHODS: HRR was defined as the difference between the heart rate at peak exercise and that at 2 min after the finish of exercise using symptom-limited maximal graded bicycle ergometer exercise testing. The relationships between HRR with the grade of static and dynamic component of classification of sports, age, and body mass index (BMI) were estimated. SUBJECTS: The subjects were 720 male athletes participating in the National Sports Festival Japan in 2005-2008 and age-matched 28 sedentary controls. RESULTS: HRR was significantly correlated (p<0.0001) with the higher grade of dynamic component of sports, younger age, and lower BMI in both univariate and multivariate analysis. CONCLUSIONS: HRR of top athletes is predicted by increased dynamic component of sports, younger age, and lower BMI.

Products of thymine oxygenation by a non-heme oxygenation model, Fe(II)(MeCN)6(2+)-Ac2O-H2O2, and the transition state model between oxoiron and thymine.

Oxidative thymine damage was investigated using a new non-heme oxygenation model, Fe(MeCN)6(2+)-H2O2-Ac2O, based on high-spin Fe(MeCN)6(2+) in a non-aqueous solution, Ac2O-MeCN. Thymine and 1,3-dimethylthymine oxidized by the system gave the corresponding trans-thymine glycol derivatives in good yield. Thymineglycol is equivalent to an oxidative product as a measure of oxidative DNA damage in living cells. It is suggested that the activation of Fe(MeCN)6(2+)-H2O2-Ac2O in Ac2O-MeCN forms the oxoiron O=Fe(IV)(AcO)(MeCN)4(+) as an active species via a hetelolytic two-electron mechanism, not a Haber-Weiss-Fenton-type reaction with a one-electron process by treatment with a radical scavenger. In addition, we also demonstrated the transition state (TS) for the interaction between thymine and O=Fe(IV)(AcO)(MeCN)4(+) in the triplet spin (spin multiplicity; M=3). This model of oxidative thymine damage may provide new insight into the oxidative mechanism of thymine glycol production in non-aqueous reactions of thymine.

Flat hydrogel substrate for atomic force microscopy to observe liposomes and lipid membranes.

In order to avoid denaturation of biomolecules due to strong adsorption on solid surfaces, a soft substrate has to be used for atomic force microscopy (AFM) observation. We propose a hydrophilic agarose gel surface as a soft substrate for AFM to observe liposomes and lipid membranes. Although our simple method does not require any delicate control at the molecular level, an agarose gel surface can be simply flattened to 0.3 nm in roughness using an atomically flat solid surface during gelation. The AFM images revealed that liposomes were unruptured on the gel surface at low liposome density, whereas an unruptured state was difficult to obtain on a solid surface like mica. This indicates that the weak interaction between the liposome and the soft surface inhibits the liposome from rupturing, and also that the surface rougher than the solid surface prevents lateral diffusion of the liposomes along the surface to be fused. Increasing the liposome density resulted in a lipid membrane at various thicknesses forming on the hydrogel surface by the fusion and rupture of liposomes. Using the soft substrate, it can be expected to promote investigations of structures and functions of biomolecules at the nanometer scale under physiological conditions with AFM.

Electrostatic force spectroscopy on insulating surfaces: the effect of capacitive interaction.

Scanning surface probes delivered from atomic force microscopy (AFM) are expected to investigate local electrostatic properties on insulating surfaces by forces. Electrostatic force spectroscopy is especially suitable to clarify the capacitive interaction. In order to perform it at a well-defined tip-surface separation, we developed a dynamic mode, in which the tip-surface separation is regulated by maintaining the cantilever oscillation amplitude with an active feedback, while the electrostatic force gradient is simultaneously detected with a variable resonant frequency shift. Using the method, it turns out that the quadratic dependence of the electrostatic force gradient on an applied bias observed on an insulating Al(2)O(3)(0001) is comparable to those on a metallic Au(111). It results from the potential difference between the tip and the insulator surface being only one order smaller than that between the tip and the metal surface despite the spacing between electrodes for the insulator being 10(6) times larger than for the metal, because the capacitive interaction is modified primarily between the sharp AFM tip and the surface.

Profiling of gene-dependent translational progress in cell-free protein synthesis by real-space imaging.

In general, gene-dependent translational progress affects the efficiency of protein expression. To evaluate the translational progress of protein synthesis, it is necessary to trace the time course of translation as well as the quantity of products. Here we present a new method for tracking translation steps in cell-free protein synthesis using atomic force microscopy (AFM). The cell-free protein synthesis system is useful to track the inherent translational progress of a target gene, whereas conventional UV absorption measurement coupled with density gradient fractionation is difficult to analyze such small sample quantities. Because the high resolution of AFM enables us to clearly count the number of ribosomes included in polysomes, polysome profiles can be obtained directly without complicated fractionation. With this method, we could elucidate the detailed polysome profile with only 1 microl of sample solution. We observed the translational progress of green fluorescent protein synthesis, a model of high-expression protein, as well as human retinoid X receptor. Detailed polysome profiles showed different patterns of translational progress and were clearly associated with the results of time-dependent protein expression. Our study suggests the possibility for comprehensive character analysis of inherent gene-dependent translational progress.

Electrostatic force microscopy: imaging DNA and protein polarizations one by one.

We present electrostatic force microscopy images of double-stranded DNA and transcription complex on an insulating mica substrate obtained with molecular resolution using a frequency-mode noncontact atomic force microscope. The electrostatic potential images show that both DNA and transcription complexes are polarized with an upward dipole moment. Potential differences of these molecules from the mica substrate enabled us to estimate dipole moments of isolated DNA and transcription complex in zero external field to be 0.027 D/base and 0.16 D/molecule, respectively. Scanning capacitance microscopy demonstrates characteristic contrast inversion between DNA and transcription complex images, indicating the difference in electric polarizability of these molecules. These findings indicate that the electrostatic properties of individual biological molecules can be imaged on an insulator substrate while retaining complex formation.

Atomic force microscopy imaging of supramolecular organization of hyaluronan and its receptor CD44.

Hyaluronan is a major component of extracellular matrix and involved in a variety of important biological processes such as cell motility, proliferation, differentiation, and survival. However, the structure of hyaluronan and the mode of interaction between hyaluronan and its receptor remain to be fully elucidated. Here, we visualized directly the structure of hyaluronan by nanoscale imaging using atomic force microscopy (AFM), and analyzed the pattern of interaction with its cell surface receptor CD44. We observed by AFM that hyaluronan formed honeycomb-like network structures, to which the recombinant protein of CD44 extracellular domain intensively adhered. The pattern of the meshwork varied with the concentration of hyaluronan and also with its molecular weight. These observations suggest that the network structure might account for the properties of hyaluronan of being like an elastic gel at high concentration, and that the structure varying in relation to the molecular weight may cause the difference in the biological activities of the hyaluronan.

Improvement of the cleanability of pseudo-sensitized stainless steel surfaces by solution treatment.

Type 316L stainless steel particles were pseudo-sensitized by being heated at 700 degrees C for 100 h under a reduced pressure of 1.3 x 10(-3) Pa. Pseudo-sensitization treatment resulted in the formation of chromium-rich precipitates at the outermost surfaces of the stainless steel particles. The curve for the apparent surface charge density (sigma app) of the pseudo-sensitized particles showed a more basic character compared with the curve for the sigma app of the original particles. There was no significant difference between the amounts of bovine serum albumin (BSA) adsorbed on the original and the pseudo-sensitized particles. On the contrary, the efficiency of BSA removal from the pseudo-sensitized particles during batch-wise and continuous cleaning operations with 0.1M NaOH solution were significantly smaller than that for the original particles. It was indicated that the extremely lowered cleanability of the pseudo-sensitized particles was caused by a marked increase in the positive sigma app values after the pseudo-sensitization. Solution treatment of the pseudo-sensitized particles at 1,050 degrees C for 1 h under a reduced pressure of 1.3 x 10(-3) Pa could put again the chromium precipitates into a solid solution, thereby returning the surface chemical composition and the sigma app nearly to the original states. In addition, the solution-treated particles showed a good cleanability comparable to that of the original particles. These results demonstrated that solution treatment could improve the lowered cleanability of the pseudo-sensitized stainless steel surfaces.

Synthesis of nanometer-scale porphyrin wheels of variable size.

Starting from 1,3-phenylene linked diporphyrin zinc(II) complex 2ZA, repeated stepwise Ag I-promoted coupling reactions provided linear oligomers from 2nZA up to 128ZA. Of these zigzag shaped porphyrin arrays, the Ag I-promoted intramolecular cyclization reaction of 2 nZA (n=5, 6, 8, 9, 12, and 16) under dilute conditions gave the corresponding cyclic porphyrin wheels C2nZA (n=5, 6, 8, 9, 12, and 16), whereas large arrays 2nZA (n=24, 32, and 48) did not provide cyclic porphyrin products. These large discrete porphyrin arrays and wheels were fully characterized by means of 1H NMR spectroscopy, MALDI-TOF mass spectrometry, UV/Vis absorption spectroscopy, GPC-HPLC analysis, and the scanning tunneling microscopy (STM) technique. The STM images of C12ZA and C18ZA reveal their large circular structures. In the cyclic structures of C2nZA in solution, however, the gradual decrease in fluorescence quantum yields and fluorescence lifetimes are observed, reflecting some conformational heterogeneities. Collectively, the present work provides an important contribution to the construction of fully covalently linked large cyclic arranged porphyrin arrays with ample electronic interactions as a model of light-harvesting antenna.

A hexagonal prismatic porphyrin array: synthesis, STM detection, and efficient energy hopping in near-infrared region.

A belt-shaped hexagonal cyclic porphyrin array 2 that comprises of six meso-meso, beta-beta, beta-beta triply linked diporphyrins 3 bridged by 1,3-phenylene spacers is prepared by oxidation from cyclic dodecameric array 1 consisting of six meso-meso directly linked diporphyrins 4 with DDQ and Sc(OTf)3. The absorption spectrum of 2 is similar to that of the constituent subunit 3 but shows a slight red-shift for the Q-bands in near-infrared (NIR) region, indicating the exciton coupling between the neighboring diporphyrin chromophores. Observed total exciton coupling energies in the absorption spectra were largely matched with the calculated values based on point-dipole exciton coupling approximation. It was found that the experimental exciton coupling strength (292 cm(-1)) of the Q-band in 2 is slightly larger than the calculated one (99 cm(-1)), indicating that the electronic communications are enhanced through 1,3-phenylene linkers in hexameric macromolecule. A rate of the excitation energy hopping (EEH) that occurs in 2 at the lowest excited singlet state in the near-infrared region has been determined to be (1.8 ps)(-1) on the basis of the pump-power dependent femtosecond transient absorption (TA) and the transient absorption anisotropy (TAA) decay measurements. The 2 times faster EEH rate of 2 than that of 1 (4.0 ps)(-1) mainly comes from involving through-bond energy transfer among diporphyrin subunits via 1,3-phenylene bridges as well as Förster-type through-space EEH processes. STM measurement of 2 in the Cu(100) surface revealed that it takes several discrete conformations with respect to the relative orientation of neighboring diporphyrins. Collectively, an effective EEH in the NIR region is realized in 2 due largely to the intensified oscillator strength in the S(1) state (Q-band) and the close proximity held by 1,3-phenylene spacers.

Discrimination of Brugada syndrome patients from individuals with the saddle-back type ST-segment elevation using a marker of the standard 12-lead electrocardiography.

BACKGROUND: In the clinical situation, the saddle-back (S-B) type is more frequently detected than the coved type. In the present study, the discrimination of Brugada syndrome from the S-B type individuals using a marker of the standard 12-lead electrocardiography (ECG) was attempted. METHODS AND RESULTS: The study group consisted of 55 individuals with the S-B type in whom pilsicainide provocation test (PLC test) was carried out. The time from the onset of the QRS wave in lead V(2) (IV (2)) to the peak of the late R-like wave in the QRS wave (PV(2)), and the time from IV(2) to the offset of the QRS wave in lead V(5) (EV(5)) were measured. The coved type was induced by the PLC test in 29 cases (N-C group), but not in the remaining 26 cases (N-N group). The (IV(2) -PV(2)) - (IV(2) - EV(5)) value before the PLS test was greater in the N-C group than in the N-N group. The negative predictive value of ;(IV(2) - PV(2)) - (IV(2) - EV(5)) > or =0' was 76.4% for the prediction of a positive PLC test. CONCLUSIONS: A ;(IV(2) - PV(2)) - (IV(2) - EV(5)) > or =0' is a useful ECG marker for the discrimination of Brugada syndrome in the S-B type individuals.

A directly fused tetrameric porphyrin sheet and its anomalous electronic properties that arise from the planar cyclooctatetraene core.

Oxidation of a directly meso-meso linked cyclic porphyrin tetramer 2 gave a porphyrin sheet 3. The symmetric square structure of 3 is indicated by its simple 1H NMR spectrum that exhibits only two signals for the porphyrin beta-protons. The absorption spectrum of 3 displays characteristic Soret-like broad bands and weak Q-bands, and its magnetic circular dichroism (MCD) spectrum exhibits a negative Faraday A term at the 762 nm band as a rare case, indicating the absorption as a transition from a nondegenerate level to a degenerate level. A slightly longer S1-state (1.1 ps) and smaller TPA cross section (2750 GM) than a tetrameric linear porphyrin tape also indicate its unique electronic properties. The porphyrin sheet 3 forms stable 1:2 complexes with guest molecules G1 and G2, whose 1H NMR spectra exhibit remarkable downfield shifts for the guest protons that are located just above the cyclooctatetraene (COT) core of 3, whereas the imidazolyl protons bound to the zinc(II) porphyrin local cores are observed at slightly upfield positions. These results have been qualitatively accounted for in terms of the presence of a strong paratropic ring current around the COT core that propagates through the whole pi-electronic network of 3, hence competing with and cancelling the weak diatropic ring currents of the local zinc(II) porphyrins. This explanation was supported by DFT calculation performed at the GIAO-B3LYP/6-31G level, which indicated large positive NICS values within the COT core and small NICS values within the local zinc(II) porphyrins.

Population pharmacokinetic and pharmacodynamic analysis of a class IC antiarrhythmic, pilsicainide, in patients with cardiac arrhythmias.

Population pharmacokinetics (PK) of a sodium channel-blocking antiarrhythmic, pilsicainide, was studied using the nonlinear mixed-effects modeling technique in 91 patients with cardiac arrhythmias (80 suspected Brugada syndrome [BrS] and 11 with atrial fibrillation) who received an intravenous infusion of 10 mg of the drug. Population pharmacodynamic (PD) analysis was also performed using an effect compartment model. PD responses were assessed by changes in electrocardiogram (ECG) pattern (BrS-like elevation of ST-segment) and conduction parameters. The final PK model showed that gender (values were 50% lower in women than in men) and creatinine clearance were significant (P < .01) covariates of weight-normalized systemic clearance of pilsicainide. Patients who showed a BrS-like ECG pattern after the drug administration also showed a significantly (P < .01) greater prolongation in His-Purkinje conduction compared to the remaining patients. In conclusion, female gender, renal dysfunction, and the drug-induced BrS-like ECG morphology may be associated with augmented ECG responses to pilsicainide.

Giant porphyrin wheels with large electronic coupling as models of light-harvesting photosynthetic antenna.

Starting from a 1,3-phenylene-linked diporphyrin zinc(II) complex 2ZA, repeated stepwise Ag(I)-promoted coupling reactions provided linear oligomers 4ZA, 6ZA, 8ZA, and 12ZA. The intramolecular cyclization reaction of 12ZA under dilute conditions (1x10(-6) M) gave porphyrin ring C12ZA with a diameter of approximately 35 A in 60% yield. This synthetic strategy has been applied to a 1,3-phenylene-linked tetraporphyrin 4ZB to provide 8ZB, 12ZB, 16ZB, 24ZB, and 32ZB. The intramolecular coupling reaction of 24ZB gave a larger 24-mer porphyrin ring C24ZB with a diameter of approximately 70 A in 34% yield. These two large porphyrin rings were characterized by means of 1H NMR spectroscopy, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectroscopy, UV-visible spectroscopy, gel permeation chromatography (GPC) analysis, and scanning tunneling microscopy (STM) techniques. The STM images of C12ZA reveal largely circular structures, whereas those of C24ZB exhibit mostly ellipsoidal shapes, indicating more conformational flexibility of C24ZB. Similar to the case of C12ZA, the efficient excitation energy transfer along the ring has been confirmed for C24ZB by using the time-correlated single-photon counting (TCSPC) and picosecond transient absorption anisotropy (TAA) measurements, and occurs with a rate of (35 ps)(-1) for energy hops between neighboring tetraporphyrin subunits. Collectively, the present work provides an important step for the construction of large cyclic-arranged porphyrin arrays with ample electronic interactions as a model of light-harvesting antenna.