The application of atomic force microscopy in mineral flotation.

During the past years, atomic force microscopy (AFM) has matured to an indispensable tool to characterize nanomaterials in colloid and interface science. For imaging, a sharp probe mounted near to the end of a cantilever scans over the sample surface providing a high resolution three-dimensional topographic image. In addition, the AFM tip can be used as a force sensor to detect local properties like adhesion, stiffness, charge etc. After the invention of the colloidal probe technique it has also become a major method to measure surface forces. In this review, we highlight the advances in the application of AFM in the field of mineral flotation, such as mineral morphology imaging, water at mineral surface, reagent adsorption, inter-particle force, and bubble-particle interaction. In the coming years, the complementary characterization of chemical composition such as using infrared spectroscopy and Raman spectroscopy for AFM topography imaging and the synchronous measurement of the force and distance involving deformable bubble as a force sensor will further assist the fundamental understanding of flotation mechanism.

Preparation of flavocoenzyme isotopologues by biotransformation of purines.

Isotope-labeled flavins are crucial reporters for many biophysical studies of flavoproteins. A purine-deficient Escherichia coli strain engineered for expression of the ribAGH genes of Bacillus subtilis converts isotope-labeled purine supplements into the riboflavin precursor, 6,7-dimethyl-8-ribityllumazine, with yields up to 40%. The fermentation products can subsequently be converted into isotope-labeled riboflavin and the cognate flavocoenzymes, FMN and FAD, by in vitro biotransformation with better than 90% yield. Using this approach, more than 100 single or multiple (13)C-, (15)N-, (17)O-, and (18)O-labeled isotopologues of these cofactors and ligands become easily accessible, enabling advanced ligand-based spectroscopy of flavoproteins and lumazine receptor proteins at unprecedented resolution.

HIPEC ROC I: a phase I study of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion followed by postoperative intravenous platinum-based chemotherapy in patients with platinum-sensitive recurrent epithelial ovarian cancer.

This phase I study tested the safety, feasibility, pharmacokinetics and pharmacodynamics of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion (HIPEC) in patients with platinum-sensitive recurrent epithelial ovarian cancer (EOC) undergoing secondary cytoreductive surgery followed by postoperative platinum-based intravenous chemotherapy. Twelve patients with operable, recurrent platinum-sensitive EOC (recurrence ≥6 months after first-line therapy) were included according to the classical 3+3 dose-escalation design at three dose levels-60, 80 and 100 mg/m(2). After surgical cytoreduction, a single dose of cisplatin was administered via HIPEC for 90 min at 41-43°C. Postoperatively, all patients were treated with standard intravenous platinum-based combination chemotherapy. One of six patients experienced a dose-limiting toxicity (grade 3 renal toxicity) at a dose of 100 mg/m(2). The remaining five patients treated with 100 mg/m(2) tolerated their treatment well. The recommended phase II dose was established at 100 mg/m(2). The mean peritoneal-to-plasma AUC ratio was 19·5 at the highest dose level. Cisplatin-induced DNA adducts were confirmed in tumor samples. Common postoperative grade 1-3 toxicities included fatigue, postoperative pain, nausea, and surgical site infection. The ability to administer standard intravenous platinum-based chemotherapy after HIPEC was uncompromised. Cisplatin administered as HIPEC at a dose of 100 mg/m(2) has an acceptable safety profile in selected patients undergoing secondary cytoreductive surgery for platinum-sensitive recurrent EOC. Favorable pharmacokinetic and pharmacodynamic properties of HIPEC with cisplatin were confirmed at all dose levels, especially at 100 mg/m(2). The results are encouraging to determine the efficacy of HIPEC as a complementary treatment in patients with EOC.

Comparison of PV signal quality using a novel circular mapping and ablation catheter versus a standard circular mapping catheter.

PURPOSE: Recently, new catheter technologies have been developed for atrial fibrillation (AF) ablation. We investigate the diagnostic accuracy of a circular mapping and pulmonary vein ablation catheter (PVAC) compared with a standard circular mapping catheter (Orbiter) and the influence of filter settings on signal quality. METHODS: After reconstruction of the left atrium by three-dimensional atriography, baseline PV potentials (PVP) were recorded consecutively with PVAC and Orbiter in 20 patients with paroxysmal AF. PVPs were compared and attributed to predefined anatomical PV segments. Ablation was performed in 80 PVs using the PVAC. If isolation of the PVs was assumed, signal assessment of each PV was repeated with the Orbiter. If residual PV potentials could be uncovered, different filter settings were tested to improve mapping quality of the PVAC. Ablation was continued until complete PV isolation (PVI) was confirmed with the Orbiter. RESULTS: Baseline mapping demonstrated a good correlation between the Orbiter and PVAC. Mapping accuracy using the PVAC for mapping and ablation was 94% (74 of 79 PVs). Additional mapping with the Orbiter improved the PV isolation rate to 99%. Adjustment of filter settings failed to improve quality of the PV signals compared with standard filter settings. CONCLUSIONS: Using the PVAC as a stand-alone strategy for mapping and ablation, one should be aware that in some cases, different signal morphology mimics PVI isolation. Adjustment of filter settings failed to improve signal quality. The use of an additional mapping catheter is recommended to become familiar with the particular signal morphology during the first PVAC cases or whenever there is a doubt about successful isolation of the pulmonary veins.

Template-based preparation of free-standing semiconducting polymeric nanorod arrays on conductive substrates.

We describe the synthesis and characterization of a cross-linkable siloxane-derivatized tetraphenylbenzidine (DTMS-TPD), which was used for the fabrication of semiconducting highly ordered nanorod arrays on conductive indium tin oxide or Pt-coated substrates. The stepwise process allow fabricating of macroscopic areas of well-ordered free-standing nanorod arrays, which feature a high resistance against organic solvents, semiconducting properties and a good adhesion to the substrate. Thin films of the TPD derivate with good hole-conducting properties could be prepared by cross-linking and covalently attaching to hydroxylated substrates utilizing an initiator-free thermal curing at 160 degrees C. The nanorod arrays composed of cross-linked DTMS-TPD were fabricated by an anodic aluminum oxide (AAO) template approach. Furthermore, the nanorod arrays were investigated by a recently introduced method allowing to probe local conductivity on fragile structures. It revealed that more than 98% of the nanorods exhibit electrical conductance and consequently feature a good electrical contact to the substrate. The prepared nanorod arrays have the potential to find application in the fabrication of multilayered device architectures for building well-ordered bulk-heterojunction solar cells.

Mapping of local conductivity variations on fragile nanopillar arrays by scanning conductive torsion mode microscopy.

A gentle method that combines torsion mode topography imaging with conductive scanning force microscopy is presented. By applying an electrical bias voltage between tip and sample surface, changes in the local sample conductivity can be mapped. The topography and local conductivity variations on fragile free-standing nanopillar arrays were investigated. These samples were fabricated by an anodized aluminum oxide template process using a thermally cross-linked triphenylamine-derivate semiconductor. The nanoscale characterization method is shown to be nondestructive. Individual nanopillars were clearly resolved in topography and current images that were recorded simultaneously. Local current-voltage characteristics suggest a space-charge limited conduction in the semiconducting nanopillars.

Hyperbaric oxygen induces apoptosis via a mitochondrial mechanism.

During therapeutic hyperbaric oxygenation lymphocytes are exposed to high partial pressures of oxygen. This study aimed to analyze the mechanism of apoptosis induction by hyperbaric oxygen. For intervals of 0.5-4 h Jurkat-T-cells were exposed to ambient air or oxygen atmospheres at 1-3 absolute atmospheres. Apoptosis was analyzed by phosphatidylserine externalization, caspase-3 activation and DNA-fragmentation using flow cytometry. Apoptosis was already induced after 30 min of hyperbaric oxygenation (HBO, P < 0.05). The death receptor Fas was downregulated. Inhibition of caspase-9 but not caspase-8 blocked apoptosis induction by HBO. Hyperbaric oxygen caused a loss of mitochondrial membrane potential and caspase-9 induction. The mitochondrial pro-survival protein Bcl-2 was upregulated, and antagonizing Bcl-2 function potentiated apoptosis induction by HBO. In conclusion, a single exposure to hyperbaric oxygenation induces lymphocyte apoptosis by a mitochondrial and not a Fas-related mechanism. Regulation of Fas and Bcl-2 may be regarded as protective measures of the cell in response to hyperbaric oxygen.

Low serum alpha-tocopherol and selenium are associated with accelerated apoptosis in severe sepsis.

During sepsis, a severe systemic disorder, micronutrients often are decreased. Apoptosis is regarded as an important mechanism in the development of often significant immunosuppression in the course of the disease. This study aimed to investigate alpha-tocopherol and selenium in reference to apoptosis in patients with sepsis. 16 patients were enrolled as soon as they fulfilled the criteria of severe sepsis. 10 intensive care patients without sepsis and 11 healthy volunteers served as controls. alpha-Tocopherol, selenium and nucleosomes were measured in serum. Phosphatidylserine externalization and Bcl-2 expression were analyzed in T-cells by flow cytometry. Serum alpha-tocopherol and selenium were decreased in severe sepsis but not in non-septic critically ill patients (p < 0.05). Conversely, markers of apoptosis were increased in sepsis but not in critically ill control patients: Nucleosomes were found to be elevated 3 fold in serum (p < 0.05) and phosphatidylserine was externalized on an expanded subpopulation of T-cells (p < 0.05) while Bcl-2 was expressed at lower levels (p < 0.05). The decrease of micronutrients correlated with markers of accelerated apoptosis. Accelerated apoptosis in sepsis is associated with low alpha-tocopherol and selenium. The results support the investigation of micronutrient supplementation strategies in severe sepsis.

LocaLisa catheter navigation reduces fluoroscopy time and dosage in ablation of atrial flutter: a prospective randomized study.

INTRODUCTION: Catheter ablation has become a well-established therapy for isthmus-dependent right atrial flutter (AFL). Recently, mapping and ablation of AFL have been performed using sophisticated three-dimensional mapping systems, such as electroanatomic and noncontact mapping systems. The LocaLisa system enables nonfluoroscopic navigation of intracardiac electrode catheters based on impedance changes related to catheter movements in transthoracic current fields. The aim of this randomized prospective study was to compare the efficacy of the LocaLisa system with the conventional mapping/ablation approach for radiofrequency ablation of AFL. METHODS AND RESULTS: Fifty consecutive patients with AFL (39 men and 11 women; age 65 +/- 10 years) were studied. The patients were randomly assigned to undergo radiofrequency ablation guided by a conventional fluoroscopy-based approach (24 patients) or by the LocaLisa system (26 patients). Ablation success rate and documentation of bidirectional isthmus block were 100% in both groups. Compared with fluoroscopy-guided approaches, LocaLisa-guided procedures demonstrated a reduction in total fluoroscopy time from 15.9 +/- 10.6 minutes to 7.5 +/- 6.5 minutes (P < 0.005). Total fluoroscopy dosage was reduced from 21.0 +/- 19.8 to 8.7 +/- 9.5 Gycm2 (P < 0.05). Fluoroscopy time required for ablation was significantly shortened in the LocaLisa group (2.6 +/- 2.6 min) compared with the conventional approach group (11 +/- 10 min, P < 0.0005). In 9 (35%) of 26 patients, the ablation could be performed with a fluoroscopy time < or = 1 minute. There were no significant differences with regard to the number of radiofrequency applications, fluoroscopy time needed for diagnostic reasons, total procedure time, or other ablation data. CONCLUSION: Compared with the conventional approach, the LocaLisa system significantly reduces the fluoroscopy times needed for ablation of typical AFL.

Topical alpha-tocotrienol supplementation inhibits lipid peroxidation but fails to mitigate increased transepidermal water loss after benzoyl peroxide treatment of human skin.

Benzoyl peroxide (BPO) is a commonly used drug in the treatment of acne vulgaris, but it induces unwanted side effects related to stratum corneum (SC) function. Since it has been recently shown to oxidize SC antioxidants, it was hypothesized that antioxidant supplementation may mitigate the BPO-induced SC changes. To test this, 11 subjects were selected to be topically supplemented with alpha-tocotrienol (5% w/vol) for 7 d on defined regions of the upper back, while the contralateral region was used for vehicle-only controls. Starting on day 8, all test sites were also treated with BPO (10%) for 7 d; the alpha-tocotrienol supplementation was continued throughout the study. A single dose of BPO depleted 93.2% of the total vitamin E. While continuing the BPO exposure for 7 d further depleted vitamin E in both vehicle-only and alpha-tocotrienol-treated sites, significantly more vitamin E remained in the alpha-tocotrienol-treated areas. Seven BPO applications increased lipid peroxidation. Alpha-tocotrienol supplementation significantly mitigated the BPO-induced lipid peroxidation. The transepidermal water loss was increased 1.9-fold by seven BPO applications, while there was no difference between alpha-tocotrienol treatment and controls. The data suggest that alpha-tocotrienol supplementation counteracts the lipid peroxidation but not the barrier perturbation in the SC induced by 10% BPO.

Circumferential mapping and electric isolation of pulmonary veins in patients with atrial fibrillation.

Information about the clinical efficacy and complications of the circumferential mapping and isolation of the pulmonary veins (PVs) in patients with atrial fibrillation (AF) is still limited. The present study included 75 patients (mean age 58 +/- 11 years, 20 women) with paroxysmal (n = 69) or persistent AF (n = 6). Mapping of PVs was performed with a circumferential mapping catheter. After preferential PV-left atrium (LA) electric inputs were defined, radiofrequency ablation was performed until complete isolation of the PVs from the LA was achieved. A total of 226 PVs were mapped; 195 (86%) showed typical PV potentials. Complete isolation of PVs from the LA was achieved in 173 PVs (89%). Detailed follow-up, including 7-day Holter monitoring at 1, 4, 9, and 12 months after intervention was performed. If AF reoccurred, PVs were mapped and reisolated. After a mean follow-up period of 230 +/- 133 days, 38 of 75 patients (51%) were in sinus rhythm. At 1, 4, and 9 months of follow-up, 31 of 65 patients (48%), 36 of 53 patients (68%, p = 0.04 as compared with the first month), and 21 of 28 patients (75%, p = 0.025 as compared with the first month), respectively, were in sinus rhythm. During follow-up, 30 patients (40%) underwent a second ablation procedure due to recurrence. Recurrences were related to resumption of PV muscle-left atrial conduction (27 patients) and/or extra PV foci (12 patients) or nonablated PVs (8 patients). Complications occurred in 17 patients (22%). PV stenosis was detected in 13 patients (25% to 50% in 7 patients and >50% in 6 patients). Pericardial effusion occurred in 4 patients. It was concluded that isolation of the PV from the LA is moderately effective in the prevention of AF recurrence and could be associated with serious acute and long-term complications.

Electrophysiologic characteristics of the spontaneous onset and termination of atrial fibrillation.

Electrophysiologic characterization of the onset and termination of atrial fibrillation (AF) is poorly defined. Our study population consisted of 21 consecutive patients (mean age 58 +/- 9 years, 6 women) with intermittent (10 patients) or persistent (11 patients) AF. Mapping of the left atrium (LA) and the right atrium (RA) during initiation and termination of AF was performed with a 64-electrode basket catheter. A total of 92 spontaneous AF onsets (in 16 patients) and 63 spontaneous AF terminations were analyzed. Irrespective of the origin of the triggering atrial premature complex (APC), the onset of AF was preceded by an intermediary rhythm that consisted of repetitive firing from the focus that generated the initial APC, reentry around the mitral annulus, or typical atrial flutter. The earliest fibrillatory activity was constantly produced by circumvented regions (generators) localized most frequently in the posterior wall of the LA. Generators of fibrillatory activity were not observed in the RA for any of the patients. In the RA, AF is maintained by a mixture of macro-reentry and driving wave fronts of left atrial origin. Four modes of AF termination were observed: a multifocal rhythm (19 episodes, 30%), left atrial tachycardia (17 episodes, 27%), direct conversion to sinus rhythm (15 episodes, 24%), and conversion to typical atrial flutter (12 episodes, 19%). A repetitive rapid rhythm initiated most often by APCs plays a crucial role in the initiation of AF via activation of the generators of fibrillatory activity. The LA plays a central role in the initiation of AF by serving as a substrate for generators of fibrillatory activity. Termination of AF consists of a heterogenous group of unstable rhythms.

Biatrial multisite mapping of atrial premature complexes triggering onset of atrial fibrillation.

Pulmonary veins are considered to be the most common origin of the focal activity that triggers the onset of atrial fibrillation (AF). However, little is known about the importance of ectopic activity located outside the pulmonary veins. This study included 45 patients (8 women and 37 men, mean age 55 +/- 12 years) with paroxysmal (n = 25) and persistent (n = 20) AF in whom multisite mapping of the right and left atria was performed using a 64-electrode basket catheter (n = 21) or a noncontact mapping system (n = 24). Spontaneous or orciprenaline-induced atrial premature complexes (APCs) were mapped. In all, 94 AF onsets from 38 distinct foci in 30 patients were observed and analyzed. Of these foci, 20 (53%) were located in pulmonary veins and 18 (47%) were located outside the pulmonary veins in other parts of the atria. In 22 patients (73%), AF was reproducibly induced by APCs from a single focus (59 episodes). In 8 patients (27%), AF originated from 2 distinct foci (35 episodes). Additionally, 20 of 30 patients (67%) who developed AF had APCs in different locations not inducing AF. APCs inducing AF had shorter coupling intervals than APCs not inducing AF (307 +/- 54 vs 409 +/- 76 ms, p <0.001). This study showed that 47% of ectopic foci triggering the onset of AF were located outside the pulmonary veins in extravenous parts of the left atrium and the right atrium, and 27% of patients had AF onsets of bifocal origin. These data challenge the current opinion that extrapulmonary foci play a minor role in inducing AF.