Successive Injections Research Articles

Integrin-facilitated transcytosis for enhanced penetration of advanced gliomas by poly(trimethylene carbonate)-based nanoparticles encapsulating paclitaxel

The treatment of cerebral tumor, especially advanced gliomas, represents one of the most formidable challenges in oncology. In this study, integrin-mediated poly(trimethylene carbonate)-based nanoparticulate system (c(RGDyK)–NP) was proposed as a delivery vehicle for enhancing drug penetration and chemotherapy of malignant gliomas. Following the recognition by integrin proteins on cell surface, c(RGDyK)–NP could be energy-dependently internalized by human U87MG glioma cells through a multiple endocytic pathway. The tumor penetration, homing specificity and anticancer efficacy of PTX-loaded c(RGDyK)–NP (c(RGDyK)–NP/PTX) were performed on the 3D glioma spheroids, the U87MG glioma cells and the intracranial glioma mice model, respectively. Compared with conventional nanoparticles (NP/PTX) and Taxol, c(RGDyK)–NP/PTX showed the strongest penetration and accumulation into 3D glioma spheroids, an obvious microtubule stabilization effect to U87MG glioma cells, a significant homing specificity to malignant glioma in vivo, and an extended median survival time in the intracranial glioma-bearing mice. Furthermore, preliminary in vivo subacute toxicity was also evaluated by measuring the histopathology, blood cell counts and clinical biochemistry parameters, and the results revealed no obvious subacute toxicity to hematological system, major organs or tissues were observed post successive intravenous injection of c(RGDyK)–NP. Therefore, our results suggested that cyclic RGD-conjugated PEG–PTMC nanoparticle could be a promising vehicle for enhancing the penetration and cxhemotherapy of high-grade malignant gliomas.

Liposome sensing and monitoring by organic electrochemical transistors integrated in microfluidics

BackgroundOrganic electrochemical transistors (OECTs), which are becoming more and more promising devices for applications in bioelectronics and nanomedicine, are proposed here as ideally suitable for sensing and real time monitoring of liposome-based structures. This is quite relevant since, currently, the techniques used to investigate liposomal structures, their stability in different environments as well as drug loading and delivery mechanisms, operate basically off-line and/or with pre-prepared sampling. MethodsOECTs, based on the PEDOT:PSS conductive polymer, have been employed as sensors of liposome-based nanoparticles in electrolyte solutions to assess sensitivity and monitoring capabilities based on ion-to-electron amplified transduction. ResultsWe demonstrate that OECTs are very efficient, reliable and sensitive devices for detecting liposome-based nanoparticles on a wide dynamic range down to 10−5mg/ml (with a lowest detection limit, assessed in real-time monitoring, of 10−7mg/ml), thus matching the needs of typical drug loading/drug delivery conditions. They are hence particularly well suited for real-time monitoring of liposomes in solution. Furthermore, OECTs are shown to sense and discriminate successive injection of different liposomes, so that they could be good candidates in quality-control assays or in the pharmaceutical industry. General significanceDrug loading and delivery by liposome-based structures is a fast growing and very promising field that will strongly benefit from real-time, highly sensitive and low cost monitoring of their dynamics in different pharma and biomedical environments, with a particular reference to the pharmaceutical and production processes, where a major issue is monitoring and measuring the formation and concentration of liposomes and the relative drug load. The demonstrated ability to sense and monitor complex bio-structures, such as liposomes, paves the way for very promising developments in biosensing and nanomedicine. This article is part of a Special Issue entitled Organic Bioelectronics—Novel Applications in Biomedicine.

A immunosensor for the diagnosis of canine distemper virus infection using SPR and EIS

Canine distemper virus (CDV) is a viral disease that affects dogs and many other carnivores. Clinical diagnosis of CDV is difficult due to the broad spectrum of signs that may be confounded with other respiratory and enteric diseases of dogs. Laboratory analysis is required to diagnose suspected cases. In this study, surface plasmon resonance (SPR) and electrochemical impedance spectroscopy (EIS) methodologies were developed for the detection of canine distemper virus simultaneously. The assay exhibited high specificity, as all the negative controls were not mistakenly detected. The CDV concentration was determined from successive injections into the apparatus, with a linear range from 1.1 to 116.0 ng mL−1. The system exhibited good reproducibility with 4.5% variation between runs after regeneration of the coated surface with a solution of 0.1 M glycine–HCL (pH 3.0). The capacitance and resistance values of the modified interface were calculated from EIS data using an equivalent circuit. It was possible to measure CDV in highly concentrated viruses with good specificity and reproducibility.

Longstanding refractory pseudophakic cystoid macular edema resolved using intravitreal 0.7 mg dexamethasone implants

BackgroundRefractory pseudophakic cystoid macular edema (PCME) following cataract surgery has long posed a challenge to clinicians, but intravitreal injections with a sustained delivery 0.7 mg dexamethasone implant has emerged as a promising therapy for this condition.ObjectiveTo present a case of longstanding and refractory PCME with complete remission through 189 days of follow-up after two successive injections with intravitreal dexamethasone implants.Case reportA 59-year-old male had experienced metamorphopsia for approximately 4 years and had been diagnosed with PCME 15 months earlier. Since the time of the diagnosis, the condition had been refractory to both subtenon triamcinolone acetonide and a total of five injections with intravitreal ranibizumab. After the last injection with ranibizumab, central subfield mean thickness was 640 μm, and the best corrected visual acuity was 78 Early Treatment Diabetic Retinopathy Study letters. Following an intravitreal injection with a dexamethasone implant, the macular edema resolved at the next follow-up. The macular edema returned 187 days after the first injection and was treated with another intravitreal dexamethasone implant. Again, the macular edema subsided completely, and best corrected visual acuity improved to 84 Early Treatment Diabetic Retinopathy Study letters, a condition which was maintained through an additional 189 days of follow-up.ConclusionChronic PCME is traditionally a difficult condition to treat, but we are encouraged by the optimal response experienced with intravitreal sustained release dexamethasone implants in our patient whose longstanding PCME had been refractory to previous treatments with both subtenon triamcinolone and intravitreal ranibizumab. In this case, the condition appeared to be fully reversible once inflammation was controlled, but the need for monitoring and repeated injections remains an issue of concern.

Low-dose morphine elicits ventilatory excitant and depressant responses in conscious rats: Role of peripheral μ-opioid receptors.

The systemic administration of morphine affects ventilation via a mixture of central and peripheral actions. The aims of this study were to characterize the ventilatory responses elicited by a low dose of morphine in conscious rats; to determine whether tolerance develops to these responses; and to determine the potential roles of peripheral μ-opioid receptors (μ-ORs) in these responses. Ventilatory parameters were monitored via unrestrained whole-body plethysmography. Conscious male Sprague-Dawley rats received an intravenous injection of vehicle or the peripherally-restricted μ-OR antagonist, naloxone methiodide (NLXmi), and then three successive injections of morphine (1 mg/kg) given 30 min apart. The first injection of morphine in vehicle-treated rats elicited an array of ventilatory excitant (i.e., increases in frequency of breathing, minute volume, respiratory drive, peak inspiratory and expiratory flows, accompanied by decreases in inspiratory time and end inspiratory pause) and inhibitory (i.e., a decrease in tidal volume and an increase in expiratory time) responses. Subsequent injections of morphine elicited progressively and substantially smaller responses. The pattern of ventilatory responses elicited by the first injection of morphine was substantially affected by pretreatment with NLXmi whereas NLXmi minimally affected the development of tolerance to these responses. Low-dose morphine elicits an array of ventilatory excitant and depressant effects in conscious rats that are subject to the development of tolerance. Many of these initial actions of morphine appear to involve activation of peripheral μ-ORs whereas the development of tolerance to these responses does not.

Coronary vasospasm while treating supraventricular tachycardia: is adenosine really to blame?

Coronary artery spasm has been reported during adenosine stress testing. Herein, we describe a transient ST-segment elevation following adenosine therapy for supraventricular tachycardia. A 38-year-old male presented to the emergency department with palpitations. Electrocardiogram showed supraventricular tachycardia with short RP interval. Vagal maneuvers were unsuccessful. Adenosine was then administered in two successive injections of 6 and 12 mg dosages, respectively. A subsequent 12-lead electrocardiogram revealed ST-segment elevation in inferior leads with reciprocal changes. Coronary angiography disclosed nonobstructive coronary disease. A postprocedure electrocardiogram exhibited normal sinus rhythm with nonspecific T wave abnormalities. Cardiac biomarkers were elevated with a peak troponin I of 0.32. Echocardiogram depicted bicuspid aortic valve and normal systolic function. Electrophysiological study revealed a concealed left accessory pathway and successful radiofrequency ablation was performed. Given the dynamic changes in the electrocardiogram, we hypothesize that this event was most likely a coronary vasospasm. The mechanism of coronary spasm following adenosine injection remains uncertain. Potential mediators include KATP channels and adenosine-2 receptors.

Controlled Synthesis of CdSe Tetrapods with High Morphological Uniformity by the Persistent Kinetic Growth and the Halide-Mediated Phase Transformation

We report scalable controlled synthesis of CdSe tetrapods with high morphological uniformity based on the continuous precursor injection (CPI) approach with halide ligands. The CPI approach involves the successive injection of precursors into the seed solution at a controlled rate so that the reaction condition remains in the kinetic growth regime. To initiate the successful development of tetrapod structure, the controlled amount of halide ligands are added during the reaction, which triggered the formation of wurtzite arms on {111}-facets of the zincblende seeds. The formation of the wurtzite phase is responsible for the halide-mediated displacement of oleate ligands, destabilizing the embryonic CdSe phase on the zincblende seeds enabling the phase transformation to more stable wurtzite phase on the hexagonal {111}-facets. On the basis of these halide-mediated phase transformation of CdSe nanocrystals and the persistent kinetic growth induced by the CPI approach, well-defined CdSe tetrapods with control...

Esophageal dilation with integrated balloon imaging: initial evaluation in a porcine model

When treating achalasia, balloon dilation is often combined with fluoroscopy to allow the lower esophageal sphincter to be visualized as it is being dilated. We sought to evaluate a new balloon dilation technology, EsoFLIP, which allows the shape of the balloon to be visualized in a nonradiographic manner by using impedance planimetry electrodes located within the dilation balloon. Two pigs weighing 35 kg were used. The EsoFLIP balloon dilator was introduced under endoscopic visualization. Successive injections of 50, 60, 70 and 85 mL into the dilation balloon permitted dilations at increasing diameters to be achieved. Following each dilation fluid was withdrawn to leave 30 mL in the balloon and an EsoFLIP image was captured to track progressive dilation of the gastroesophageal junction (GEJ). The EsoFLIP catheter was safely deployed in the two pigs and no complications were noted. For pig 1, during dilation, the measured balloon diameter at the waist was 24.1, 28.9, 29.2 and 30.0 mm for balloon dilation volumes of 50, 60, 70 and 85 mL respectively. For pig 2 the corresponding diameter at the waist was 22.8, 27.1, 28.5 and 29.4 mm. The GEJ diameter increased from 12.5 and 12.4 mm to 17.4 and 17.5mm for pigs 1 and 2 respectively. Distensibility of the GEJ in pig 1 increased from 2.3 mm(2)/mmHg before to 4.4 mm(2)/mmHg after dilation and in pig 2 from 4.4 to 9.6 mm(2)/mmHg. The GEJ substantively achieved its final diameter after the dilation using just 50 mL in the balloon. We demonstrated technical feasibility and safety of the EsoFLIP dilator in a porcine model. Further studies in humans with achalasia remain to be conducted, which, besides demonstrating technical feasibility, should also evaluate the use of distensibility measurements taken during dilation to predict outcomes.

Synthesis and Structural, Optical, and Dynamic Properties of Core/Shell/Shell CdSe/ZnSe/ZnS Quantum Dots

We have synthesized core/shell/shell (CSS) CdSe/ZnSe/ZnS quantum dots (QDs) and investigated their exciton dynamics using time correlated single photon counting (TCSPC). The unique synthetic method combines hot injection with successive injection of precursors in one pot. Transmission electron microscopy (TEM) shows that CSS QDs were 6 ± 2 nm in diameter. The elemental composition, determined by energy dispersive X-ray spectroscopy, was 3.3% cadmium, 8.6% selenium, 42.3% sulfur, and 45.8% zinc by mole. Photoluminescence spectroscopy (PL) showed that the PL quantum yield is increased from 0.9% for CdSe to 25% for CSS. Global fitting was used for the analysis of exciton dynamics for CdSe, CdSe/ZnS core/shell, and CSS QDs. The decays of the PL spectra for CdSe and CdSe/ZnS were fit with triple exponentials with lifetimes of 0.7, 8, and 30 ns and 0.7, 10, and 30 ns respectively, while the CSS spectrum was fit with a double exponential with lifetimes of 12 and 30 ns. We attribute the 0.7 ns component to nonradiative recombination through dangling bonds at the CdSe surface or at crystal lattice dislocations at the CdSe/ZnS interface. This study clearly demonstrates that the CSS approach can be used to substantially improve the optical properties of QDs desired for various applications.

Validation and scale‐up of plasmid DNA purification by phenyl‐boronic acid chromatography

This study addresses the feasibility of scaling-up the removal of host cell impurities from plasmid DNA (pDNA)-containing Escherichia coli lysates by phenyl-boronic (PB) acid chromatography using columns packed with 7.6 and 15.2 cm(3) of controlled porous glass beads (CPG) derivatized with PB ligands. Equilibration was performed with water at 10 cm(3) /min and no conditioning of the lysate feed was required. At a ratio of lysate feed to adsorbent volume of 1.3, 93-96% of pDNA was recovered in the flow through while 66-71% of impurities remained bound (~2.5-fold purification). The entire sequence of loading, washing, elution, and re-equilibration was completed in 20 min. Run-to-run consistency was observed in terms of chromatogram features and performance (yield, purification factor, agarose electrophoresis) across the different amounts of adsorbent (0.75-15.2 cm(3) ) by performing successive injections of lysates prepared independently and containing 3.7 or 6.1 kbp plasmids. The column productivity at large scale was 4 dm(3) of alkaline lysate per hour per dm(3) of PB-CPG resin. The method is rapid, reproducible, simple, and straightforward to scale-up. Furthermore, it is capable of handling heavily contaminated samples, constituting a good alternative to purification techniques such as isopropanol precipitation, aqueous two-phase systems, and tangential flow filtration.

PHYSICOCHEMICAL CHARACTERISTICS OF SEMEN FROM BUFFALO BULLS (BUBALUS BUBALIS) AS AFFECTED BY TREATMENT OF TWO DIFFERENT DOSES OF RECOMBINANT BOVINE SOMATOTROPIN (rbST)

SUMMARY A total of 15 buffalo bulls were divided into three comparable experimental groups to study the effect of two different doses of recombinant bovine somatotropin (rbST) on physical and chemical characteristics of semen during the hot months of the year (April to September). The first group (G1) was left untreated and served as control, while the 2 nd (G2) and 3 rd (G3) groups were injected subcutaneously either with 250 or 500 mg Somatech ® /14 days/animal for eight successive injections, respectively. Bulls had an initial body weight around 350.9 kg and aged 16 to 18 months. Blood samples were collected fortnightly to determine testosterone and insulin like growth factor-I (IGF-I) in peripheral blood plasma, while semen was collected twice weekly to determine semen traits. Treated groups with rbST had higher (P 0.05), and sperm abnormalities were lower (P>0.05) in (G2) compared to (G1). IGF-I was higher (P<0.05) in rbST treated bulls (776 and 876 ng/ml, for G2 and G3, resp.) than that in G1 (594.7 ng/ml). Similar trend was observed for testosterone concentration being lower (P<0.05) in G1 (5.62 ng/ml) compared to G2 and G3 (8.08 and 9.78 ng/ ml, resp.). In conclusion, treated buffalo bulls with rbST either 500 mg or 250 mg /14 days/animal/ eight injections improved semen physical characteristics favorably to the 250 mg dose.

Immune modulating effects of malathion with the role of bradykinin potentiating factor in juvenile male rats

Background: The use of malathion as an insecticide, is accompanied by the appearance of many adverse effects. Objective: To verify the immunological characteristics of malathion and to determine whether Bradykinin Potentiating Factor (BPF) is able to counteract these effects, and to emphasize the affected pathophysiological mechanisms. Material and methods: Juvenile rats were divided into three groups: animals received a vehicle (control group), malathion (malathion group), or malathion then BPF (BPF group). Each group included three subgroups, which were sacrificed two days after two, four, and six weeks of malathion exposure respectively. BPF subgroups were exposed to malathion, then treated with single, double, and triple successive IP injections of BPF respectively. Results: The concentration of total globulin, total immunoglobulins, IgG, IgM, circulatory immune complexes, total number of RBC &amp; platelets, and hemoglobin concentrations decreased significantly in malathion-exposed animals. The number of total leucocytes and lymphocytes increased. Histopathological changes of bone marrow and spleen after malathion exposure were consistent with these findings. Recovery of bone marrow and splenic changes, normalization of peripheral blood elements, reduction of elevated proinflammatory markers (IL-2, IL-4 and TNF-α), total plasma peroxide and oxidative stress index (OSI) while increased total antioxidant capacity (TAC) were observed after double and triple injections of BPF. Our results suggest that exposure to malathion has negative effects on immune function that was mediated through alteration of cytokines, antioxidants and direct damage of BM. Also, BPF can ameliorate both physiological and morphological changes.

Multichannel Bipotentiostat Integrated With a Microfluidic Platform for Electrochemical Real-Time Monitoring of Cell Cultures

An electrochemical detection system specifically designed for multi-parameter real-time monitoring of stem cell culturing/differentiation in a microfluidic system is presented. It is composed of a very compact 24-channel electronic board, compatible with arrays of microelectrodes and coupled to a microfluidic cell culture system. A versatile data acquisition software enables performing amperometry, cyclic voltammetry and impedance spectroscopy in each of the 12 independent chambers over a 100 kHz bandwidth with current resolution down to 5 pA for 100 ms measuring time. The design of the platform, its realization and experimental characterization are reported, with emphasis on the analysis of impact of input capacitance (i.e., microelectrode size) and microfluidic pump operation on current noise. Programmable sequences of successive injections of analytes (ferricyanide and dopamine) and rinsing buffer solution as well as the impedimetric continuous tracking for seven days of the proliferation of a colony of PC12 cells are successfully demonstrated.

Microfluidic reflectometric interference spectroscopy-based sensing for exploration of protein–protein interaction conditions

A microfluidic reflectometric interference spectroscopy (RIfS) system was adopted for the investigation of protein–protein interaction (PPI). The influence of reaction conditions (pH and temperature) on the antigen–antibody reaction of alpha-fetoprotein (AFP) and its monoclonal antibody (anti-AFP) as a model of PPI was investigated in real time with a label-free fusion, where anti-AFP was covalently immobilized on the carboxylated silicon nitride sensor chips via amide bonds. Optimal pH and temperature were rapidly found by successive and alternate injections of AFP and the regeneration solution (glycine-HCl, pH 1.5) onto the anti-AFP immobilized sensor chip. The resultant optimized reaction conditions (30°C, pH 5.0) gave a 10 times higher detection limit, compared with the response under the commonly employed conditions (25°C, pH 7.4). The proposed system was revealed to provide rapid tracking response against the change in temperature and pH. Consequently, the proposed RIfS system has a potential for the effective tool towards PPI analyses.

Insonation of Targeted Microbubbles Produces Regions of Reduced Blood Flow Within Tumor Vasculature

In ultrasound molecular imaging, a sequence of high-pressure ultrasound pulses is frequently applied to destroy bound targeted microbubbles, to quantify accumulated microbubbles or to prepare for successive microbubble injections; however, the potential for biological effects from such a strategy has not been fully investigated. Here, we investigate the effect of high-pressure insonation of bound microbubbles and the potential for thrombogenic effects. A total of 114 mice carrying either Met-1 or neu deletion mutant (NDL) tumors was insonified (Siemens Sequoia system, 15L8 transducer, 5-MHz color-Doppler pulses, 4 or 2 MPa peak-negative pressure, 8.1-millisecond pulse repetition period, 6-cycle pulse length, and 900-millisecond insonation). Microbubbles conjugated with cyclic-arginine-glycine-aspartic acid (cRGD) or cyclic-aspartic-acid-glycine-tyrosine (3-NO)-glycine-hydroxyproline-asparagine (LXY-3) peptides or control (no peptide) microbubbles were injected, and contrast pulse sequencing was used to visualize the flowing and bound microbubbles. An anti-CD41 antibody was injected in a subset of animals to block potential thrombogenic effects. After the accumulation of targeted microbubbles and high-pressure (4 MPa) insonation, reduced blood flow, as demonstrated by a reduction in echoes from flowing microbubbles, was observed in 20 Met-1 mice (71%) and 4 NDL mice (40%). The area of low image intensity increased from 22 ± 13% to 63 ± 17% of the observed plane in the Met-1 model (P < 0.01) and from 16 ± 3% to 45 ± 24% in the NDL model (P < 0.05). Repeated microbubble destruction at 4 MPa increased the area of low image intensity to 76.7 ± 13.4% (P < 0.05). The fragmentation of bound microbubbles with a lower peak-negative pressure (2 MPa) reduced the occurrence of the blood flow alteration to 28% (5/18 Met-1 tumor mice). The persistence of the observed blood flow change was approximately 30 minutes after the microbubble destruction event. Dilated vessels and enhanced extravasation of 150 kDa fluorescein-isothiocyanate (FITC)-dextran were observed by histology and confocal microscopy. Preinjection of an anti-CD41 antibody blocked the reduction of tumor blood flow, where a reduction in blood flow was observed in only 1 of 26 animals. High-pressure fragmentation of microbubbles bound to tumor endothelial receptors reduced blood flow within 2 syngeneic mouse tumor models for ∼30 minutes. Platelet activation, likely resulting from the injury of small numbers of endothelial cells, was the apparent mechanism for the flow reduction.

Self-Focusing by Ostwald Ripening: A Strategy for Layer-by-Layer Epitaxial Growth on Upconverting Nanocrystals

We demonstrate a novel epitaxial layer-by-layer growth on upconverting NaYF(4) nanocrystals (NCs) utilizing Ostwald ripening dynamics tunable both in thickness and composition. Injection of small sacrificial NCs (SNCs) as shell precursors into larger core NCs results in the rapid dissolution of the SNCs and their deposition onto the larger core NCs to yield core-shell structured NCs. Exploiting this NC size dependent dissolution/growth, the shell thickness can be controlled either by manipulating the number of SNCs injected or by successive injection of SNCs. In either of these approaches, the NCs self-focus from an initial bimodal distribution to a unimodal distribution (σ <5%) of core-shell NCs. The successive injection approach facilitates layer-by-layer epitaxial growth without the need for tedious multiple reactions for generating tunable shell thickness, and does not require any control over the injection rate of the SNCs, as is the case for shell growth by precursor injection.

Néovascularisation choroïdienne sur un ostéome choroïdien : traitement par bévacizumab et suivi par OCT Spectral-Domain

Choroidal osteoma is a rare, ossifying tumor, which, while benign, may be complicated by choroidal neovascularization. An 11-year-old boy presented with blurred vision in the right eye for few days. Fundus examination showed bulky lesion in the posterior pole containing a sub-retinal hemorrhage. The geographic borders and color of the mass were typical of choroidal osteoma despite the unusual macular location. The diagnosis was confirmed by ultrasonography. The patient was treated with three successive intravitreal injections of 1.25 mg/0.05 mL bevacizumab (IVB) under general anesthesia, due to recurrences of neovascular activity. SD-OCT in EDI mode was carried out prior to each injection. SD-OCT before and after each bevacizumab injection confirmed regression of serous retinal detachment (SRD) at various locations throughout the lesion, especially in the hemorrhagic zone. It also allowed us to differentiate the active decalcified zones from the inactive calcified zones and to follow treatment response. The treatment of choroidal neovascularization (CNV) secondary to choroidal osteoma is not well defined. As for other etiologies of CNV, anti-VEGF agents (such as bevacizumab) appear to be effective in regressing CNV and improving visual function. In our young patient, general anesthesia was necessary to administer each injection. SD-OCT allows diagnostic confirmation and follow-up of treatment. EDI mode is helpful in studying the choroid and the osteoma. We report a rare case of macular choroidal osteoma, examined by SD-OCT. CNV required several anti-VEGF injections, with good anatomical and functional results.

Chemo- and enantio-selective method for the analysis of amino acids by capillary electrophoresis with in-capillary derivatization

A novel dual chiral CE method was developed for the separation of l- and d-amino acids (AAs), using in-capillary derivatization with 9-fluoroenylmethyl chloroformate (FMOC). Firstly, using pre-column derivatization, the enantioseparation of FMOC–AAs was optimized according to the nature of cyclodextrins (CD). A background electrolyte (BGE) composed of 30mM β-CD, 30mM octakis(2,3-dihydroxy-6-O-sulfo)-γ-CD (OS-γ-CD), 40mM tetraborate and 15% isopropanol (IPA) was selected and led to 17 baseline resolved pairs (Rs=1.7–5.8) and two partially resolved pairs (Lys, Rs=0.5 and Arg, Rs=1.2). Experimental conditions for in-capillary derivatization were then optimized. Several parameters, such as mixing voltage and time, concentration of labeling solution and the length of the spacer plug were studied. The optimal conditions for in-capillary derivatization procedure were obtained using successive hydrodynamic injections (30mbar) of AAs for 2s, borate buffer for 4s and 10mM FMOC solution for 6s, followed by a mixing at 3kV for 72s and wait time of 1min. Moreover, a particular attention was paid to improve separation chemoselectivity. The effect on stereoselectivity and chemoselectivity of different factors, such as decrease of pH and tetraborate concentration and the addition of sodium dodecyl sulfate (SDS), was investigated using the in-capillary derivatization procedure. The best separation of a standard mixture of ten AA racemates was observed using a BGE containing 30mM β-CD, 30mM OS-γ-CD, 25mM SDS, 40mM sodium tetraborate and 17% IPA.

Direct determination of δ(D) and δ(18O) in water samples using cavity ring down spectrometry: Application to bottled mineral water

The repeatability, reproducibility and accuracy of the direct measurement of δ(D) and δ(18O) isotopes in water samples were evaluated using Cavity Ring-Down Spectrometry, and values comparable with the Isotopic Ratio Mass Spectrometry were obtained. Memory effect correction was negligible after five successive injections, and the time for each sample analysis was approximately 70minutes. Application of the method to Brazilian bottled mineral water has shown that it is possible to trace the origin of the water to at least the state level within Brazilian geographical regions. National and regional meteoric water lines were constructed with substantial differences between geographical regions, in particular for the central region of the country, with a slope coefficient of approximately seven and no deuterium excess.

The 1963–1964 eruption of Agung volcano (Bali, Indonesia)

The February 1963 to January 1964 eruption of Gunung Agung, Indonesia’s largest and most devastating eruption of the twentieth century, was a multi-phase explosive and effusive event that produced both basaltic andesite tephra and andesite lava. A rather unusual eruption sequence with an early lava flow followed by two explosive phases, and the presence of two related but distinctly different magma types, is best explained by successive magma injections and mixing in the conduit or high level magma chamber. The 7.5-km-long blocky-surfaced andesite lava flow of ∼0.1 km3 volume was emplaced in the first 26 days of activity beginning on 19 February. On 17 March 1963, a major moderate intensity (∼4 × 107 kg s−1) explosive phase occurred with an ∼3.5-h-long climax. This phase produced an eruption column estimated to have reached heights of 19 to 26 km above sea level and deposited a scoria lapilli to fine ash fall unit up to ∼0.2 km3 (dense rock equivalent—DRE) in volume, with Plinian dispersal characteristics, and small but devastating scoria-and-ash flow deposits. On 16 May, a second intense 4-h-long explosive phase (2.3 × 107 kg s−1) occurred that produced an ∼20-km-high eruption column and deposited up to ∼0.1 km3 (DRE) volume of similar ash fall and pyroclastic flow deposits, the latter of which were more widespread than in the March phase. The two magma types, porphyritic basaltic andesite and andesite, are found as distinct juvenile scoria populations. This indicates magma mixing prior to the onset of the 1963 eruption, and successive injections of the more mafic magma may have modulated the pulsatory style of the eruption sequence. Even though a total of only ∼0.4 km3 (DRE volume) of lava, scoria and ash fall, and scoria-and-ash pyroclastic flow deposits were produced by the 1963 eruption, there was considerable local damage caused mainly by a combination of pyroclastic flows and lahars that formed from the flow deposits in the saturated drainages around Agung. Minor explosive activity and lahar generation by rainfall persisted into early 1964. The climactic events of 17 March and 16 May 1963 managed to inject ash and sulfur-rich gases into the tropical stratosphere.