Uptake of methanol on mixed HNO3/H2O clusters: An absolute pickup cross section.

The uptake of atmospheric oxidized organics on acid clusters is relevant for atmospheric new particle formation. We investigate the pickup of methanol (CH3OH) on mixed nitric acid-water clusters (HNO3)M(H2O)N by a combination of mass spectrometry and cluster velocity measurements in a molecular beam. The mass spectra of the mixed clusters exhibit (HNO3)m(H2O)nH+ series with m = 0-3 and n = 0-12. In addition, CH3OH·(HNO3)m(H2O)nH+ series with very similar patterns appear in the spectra after the methanol pickup. The velocity measurements prove that the undoped (HNO3)m(H2O)nH+ mass peaks in the pickup spectra originate from the neutral (HNO3)M(H2O)N clusters which have not picked up any CH3OH molecule, i.e., methanol has not evaporated upon the ionization. Thus the fraction of the doped clusters can be determined and the mean pickup cross section can be estimated, yielding σs¯≈ 20 Å2. This is compared to the lower estimate of the mean geometrical cross section σg¯≈ 60 Å2 obtained from the theoretical cluster geometries. Thus the "size" of the cluster corresponding to the methanol pickup is at least 3-times smaller than its geometrical size. We have introduced a method which can yield the absolute pickup cross sections relevant to the generation and growth of atmospheric aerosols, as illustrated in the example of methanol and nitric acid clusters.

Imaging of hydrogen halides photochemistry on argon and ice nanoparticles.

The photodissociation dynamics of HX (X = Cl, Br) molecules deposited on large ArN and (H2O)N, N̄ ≈ 10(2)-10(3), clusters is investigated at 193 nm using velocity map imaging of H and Cl photofragments. In addition, time-of-flight mass spectrometry after electron ionization complemented by pickup cross section measurements provide information about the composition and structure of the clusters. The hydrogen halides coagulate efficiently to generate smaller (HX)n clusters on ArN upon multiple pickup conditions. This implies a high mobility of HX molecules on argon. On the other hand, the molecules remain isolated on (H2O)N. The photodissociation on ArN leads to strong H-fragment caging manifested by the fragment intensity peaking sharply at zero kinetic energy. Some of the Cl-fragments from HCl photodissociation on ArN are also caged, while some of the fragments escape the cluster directly without losing their kinetic energy. The images of H-fragments from HX on (H2O)N also exhibit a strong central intensity, however, with a different kinetic energy distribution which originates from different processes: the HX acidic dissociation followed by H3O neutral hydronium radical formation after the UV excitation, and the slow H-fragments stem from subsequent decay of the H3O. The corresponding Cl-cofragment from the photoexcitation of the HCl·(H2O)N is trapped in the ice nanoparticle.

Irregular shapes of water clusters generated in supersonic expansions.

We report cross sections for pickup of guest molecules on neutral argon and water clusters with the mean sizes in the range from N = 50 to 600. The experiments are supported by molecular dynamics simulations and analytical models based on the interaction potentials. The cross sections for argon clusters are consistent with their assumed spherical shape and follow approximately the theoretically justified N(1/3) dependence. On the other hand, the cross sections of water clusters depart from this dependence and are considerably larger starting from N ≥ 300. We interpret this increase of cross section by the occurrence of highly irregular shapes of water clusters produced in the supersonic expansion of water vapor under the conditions of the large cluster generation.

Energy and charge transfer in ionized argon coated water clusters.

We investigate the electron ionization of clusters generated in mixed Ar-water expansions. The electron energy dependent ion yields reveal the neutral cluster composition and structure: water clusters fully covered with the Ar solvation shell are formed under certain expansion conditions. The argon atoms shield the embedded (H2O)n clusters resulting in the ionization threshold above ≈15 eV for all fragments. The argon atoms also mediate more complex reactions in the clusters: e.g., the charge transfer between Ar(+) and water occurs above the threshold; at higher electron energies above ~28 eV, an excitonic transfer process between Ar(+)* and water opens leading to new products Ar(n)H(+) and (H2O)(n)H(+). On the other hand, the excitonic transfer from the neutral Ar* state at lower energies is not observed although this resonant process was demonstrated previously in a photoionization experiment. Doubly charged fragments (H2O)(n)H2(2+) and (H2O)(n)(2+) ions are observed and Intermolecular Coulomb decay (ICD) processes are invoked to explain their thresholds. The Coulomb explosion of the doubly charged cluster formed within the ICD process is prevented by the stabilization effect of the argon solvent.

Ionization of large homogeneous and heterogeneous clusters generated in acetylene-Ar expansions: cluster ion polymerization.

Pure acetylene and mixed Ar-acetylene clusters are formed in supersonic expansions of acetylene/argon mixtures and analysed using reflectron time-of-flight mass spectrometer with variable electron energy ionization source. Acetylene clusters composed of more than a hundred acetylene molecules are generated at the acetylene concentration of ≈8%, while mixed species are produced at low concentrations (≈0.7%). The electron energy dependence of the mass spectra revealed the ionization process mechanisms in clusters. The ionization above the threshold for acetylene molecule of 11.5 eV results in the main ionic fragment progression (C2H2)n(+). At the electron energies ≥21.5 eV above the CH+CH(+) dissociative ionization limit of acetylene the fragment ions nominally labelled as (C2H2)nCH(+), n ≥ 2, are observed. For n ≤ 7 these fragments correspond to covalently bound ionic structures as suggested by the observed strong dehydrogenation [(C2H2)n - k × H](+) and [(C2H2)nCH - k × H](+). The dehydrogenation is significantly reduced in the mixed clusters where evaporation of Ar instead of hydrogen can stabilize the nascent molecular ion. The C3H3(+) ion was previously assigned to originate from the benzene molecular ion; however, the low appearance energy of ≈13.7 eV indicates that a less rigid covalently bound structure of C6H6(+) ion must also be formed upon the acetylene cluster electron ionization. The appearance energy of Arn(C2H2)(+) fragments above ≈15.1 eV indicates that the argon ionization is the first step in the fragment ion production, and the appearance energy of Arn≥2(C2H2)m≥2(+) at ≈13.7 eV is discussed in terms of an exciton transfer mechanism.

Uptake of atmospheric molecules by ice nanoparticles: pickup cross sections.

Uptake of several atmospheric molecules on free ice nanoparticles was investigated. Typical examples were chosen: water, methane, NO(x) species (NO, NO(2)), hydrogen halides (HCl, HBr), and volatile organic compounds (CH(3)OH, CH(3)CH(2)OH). The cross sections for pickup of these molecules on ice nanoparticles (H(2)O)(N) with the mean size of N≈260 (diameter ~2.3 nm) were measured in a molecular beam experiment. These cross sections were determined from the cluster beam velocity decrease due to the momentum transfer during the pickup process. For water molecules molecular dynamics simulations were performed to learn the details of the pickup process. The experimental results for water are in good agreement with the simulations. The pickup cross sections of ice particles of several nanometers in diameter can be more than 3 times larger than the geometrical cross sections of these particles. This can have significant consequences in modelling of atmospheric ice nanoparticles, e.g., their growth.

Laparoscopic resection for recurrent Crohn's disease: safety, feasibility and short-term outcomes.

AIM: The safety, feasibility and short-term outcomes of laparoscopic resection were assessed in patients with recurrent ileocolic Crohn's disease. METHOD: A consecutive series of patients was identified from a prospectively collated database. Data included patient demographics, previous medical and surgical treatment, operative details and postoperative course. Data from the original index open operation were collected retrospectively by review of the case notes. RESULTS: Between 2005 and 2009, 27 patients [21 women, mean (range) age 31 years (16-51 years)] underwent laparoscopic resection for recurrent ileocolic Crohn's disease. All had histologically confirmed recurrent disease at the ileocolic anastomosis. Five (18.5%) patients required extended resection for Crohn's colitis, three (11.1%) had fistulating disease and one (3.4%) patient had a psoas abscess. The median (range) operative time was 110 min (70-170 min) with a conversion rate of two (7.4%) of 27 patients. The length of stay was 4 days (2-7 days) with time to return to work or full activity of 3.5 weeks (2-7 weeks). CONCLUSION: Laparoscopic resection of recurrent ileocolic Crohn's disease is safe, feasible and associated with short-term benefits.

Trends towards increased use of the laparoscopic approach in colorectal surgery.

AIM: The aim of the study was to identify the trend towards laparoscopic resection in the practice of one surgeon and to determine whether the default approach to all colorectal procedures could be by means of minimally invasive techniques with an associated low rate of conversion. METHOD: A prospective database of primary colorectal resections under the care of one colorectal surgeon collected between July 2003 and December 2008 was analysed to determine the trend in the use of the laparoscopic approach and the rate of conversion of an intention-to-treat policy for laparoscopic procedures. Patients with recurrent rectal or colonic malignancy were excluded from the study. RESULTS: A total of 598 patients underwent elective colorectal resection of which 371 (62%) were carried out laparoscopically with a rate of conversion of 3.2%. The proportion of all colorectal resections that were undertaken laparoscopically in the first 1 year was 26% (22/85) (no conversions). This proportion rose to 100% (127/127) in the fifth year of the study of which 4.0% were converted. The introduction of more complex procedures did not have an adverse effect on the trend towards more laparoscopic resections The commencement of a laparoscopic colorectal fellowship in 2006 was associated with a marked increase in the number of laparoscopic cases. CONCLUSION: A conscious decision to make the laparoscopic approach the default for all colorectal resections can be achieved safely with a low conversion rate. This can be achieved within the context of training a 'novice' laparoscopic colorectal surgeon.

Multimedia article. Laparoscopic abdominosacral composite resection.

Primary rectal cancer with direct invasion into the sacrum requires en bloc resection that encompasses both the rectum and the sacrum. Application of laparoscopic techniques to the abdominal component should potentially provide the patient with the short-term benefits of a minimally invasive approach and permit adequate mobilization to permit completion of the procedure via the transsacral route. The aim of this video was to describe the operative details of such a technique.

Laparoscopic management of an obstructed obturator hernia: should laparoscopic assessment be the default option?

An obturator hernia is a rare diagnosis that is frequently missed. Patients present with few clinical signs to identify the cause, apart from symptoms of intestinal obstruction. Therefore, obturator hernias are often diagnosed at exploratory laparotomy. The use of computed tomography (CT) has increased the chance of definitive preoperative diagnosis. However, despite these advances, patients who present acutely will frequently undergo an open procedure rather than laparoscopy. We present a case of an acute obstructed obturator hernia diagnosed in a 62-year-old female that was successfully managed laparoscopically.

Pharmacokinetic studies of (-)-deprenyl and some of its metabolites in mouse.

(-)-Deprenyl is a selective irreversible inhibitor of MAO-B. The parent compound is responsible for the enzyme inhibitory effect, but its metabolites are also playing a role in the complex pharmacological activity of the substance. In the present studies male NMRI mice were treated orally, subcutaneously, intraperitoneally and intravenously with 5 mg/kg of (-)-deprenyl. The time related changes of the plasma concentrations of the parent compound and its main metabolites (methamphetamine, desmethyl-deprenyl and amphetamine) were determined by GC/ MSD technique. The main pharmacokinetic parameters (C(max), t(max), t1/2beta, AUC(0-6), AUC(0-infinity)) have been calculated. (-)-Deprenyl is well absorbed after oral and parental treatment. The peak concentrations (C(max)) were reached at 15 min after treatment and the absorption was followed by a fast elimination (t1/2beta < or = 2h). (-)-Deprenyl has an intensive "first pass" metabolism after oral treatment; only 25% of the parent compound reaches the systemic circulation. Increased bioavailability was detected after subcutaneous (87.1%) and intraperitoneal (78.7%) administration. The main metabolic pathway of (-)-deprenyl is the N-depropargylation, leading to the formation of methamphetamine. N-demethylation of (-)-deprenyl leads to formation of desmethyl-deprenyl. Amphetamine is produced from both former metabolites. After oral treatment the plasma concentrations of methamphetamine are higher during the first 6 h than that of (-)-deprenyl, while the opposite was found after parental treatment. The results indicate, that (-)-deprenyl, a potent MAO-B inhibitor, might induce a different spectrum of activity (e.g. antidepressant), when it is administered parenterally (transdermally). The new spectrum can be due to the special pharmacokinetic behaviour of the inhibitor.

Detection of Nepsilon-monomethyllysine using high-performance liquid chromatography and high-performance liquid chromatography-mass spectrometry.

Nepsilon-Monomethyllysine was identified in the serum, urine, brain, and liver samples of rats treated per os with L-deprenyl. The identification procedure included reaction with Fmoc chloride, clean-up, and analysis using HPLC-UV-MS. Oral administration of (-)-N-14C-methyl-N-propynyl(2-phenyl-1-methyl)ethylammonium hydrochloride L-deprenyl) to rats resulted in transfer of the radiolabelled methyl group to the Nepsilon-amino group of the endogenous lysine. The radiolabelled Nepsilon-monomethyllysine was urinary eliminated together with the other radiolabelled deprenyl metabolites, such as deprenyl-N-oxide and methamphetamine. The presence of Nepsilon-monomethyllysine has also been traced, and its concentrations were compared in the serum, liver and brain of rats subjected to L-deprenyl treatment. Methyl group transfer from the L-deprenyl to endogenous compounds; and the urinary elimination of their products may offer a vital way to eliminate or to decrease the degree of drug transmethylation to the lysine constituents of blood vessels' proteins.

HPLC and HPLC-MS analysis of urinary N(epsilon)-monomethyl-lysine.

Administration of (14)C-labelled L-deprenyl to rats results in the urinary elimination of a 14C-labelled compound. The 9-fluorenylmethoxycarbonyl chloride-reacted urine sample is fractionated by high-performance liquid chromatography (HPLC) on an octadecyl silica stationary phase. N(epsilon)-Monomethyl-lysine is identified in the fraction containing the majority of the radioactivity. Structural elucidation is carried out using HPLC-mass spectrometry in atmospheric pressure chemical ionization mode. Identification of the 14C-labelled fragment in Ne-monomethyl-lysine is an experimental proof that an N-methylated amino acid is generated by transmethylation from a well-known drug. This type of transmethylation may have basic importance in the positive side effects of certain drugs.

Combined image guidance excision of non-palpable breast lesions.

When mammogramography detects a non-palpable lesion the surgeons may be called upon to establish a diagnosis. Various techniques are currently employed. We describe a technique, which can be used both for diagnostic and for therapeutic procedures. The technique essentially involves localising the tip of a guide-wire, placed under mammographic guidance, with ultrasound scanning. This minimises many of the problems encountered with wire guided excision. We conducted a prospective non-randomised study using our combined image guidance technique (CIG) for patients undergoing diagnostic (n = 24) and therapeutic biopsy (n = 13). We found that significantly smaller diagnostic biopsy weights were achievable using CIG, compared to non-CIG techniques. Reduced biopsy weights are recommended by current guidelines.

HPLC analysis of metabolically produced formaldehyde.

Radiolabelled (-)-deprenyl is orally administered to rats, and urinary elimination of radiolabelled formaldehyde is detected. The separation is performed using high-performance liquid chromatography on octadecyl-silica stationary phase. Both the radioactivity and the UV absorbance of the dinitrophenylhydrazine formaldehyde peak are determined. Formaldehyde generation takes place by N-demethylation. Low levels of formaldehyde may have a beneficial role in counterbalancing the oxidative stress of the everyday person's life.

drumstick, bowl, and lines are required for patterning and cell rearrangement in the Drosophila embryonic hindgut.

The Drosophila embryonic hindgut is a robust system for the study of patterning and morphogenesis of epithelial organs. We show that, in a period of about 10 h, and in the absence of significant cell division or apoptosis, the hindgut epithelium undergoes morphogenesis by changes in cell shape and size and by cell rearrangement. The epithelium concomitantly becomes surrounded by visceral mesoderm and is characterized by distinct gene expression patterns that forecast the development of three morphological subdomains: small intestine, large intestine, and rectum. At least three genes encoding putative transcriptional regulators, drumstick (drm), bowl, and lines (lin), are required to establish normal hindgut morphology. We show that the defect in hindgut elongation in drm, bowl, and lin mutants is due, in large part, to the requirement of these genes in the process of cell rearrangement. Further, we show that drm, bowl, and lin are required for patterning of the hindgut, i.e., for correct expression in the prospective small intestine, large intestine, and rectum of genes encoding cell signals (wingless, hedgehog, unpaired, Serrate, dpp) and transcription factors (engrailed, dead ringer). The close association of both cell rearrangement and patterning defects in all three mutants suggest that proper patterning of the hindgut into small intestine and large intestine is likely required for its correct morphogenesis.

Drosophila arc encodes a novel adherens junction-associated PDZ domain protein required for wing and eye development.

Loss of arc function results in a downwardly curved wing and smaller eyes with a reduced number of ommatidia. Consistent with this phenotype, molecular analysis shows that arc mRNA and protein are expressed in the wing imaginal disc and in clusters of cells in the morphogenetic furrow of the eye imaginal disc. The 36-kb arc transcription unit contains 10 exons that are spliced to form a 5. 5-kb mRNA. The encoded Arc protein is 143,000 Da and contains two PDZ (PSD-95, Discs large, ZO-1) domains; there is no close structural similarity to other PDZ proteins. In addition to its expression in imaginal discs, arc is expressed during embryogenesis in epithelia undergoing morphogenesis, including the invaginating posterior midgut, evaginating Malpighian tubule buds, elongating hindgut, invaginating salivary glands, intersegmental grooves, and developing tracheae. Arc protein colocalizes with Armadillo (beta-catenin) to the apical (luminal) surface of these developing epithelia, indicating that it is associated with adherens junctions. Genes that are required for patterning of embryonic epithelia (e.g., tailless, Krüppel, fork head, and brachyenteron) or for progression of the morphogenetic furrow (i. e., hedgehog) are required to establish or maintain the regional expression of arc. Misexpression of arc in the eye imaginal discs results in rough and larger eyes with fused ommatidia. We propose that arc affects eye development by modulating adherens junctions of the developing ommatidium.

The control of cell fate in the embryonic visual system by atonal, tailless and EGFR signaling.

We describe here the role of the transcription factors encoding genes tailless (tll), atonal (ato), sine oculis (so), eyeless (ey) and eyes absent (eya), and EGFR signaling in establishing the Drosophila embryonic visual system. The embryonic visual system consists of the optic lobe primordium, which, during later larval life, develops into the prominent optic lobe neuropiles, and the larval photoreceptor (Bolwig's organ). Both structures derive from a neurectodermal placode in the embryonic head. Expression of tll is normally confined to the optic lobe primordium, whereas ato appears in a subset of Bolwig's organ cells that we call Bolwig's organ founders. Phenotypic analysis, using specific markers for Bolwig's organ and the optic lobe, of tll loss- and gain-of-function mutant embryos reveals that tll functions to drive cells to optic lobe as opposed to Bolwig's organ fate. Similar experiments indicate that ato has the opposite effect, namely driving cells to a Bolwig's organ fate. Since we can show that tll and ato do not regulate each other, we propose a model wherein tll expression restricts the ability of cells to respond to signaling arising from ato-expressing Bolwig's organ pioneers. Our data further suggest that the Bolwig's organ founder cells produce Spitz (the Drosophila TGFalpha homolog) signal, which is passed to the neighboring secondary Bolwig's organ cells where it activates the EGFR signaling cascade and maintains the fate of these secondary cells. The regulators of tll expression in the embryonic visual system remain elusive, as we were unable to find evidence for regulation by the 'early eye genes' so, eya and ey, or by EGFR signaling.

Identification of genes controlling malpighian tubule and other epithelial morphogenesis in Drosophila melanogaster.

The Drosophila Malpighian tubule is a model system for studying genetic mechanisms that control epithelial morphogenesis. From a screen of 1800 second chromosome lethal lines, by observing uric acid deposits in unfixed inviable embryos, we identified five previously described genes (barr, fas, flb, raw, and thr) and one novel gene, walrus (wal), that affect Malpighian tubule morphogenesis. Phenotypic analysis of these mutant embryos allows us to place these genes, along with other previously described genes, into a genetic pathway that controls Malpighian tubule development. Specifically, wal affects evagination of the Malpighian tubule buds, fas and thr affect bud extension, and barr, flb, raw, and thr affect tubule elongation. In addition, these genes were found to have different effects on development of other epithelial structures, such as foregut and hindgut morphogenesis. Finally, from the same screen, we identified a second novel gene, drumstick, that affects only foregut and hindgut morphogenesis.

Pharmacokinetics of deramciclane in rabbits.

The pharmacokinetics of deramciclane (CAS 120444-78-8, EGIS-3886) was investigated in rabbits after i.v., p.o. and s.c. administration of 3 mg/kg 14C-phenyl-deramciclane. The plasma, concentration-time curves of total radioactivity, the parent compound (deramciclane) and its N-demethylated metabolite (EGIS-7056) were determined. The radioactivity level was measured by liquid scintillation technique while the concentration of the parent compound and its metabolite was determined by gas chromatography-mass spectrometry detection. The p.o. and i.v. studies were carried out on the same group of animals, while a separate group of rabbits was used for studying s.c. absorption. Deramciclane was readily absorbed after p.o. and s.c. treatment (tmax 1.0 to 1.4 h). The terminal elimination half-life (t1/2 beta) of the parent compound fell between 5.8 to 7.1 h, while that of the total radioactivity ranged from 21.6 and 26.0 h. The absolute bioavailability of deramciclane calculated from the AUC0-infinity values was found to be 43 and 60% after p.o. and s.c. treatment. The apparent volume of distribution (Vd) and the whole body clearance (Cl) of deramciclane after i.v. administration were 25.0 +/- 7.1 l/kg and 2.6 +/- 0.5 l/h/kg, respectively. The AUC0-infinity values of the parent compound varied between 4.6 and 7.9% of that of total radioactivity, suggesting that deramciclane was subjected to intensive metabolic conversion. The AUC0-infinity of N-desmethyl-deramciclane was 5.7%, compared to that of the parent compound after i.v. administration.