UV photofragmentation and IR spectroscopy of cold, G-type ß-O-4 and ß-ß dilignol-alkali metal complexes: structure and linkage-dependent photofragmentation.

Ultraviolet photofragmentation spectroscopy and infrared spectroscopy were performed on two prototypical guaiacyl (G)-type dilignols containing ß-O-4 and ß-ß linkages, complexed with either lithium or sodium cations. The complexes were generated by nanoelectrospray ionization, introduced into a multistage mass spectrometer, and subsequently cooled in a 22-pole cold ion trap to T ≈ 10 K. A combination of UV photofragment spectroscopy and IR-UV double resonance spectroscopy was used to characterize the preferred mode of binding of the alkali metal cations and the structural changes so induced. Based on a combination of spectral evidence provided by the UV and IR spectra, the Li(+) and Na(+) cations are deduced to preferably bind to both dilignols via their linkages, which constitute unique, oxygen-rich binding pockets for the cations. The UV spectra reflect this binding motif in their extensive Franck-Condon activity involving low-frequency puckering motions of the linkages in response to electronic excitation. In the pinoresinol•Li(+)/Na(+) complexes involving the ß-ß linkage, the spectra also showed an inherent spectral broadening. The photofragment mass spectra are unique for each dilignol•Li(+)/Na(+) complex, many of which are also complementary to those produced by collision-induced dissociation (CID), indicating the presence of unique excited state processes that direct the fragmentation. These results suggest the potential for site-selective fragmentation and for uncovering fragmentation pathways only accessed by resonant UV excitation of cold lignin ions.

Preoperative ultrasonography for tumor thickness evaluation in guiding management in patients with early oral tongue squamous cell carcinoma.

OBJECTIVES: (1) To assess the statistical correlation between the tumor thickness (TT) by ultrasonography (USG) and microscopic measurement in cases of early oral tongue squamous cell carcinoma (OTSCC). (2) To assess the predictive capacity of TT by ultrasound in detecting nodal metastasis. MATERIALS AND METHODS: Prospective analysis was performed in 24 patients for a period of 2 years from 2012 to 2013. Nodal status and TT measurement was done preoperatively by neck and intraoral USG respectively in cases of early (pT1 & T2, clinically N0) OTSCC. As per the institution protocol after histopathological confirmation of malignancy, all patients underwent resection of primary lesion and ipsilateral elective neck dissection (Level - I to IV). Measurement of TT was obtained intraoperatively from fresh glossectomy specimen and postoperatively from histopathological paraffin section examination. The statistical correlation between TT measured by USG and histopathology was assessed by Pearson's correlation coefficient. Chi-square test was used to find the association of pathological T stage, TT with pathological nodal status. RESULTS: Significant statistical correlation was seen between TT by USG and microscopic measures. Between the two, TT measurements were within 1 mm in 37.5% (9/24) of cases, within 2 mm in 29.16% (7/24), and was greater than 2 mm in 8 cases. The Pearson's correlation r is 0.678 (P < 0.001) and ICC (interclass correlation coefficient) is 0.808. The average difference between microscopic and US thickness (Bias) is -0.14637 and the limits of agreement is (4.717, -4.863) with 95% limits of agreement. The rate of occult nodal metastasis was 16.6% and TT of <4 mm had no incidence of nodal metastasis. CONCLUSION: Ultrasonographic evaluation is reliable and cost-effective tool to measure the TT preoperatively, which will be of help in deciding the management in early OTSCC. TT of 4 mm and above was predictor of occult cervical nodal metastasis.

Role of dual time fluorodeoxyglucose (FDG) positron emission tomography-computed tomography in identifying co-existing inflammatory and malignant disease: Who holds it (FDG) longer?

18-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is an integral part of imaging in the follow-up of head and neck malignancies. Very often distinguishing inflammatory/infective from malignant recurrence cannot be made confidently with standard uptake value (SUV) alone, as inflammatory lesions have shown to have a very high SUV, and in some cases both can co-exist. In such doubtful cases, dual time PET-CT (3-5 h delayed) is of paramount importance in confidently differentiating inflammatory/infective from a malignant cause.

Effect of a chiral 4-alkyl substituent in hallucinogenic amphetamines.

The potency of hallucinogenic amphetamine derivatives of the 1-(2,5-dimethoxy-4-alkylphenyl)-2-aminopropane type drops dramatically when the length of the 4-alkyl substituent exceeds propyl or when the substituent is branched. This investigation was directed toward evaluating changes in behavioral and biochemical pharmacology resulting from introducing chirality into the 4-alkyl group of such analogues. Two diastereoisomeric derivatives of this class containing a 4-(R or S)-2-butyl substituent, 11a,b, respectively, were studied. A slight but nonsignificant potency difference in d-lysergic acid diethylamide tartrate (LSD)-like discriminative stimulus properties and equal affinity for [125I]-(R)-(2,5-dimethoxy-4-iodophenyl) isopropylamine-labeled serotonin 5-HT2A/C radioligand-binding sites were observed. Thus, the portion of the receptor that interacts with the 4-alkyl substituent on hallucinogenic amphetamines does not present a highly asymmetric environment to the ligand. However, since both test drugs had higher binding affinity but lower LSD-like behavioral potency than the prototype compound with a 4-methyl group ((2,5-dimethoxy-4-methylphenyl)isopropylamine, 2), 11a,b may differ in their receptor agonist efficacy from more behaviorally active compounds such as 2.

An exceptional hydroboration of substituted fluoroolefins providing tertiary alcohols.

[reaction--see text] A rare hydroboration-oxidation providing tertiary-alcohols has been achieved in the case of 1,1,2-perfluoroalkyl(aryl)ethylenes. The hydroboration of substituted perfluoroalkyl(aryl)ethylenes with dichloroborane reveals that the regioselectivity does not entirely depend on the electronics of the fluoroolefins.

Efficient intramolecular asymmetric reductions of alpha-, beta-, and gamma-keto acids with diisopinocampheylborane.

[figure: see text] alpha-, beta-, and gamma-Keto acids are reduced with diisopinocampheylborane at room temperature to the corresponding hydroxy acids with predictable stereochemistry in very high ee. The gamma-hydroxy acids produced were conveniently cyclized to the corresponding lactones. This provides a simple synthesis of 4-hexanolide, a component of the pheromone secreted by the female dermestid beetle Trogoderma glabrum.

Asymmetric synthesis of umuravumbolide.

[figure: see text] This first asymmetric synthesis of enantiopure desacetylumuravumbolide and umuravumbolide via asymmetric reduction, allylboration, and ring-closing metathesis confirms their revised structures and configurations. A convenient procedure to upgrade the enantiopurity of alpha,beta-acetylenic alcohols is also described.

Prevention of posttraumatic axon sprouting by blocking collapsin response mediator protein 2-mediated neurite outgrowth and tubulin polymerization.

Epileptogenesis following traumatic brain injury (TBI) is likely due to a combination of increased excitability, disinhibition, and increased excitatory connectivity via aberrant axon sprouting. Targeting these pathways could be beneficial in the prevention and treatment of posttraumatic epilepsy. Here, we tested this possibility using the novel anticonvulsant (R)-N-benzyl 2-acetamido-3-methoxypropionamide ((R)-lacosamide [LCM]), which acts on both voltage-gated sodium channels and collapsin response mediator protein 2 (CRMP2), an axonal growth/guidance protein. LCM inhibited CRMP2-mediated neurite outgrowth, an effect phenocopied by CRMP2 knockdown. Mutation of LCM-binding sites in CRMP2 reduced the neurite inhibitory effect of LCM by ∼8-fold. LCM also reduced CRMP2-mediated tubulin polymerization. Thus, LCM selectively impairs CRMP2-mediated microtubule polymerization, which underlies its neurite outgrowth and branching. To determine whether LCM inhibits axon sprouting in vivo, LCM was injected into rats subjected to partial cortical isolation, an animal model of posttraumatic epileptogenesis that exhibits axon sprouting in cortical pyramidal neurons. Two weeks following injury, excitatory synaptic connectivity of cortical layer V pyramidal neurons was mapped using patch clamp recordings and laser scanning photostimulation of caged glutamate. In comparison with injured control animals, there was a significant decrease in the map size of excitatory synaptic connectivity in LCM-treated rats, suggesting that LCM treatment prevented enhanced excitatory synaptic connectivity due to posttraumatic axon sprouting. These findings suggest, for the first time, that LCM's mode of action involves interactions with CRMP2 to inhibit posttraumatic axon sprouting.

A facile synthesis of perfluoroalkyl vinyl iodides and their palladium-mediated cross-coupling reactions.

Catalytic amounts of zinc, as low as 10 mol %, in the presence of trifluoroacetic acid (TFA) initiate the radical addition of perfluoroalkyl iodides to terminal alkynes with high regio- and stereoselectivities. Palladium-mediated cross-coupling of these (E)-perfluoroalkyl vinyl iodides allows for a facile synthesis of potentially useful fluoroorganic intermediates.

Imaging spectrum of bronchial carcinoid--a case of central bronchial obstructing lesion.

Here one case of bronchial carcinoid is reported, which presented as intrabronchial obstructing lesion with sequelae. Carcinoid syndrome is quite uncommon with bronchial carcinoids and x-ray or CT usually gives non-specific appearances. Still, the relatively younger age group of patients and presence of obstructing lesions in major bronchi with features like extraluminal extension and mucoid impactions are helpful signs. However, a few instances of carcinoid mimics do occur during imaging studies, like other types of intrabronchial tumours and long standing foreign bodies.

Effect of acute and chronic fluoxetine on extracellular dopamine levels in the caudate-putamen and nucleus accumbens of rat.

Recent studies indicate that an increase in serotonergic (5-HT) activity in the nucleus accumbens (NAc) produces an increase in dopamine (DA) release, providing a possible mechanism for the involvement of DA in the therapeutic action of selective serotonin reuptake inhibitor (SSRI) antidepressants. However, acutely administered fluoxetine (2.5, 5.0, or 10.0 mg/kg, i.p.) failed to elevate extracellular levels of DA, or its metabolites in the NAc or caudate-putamen (CP). In fact, the highest dose produced a small (20%) decrease in DA levels in the NAc. Extracellular levels of the 5-HT metabolite 5HIAA were consistently decreased at all doses of fluoxetine in both structures. Since SSRIs generally require several weeks of treatment to be effective clinically, a second experiment examined the effect of chronic administration of fluoxetine. Chronic (21 day) daily treatment with 5 mg/kg had no effect on NAc basal levels of DA, DA metabolites, or 5HIAA, relative to a saline-treated control group. Finally, pretreatment with fluoxetine appeared to slightly enhance the elevation of NAc DA induced by an injection of cocaine (10 mg/kg, i.p.), an effect that was not quite significant (P < .06). In conclusion, the 5-HT-induced facilitation of NAc DA neurotransmission described in the literature may not be relevant to the therapeutic action of fluoxetine.