Biomedical subjects
J Chandrasekhar
Publications and source records attributed to J Chandrasekhar.
Use of interventional radiology in the management of mediastinitis of odontogenic origin.
Descending necrotising mediastinitis is a rare complication of odontogenic infection. The key to diagnosis is to maintain a high index of suspicion when antibiotics and adequate surgical drainage do not lead to resolution of symptoms. Open thoracic operation to drain mediastinal collections is potentially lethal and interventional radiological techniques are thought to reduce mortality. We report the use of interventional radiology in the diagnosis, monitoring and treatment of this condition and illustrate our experience with three case reports.
Controlling chemistry with cations: photochemistry within zeolites.
The alkali ions present in the supercages of zeolites X and Y interact with included guest molecules through quadrupolar (cation-pi), and dipolar (cation-carbonyl) interactions. The presence of such interactions can be inferred through solid-state NMR spectra of the guest molecules. Alkali ions, as illustrated in this article, can be exploited to control the photochemical and photophysical behaviors of the guest molecules. For example, molecules that rarely phosphoresce can be induced to do so within heavy cation-exchanged zeolites. The nature (electronic configuration) of the lowest triplet state of carbonyl compounds can be altered with the help of light alkali metal ions. This state switch (n pi*-pi pi*) helps to bring out reactivity that normally remains dormant. Selectivity obtained during the singlet oxygen oxidation of olefins within zeolites illustrates the remarkable control that can be exerted on photoreactions with the help of a confined medium that also has active sites. The reaction cavities of zeolites, like enzymes, are not only well-defined and confined, but also have active sites that closely guide the reactant molecule from start to finish. The examples provided here illustrate that zeolites are far more useful than simple shape-selective catalysts.
Light-induced geometric isomerization of 1,2-diphenylcyclopropanes included within Y zeolites: role of cation-guest binding.
Through a systematic study of several diphenylcyclopropane derivatives, we have inferred that the cations present within a zeolite control the excited-state chemistry of these systems. In the parent 1,2-diphenylcylopropane, the cation binds to the two phenyl rings in a sandwich-type arrangement, and such a mode of binding prevents cis-to-trans isomerization. Once an ester or amide group is introduced into the system (derivatives of 2beta,3beta-diphenylcyclopropane-1alpha-carboxylic acid), the cation binds to the carbonyl group present in these chromophores and such a binding has no influence on the cis-trans isomerization process. Cation-reactant structures computed at density functional theory level have been very valuable in rationalizing the observed photochemical behavior of diphenylcyclopropane derivatives included in zeolites. While the parent system, 1,2-diphenylcylopropane, has been extensively investigated in the context of chiral induction in solution, owing to its failure to isomerize from cis to trans, the same could not be investigated in zeolites. However, esters of 2beta,3beta-diphenylcyclopropane-1alpha-carboxylic acid could be studied within zeolites in the context of chiral induction. Chiral induction as high 20% ee and 55% de has been obtained with selected systems. These numbers, although low, are much higher than what has been obtained in solution with the same system or with the parent system by other investigators (maximum approximately 10% ee).
Structural effects on the formation of proton and alkali metal ion adducts of apolar, neutral peptides: electrospray ionization mass spectrometry and Ab initio theoretical studies.
Apolar, neutral peptides have been shown to ionize extremely well under the conditions used for electrospray ionization mass spectrometry (ESIMS). Peptides for which the conformations have been independently determined in solution and in crystals have been examined by ESIMS. Studies of peptide helices ranging from 7 to 18 residues reveal that shorter helices yield exclusively singly charged ions, while in larger helices multiply charged species are detectable. Multiple sites for protonation/metallation are introduced in the helix by proline insertion or by changing the chirality in the residue. The preferred site of cation binding to helices may be the C-terminus end, where three free CO groups are available for chelation. Ab initio and DFT calculations at several levels have been carried out for the binding of H+, Li+, Na+, and K+ to CHO-(Gly)3)-OMe. The results reveal that metallation in helices is favoured by chelation to carbonyl groups at the C-terminus, while protonation involved two carbonyl groups and thus favour a 10-membered cyclic hydrogen-bonded structure. In -strands, metallation/protonation occurs at isolated carbonyl groups. Collision induced fragmentation of hydrophobic peptides under ESI conditions reveals that helix fragmentation occurs predominantly from the C-terminus, while in -hairpins cleavage occurs simultaneously at multiple sites.
Re: SHO induction course in oral and maxillofacial surgery.
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Pleomorphic adenoma of the lacrimal gland: case report.
Lacrimal gland tumours are rare. We present a case of a lacrimal gland pleomorphic adenoma in a 19-year-old man. The tumour was removed and he has made an uncomplicated recovery, with no sign of recurrence after nine months of follow-up. We will keep him under long-term review.
Modeling of ion permeation in calcium and sodium channel selectivity filters.
Structure-function studies have shown that it is possible to convert a sodium channel to a calcium-selective channel by a single amino acid substitution in the selectivity filter locus. Ion permeation through the "model selectivity filter" was modeled with a reduced set of functional groups representative of the constituent amino acid side chains. Force-field minimizations were conducted to obtain the energy profile of the cations as they get desolvated and bind to the "model selectivity filter." The calculations suggest that the ion selectivity in the calcium channel is due to preferential binding, whereas in the sodium channel it is due to exclusion. Energetics of displacement of a bound cation from the calcium "model selectivity filter" by another cation suggest that "multi-ion mechanism" reduces the activation barrier for ion permeation. Thus, the simple model captures qualitatively most of the conduction characteristics of sodium and calcium channels. However, the computed barriers for permeation are fairly large, suggesting that ion interaction with additional residues along the transport path may be essential to effect desolvation.
Electronic control of facial selection in additions to sterically unbiased ketones and olefins.
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Oxypentifylline in the management of recurrent aphthous oral ulcers: an open clinical trial.
OBJECTIVE: The purpose of this study was to determine the efficacy of oxypentifylline in the treatment of recurrent oral aphthous ulcers and to compare the results with those of previous studies. STUDY DESIGN: A 6-week open trial and a patient survey regarding pain were conducted at the Oral and Maxillofacial Surgery Unit, City General Hospital, Carlisle. Twenty-four patients (11 male and 13 female) were selected from sequential referrals involving complaints of recurrent oral ulcers. A 2-week pretrial period was used to record data pertaining to the occurrence, duration, and pain associated with ulcers. A 4-week period of treatment with oxypentifylline (400 mg administered orally 3 times daily) was followed by an assessment of improvement at the end of 6 weeks. RESULTS: The results were comparable to those of previous studies, with positive responses seen in 63.6% of male patients and 61.5% of female patients. However, recurrence of ulcers was noted in all patients once the drug was discontinued. This was attributed to the small size of the patient sample studied and to the relatively short duration of treatment. No significant side effects were noted. CONCLUSIONS: Double-blind, controlled studies are indicated for a definitive assessment of the efficacy of oxypentifylline in the management of recurrent oral aphthous ulcers. The encouraging results of this study support the suggestion that the use of oxypentifylline be considered in refractory cases of recurrent oral aphthous ulcers.
Conformational interconversions in peptide beta-turns: analysis of turns in proteins and computational estimates of barriers.
The two most important beta-turn features in peptides and proteins are the type I and type II turns, which differ mainly in the orientation of the central peptide unit. Facile conformational interconversion is possible, in principle, by a flip of the central peptide unit. Homologous crystal structures afford an opportunity to structurally characterize both possible conformational states, thus allowing identification of sites that are potentially stereochemically mobile. A representative data set of 250 high-resolution (</=2.0 A), non-homologous protein crystal structures and corresponding variant and homologous entries, obtained from the Brookhaven Protein Data Bank, was examined to identify turns that are assigned different conformational types (type I/type II) in related structures. A total of 55 examples of beta-turns were identified as possible candidates for a stereochemically mobile site. Of the 55 examples, 45 could be classified as a potential site for interconversion between type I and type II beta-turns, while ten correspond to flips from type I' to type II' structures. As a further check, the temperature factors of the central peptide unit carbonyl oxygen atom of the 55 examples were examined. The analysis reveals that the turn assignments are indeed reliable. Examination of the secondary structures at the flanking positions of the flippable beta-turns reveals that seven examples occur in the loop region of beta-hairpins, indicating that the formation of ordered secondary structures on either side of the beta-turn does not preclude local conformational variations. In these beta-turns, Pro (11 examples), Lys (nine examples) and Ser (seven examples) were most often found at the i+1 position. Glycine was found to occur overwhelmingly at position i+2 (28 examples), while Ser (seven examples) and Asn (six examples) were amongst the most frequent residues. Activation energy barriers for the interconversion between type I and type II beta-turns were computed using the peptide models Ac-Pro-Aib-NHMe and Ac-Pro-Gly-NHMe within the framework of the AM1 semi-empirical molecular orbital procedure. In order to have a uniform basis for comparison and to eliminate the distracting influence of the deviation of backbone dihedral angles from that expected for ideal beta-turns, the dihedral angles phii+1 and psii+2 were fixed at the ideal values (phii+1=-60 degrees and psii+2=0 degrees). The other two angles (psii+1 and phii+2) were varied systematically to go from type II to type I beta-turn structures. The computational results suggest that there exists one stereospecific, concerted flip of the central peptide unit involving correlated single bond rotation that can occur with an activation barrier of the order of 3 kcal/mol. The results presented here suggest that conformational variations in beta-turns are observed in protein crystal structures and such changes may be an important dynamic feature in solution.
Computer simulations of organic reactions in solution.
Quantum and statistical mechanics have been used to determine energy profiles for the SN2 reaction of Cl- + CH3Cl in the gas phase, in aqueous solution, and in liquid DMF. The energy profile in the gas phase has the characteristic double-well form featuring unsymmetrical ion-dipole complexes as minima and a symmetrical transition state. Hydration causes the reaction surface to become almost unimodal and increases the barrier significantly. The reaction profile in DMF is intermediate between those for the gas phase and aqueous solution. The ion-dipole complexes are still free energy minima in DMF. Thus, the reaction in DMF involves initial formation of the complex before the rate-determining step. The computed results are shown to be in good accord with experimental free energies of activation. The same technique has been applied to the addition reaction of OH- + H2C = O in the gas phase and aqueous solution. Ab initio 6-31 + G* calculations indicate that the reaction proceeds essentially without activation in the gas phase. Hydration introduces a substantial energy barrier. The transition state in water has been located at a C-O separation of roughly 2 A. A key finding for both reactions is that the activation barriers induced by hydration result primarily from change in strengths rather than in numbers of solute-water hydrogen bonds along the reaction paths.