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Vincent van Gogh and the thujone connection.

During his last two years Vincent van Gogh experienced fits with hallucinations that have been attributed to a congenital psychosis. But the artist admitted to episodes of heavy drinking that were amply confirmed by colleagues and there is good evidence to indicate that addiction to absinthe exacerbated his illness. Absinthe was distilled from an alcoholic steep of herbs. Wormwood (Artemisia absinthium) was the most significant constituent because it contributed thujone. This terpene can cause excitation, convulsions that mimic epilepsy, and even permanent brain damage. Statements in van Gogh's letters and from his friends indicate that he had an affinity for substances with a chemical connection to thujone; the documented examples are camphor and pinene. Perhaps he developed an abnormal craving for terpenes, a sort of pica, that would explain his attempts to eat paints and so on, which were previously regarded as unrelated absurdities.

Alcoholic Beverages↗

[Spectral analysis of the EEG of the healthy rat and the rat genetically predisposed to seizure susceptibility].

EEGs of motor and visual cortical zones, hippocampus, caudate nucleus and intralaminal-thalamic nuclei were recorded in two rat strains in "awake-immobility" state and subjected to visual and spectral analyses. KM rats genetically predisposed to audiogenic seizures were shown to differ from unpredisposed Wistar rats in weakening of the relative power of theta rhythm and intensification of the large-amplitude irregular activity in hippocampus and neocortex as well as in reinforcement of the generalized spindle activity. As a result of prolonged application of gradually increasing camphor doses seizure susceptibility reduction in KM rats correlated with EEG spectral density changing to Wistar rats EEG characteristics. The probable role of the brain stem reticular formation mechanisms in the enhanced convulsibility and accompanying EEG pattern are discussed.

Acoustic Stimulation↗

[Development of olfactory epithelial grafts in the anterior chamber of the eye].

Olfactory epithelium of newborn rats was transplanted into the anterior eye chamber of the adult rat. Within 6-8 weeks the transplants increased in weight by a factor of 20-50. Morphological analysis has shown the cells similar to olfactory sensory neurones in the grafts. Electroolfactograms obtained with n-amyl acetate and camphor had the amplitude of about three times less and the duration of about 8-10 times more than those from the normal olfactory epithelium at the same concentration of stimuli. Within six hours after 3H-beta-alanine had been introduced into the anterior eye chamber, 72% of the label were present in the carnosine fraction. The data obtained suggest that olfactory sensory neurones appear in the olfactory epithelium grafts into the anterior eye chamber.

Animals↗

Cyclodextrin-stabilized volatile substances for inhalation therapy.

Diapulmon (Chinoin) which comprise camphor, 1-menthol, eucalyptus oil and quinine dissolved in sunflower oil (Oleum helianthi) is marketed in ampoules of 2 ml but utilized almost exclusively for inhalation therapy. Complexing the active ingredients of Diapulmon with beta-cyclodextrin (beta-CD) a stable non hygroscopic microcrystalline substance is obtained. When this powder sprinkled on hot water, the included volatile compounds are gradually released and the desired pharmacological effect can be brought about.

Camphor↗

Acaricidal agents of natural origin against Psoroptes cuniculi.

Lavandula angustifolia Miller essential oil and some of its main constituents, i.e. linalool, linalyl acetate, and camphor were tested in vitro for their bioactivities against Psoroptes cuniculi (Delafond, 1859), mite of the rabbit. The essential oil and linalool were found to have very powerful miticidal activities.

Acyclic Monoterpenes↗

In vitro inhibition of bacteria from root canals of primary teeth by various dental materials.

The primary tooth pulpectomy is a common clinical procedure. The choice of filling material is important to the success rate, but antibacterial properties of such materials against organisms known to inhabit infected primary root canals have not been well documented. This study compared the antibacterial effectiveness of 10 materials: 1. Calcium hydroxide mixed with camphorated parachlorophenol (Ca(OH)2+CPC) 2. Calcium hydroxide mixed with sterile water (Ca(OH)2+H2O) 3. Zinc oxide mixed with CPC (ZnO+CPC) 4. Zinc oxide mixed with eugenol (ZOE) 5. ZOE mixed with formocresol (ZOE+FC) 6. Zinc oxide mixed with sterile water (ZnO+H2O) 7. ZOE mixed with chlorhexidine dihydrochloride (ZOE+CHX) 8. Kri paste 9. Vitapex paste 10. Vaseline (control) These materials were compared against microbial specimens obtained from 13 infected primary teeth by using an agar diffusion assay. The results suggest that the materials could be divided into three categories. Category I, with the strongest antibacterial effect included ZnO+CPC, Ca(OH)2+CPC, and ZOE+FC. Category II, with a medium antibacterial effect included ZOE+CHX, Kri, ZOE, and ZnO+H2O. Category III, with no or minimal antibacterial effect included Vitapex, Ca(OH)2+H2O, and Vaseline. There were no significant differences within each category, but there were significant differences between the categories. The one exception was the antibacterial effect of ZOE+FC which was not significantly different from ZOE+CHX, Kri, or ZOE.

Analysis of Variance↗

Inhibition of pure cultures of oral bacteria by root canal filling materials.

This study compared the antimicrobial effectiveness of nine dental materials and a negative control agent against 21 strains or species of bacteria using an agar diffusion assay. The materials were: 1. Camphorated parachlorophenol mixed with calcium hydroxide (CPC + Ca(OH)2). 2. CPC mixed with zinc oxide (CPC + ZnO). 3. Formocresol mixed with zinc oxide and eugenol (FC + ZOE). 4. Chlorhexidine mixed with ZOE (CHX + ZOE). 5. Kri paste. 6. ZOE. 7. Zinc oxide mixed with sterile water (ZnO + H2O). 8. Calcium hydroxide mixed with sterile water (Ca(OH)2 + H2O). 9. Vitapex. 10. Vaseline (control). The test bacteria represented species commonly isolated from nonvital primary and permanent tooth root canals. The antimicrobial effectiveness of the materials was divided into five groups based on the diameters of the zones of inhibition against all test bacteria and distribution of the data. All materials except Vaseline showed antimicrobial activity against some of the 21 organisms. Generally, all materials inhibited gram-negative anaerobic bacteria more effectively than aerotolerant gram-negative or gram-positive bacteria. Materials containing CPC or FC (except Kri paste) produced strong or medium strong inhibition against most bacteria. CHX + ZOE, Kri paste, ZnO + H2O, and ZOE inhibited all or most bacteria, but to lesser extent than CPC + Ca(OH)2, CPC + ZnO, or FC + ZOE. Ca(OH)2 + H2O, Vitapex, and Vaseline generally were nonihibitory. The findings should allow a comparative evaluation of antimicrobial effectiveness to be made of materials commonly used in pulpectomy procedures with primary teeth.

Anti-Infective Agents, Local↗

An in vitro test model for investigation of disinfection of dentinal tubules infected with Enterococcus faecalis.

The aim of the present study was to develop an in vitro test model from human teeth to comparatively examine antibacterial effectiveness of calcium hydroxide, parachlorophenol (PCP) and camphorated parachlorophenol (CPCP) against Enterococcus faecalis in infected root canals. Cylindrical dentin specimens were prepared from freshly extracted human maxillary anterior teeth. The specimens were inoculated with E. faecalis and then medicated with either CPCP, PCP or Ca(OH)2. The disinfecting efficacy of these agents was tested by collecting dentin chips from the inner ("canal") walls of the specimens and counting viable E. faecalis. The dentin chips were diluted and a classical bacterial count technique was used for recovery of E. faecalis strains of 5% sheep blood agar. The effectiveness of CPCP and PCP at one day was superior to the effectiveness of Ca(OH)2. In the three-day group, CPCP was the most effective, followed by Ca(OH)2. The experimental model used in this study may be useful for investigation of the effect of intracanal medicaments on microorganisms lodged in the root dentinal tubules.

Calcium Hydroxide↗

Nicobrevin for smoking cessation.

BACKGROUND: Nicobrevin is a proprietary product marketed as an aid to smoking cessation. It contains quinine, menthyl valerate, camphor and eucalyptus oil. OBJECTIVES: The objective of this review was to assess the effects of Nicobrevin on long term smoking cessation SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register. SELECTION CRITERIA: Randomized trials comparing Nicobrevin to placebo or an alternative therapeutic control, which reported smoking cessation with at least six months follow up. DATA COLLECTION AND ANALYSIS: Data were sought on the outcome, method of randomization, and completeness of follow up. MAIN RESULTS: We identified no trials meeting the full inclusion criteria including long-term follow up. AUTHORS' CONCLUSIONS: There is no evidence available from long-term trials that Nicobrevin can aid smoking cessation.

Humans↗

Chiral separation of amino acid esters by micellar electrokinetic chromatography.

Micellar electrokinetic chromatography (MEKC) was used for the chiral separation of uncharged analytes (C- and N-protected amino acids). Sodium dodecyl sulfate (SDS) was the micelle forming agent, and different cyclodextrin (CD) derivatives were added as chiral selectors. Suitable conditions for the enantioseparation were found by variation of the separation conditions. The influence of addition of organic solvents like acetonitrile or methanol, and other chiral additives (camphor-10-sulfonic acid, malic acid) was examined. The addition of an organic modifier resulted in different effects on micelle formation, and thereby on the separation. The used chiral additives did not improve the selectivity. Furthermore, dependence of the electroosmotic flow (EOF), and the capacity factors on the concentration of CDs was investigated. Increasing the CD concentration, both the EOF to a smaller extent as well as the capacity factors decrease. Nevertheless, the enantioseparation is improved with a CD-concentration up to 30 mM. Higher CD-concentrations reduce the separation of the analytes.

Acetonitriles↗

The role of mass spectrometry in medicinal plant research.

In phytochemical and chemotaxonomic research work mass spectrometry plays an outstandingly important role. Using gas chromatography/mass spectrometry (GC/MS) we established the chemotaxa of Tanacetum vulgare L. Chemotypes with essential oils containing 60-90% of artemisia ketone, carveol, dihydrocarvone, myrtenol, umbellulone, terpinen-4-ol, davanone, and Tagetes species containing various essential oils can be clearly distinguished by their spectra; we examined many variations of Tagetes erecta, T. lucida, T. minuta, T. patula and T. tenuifolia. We have identified alpha-beta-pinene-, 1,8-cineol-, linalool-, camphor-, nerol-, geraniol- and gamma-gurjonene as components of Achillea distans L. Injecting the essential oil direct from the oil-secreting organs of T. minuta plants we identified using GC/MS 6-10 and 16% eugenol from the involucral bract and hypsophyll, respectively, as well as beta-ocimene, dihydrotagetone, tagetone, Z- and E-ocimenones. In the course of studies on essential fatty acids Borago officinalis and Lappula squarrosa were selected from 70 species of the family Boraginaceae to obtain seed oil as a source of gamma-linolenic acid, and for the PG synthesis we isolated several grams of gamma-linolenic acid, as well as C18:4, i.e. octadecatetraenic acid, from L. squarrosa on the basis of the mass spectra. From the seed oil of Aquilegia vulgaris C18:3 (5) from the oil of Limnanthes dougloasii C20:1 (5) and from the seed oils of Delphinium consolida and of Tropaeolum species (T. majus, T. minus, T. peregrinum) C20:1 (11) fatty acids were identified on the basis of spectra.

Fatty Acids↗

Preparation of highly conductive, self-assembled gold/polyaniline nanocables and polyaniline nanotubes.

One-dimensional gold/polyaniline (Au/PANI-CSA) coaxial nanocables with an average diameter of 50-60 nm and lengths of more than 1 mum were successfully synthesized by reacting aniline monomer with chlorauric acid (HAuCl(4)) through a self-assembly process in the presence of D-camphor-10-sulfonic acid (CSA), which acts as both a dopant and surfactant. It was found that the formation probability and the size of the Au/PANI-CSA nanocables depends on the molar ratio of aniline to HAuCl(4) and the concentration of CSA, respectively. A synergistic growth mechanism was proposed to interpret the formation of the Au/PANI-CSA nanocables. The directly measured conductivity of a single gold/polyaniline nanocable was found to be high (approximately 77.2 S cm(-1)). Hollow PANI-CSA nanotubes, with an average diameter of 50-60 nm, were also obtained successfully by dissolving the Au nanowire core of the Au/PANI-CSA nanocables.

Journal Article↗

Differential specificity in the glomerular response profiles for alicyclic, bicyclic, and heterocyclic odorants.

As part of our ongoing effort to relate stimulus to response in the olfactory system, we tested the hypothesis that the unique chemical structures and odors of various cyclic odorants would be associated with unique spatial response patterns in the glomerular layer of the rat olfactory bulb. To this end, rats were exposed to sets of odorants, including monocyclic hydrocarbons, bicyclic compounds, and various heterocyclic structures containing oxygen or nitrogen in the ring. Relative activity across the entire layer was assessed by mapping uptake of 2-deoxyglucose into anatomically standardized data matrices. Whereas monocyclic hydrocarbons evoked patterns similar to those evoked by open-chained hydrocarbon odorants, a set of bicyclic compounds with structures and odors similar to camphor evoked uptake in paired ventral domains not previously associated with any other odorant chemical structures. Despite their unique odors as judged by humans, heterocyclic odorants either evoked uptake in previously characterized areas corresponding to their functional groups or stimulated weak or patchy patterns involving isolated glomeruli. Although the patchiness of the patterns may be partially related to the rigidity of the compounds, which would be expected to restrict their interactions to only a few receptors, the weakness of the patterns suggests the possibility of species-specific odorant representations. We conclude that, whereas some of the novel cyclic structures indeed were represented by unique patterns in the rat bulb, other unique structures were poorly represented, even when they evoked intense and unique odors in humans.

Animals↗

Development of a novel method for synthesis of a polymeric ultrasound contrast agent.

Medical ultrasound is a highly valuable diagnostic tool, especially when compared with other imaging modalities. It is a noninvasive, real-time, portable, extremely safe method compared with X-ray and inexpensive relative to magnetic resonance imaging. However, ultrasound is limited in its ability to distinguish between diseased and normal tissue. This limitation has led to the development of contrast agents. We have produced novel poly (lactic-co-glycolic) acid air-filled microcapsules that work well as ultrasound contrast agents, giving up to 24 and 25 dB enhancement when insonated in the medical imaging range at 5 and 7.5 MHz, respectively. The capsules were fabricated by modifying a double emulsion method to encapsulate camphor in the oil phase and ammonium carbonate in the aqueous phase, and later sublime the encapsulated material, leaving voids capable of being filled with a gas in their place. The role of the surfactant, poly vinyl alcohol, solution temperature, was studied and found to play an important role in the morphology of the capsules, altering their acoustic response.

Dose-Response Relationship, Drug↗

Application of the frozen atom approximation to the GB/SA continuum model for solvation free energy.

The generalized Born/surface area (GB/SA) continuum model for solvation free energy is a fast and accurate alternative to using discrete water molecules in molecular simulations of solvated systems. However, computational studies of large solvated molecular systems such as enzyme-ligand complexes can still be computationally expensive even with continuum solvation methods simply because of the large number of atoms in the solute molecules. Because in such systems often only a relatively small portion of the system such as the ligand binding site is under study, it becomes less attractive to calculate energies and derivatives for all atoms in the system. To curtail computation while still maintaining high energetic accuracy, atoms distant from the site of interest are often frozen; that is, their coordinates are made invariant. Such frozen atoms do not require energetic and derivative updates during the course of a simulation. Herein we describe methodology and results for applying the frozen atom approach to both the generalized Born (GB) and the solvent accessible surface area (SASA) parts of the GB/SA continuum model for solvation free energy. For strictly pairwise energetic terms, such as the Coulombic and van-der-Waals energies, contributions from pairs of frozen atoms can be ignored. This leaves energetic differences unaffected for conformations that vary only in the positions of nonfrozen atoms. Due to the nonlocal nature of the GB analytical form, however, excluding such pairs from a GB calculation leads to unacceptable inaccuracies. To apply a frozen-atom scheme to GB calculations, a buffer region within the frozen-atom zone is generated based on a user-definable cutoff distance from the nonfrozen atoms. Certain pairwise interactions between frozen atoms in the buffer region are retained in the GB computation. This allows high accuracy in conformational GB comparisons to be maintained while achieving significant savings in computational time compared to the full (nonfrozen) calculation. A similar approach for using a buffer region of frozen atoms is taken for the SASA calculation. The SASA calculation is local in nature, and thus exact SASA energies are maintained. With a buffer region of 8 A for the frozen-atom cases, excellent agreement in differences in energies for three different conformations of cytochrome P450 with a bound camphor ligand are obtained with respect to the nonfrozen cases. For various minimization protocols, simulations run 2 to 10.5 times faster and memory usage is reduced by a factor of 1.5 to 5. Application of the frozen atom method for GB/SA calculations thus can render computationally tractable biologically and medically important simulations such as those used to study ligand-receptor binding conformations and energies in a solvated environment.

Macromolecular Substances↗

Analysis of molecular recognition: steric electrostatic and hydrophobic complementarity.

We discuss three important aspects of molecular recognition: steric, electrostatic and hydrophobic. Steric fit means that interacting atoms may not approach each other beyond their van der Waals radii and, simultaneously, crevices should be filled as densely as possible. Electrostatic fit requires the maximum ionic and polar (hydrogen bond or other) interaction between host and guest atoms while the hydrophobic fit corresponds to the association trend between apolar groups in an aqueous medium. Space-filling models, obtained by molecular graphics, illustrate steric complementarity while we use molecular electrostatic potentials (MEPs) and fields (MEFs) to investigate electrostatic and hydrophobic matching. Molecular regions with negative and positive MEPs attract and repel a positive probe charge, respectively, so we consider them as attracting each other. Furthermore we postulate that regions with MEFs of similar magnitude tend to associate more strongly than those with very different fields (similis simili gaudet principle). We apply the above rules to the study of complementarity in the trypsin-BPTI complex and in a crystalline association between styrene epoxide as guest and a camphor-based anthracene derivative as host. We discuss molecular similarity on the same footing as complementarity and give some examples on the application of the concept to the rationalization of relative strengths of trypsin inhibitors.

Allosteric Site↗

New DEFT sequences for the acquisition of one-dimensional carbon NMR spectra of small unlabelled molecules.

The acquisition time and quality of 1D 13C{1H} spectra can be improved substantially by using a modified driven equilibrium Fourier transform (DEFT) sequence, which is specifically designed to compensate for the effects of B1 inhomogeneity, pulse miscalibration and frequency offsets. The new sequence, called uniform driven equilibrium Fourier transform (UDEFT), returns the carbon magnetization with a high accuracy along its equilibrium position after each transient is complete. Thus, the sequence allows the use of relaxation delays (RD), which are much shorter than the carbon T1 of the molecule, thereby speeding up the acquisition process of 1D 13C{1H} spectra. To achieve this level of performance, UDEFT employs a refocusing element constituted by a composite adiabatic carbon pulse surrounded by two 90 degrees carbon pulses whose phases are designed to compensate for 90 degrees pulse miscalibrations in an MLEV manner (90 degrees+x-tau(FID)-180+y(Adia)-tau-90 degrees+x-180 degrees+x(Adia)). A version of the UDEFT sequence allows recording 1D 13C{1H} spectra devoid of heteronuclear NOE by using a matched adiabatic 1H decoupling scheme where an even number of 180 degrees adiabatic pulses is applied during the UDEFT module. Spectra of a solution of 300 mM camphor that contains some carbon nuclei with very long T1 relaxation times (90 s and 78 s) were acquired with 128 scans in 10 min using a 5 s relaxation delay.

Journal Article↗