Dnmt3a2: a hub for enhancing cognitive functions.

The mechanisms responsible for fear memory formation and extinction are far from being understood. Uncovering the molecules and mechanisms regulating these processes is vital for identifying molecular targets for the development of novel therapeutic strategies for anxiety and fear disorders. Cognitive abilities require the activation of gene expression necessary to the consolidation of lasting changes in neuronal function. In this study we established a key role for an epigenetic factor, the de novo DNA methyltransferase, Dnmt3a2, in memory formation and extinction. We found that Dnmt3a2 overexpression in the hippocampus of young adult mice induced memory enhancements in a variety of situations; it converted a weak learning experience into long-term memory, enhanced fear memory formation and facilitated fear memory extinction. Dnmt3a2 overexpression was also associated with the increased expression of plasticity-related genes. Furthermore, the knockdown of Dnmt3a2 expression impaired the animals' ability to extinguish memories, identifying Dnmt3a2 as a key player in extinction. Thus, Dnmt3a2 is at the core of memory processes and represents a novel target for cognition-enhancing therapies to ameliorate anxiety and fear disorders and boost memory consolidation.

Structural and orientation effects on electronic energy transfer between silicon quantum dots with dopants and with silver adsorbates.

Starting from the atomic structure of silicon quantum dots (QDs), and utilizing ab initio electronic structure calculations within the Förster resonance energy transfer (FRET) treatment, a model has been developed to characterize electronic excitation energy transfer between QDs. Electronic energy transfer rates, KEET, between selected identical pairs of crystalline silicon quantum dots systems, either bare, doped with Al or P, or adsorbed with Ag and Ag3, have been calculated and analyzed to extend previous work on light absorption by QDs. The effects of their size and relative orientation on energy transfer rates for each system have also been considered. Using time-dependent density functional theory and the hybrid functional HSE06, the FRET treatment was employed to model electronic energy transfer rates within the dipole-dipole interaction approximation. Calculations with adsorbed Ag show that: (a) addition of Ag increases rates up to 100 times, (b) addition of Ag3 increases rates up to 1000 times, (c) collinear alignment of permanent dipoles increases transfer rates by an order of magnitude compared to parallel orientation, and (d) smaller QD-size increases transfer due to greater electronic orbitals overlap. Calculations with dopants show that: (a) p-type and n-type dopants enhance energy transfer up to two orders of magnitude, (b) surface-doping with P and center-doping with Al show the greatest rates, and (c) KEET is largest for collinear permanent dipoles when the dopant is on the outer surface and for parallel permanent dipoles when the dopant is inside the QD.

The nuclear calcium signaling target, activating transcription factor 3 (ATF3), protects against dendrotoxicity and facilitates the recovery of synaptic transmission after an excitotoxic insult.

The focal swellings of dendrites ("dendritic beading") are an early morphological hallmark of neuronal injury and dendrotoxicity. They are associated with a variety of pathological conditions, including brain ischemia, and cause an acute disruption of synaptic transmission and neuronal network function, which contribute to subsequent neuronal death. Here, we show that increased synaptic activity prior to excitotoxic injury protects, in a transcription-dependent manner, against dendritic beading. Expression of activating transcription factor 3 (ATF3), a nuclear calcium-regulated gene and member of the core gene program for acquired neuroprotection, can protect against dendritic beading. Conversely, knockdown of ATF3 exacerbates dendritic beading. Assessment of neuronal network functions using microelectrode array recordings revealed that hippocampal neurons expressing ATF3 were able to regain their ability for functional synaptic transmission and to participate in coherent neuronal network activity within 48 h after exposure to toxic concentrations of NMDA. Thus, in addition to attenuating cell death, synaptic activity and expression of ATF3 render hippocampal neurons more resistant to acute dendrotoxicity and loss of synapses. Dendroprotection can enhance recovery of neuronal network functions after excitotoxic insults.

Nuclear calcium signaling regulates nuclear export of a subset of class IIa histone deacetylases following synaptic activity.

In neurons, dynamic changes in the subcellular localization of histone deacetylases (HDACs) are thought to contribute to signal-regulated gene expression. Here we show that in mouse hippocampal neurons, synaptic activity-dependent nucleo-cytoplasmic shuttling is a common feature of all members of class IIa HDACs, which distinguishes them from other classes of HDACs. Nuclear calcium, a key regulator in neuronal gene expression, is required for the nuclear export of a subset of class IIa HDACs. We found that inhibition of nuclear calcium signaling using CaMBP4 or increasing the nuclear calcium buffering capacity by means of expression of a nuclear targeted version of parvalbumin (PV.NLS-mC) led to a build-up of HDAC4 and HDAC5 in the cell nucleus, which in the case of PV.NLS-mC can be reversed by nuclear calcium transients triggered by bursts of action potential firing. A similar nuclear accumulation of HDAC4 and HDAC5 was observed in vivo in the mouse hippocampus following stereotaxic delivery of recombinant adeno-associated viruses expressing either CaMBP4 or PV.NLS-mC. The modulation of HDAC4 activity either by RNA interference-mediated reduction of HDAC4 protein levels or by expression of a constitutively nuclear localized mutant of HDAC4 leads to changes in the mRNA levels of several nuclear calcium-regulated genes with known functions in acquired neuroprotection (atf3, serpinb2), memory consolidation (homer1, arc), and the development of chronic pain (ptgs2, c1qc). These results identify nuclear calcium as a regulator of nuclear export of HDAC4 and HDAC5. The reduction of nuclear localized HDACs represents a novel transcription-promoting pathway stimulated by nuclear calcium.

Nuclear calcium signaling in spinal neurons drives a genomic program required for persistent inflammatory pain.

Persistent pain induced by noxious stimuli is characterized by the transition from normosensitivity to hypersensitivity. Underlying mechanisms are not well understood, although gene expression is considered important. Here, we show that persistent nociceptive-like activity triggers calcium transients in neuronal nuclei within the superficial spinal dorsal horn, and that nuclear calcium is necessary for the development of long-term inflammatory hypersensitivity. Using a nucleus-specific calcium signal perturbation strategy in vivo complemented by gene profiling, bioinformatics, and functional analyses, we discovered a pain-associated, nuclear calcium-regulated gene program in spinal excitatory neurons. This includes C1q, a modulator of synaptic spine morphogenesis, which we found to contribute to activity-dependent spine remodelling on spinal neurons in a manner functionally associated with inflammatory hypersensitivity. Thus, nuclear calcium integrates synapse-to-nucleus communication following noxious stimulation and controls a spinal genomic response that mediates the transition between acute and long-term nociceptive sensitization by modulating functional and structural plasticity.

Optical absorbance of doped Si quantum dots calculated by time-dependent density functional theory with partial electronic self-interaction corrections.

The optical properties of Si quantum dots (QDs) with phosphorous and aluminum dopants have been calculated with the recently tested Heyd-Scuseria-Ernzerhof (HSE) density functionals to ascertain the effect of functional corrections to electronic self-interaction. New results have been obtained for 20 crystalline and amorphous structures of Si(29) and Si(35) quantum dots and are compared to our previous results obtained using the PW91∕PW91 functionals. The bandgaps are greater in magnitude and shifted to higher energies in HSE calculations compared to PW91 calculations, and the absorption spectrum is blueshifted in HSE. Trends in the shifts of absorbances due to doping are similar for both sets of calculations, with doped QDs absorbing at lower photon energies than undoped QDs. Consistent with previous results, the bandgaps of QDs are found to decrease as the size of the QD increases, and the absorption spectra of amorphous QDs are redshifted compared to those of crystalline structures. The molecular orbitals involved in the transitions with the largest oscillator strengths show that the electron density moves towards the surface of the quantum dot as the structure is excited. The lifetimes of photoexcited states were found to differ substantially between the two functionals due to their sensitivity to the overlaps of initial and final orbitals. Comparison with available experimental and independent theoretical results supports the conclusion that the HSE functional better matches experimental results due to the partial inclusion of Hartree-Fock exchange.

Nuclear calcium-VEGFD signaling controls maintenance of dendrite arborization necessary for memory formation.

The role of neuronal dendrites is to receive and process synaptic inputs. The geometry of the dendritic arbor can undergo neuronal activity-dependent changes that may impact the cognitive abilities of the organism. Here we show that vascular endothelial growth factor D (VEGFD), commonly known as an angiogenic mitogen, controls the total length and complexity of dendrites both in cultured hippocampal neurons and in the adult mouse hippocampus. VEGFD expression is dependent upon basal neuronal activity and requires nuclear calcium-calmodulin-dependent protein kinase IV (CaMKIV) signaling. Suppression of VEGFD expression in the mouse hippocampus by RNA interference causes memory impairments. Thus, nuclear calcium-VEGFD signaling mediates the effect of neuronal activity on the maintenance of dendritic arbors in the adult hippocampus and is required for cognitive functioning. These results suggest that caution be employed in the clinical use of blockers of VEGFD signaling for antiangiogenic cancer therapy.

Nuclear calcium sensors reveal that repetition of trains of synaptic stimuli boosts nuclear calcium signaling in CA1 pyramidal neurons.

Nuclear calcium is a key signal in the dialogue between synapse and nucleus that controls the genomic responses required for persistent adaptations, including memory and acquired neuroprotection. The amplitude and duration of nuclear calcium transients specify activity-induced transcriptional changes. However, the precise relationship between synaptic input and nuclear calcium output is unknown. Here, we used stereotaxic delivery to the rat brain of recombinant adeno-associated viruses encoding nuclear-targeted calcium sensors to assess nuclear calcium transients in CA1 pyramidal neurons after stimulation of the Schaffer collaterals. We show that in acute hippocampal slices, a burst of synaptic activity elicits a nuclear calcium signal with a regenerative component at above-threshold stimulation intensities. Using classical stimulation paradigms (i.e., high-frequency stimulation (HFS) and θ burst stimulation (TBS)) to induce early LTP (E-LTP) and transcription-dependent late LTP (L-LTP), we found that the magnitude of nuclear calcium signals and the number of action potentials activated by synaptic stimulation trains are greatly amplified by their repetition. Nuclear calcium signals and action potential generation were reduced by blockade of either NMDA receptors or L-type voltage-gated calcium channels, but not by procedures that lead to internal calcium store depletion or by blockade of metabotropic glutamate receptors. These findings identify a repetition-induced switch in nuclear calcium signaling that correlates with the transition from E-LTP to L-LTP, and may explain why the transcription-dependent phase of L-LTP is not induced by a single HFS or TBS but requires repeated trains of activity. Recombinant, nuclear-targeted indicators may prove useful for further analysis of nuclear calcium signaling in vivo.

Hypoxic/ischemic conditions induce expression of the putative pro-death gene Clca1 via activation of extrasynaptic N-methyl-D-aspartate receptors.

The stimulation of extrasynaptic N-methyl-D-aspartate (NMDA) receptors triggers cell death pathways and has been suggested to play a key role in cell degeneration and neuron loss associated with glutamate-induced excitotoxicity. In contrast, synaptic NMDA receptors promote neuronal survival. One mechanism through which extrasynaptic NMDA receptors damage neurons may involve Clca1, which encodes a putative calcium-activated chloride channel. Here we show that Clca1 expression is induced in cultured rat hippocampal neurons exposed to oxygen/glucose-free media; this induction is mediated by a signaling pathway activated by extrasynaptic NMDA receptors. Clca1 mRNA levels also increased in the gerbil hippocampus following a transient forebrain ischemia caused by bilateral carotid occlusion. Microelectrode array recordings revealed that oxygen-glucose deprivation enhances hippocampal network firing rates, which induces c-fos transcription through a signaling pathway that, in contrast to Clca1, is activated by synaptic but not extrasynaptic NMDA receptors. Thus, conditions of low oxygen/glucose lead to the activation of both extrasynaptic and synaptic NMDA receptors that regulate distinct target genes. Clca1 may be part of the genomic death program triggered by extrasynaptic NMDA receptors; it could be a marker for ischemic brain damage and a possible target for therapeutic interventions.

The Wada test in Austrian, Dutch, German, and Swiss epilepsy centers from 2000 to 2005: a review of 1421 procedures.

Twenty-six Austrian, Dutch, German, and Swiss epilepsy centers were asked to report on use of the Wada test (intracarotid amobarbital procedure, IAP) from 2000 to 2005 and to give their opinion regarding its role in the presurgical diagnosis of epilepsy. Sixteen of the 23 centers providing information had performed 1421 Wada tests, predominantly the classic bilateral procedure (73%). A slight nonsignificant decrease over time in Wada test frequency, despite slightly increasing numbers of resective procedures, could be observed. Complication rates were relatively low (1.09%; 0.36% with permanent deficit). Test protocols were similar even though no universal standard protocol exists. Clinicians rated the Wada test as having good reliability and validity for language determination, whereas they questioned its reliability and validity for memory lateralization. Several noninvasive functional imaging techniques are already in use. However, clinicians currently do not want to rely solely on noninvasive functional imaging in all patients.

Structural, biochemical, and physiological characterization of C4 photosynthesis in species having two vastly different types of kranz anatomy in genus Suaeda (Chenopodiaceae).

C (4) species of family Chenopodiaceae, subfamily Suaedoideae have two types of Kranz anatomy in genus Suaeda, sections Salsina and Schoberia, both of which have an outer (palisade mesophyll) and an inner (Kranz) layer of chlorenchyma cells in usually semi-terete leaves. Features of Salsina (S. AEGYPTIACA, S. arcuata, S. taxifolia) and Schoberia type (S. acuminata, S. Eltonica, S. cochlearifoliA) were compared to C (3) type S. Heterophylla. In Salsina type, two layers of chlorenchyma at the leaf periphery surround water-storage tissue in which the vascular bundles are embedded. In leaves of the Schoberia type, enlarged water-storage hypodermal cells surround two layers of chlorenchyma tissue, with the latter surrounding the vascular bundles. The chloroplasts in Kranz cells are located in the centripetal position in Salsina type and in the centrifugal position in the Schoberia type. Western blots on C (4) acid decarboxylases show that both Kranz forms are NAD-malic enzyme (NAD-ME) type C (4) species. Transmission electron microscopy shows that mesophyll cells have chloroplasts with reduced grana, while Kranz cells have chloroplasts with well-developed grana and large, specialized mitochondria, characteristic of NAD-ME type C (4) chenopods. In both C (4) types, phosphoenolpyruvate carboxylase is localized in the palisade mesophyll, and Rubisco and mitochondrial NAD-ME are localized in Kranz cells, where starch is mainly stored. The C (3) species S. heterophylla has Brezia type isolateral leaf structure, with several layers of Rubisco-containing chlorenchyma. Photosynthetic response curves to varying CO (2) and light in the Schoberia Type and Salsina type species were similar, and typical of C (4) plants. The results indicate that two structural forms of Kranz anatomy evolved in parallel in species of subfamily Suaedoideae having NAD-ME type C (4) photosynthesis.

Excision of the coronary orifices in arterial switch operation: "O" like obstructive and "U" like unobstructive?

BACKGROUND: Stenoses of the neo-pulmonary artery (NPA) may complicate follow-up of the arterial switch operation (ASO). It is unknown whether the type of patch covering the coronary excision defects ("O"- or "U"-shaped) might influence this complication. METHODS: Echocardiographically and invasively measured NPA pressure-gradients were evaluated retrospectively in 95 children after ASO. Median follow-up was 5.8 years. Defects had been covered with pericardial patches: O/O and U/U (left/right) 34 x each, and 27 x in mixed combinations. The frequency of NPA stenoses requiring re-interventions was registered. RESULTS: Median of the peak instantaneous echocardiographic pressure gradient was 23 mmHg (interquartile range, IQR: 16 - 49, n = 34) in O/O, and 19 mmHg (IQR: 13 - 23, n = 34) in U/U; p < 0.034, t-test. Invasively measured gradients were 49 mmHg (IQR: 17 - 65, n = 12) in O/O, and 12 mmHg (IQR: 7-21, n = 28) in U/U; p < 0.001. One child per O/O- and U/U-group underwent balloon angioplasty of the neo-pulmonary root. Five children of the O/O-group had to undergo repeat surgery, whereas only one child in the U/U-group required repeat surgery ( p < 0.34). CONCLUSIONS: The preferential type of covering the NPA coronary excision sites in ASO should be U-shaped.

Acoustomechanical properties of open TTP titanium middle ear prostheses.

OBJECTIVE: The purpose of the study was to identify acoustcomechanical properties of various biostable and biocompatible materials to create a middle ear prosthesis with the following properties: (i) improved handling including a good view of the head of the stapes or footplate and adjustable length, (ii) improved acoustical characteristics that are adequate for ossiculoplastic. The identified material should serve to build CE and FDA approved prostheses for clinical use in patients. METHODS: Test models made of Teflon, polyetheretherketone, polyethylenterephtalate, polysulfone, gold, Al2O3 ceramics, carbon and titanium were investigated for their potential to fulfill the requirements. Acoustical properties were investigated by laser Doppler velocimetry (LDV) in mechanical middle ear models (MMM). Measured data were fed in to a recently created computer model of the middle ear (multibody systems approach, MBS). Using computer-aided design (CAD) measured and computed data allowed creation and fine precision of titanium prostheses (Tübingen Titanium Protheses, TTP). Their handling was tested in temporal bones. Acoustomechanical properties were investigated using the MBS and mechanical middle ear models. MAIN OUTCOME MEASURES: Input impedance, mass, stiffness, and geometry of test models and prostheses were determined. Furthermore, their influence on the intraprosthetic transfer functions and on coupling to either tympanic membrane or stapes was investigated. RESULTS: Final results were FDA- and CE-approved filigreed titanium prostheses with an open head that fulfilled the four requirements detailed above. The prostheses (TTP) were developed in defined lengths of between 1.75 and 3.5 mm (partial) and 3.0 and 6.5 mm (total) as well as in adjustable lengths (TTP-Vario). CONCLUSIONS: The results suggest acoustomechanical advantages of TTPs because they combine a significantly low mass with high stiffness. In contrast to closed prostheses, the open head and filigreed design allow an excellent view of the prosthesis foot during coupling to the head or footplate of stapes, contributing to an improved intraoperative reliability of prosthesis coupling.

Language lateralization by Wada test and fMRI in 100 patients with epilepsy.

Comparing the determination of language dominance using fMRI with results of the Wada test in 100 patients with different localization-related epilepsies, the authors found 91% concordance between both tests. The overall rate of false categorization by fMRI was 9%, ranging from 3% in left-sided temporal lobe epilepsy (TLE) to 25% in left-sided extratemporal epilepsy. Language fMRI might reduce the necessity of the Wada test for language lateralization, especially in TLE.

Collateral circulation is an independent radiological predictor of outcome after thrombolysis in acute ischaemic stroke.

We tested the hypothesis that the type of vascular occlusion, recanalisation and collateralisation are predictive of outcome after thrombolytic therapy in acute ischaemic stroke. We carried out angiography and local intra-arterial (97) or systemic (14) thrombolysis within 6 h of the onset in patients with an ischaemic stroke in the territory of the internal carotid artery. Early ischaemic signs (EIS) on pretreatment CT and angiographic findings were classified and analysed in relation to clinical outcome at 3 months. A favourable outcome (Barthel index [BI]>/= 90) was found in 40% of patients with an occlusion of the middle cerebral artery trunk whereas intracranial occlusion of the internal carotid artery ("carotid T occlusion") was followed by death or severe disability (BI<50) in 87%. Significant univariate predictors of favourable outcome were occlusion type ( P<0.01), recanalisation ( P<0.01) and collateralisation ( P<0.01). However, multivariate analysis revealed a significant relationship only between collateralisation and favourable outcome (odds ratio 5.9, 95% confidence interval 1.3-26.7, P=0.02). EIS were not predictive in either case. Occlusion type and recanalisation, are related to outcome only if adequate collateralisation prevents infarction until recanalisation occurs.

Epilepsy surgery outcome in children with focal epilepsy due to tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is frequently associated with focal epilepsy due to cerebral tubers. Seizures are the first symptoms in most patients with brain involvement. These epilepsies are frequently severe, drug-resistant and may have a negative impact on the child's global development. Although most epilepsies are multicentric, these patients may be candidates for epilepsy surgery, if it is possible to determine a leading epileptogenic tuber. Nine patients with TSC were examined with long-term video-EEG monitoring, different neuroimaging techniques and neuropsychological tests. A main epileptogenic tuber could be identified in all of our patients. We found good correlations between neuroimaging and EEG. Surgery was performed in eight patients. Seizure outcome was good in all. Two patients became seizure-free, one patient had a single prolonged seizure five days postoperatively, four patients had a significant seizure reduction of more than 75 % and one patient had a seizure reduction of more than 50 % after surgery without additional neurologic deficits. In conclusion, patients with TSC and drug-resistant epilepsy may benefit from epilepsy surgery with reduction in frequency and severity of seizures as well as improved mental and behavioural development leading to a better quality of life. In view of recent developments in functional and metabolic imaging, primary epileptogenic lesions will be more easily detectable in patients with diffuse brain involvement in TSC and surgical treatment may be more specifically applied at an earlier age to a selected subgroup of patients with this disorder.

Kranz anatomy is not essential for terrestrial C4 plant photosynthesis.

An important adaptation to CO2-limited photosynthesis in cyanobacteria, algae and some plants was development of CO2-concentrating mechanisms (CCM). Evolution of a CCM occurred many times in flowering plants, beginning at least 15-20 million years ago, in response to atmospheric CO2 reduction, climate change, geological trends, and evolutionary diversification of species. In plants, this is achieved through a biochemical inorganic carbon pump called C4 photosynthesis, discovered 35 years ago. C4 photosynthesis is advantageous when limitations on carbon acquisition are imposed by high temperature, drought and saline conditions. It has been thought that a specialized leaf anatomy, composed of two, distinctive photosynthetic cell types (Kranz anatomy), is required for C4 photosynthesis. We provide evidence that C4 photosynthesis can function within a single photosynthetic cell in terrestrial plants. Borszczowia aralocaspica (Chenopodiaceae) has the photosynthetic features of C4 plants, yet lacks Kranz anatomy. This species accomplishes C4 photosynthesis through spatial compartmentation of photosynthetic enzymes, and by separation of two types of chloroplasts and other organelles in distinct positions within the chlorenchyma cell cytoplasm.

Procalcitonin as a diagnostic marker in patients with aspiration after closed head injury.

BACKGROUND: Aspiration of gastric content frequently induces early onset of pneumonia in patients with impaired consciousness after closed head injury and thus worsens the prognosis. Early detection of aspiration and appropriate therapy are essential. The purpose of the study was to assess the diagnostic value of procalcitonin (ProCT) in aspiration of gastric content and to evaluate its prognostic impact in patients with closed head injury. METHODS: Twenty-three patients with isolated closed head injury (Glasgow Coma Scale [GCS] score < or = 8) were studied. Bronchoscopy was done on admission; chest radiographs and routine laboratory examination including C-reactive protein were performed daily. ProCT was analyzed 12, 24, 36 and 72 hours after trauma using an immunoluminometric assay. RESULTS: ProCT was higher throughout the study period in 9 patients with persistent radiological signs suspect for aspiration of gastric content and there was evidence of aspiration of gastric content during bronchoscopy on admission. Median ProCT values of 1.397 ng/ml (range, 0.372 to 8.358 ng/ml) on admission increased to 2.144 ng/ml (range, 0.716 to 6.910 ng/ml) 24 hours after trauma, and then decreased to baseline values of 1.711 ng/ml (range, 0.611 to 6.639 ng/ml) as early as 36 hours after trauma. In patients without signs of aspiration of gastric content, ProCT values did not exceed 0.418 ng/ml. Non-survivors had higher serum levels of ProCT throughout the study period. CONCLUSION: Our findings suggest that ProCT is a useful diagnostic marker for detecting aspiration of gastric content while the prognostic value of ProCT for predicting survival after isolated closed head injury was moderate.

New observations on the secondary chemistry of world Ephedra (Ephedraceae).

For several millennia, stem extracts of Ephedra (Ephedraceae, Gnetales) have been used as folk medicines in both the Old and New World. Some species were used in treatments of questionable efficacy for venereal disease in North America during the last century. Many Eurasian species produce phenylethylamine alkaloids, mostly ephedrine and pseudoephedrine, that interact with adrenergic receptors in the mammalian sympathetic nervous system. Asian Ephedra have been used recently in the clandestine manufacture of a street drug, methamphetamine. Although ephedrine alkaloids are not detectable in New World species of Ephedra, together with Asian species they contain other nitrogen-containing secondary metabolites with known neuropharmacological activity. Many mesic and particularly xeric species worldwide accumulate substantial amounts of quinoline-2-carboxylic acids, or kynurenates, in their aerial parts. Many species of Ephedra accumulate cyclopropyl amino acid analogues of glutamate and proline in their stems and roots, and particularly in the seed endosperm. Mesic species synthesize substantial amounts of three L-2-(carboxycyclopropyl)glycine stereomers rarely seen in nature. A cyclopropyl analogue of proline with known antimicrobial activity, cis-3,4-methanoproline, is found in large amounts in the stems and seeds of many Ephedra species. The ability to synthesize cyclopropyl amino acids may be an ancestral feature in the taxon. The natural function in the taxon of these three groups of secondary compounds remains to be established.

A prospective randomized trial comparing the cuffed oropharyngeal airway (COPA) with the laryngeal mask for elective minor surgery in female patients.

OBJECTIVE: The cuffed oropharyngeal airway (COPA), a modified Guedel-type airway with a cuff at the distal end, has recently been introduced into anesthetic practice. The aim of this study was to compare the COPA with the well established laryngeal mask airway (LMA). Special consideration was granted to the difficult airway. PATIENTS AND METHODS: Two hundred and fifty-two women of ASA class I or II undergoing elective gynecological or breast surgery under general anesthesia were randomly assigned to either cuffed oropharyngeal or laryngeal mask airway management. Insertion and removal of the device, airway maintenance throughout the procedure, and postoperative course and complications were assessed. RESULTS: A patent airway was obtained with either device in all patients. Global first-time success rates for insertion were similar in the two study groups. Initial failure of correct placement occurred more frequently in the COPA as compared to the LMA group if the interincisor gap was < 5 cm and mandibular protrusion impossible (p < 0.01). Neither thyromental distance nor Mallampati scores nor body mass index (BMI) were of relevance for insertion success. The incidence of postoperative complaints and of mucosal injuries was significantly higher with the LMA. CONCLUSION: On the whole, high overall success and low complication rates render COPA and LMA equally suitable for routine anesthetic airway management.