The conduction of protons in different stereoisomers of dioxolane-linked gramicidin A channels.
(9/1668)
Two different stereoisomers of the dioxolane-linked gramicidin A (gA) channels were individually synthesized (the SS and RR dimers;. Science. 244:813-817). The structural differences between these dimers arise from different chiralities within the dioxolane linker. The SS dimer mimics the helicity and the inter- and intramolecular hydrogen bonding of the monomer-monomer association of gA's. In contrast, there is a significant disruption of the helicity and hydrogen bonding pattern of the ion channel in the RR dimer. Single ion channels formed by the SS and RR dimers in planar lipid bilayers have different proton transport properties. The lipid environment in which the different dimers are reconstituted also has significant effects on single-channel proton conductance (g(H)). g(H) in the SS dimer is about 2-4 times as large as in the RR. In phospholipid bilayers with 1 M [H(+)](bulk), the current-voltage (I-V) relationship of the SS dimer is sublinear. Under identical experimental conditions, the I-V plot of the RR dimer is supralinear (S-shaped). In glycerylmonooleate bilayers with 1 M [H(+)](bulk), both the SS and RR dimers have a supralinear I-V plot. Consistent with results previously published (. Biophys. J. 73:2489-2502), the SS dimer is stable in lipid bilayers and has fast closures. In contrast, the open state of the RR channel has closed states that can last a few seconds, and the channel eventually inactivates into a closed state in either phospholipid or glycerylmonooleate bilayers. It is concluded that the water dynamics inside the pore as related to proton wire transfer is significantly different in the RR and SS dimers. Different physical mechanisms that could account for this hypothesis are discussed. The gating of the synthetic gA dimers seems to depend on the conformation of the dioxolane link between gA's. The experimental results provide an important framework for a detailed investigation at the atomic level of proton conduction in different and relatively simple ion channel structures. (+info)
Nonglutamate pore residues in ion selection and conduction in voltage-gated Ca2+ channels.
(10/1668)
High-affinity, intrapore binding of Ca(2+) over competing ions is the essential feature in the ion selectivity mechanism of voltage-gated Ca(2+) channels. At the same time, several million Ca(2+) ions can travel each second through the pore of a single open Ca(2+) channel. How such high Ca(2+) flux is achieved in the face of tight Ca(2+) binding is a current area of inquiry, particularly from a structural point of view. The ion selectivity locus comprises four glutamate residues within the channel's pore. These glutamates make unequal contributions to Ca(2+) binding, underscoring a role for neighboring residues in pore function. By comparing two Ca(2+) channels (the L-type alpha(1C), and the non-L-type alpha(1A)) that differ in their pore properties but only differ at a single amino acid position near the selectivity locus, we have identified the amino-terminal neighbor of the glutamate residue in motif III as a determinant of pore function. This position is more important in the function of alpha(1C) channels than in alpha(1A) channels. For a systematic series of mutations at this pore position in alpha(1C), both unitary Ba(2+) conductance and Cd(2+) block of Ba(2+) current varied with residue volume. Pore mutations designed to make alpha(1C) more like alpha(1A) and vice versa revealed that relative selectivity for Ba(2+) over K(+) depended almost solely on pore sequence and not channel type. Analysis of thermodynamic mutant cycles indicates that the motif III neighbor normally interacts in a cooperative fashion with the locus, molding the functional behavior of the pore. (+info)
Amsorb: a new carbon dioxide absorbent for use in anesthetic breathing systems.
(11/1668)
BACKGROUND: This article describes a carbon dioxide absorbent for use in anesthesia. The absorbent consists of calcium hydroxide with a compatible humectant, namely, calcium chloride. The absorbent mixture does not contain sodium or potassium hydroxide but includes two setting agents (calcium sulphate and polyvinylpyrrolidine) to improve hardness and porosity. METHODS: The resultant mixture was formulated and subjected to standardized tests for hardness, porosity, and carbon dioxide absorption. Additionally, the new absorbent was exposed in vitro to sevoflurane, desflurane, isoflurane, and enflurane to determine whether these anesthetics were degraded to either compound A or carbon monoxide. The performance data and inertness of the absorbent were compared with two currently available brands of soda lime: Intersorb (Intersurgical Ltd., Berkshire, United Kingdom) and Dragersorb (Drager, Lubeck, Germany). RESULTS: The new carbon dioxide absorbent conformed to United States Pharmacopeia specifications in terms of carbon dioxide absorption, granule hardness, and porosity. When the new material was exposed to sevoflurane (2%) in oxygen at a flow rate of 1 l/min, concentrations of compound A did not increase above those found in the parent drug (1.3-3.3 ppm). In the same experiment, mean +/-SD concentrations of compound A (32.5 +/- 4.5 ppm) were observed when both traditional brands of soda lime were used. After dehydration of the traditional soda limes, immediate exposure to desflurane (60%), enflurane (2%), and isoflurane (2%) produced concentrations of carbon monoxide of 600.0 +/- 10.0 ppm, 580.0 +/- 9.8 ppm, and 620.0 +/-10.1 ppm, respectively. In contrast, concentrations of carbon monoxide were negligible (1-3 ppm) when the anhydrous new absorbent was exposed to the same anesthetics. CONCLUSIONS: The new material is an effective carbon dioxide absorbent and is chemically unreactive with sevoflurane, enflurane, isoflurane, and desflurane. (+info)
Structural aspects of the zona pellucida of in vitro-produced bovine embryos: a scanning electron and confocal laser scanning microscopic study.
(12/1668)
Structural aspects of the bovine zona pellucida (ZP) of in vitro-matured (IVM) oocytes and in vitro-produced (IVP) embryos were studied in two experiments to find a tentative explanation for the zona's barrier function against viral infection. In Experiment 1, the ultrastructure of the outer ZP surface was studied. The diameter (nm) and the number of the outer pores within an area of 5000 microm(2) of 10 IVM oocytes, 10 zygotes, 10 8-cell-stage embryos, and 10 morulae were evaluated by scanning electron microscopy. In oocytes and morulae, the ZP surface showed a rough and spongy appearance with numerous pores. In zygotes, the ZP surface was found to have a smooth, melted appearance with only a few pores. In 8-cell-stage embryos, both surface patterns were found. The mean number (per 5000 microm(2)) and the mean diameter of the outer pores were different between the four stages of development (P < 0.001): 1511 pores in oocytes, 1187 in zygotes, 1658 in 8-cell-stage embryos, and 3259 in morulae, with mean diameters of 182, 223, 203, and 155 nm, respectively. In Experiment 2, the continuity of the meshes (network of pores) towards the embryonic cells was examined by confocal laser scanning microscopy. Therefore, the passage through and the location in the ZP of fluorescent microspheres, with similar dimensions as bovine viral diarrhea virus (BVDV, 40-50 nm) and bovine herpesvirus-1 (BHV-1; 180-200 nm), were evaluated. For all stages, the smallest beads were detected halfway through the thickness of the ZP, whereas the beads with a size of 200 nm were found only within the outer-fourth part of the ZP. It can be concluded that the intact ZP of bovine IVM oocytes and IVP embryos are constructed in such a way that BVDV and BHV-1 should not be able to traverse the ZP and reach the embryonic cells. However, the risk exists that viral particles can be trapped in the outer layers of the ZP. (+info)
Visualization of gas flow and diffusion in porous media.
(13/1668)
The transport of gases in porous materials is a crucial component of many important processes in science and technology. In the present work, we demonstrate how magnetic resonance microscopy with continuous flow laser-polarized noble gases makes it possible to "light up" and thereby visualize, with unprecedented sensitivity and resolution, the dynamics of gases in samples of silica aerogels and zeolite molecular sieve particles. The "polarization-weighted" images of gas transport in aerogel fragments are correlated to the diffusion coefficient of xenon obtained from NMR pulsed-field gradient experiments. The technique provides a unique means of studying the combined effects of flow and diffusion in systems with macroscopic dimensions and microscopic internal pore structure. (+info)
Bone densitometry: influence of prosthetic design and hydroxyapatite coating on regional adaptive bone remodelling.
(14/1668)
The objective of this prospective study was to determine if bone densitometry can detect disparities in regional adaptive bone remodelling surrounding the cementless porous-coated femoral component of a hip prosthesis in two titanium alloy implants of different design . These prostheses were the S-ROM (n=69) and the Multilock (n=65). The Multilock implants consisted of two groups; 25 had a 50 micron layer of hydroxyapatite (HA) sprayed over the porous surface of the femoral component and the remaining 40 femoral components were not coated with HA. Densitometry was performed with dual energy X-ray absorptiometry (DXA) utilizing the LUNAR ORTHO software to analyse the seven Gruen zones. Bone mineral density measurements were obtained within a week of surgery as a baseline reference and at 6, 12, 24, 36 and 48 months thereafter. At 6 months there was significant mineral loss in all Gruen zones in the three prostheses. By 48 months there were differences in mineral loss between the three prostheses. In the zones adjacent to the porous surface, predominantly zones 1 and 7, the S-ROM exhibited 60% less mineral loss than the Multilock in zone 1, and there was no significant difference in zone 7. Compared to the Multilock-HA, the S-ROM lost 35% less mineral in zone 1, but the Multilock lost 70% less mineral than the S-ROM in zone 7. The Multilock-HA lost 37% and 75% less mineral than the Multilock in zones 1 and 7, respectively, i.e., hydroxyapatite coating tended to preserve bone stalk. Using the Gruen zone area measurements provided by the software, the S-ROM had significantly greater bone resorption in zone 7 at 24 months than either of the Multilocks, which did not differ from each other. In conclusion, DXA has shown differences in periprosthetic adaptive bone remodelling between implants of different design and composition as a function of time. (+info)
Occlusion of experimentally created fusiform aneurysms with porous metallic stents.
(15/1668)
BACKGROUND AND PURPOSE: Carotid fusiform aneurysms are most commonly treated with occlusion of the parent vessel. The purpose of our study was to assess the effectiveness of self-expanding, cobalt-alloy stents in the ablation of experimental fusiform aneurysms with preservation of the parent vessel in a carotid artery model. METHODS: Porous metallic stents were placed endovascularly along the lengths of experimentally created fusiform aneurysms in the carotid arteries of dogs; aneurysms were also created in the animals' opposite carotid arteries to serve as controls. RESULTS: Before stent placement, angiography of the carotid arteries showed large fusiform aneurysms along the lengths of the common carotid arteries and complex patterns of flow. Immediately after stent placement there was disruption of the usual flow patterns within the lumens of the fusiform aneurysms. The lumen between the wall of the aneurysm and stented carotid showed stasis of contrast material and blood. Near-complete ablation of all aneurysms was observed 8 weeks after stent placement. The stented carotid arteries remained widely patent; control aneurysms and carotid arteries were patent and unchanged. Histopathologic analysis revealed fibrotic reactive scar tissue filling the space between the stent wires and outer wall of the fusiform aneurysm. CONCLUSION: Changing blood flow dynamics within an aneurysm can promote thrombus formation. The stent promotes stasis and thrombus within the residual lumen between the stent wall and the outer wall of the aneurysm because its woven wire mesh interferes with usual blood flow patterns, which then promotes formation of thrombus and fibrosis within the residual aneurysmal lumen. (+info)
Local antithrombotic therapy using a novel porous balloon catheter.
(16/1668)
The efficacy of local treatment of thrombosis with low-dose antithrombotic drugs (heparin: 30 U/kg, or argatroban: 0.02 mg/kg) was investigated using a novel porous balloon catheter. This novel balloon catheter can deliver drug into arterial walls without causing vascular trauma. Thrombus formation was significantly inhibited in balloon-injured and locally-treated iliac arteries compared with control balloon-injured arteries in 12 dogs. In the systemic high-dose delivery group (ten times as high as the low dose), thrombus formation in injured arteries was significantly less than that of controls in 7 dogs. Low-dose systemic delivery was not effective at inhibiting this thrombus formation. Thus, local treatment with an antithrombotic drug using this novel porous balloon catheter can prevent thrombosis without influencing systemic coagulability. (+info)