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PubMed1998

Evaluation of restorative and implant alloys galvanically coupled to titanium.

OBJECTIVES: As the success of implants leads to their increasing use in restorative dentistry, attention should be devoted to the galvanic combination of restorative materials with titanium. This paper used continuous corrosion potential monitoring in conjunction with zero-resistance ammetry to obtain galvanic corrosion properties of restorative and implant materials coupled with titanium (ASTM F67-Grade II). METHODS: Direct coupling or galvanic experiments were conducted on eight restorative and implant materials coupled to titanium. Deaerated artificial saliva solution in a specifically designed corrosion cell simulated an oral crevice situation. Open circuit potentials (Eo.c.) of each material in the couple, coupled corrosion potentials (Ecouple corr), coupled corrosion current density (lcouple corr) and the resultant charge transfer were monitored. The results were analyzed using single factor ANOVA and Duncan's multiple range tests. RESULTS: Noble restorative (Au-, Ag-, and Pd-based) alloys coupled to titanium were found to be least susceptible to galvanic corrosion. Co-Cr-Mo, Ni-Cr and Fe-based alloys coupled to tatanium were found to be moderately susceptible to galvanic corrosion due to mechanical-electrochemical interaction. Ni-Cr-Be alloy coupled to titanium was found to be highly susceptible to galvanic corrosion. The in vitro test results for the titanium/Disperalloy combination does not concur with the published clinical performance of this combination, and thus warrants further investigation. SIGNIFICANCE: From the data obtained in this study and current literature profiles, acceptable restorative couples were developed for use as clinical guidelines in restorative dentistry.

Analysis of Variance↗

PubMed1997

HLA-C and -Bw typing of couples with unexplained recurrent miscarriages.

There is now evidence that the classical HLA class I molecule HLA-C is expressed on extravillous trophoblasts together with non-classical HLA-G molecules. Since clones of NK-cells are inhibited differently by supertypic epitopes associated with HLA-C and -B alleles we found it of interest to study HLA-C and -Bw polymorphism in 35 couples with recurrent miscarriage and 30 control couples with normal fecundity. All HLA assignments were undertaken by DNA techniques. The distribution of HLA-C alleles or the HLA-C associated supertypic epitopes recognized by NK1 or NK2 clones was not significantly different between patients and controls. The distribution of couples according to the number of NK1 and NK2 epitopes in the couple was similar in patients and controls. With respect to the HLA-Bw epitopes recognized by NKB1 clones, in 46% of the couples with recurrent miscarriage none of the spouses carried the HLA-Bw4 epitope compared with only 17% of the control couples (P < 0.02). It is concluded that the HLA-Bw4 epitope is carried more frequently by couples with normal fecundity than couples with recurrent miscarriage. The fetuses of couples with recurrent miscarriage are thus expected to lack expression of HLA-Bw4 epitopes on the trophoblast more often than fetuses of normal couples which might be of importance for the inhibition of NK-cell mediated antitrophoblast cytotoxicity.

Abortion, Habitual↗

PubMed2000

Investigation of the role of the carboxyl-terminal tails of the alpha and beta isoforms of the human thromboxane A(2) receptor (TP) in mediating receptor:effector coupling.

We have investigated the functional coupling of alpha and beta isoforms of the human thromboxane A(2) receptor (TP) to Galpha(16) and Galpha(12) members of the G(q) and G(12) families of heterotrimeric G proteins in human embryonic kidney (HEK) 293 cell lines HEK.alpha10 or HEK.beta3, stably over-expressing TPalpha and TPbeta, respectively. Moreover, using HEK.TP(Delta328) cells which over-express a variant of TP truncated at the point of divergence of TPalpha and TPbeta, we investigated the requirement of the C-tail per se in mediating G protein coupling and effector activation. Both TPalpha and TPbeta couple similarly to Galpha(16) to affect increases in inositol 1,4,5-trisphosphate (IP(3)) and mobilisation of intracellular calcium ([Ca(2+)](i)) in response to the TP agonist U46619. Whilst both TP isoforms mediated [Ca(2+)](i) mobilisation in cells co-transfected with Galpha(12), neither receptor generated corresponding increases in IP(3), indicating that the Galpha(12)-mediated increases in [Ca(2+)](i) do not involve PLC activation. Verapamil, an inhibitor of voltage dependent Ca(2+) channels, reduced [Ca(2+)](i) mobilisation in TPalpha and TPbeta cells co-transfected with Galpha(12) to approximately 40% of that mobilised in its absence, whereas [8-(N,N-diethylamino)-octyl-3,4, 5-trimethoxybenzoate, hydrochloride] (TMB-8), an antagonist of intracellular Ca(2+) release, had no effect on [Ca(2+)](i) mobilisation by either receptor isoform co-transfected with Galpha(12). Despite the lack of differential coupling specificity by TPalpha and TPbeta, TP(Delta328) signalled more efficiently in the absence of a co-transfected G protein compared to the wild type receptors but, on the other hand, displayed an impaired ability to couple to co-transfected Galpha(11), Galpha(12) or Galpha(16) subunits. In studies investigating the role of the C-tail in influencing coupling to the effector adenylyl cyclase, similar to TPalpha but not TPbeta, TP(Delta328) coupled to Galpha(s), leading to increased adenosine 3',5'-cyclic monophosphate (cAMP), rather than to Galpha(i). Whereas TP(Delta328) signalled more efficiently in the absence of co-transfected G protein compared to the wild type TPalpha, co-transfection of Galpha(s) did not augment cAMP generation by TP(Delta328). Hence, from these studies involving the wild type TPalpha, TPbeta and TP(Delta328), we conclude that the C-tail sequences of TP are not a major determinant of G protein coupling specificity to Galpha(11) and Galpha(16) members of the G(q) family or to Galpha(12); it may play a role in determining G(s) versus G(i) coupling and may act as a determinant of coupling efficiency.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2003

Effects of pH and molecular charge on dipolar coupling interactions of solutes in skeletal muscle observed by DQF, 1H NMR spectroscopy.

In this study we tested the effect of molecular charge and chirality as well as tissue pH on dipolar coupling interaction in skeletal muscle. These results were demonstrated by double quantum filtered, DQF, 1H NMR spectra acquired on permeable skeletal muscle samples dialyzed against buffered solutions containing three classes of solutes-electrolytes (lactate and Tris), zwitterions (alanine and glycine), and non-electrolytes (dioxane and ethanol)-as a function of pH ranging from 5.0 to 8.5. The results show that charge density on the protein filaments strongly influences dipolar coupling of solutes in muscle whereas charge on the solutes themselves has only a small effect. The frequency splitting of the dipolar coupled peaks for all the molecules tested was strongly affected by muscle pH. Higher pH increased negative charge density on the filaments and resulted in weaker dipolar coupling for anions and zwitterions but stronger coupling for the cation TRIS. Molecular charge per se or chirality did not affect the frequency splitting of the dipolar coupled peaks. The molecules, lactate, ethanol, and alanine, have scalar coupled spins and consequently a double quantum signal in solution. However, spectra acquired from these molecules in muscle showed an additional frequency splitting due to additional dipolar coupling interactions. Due to lack of scalar coupling, spectra from Tris, glycine, and dioxane showed no double quantum signal in solution but did when in muscle. All these observations can be explained by the fact that the net charge on protein filaments dominates the mechanism of dipolar coupling interactions in the highly anisotropic structures in muscle.

Abdominal Muscles↗

PubMed2002

[Impressions od couples treated with fertilization in vitro of their treatment by the IVF center].

A preliminary study was designed to evaluate, among French couples treated for in vitro fertilization, their feelings about the delivered information on IVF and the degree of satisfaction about their treatment by the center. Anonymous forms were mailed to 3,000 couples, from which 835 were returned on time to be analyzed. Most of the couples expressed their satisfaction. However, 25% were disappointed by their first consultation, too short (14%) or too long to obtain (13%), especially for those treated in a public hospital. One quarter of couples waited for more than six months before their first cycle, more often in public practice than in private one, and 80% found this time lapse too long. One third of the couples changed of unit, 62% of them because of disappointment, mostly because of their relationship with the medical team, and only 20% because of poor results. Two thirds of the couples found IVF had repercussions on their couple's life, negatively in 31% of the cases. This percentage was higher for those with unsuccessful IVF (45%) than for those who got a pregnancy (22%). Information on IVF was judged as satisfactory only for two thirds of the couples, for any kind of information, and less than half of men were told how the inseminated semen quality was. Moreover, only 57% of the couples found the information reassuring. Local conditions for semen collection were judged to be bad by 30% of the men. Finally, this study showed that efforts still have to be made by units to better treat and inform IVF couples. It also seems necessary to undertake a prospective and more detailed study to better investigate the degree of satisfaction and its parameters.

Adult↗

PubMedDate not supplied

The network properties of bipolar-bipolar cell coupling in the retina of teleost fishes.

Retinal bipolar cells exhibit a center-surround antagonistic receptive field to a light stimulus (Werblin & Dowling, 1969; Kaneko, 1970), and thus constitute an early stage of spatial information processing. We injected Lucifer Yellow and a small biotinylated tracer, biocytin, into bipolar cells of the teleost retina to examine electrical coupling in these cells. Lucifer-Yellow coupling was observed in one of 55 stained bipolar cells; the coupling pattern was one injected bipolar cell and three surrounding cells. Biocytin coupling was observed in 16 of 55 stained bipolar cells, six of which were ON center and ten OFF center. Although biocytin usually coupled to three to six bipolar cells, some OFF-center bipolar cells showed strong coupling to more than 20 cells. The biocytin-coupled bipolar cells were morphologically homologous. Membrane appositions resembling gap junctions were found between dendrites and between axon terminals of neighboring bipolar cells. In the strongest biocytin-coupled bipolar cells, the contacts between bipolar cells and cone photoreceptor cells were examined after reconstruction of the dendritic trees of five well-stained, serially sectioned OFF-center bipolar cells. Each of these bipolar cells was in contact with different numbers of cones: 11 to 20 for twin cones and two to four for single cones. This implies that, although these bipolar cells belong to the same category, the signal inputs differ among bipolar cells. Numerical simulation conducted on a hexagonal array network model demonstrated that the electrical coupling of bipolar cells can decrease the difference in input (approximately 80%) without causing significant loss of spatial resolution. Our results suggest that electrical coupling of bipolar cells has the advantage of decreasing the dispersion of input signals from cones, and permits bipolar cells of the same class to respond to light with similar properties.

Animals↗

PubMed2001

Oxidation state dependence of the geometry, electronic structure, and magnetic coupling in mixed oxo- and carboxylato-bridged manganese dimers.

Approximate density functional theory has been used to investigate changes in the geometry and electronic structure of the mixed oxo- and carboxylato-bridged dimers [Mn(2)(mu-O)(2)(O(2)CH)(NH(3))(6)](n+)and [Mn(2)(mu-O)(O(2)CH)(2)(NH(3))(6)](n+)in the Mn(IV)Mn(IV), Mn(III)Mn(IV), and Mn(III)Mn(III) oxidation states. The magnetic coupling in the dimer is profoundly affected by changes in both the bridging ligands and Mn oxidation state. In particular, change in the bridging structure has a dramatic effect on the nature of the Jahn-Teller distortion observed for the Mn(III) centers in the III/III and III/IV dimers. The principal magnetic interactions in [Mn(2)(mu-O)(2)(O(2)CH)(NH(3))(6)](n+)() involve the J(xz/xz)and J(yz/yz) pathways but due to the tilt of the Mn(2)O(2) core, they are less efficient than in the planar di-mu-oxo structure and, consequently, the calculated exchange coupling constants are generally smaller. In both the III/III and III/IV dimers, the Mn(III) centers are high-spin, and the Jahn-Teller effect gives rise to axially elongated Mn(III) geometries with the distortion axis along the Mn-O(c) bonds. In the III/IV dimer, the tilt of the Mn(2)O(2) core enhances the crossed exchange J(x)()()2(-)(y)()()2(/)(z)()()2 pathway relative to the planar di-mu-oxo counterpart, leading to significant delocalization of the odd electron. Since this delocalization pathway partially converts the Mn(IV) ion into low-spin Mn(III), the magnetic exchange in the ground state can be considered to arise from two interacting spin ladders, one is the result of coupling between Mn(IV) (S = 3/2) and high-spin Mn(III) (S = 2), the other is the result of coupling between Mn(IV) (S = 3/2) and low-spin Mn(III) (S = 1). In [Mn(2)(mu-O)(O(2)CH)(2)(NH(3))(6)](n+)(), both the III/III dimer and the lowest energy structure for the III/IV dimer involve high-spin Mn(III), but the Jahn-Teller axis is now orientated along the Mn-oxo bond, giving rise to axially compressed Mn(III) geometries with long Mn-O(c) equatorial bonds. In the IV/IV dimer, the ferromagnetic crossed exchange J(yz)()(/)(z)()()2 pathway partially cancels J(yz/yz) and, as a consequence, the antiferromagnetic J(xz/xz) pathway dominates the magnetic coupling. In the III/III dimer, the J(yz/yz) pathway is minimized due to the smaller Mn-O-Mn angle, and since the ferromagnetic J(yz)()(/)(z)()()2 pathway largely negates J(xz/xz), relatively weak overall antiferromagnetic coupling results. In the III/IV dimer, the structures involving high-spin and low-spin Mn(III) are almost degenerate. In the high-spin case, the odd electron is localized on the Mn(III) center, and the resulting antiferromagnetic coupling is similar to that found for the IV/IV dimer. In the alternative low-spin structure, the odd electron is significantly delocalized due to the crossed J(yz)()(/)(z)()()2 pathway, and cancellation between ferromagnetic and antiferromagnetic pathways leads to overall weak magnetic coupling. The delocalization partially converts the Mn(IV) ion into high-spin Mn(III), and consequently, the spin ladders arising from coupling of Mn(IV) (S = 3/2) with high-spin (S = 2) and low-spin (S = 1) Mn(III) are configurationally mixed. Thus, in principle, the ground-state magnetic coupling in the mixed-valence dimer will involve contributions from three spin-ladders, two associated with the delocalized low-spin structure and the third arising from the localized high-spin structure.

Journal Article↗

PubMed2006

An ab initio study of 15N-11B spin-spin coupling constants for borazine and selected derivatives.

Ab initio equation-of-motion coupled-cluster singles and doubles (EOM-CCSD) calculations have been performed to investigate substituent effects on coupling constants for borazine and selected substituted borazines. For molecules in which F atoms are not bonded to adjacent atoms in the ring, F substitution increases the one-bond (11)B-(15)N coupling constants involving the atom at which substitution occurs but leaves the remaining one-bond B-N coupling constants essentially unchanged. For these molecules, the magnitudes of one-bond B-N coupling constants are only slightly dependent on the number of F atoms present. Fluorine substitution at adjacent B and N atoms in the borazine ring further increases the one-bond B-N coupling constant involving the substituted atoms and has the same effect on the other one-bond coupling constants as observed for corresponding molecules in which substitution occurs at alternate sites. In contrast to the effect of F substitution, substitution of Li at either N or B decreases one-bond B-N coupling constants relative to borazine. The effects of F and Li substitution on one-bond B-N coupling constants for borazine are similar to F and Li substitution effects on (13)C-(13)C coupling constants for benzene.

Benzene↗

PubMed2002

Coupling of dopamine receptors to G proteins: studies with chimeric D2/D3 dopamine receptors.

D2 and D3 dopamine receptors belong to the superfamily of G protein-coupled receptors; they share a high degree of homology and are structurally similar. However, they differ from each other in their second messenger coupling properties. Previously, we have studied the differential coupling of these receptors to G proteins and found that while D2 receptor couples only to inhibitory G proteins, D3 receptor couples also to a stimulatory G protein, Gs. We aimed to investigate the molecular basis of these differences and to determine which domains in the receptor control its coupling to G proteins. For this purpose four chimeras were constructed, each composed of different segments of the original D2 and D3 receptors. We have demonstrated that chimeras with a third cytoplasmic loop of D2 receptor couple to Gi protein in a pattern characteristic of D2 receptor. On the other hand chimeras containing a third cytoplasmic loop of D3 receptor have coupling characteristics like those of D3 receptor, and they couple also to Gs protein. These findings demonstrate that the third cytoplasmic loop determines and accounts for the coupling of dopamine receptors D2 and D3 to G proteins.

1-Methyl-3-isobutylxanthine↗

PubMed2002

Observation of H-bond mediated 3hJH2H3 coupling constants across Watson-Crick AU base pairs in RNA.

3hJH2H3 trans-hydrogen bond scalar coupling constants have been observed for the first time in Watson-Crick AU base pairs in uniformly 15N-labeled RNA oligonucleotides using a new 2hJNN-HNN-E. COSY experiment. The experiment utilizes adenosine H2 (AH2) for original polarization and detection, while employing 2hJNN couplings for coherence transfer across the hydrogen bonds (H-bonds). The H3 protons of uracil bases are unperturbed throughout the experiment so that these protons appear as passive spins in E. COSY patterns. 3hJH2H3 coupling constants can therefore be accurately measured in the acquisition dimension from the displacement of the E. COSY multiplet components, which are separated by the relatively large 1JH3N3 coupling constants in the indirect dimension of the two-dimensional experiment. The 3hJH2H3 scalar coupling constants determined for AU base pairs in the two RNA hairpins examined here have been found to be positive and range in magnitude up to 1.8 Hz. Using a molecular fragment representation of an AU base pair, density functional theory/finite field perturbation theory (DFT/FPT) methods have been applied to attempt to predict the relative contributions of H-bond length and angular geometry to the magnitude of 3hJH2H3 coupling constants. Although the DFT/FPT calculations did not reproduce the full range of magnitude observed experimentally for the 3hJH2H3 coupling constants, the calculations do predict the correct sign and general trends in variation in size of these coupling constants. The calculations suggest that the magnitude of the coupling constants depends largely on H-bond length, but can also vary with differences in base pair geometry. The dependency of the 3hJH2H3 coupling constant on H-bond strength and geometry makes it a new probe for defining base pairs in NMR studies of nucleic acids.

Adenine↗

PubMedDate not supplied

Dynamics of spiking neurons connected by both inhibitory and electrical coupling.

We study the dynamics of a pair of intrinsically oscillating leaky integrate-and-fire neurons (identical and noise-free) connected by combinations of electrical and inhibitory coupling. We use the theory of weakly coupled oscillators to examine how synchronization patterns are influenced by cellular properties (intrinsic frequency and the strength of spikes) and coupling parameters (speed of synapses and coupling strengths). We find that, when inhibitory synapses are fast and the electrotonic effect of the suprathreshold portion of the spike is large, increasing the strength of weak electrical coupling promotes synchrony. Conversely, when inhibitory synapses are slow and the electrotonic effect of the suprathreshold portion of the spike is small, increasing the strength of weak electrical coupling promotes antisynchrony (see Fig. 10). Furthermore, our results indicate that, given a fixed total coupling strength, either electrical coupling alone or inhibition alone is better at enhancing neural synchrony than a combination of electrical and inhibitory coupling. We also show that these results extend to moderate coupling strengths.

Action Potentials↗

PubMed2001

Can skills training prevent relationship problems in at-risk couples? Four-year effects of a behavioral relationship education program.

Eighty-three couples were stratified into groups at high and low risk for relationship distress and randomized to either the Self-Regulatory Prevention and Relationship Enhancement Program (Self-PREP) or a control condition. As predicted, there were differential effects of Self-PREP on high-risk and low-risk couples. Because of low statistical power, results must be interpreted cautiously, but at 1-year follow-up high-risk couples in Self-PREP showed trends toward better communication than control couples. However, there was no difference in the communication of Self-PREP and control low-risk couples. High-risk couples receiving Self-PREP exhibited higher relationship satisfaction at 4 years than control couples, but in low-risk couples relationship satisfaction was higher in the control condition. High-risk couples seemed to benefit from skills-based relationship education, but low-risk couples did not.

Adult↗

PubMed2026

The importance of integrating genetic testing into reproductive medicine: a retrospective observational study investigating the monogenic causes of human infertility in couples considering ICSI.

The genetic landscape of human infertility is complex with diverse etiologies. Identifying the underlying etiology is crucial for guiding reproductive decisions and improving management for infertile couples. Here, we aim to report on the molecular spectrum of monogenic genetic causes of reproductive failure. Over a 3-year period, we recruited all infertile couples considering assisted reproductive technologies (ART) for whom the underlying genetic cause had been identified, in either partner, using exome sequencing (ES). Clinical data of all participants along with their hormonal profiles, sonographic findings and spermograms were recorded. The study included 50 couples with primary infertility. Clinically, male factor infertility was documented in 26 patients, female factor infertility in 10, while reproductive failure was unexplained in the remaining 14 couples. All participating couples had potentially disease-causing variants in infertility genes. ES identified variants related to male infertility in 26 men, while variants in female infertility-related genes were detected in the remaining couples (n = 24). According to ACMG classification criteria, 78% (39/50) of couples harbored pathogenic/likely pathogenic (P/LP) variants, whereas 22% (11/50) carried variants of uncertain significance (VUS). In view of the identified genetic etiologies, the cohort was stratified into two groups based on the predicted reproductive outcome: (1) couples with significantly impaired reproductive potential, and (2) couples who can have biological children using appropriate medical interventions. However, classifications involving VUS were interpreted cautiously and considered exploratory. This study provides further evidence for the molecular heterogeneity of human infertility and highlights the usefulness of genetic testing for infertile couples pursuing ARTs.

Humans↗

PubMed1990

Specificity of cell-cell coupling in rat optic nerve astrocytes in vitro.

Intercellular coupling was studied in cultured rat optic nerve astrocytes individually characterized by A2B5 antibody staining. The presence of cell coupling was assessed by injecting single cells with the low molecular weight fluorescent dye Lucifer yellow and noting dye passage into adjacent cells; cell coupling was also studied by analyzing the decay phase of current transients recorded in response to small voltage steps using whole-cell patch-clamp recording. Cell coupling was restricted to A2B5- astrocytes, the majority of which had a flat fibroblast-like appearance and was never observed in A2B5+ stellate-shaped astrocytes. Furthermore, A2B5- astrocytes showed coupling only to A2B5- and never to A2B5+ astrocytes. Analysis of current transients provided an additional indicator for cell coupling. Astrocytes that showed dye coupling to at least one neighboring cell required the sum of two exponential functions to fit current transients, whereas a single exponential function sufficed to fit transients in cells that were not dye coupled. The specificity of cell coupling in cultured rat optic nerve astrocytes suggests that predominantly A2B5- astrocytes comprise a coupled glial syncytium; this physiological feature of these cells may be a specialized adaptation for "spatial buffering," the transport of K+ away from areas of focal extracellular accumulation. On the other hand, A2B5+ astrocytes form an uncoupled subpopulation of rat optic nerve glial cells that may serve different functions.

Animals↗

PubMed1987

Conformational analysis of the deoxyribofuranose ring in DNA by means of sums of proton-proton coupling constants: a graphical method.

A graphical method is presented for the conformational analysis of the sugar ring in DNA fragments by means of proton-proton couplings. The coupling data required for this analysis consist of sums of couplings, which are referred to as sigma 1' (= J1'2' + J1'2''), sigma 2' (= J1'2' + J2'3' + J2'2''), sigma 2'' (= J1'2'' + J2''3' + J2'2'') and sigma 3' (= J2'3' + J2''3' + J3'4'). These sums of couplings correspond to the distance between the outer peaks of the H1', H2', H2'' and H3' [31P] resonances, respectively, (except for sigma 2' and sigma 2'' in the case of a small chemical shift difference between the H2' and H2'' resonances) and can often be obtained from 1H-NMR spectra via first-order measurement, obviating the necessity of a computer-assisted simulation of the fine structure of these resonances. Two different types of graphs for the interpretation of the coupling data are discussed: the first type of graph serves to probe as to whether or not the sugar ring occurs as a single conformer, and if so to analyze the coupling data in terms of the geometry of this sugar ring. In cases where the sugar ring does not occur as a single conformer, but as a blend of N- and S-type sugar puckers, the second type of graph is used to analyze the coupling data in terms of the geometry and population of the most abundant form. It is shown that the latter type of analysis can be carried out on the basis of experimental values for merely sigma 1',sigma 2' and sigma 2'', without any assumptions or restrictions concerning a relation between the geometry of the N- and S-type conformer. In addition, the question is discussed as to how insight can be gained into the conformational purity of the sugar ring from the observed fine structure of the H1' resonance. Finally, a comparison is made between experimental coupling data reported for single-stranded and duplex DNA fragments and covalent RNA-DNA hybrids on the one hand and the predicted couplings and sums of couplings presented in this paper on the other hand.

Computer Graphics↗

PubMed2005

Transferrin coupled liposomes as drug delivery carriers for brain targeting of 5-florouracil.

Diseases and disorders of the brain are extremely difficult to treat pharmacologically because most drugs are unable to pass across the blood--brain barriers. Complex multi-strand tight junctions between adjacent cerebral endothelial cells and between choroid plexus epithelial cells form a physical barrier and prevent the passage of water soluble drugs from the blood into the brain, whereas the inward passage of lipid soluble drugs is restricted by drug efflux pumps which act as a functional barrier. In the present work, a transferrin-coupled liposomal system for brain delivery of 5-florouracil has been investigated.5-florouracil and (99m)Tc-DTPA bearing non-coupled liposomes were prepared by cast film method, which were coupled with the transferrin by incubating these liposomes with transferrin in the presence of the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in saline phosphate buffer (pH 7.4). These liposomal systems were characterized for vesicle size, percent drug entrapment, and in vitro drug release. The size of the liposomes was increased on coupling with transferrin while percent drug entrapment reduced. The results of the in vitro release profile demonstrated that non-coupled liposomal formulation releases a comparatively higher percent (i.e. 74.8+/-3.21%) of drug than coupled liposomes. Results of in vivo study suggested a selective uptake of the transferrin-coupled liposomes from the brain capillary endothelial cells. In case of coupled liposomes, the level of radioactivity was 17-fold more as compared to the free radioactive agent and 13 times more with the non-coupled liposomes. Therefore, it could be concluded that using transferrin coupled liposomes the brain uptake of the drug could be enhanced.

Animals↗

PubMed1995

Estimation of the junctional resistance between electrically coupled receptor cells in Necturus taste buds.

Junctional resistance between coupled receptor cells in Necturus taste buds was estimated by modeling the results from single patch pipette voltage clamp studies on lingual slices. The membrane capacitance and input resistance of coupled taste receptor cells were measured to monitor electrical coupling and the results compared with those calculated by a simple model of electrically coupled taste cells. Coupled receptor cells were modeled by two identical receptor cells connected via a junctional resistance. On average, the junctional resistance was approximately 200-300 M omega. This was consistent with the electrophysiological recordings. A junctional resistance of 200-300 M omega is close to the threshold for Lucifer yellow dye-coupling detection (approximately 500 M omega). Therefore, the true extent of coupling in taste buds might be somewhat greater than that predicted from Lucifer yellow dye coupling. Due to the high input resistance of single taste receptor cells (> 1 G omega), a junctional resistance of 200-300 M omega assures a substantial electrical communication between coupled taste cells, suggesting that the electrical activity of coupled cells might be synchronized.

Animals↗

PubMed1994

Series coupled non-contractile elements are functionally unimportant in the isolated heart.

OBJECTIVE: In order to evaluate possible artefact in interpretations of contractile behaviour in isolated heart experiments, the relative elastances of series coupled non-contractile and contractile components of the left ventricle of the isolated heart were evaluated. METHODS: Hearts were isolated from ferrets and rabbits and mounted on a servo-controlled volume regulation device. These hearts were made to beat isovolumetrically until a selected volume perturbation was introduced. Constant flow volume withdrawals at two flow values were performed over a period of < 20 ms centred around the time of peak isovolumetric pressure. Three levels of isovolumetric pressure were produced using basal, extrasystolic, and potentiated beats. Pressure responses to volume withdrawals at two flows and three isovolumetric pressures were then analysed using a mathematical model to evaluate relative values of series coupled contractile and non-contractile elastances. To validate the analysis procedure, a non-contractile series artefact with known elastance was coupled to the left ventricle; volume perturbations were then applied to the coupled left ventricle-artefact system; responses were analysed and the estimate of series coupled non-contractile elastance was compared to the known elastance of the added artefact. RESULTS: A wide range of isovolumetric pressures [208(SD 40) mmHg] was produced in the ferret with basal, extrasystolic, and potentiated beats. A lesser range of isovolumetric pressures [50(15) mmHg] was produced in the rabbit. The mathematical model fitted the data very well in both the ferret and rabbit. The elastance of the series coupled non-contractile component could be estimated only in some ferrets. When estimated in the ferret, the elastance of the series coupled non-contractile component was never less than 4x that of the contractile component. When a series artefact of sufficiently low value was coupled with the native left ventricle, the elastance of the non-contractile component could be reliably estimated in both ferrets and rabbits and the estimated value approximated that of the added artefact. This indicated that the elastance of the series coupled non-contractile component of the native left ventricle was much higher than that of the added artefact. CONCLUSIONS: The series coupled non-contractile component of the isolated heart possesses a very much higher elastance than the contractile component. In fact, the elastance of the non-contractile component is so great that it contributes very little to the dynamic behaviour of the left ventricle. Virtually all of the elastance of the left ventricle of the isolated heart is due to the contractile component.

Animals↗