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At least 487 records · Page 27Linked to original sources
PubMed2006

Initial fixation strength of a hybrid technique for femoral ACL graft fixation.

Aperture fixation with interference screws matching the diameter of the tunnel is associated with the risk of graft laceration and graft rotation. A hybrid fixation technique (extracortical and aperture fixation) with undersized interference screws provides a higher fixation strength when compared to an aperture fixation using only a screw matching the size of the tunnel and also reduces the risk of graft laceration. This research is an experimental laboratory study. We evaluated the initial fixation strength at time-zero of an extracortical-, a hybrid- and an aperture fixation in ACL reconstruction using extracortical buttons and different sized interference screws in porcine knees. The tests were performed using a single cycle and cyclic loading protocol. Analysis of yield load, maximum load and stiffness in the single cycle loading test showed no statistically significant differences for hybrid fixation with a 1 mm undersized screw and aperture fixation with a screw matching the size of the tunnel. Cyclic loading tests showed a statistically significant difference between hybrid and aperture fixation. The use of an undersized screw alone in aperture fixation resulted in insufficient fixation strength. The initial fixation strength of the hybrid technique with undersized screws is higher compared to an interference screw fixation alone. The hybrid fixation technique is an alternative for ACL graft fixation.

Absorbable Implants↗
PubMed2003

Conformational study of linear and cyclic peptides corresponding to the 276-284 epitope region of HSV gD-1.

The results of conformational analysis of linear and cyclic peptides from the 276SALLEDPVG(284) sequence of glycoprotein D of Herpes simplex virus are presented. The epitope peptides were synthesized by SPPS and on resin cyclization was applied for preparation of cyclic compounds. Circular dichroism spectroscopy, Fourier-transform infrared spectroscopy and nuclear magnetic resonance (NMR) were used to determine of the solution structure of both linear and cyclic peptides. The results indicated that the cyclopeptides containing the core of the epitope (DPVG) as a part of the cycle have more stable beta-turn structure than the linear peptides or the cyclic analogues, where the core motif is not a part of the cycle. NMR study of H-SALLc(EDPVGK)-NH(2) confirm presence of a type I beta-turn structure which includes the DPVG epitope core.

Circular Dichroism↗
PubMed1992

Suppression of chaos by periodic oscillations in a model for cyclic AMP signalling in Dictyostelium cells.

We investigate how the introduction of cells oscillating periodically affects the behaviour of a suspension of Dictyostelium discoideum amoebae undergoing chaotic oscillations of cyclic AMP. The analysis of a model indicates that a tiny proportion of periodic cells suffices to transform chaos into periodic oscillations in such suspensions. A similar result is obtained by forcing the aperiodic oscillations by a small-amplitude, periodic input of cyclic AMP. The results provide an explanation for the observation of regular oscillations in suspensions of a putatively chaotic mutant of Dictyostelium discoideum. More generally, the results show how chaos in biological systems may disappear through the coupling with periodic oscillations.

Animals↗
PubMed2006

Geometry and cell density of rat craniofacial sutures during early postnatal development and upon in vivo cyclic loading.

Cranial sutures are unique to skull bones and consist of multiple connective tissue cell lineages such as mesenchymal cells, fibroblast-like cells, and osteogenic cells, in addition to osteoclasts. Mechanical modulation of intramembranous bone growth in the craniofacial suture is not well understood, especially during postnatal development. This study investigated whether in vivo mechanical forces regulate sutural growth responses in postnatal rats. Cyclic compressive forces with a peak-to-peak magnitude of 300 mN and 4 Hz were applied to the maxilla in each of 17-, 23-and 32-day-old rats for 20 min/day over 5 consecutive days. Computerized histomorphometric analysis revealed that cyclic loading significantly increased the average geometric widths of the premaxillomaxillary suture (PMS) to 86 +/- 7 microm, 99 +/- 12 microm, and 149 +/- 30 microm, representing 32%, 50%, and 39% increases for P17, P23, and P32 in comparison with age-matched sham controls. For the nasofrontal suture (NFS), cyclic loading significantly increased the average sutural widths to 88 +/- 15 microm, 92 +/- 10 microm, and 100 +/- 14 microm, representing 33%, 24%, and 32% increases for P17, P23, and P32 relative to age-matched controls. The average PMS cell density upon cyclic loading was 10182 +/- 132 cells/mm(2), 9752 +/- 661 cells/mm(2), and 9521 +/- 628 cells/mm(2), representing 62%, 35%, and 30% increases for P17, P23, and P32 in comparison with age-matched controls. For the NFS, cyclic loading increased the average cell density to 9884 +/- 893 cells/mm(2), 9818 +/- 1091 cells/mm(2), 9355 +/- 661 cells/mm(2), representing 44%, 46% and 40% increases at P17, P23, and P32 respectively. Osteoblast-occupied sutural bone surface was significantly greater in cyclically loaded sutures for P17, P23, and P32 than corresponding controls for both the PMS and NFS. On the other hand, cyclic loading elicited significantly higher sutural bone surface populated by osteoclast-like cells by P17 and P23 days, but not P32 days, for the PMS. For the NFS, sutural osteoclast surface was significantly higher upon cyclic loading for P23 and P32 days, but not P17. The present data demonstrate that cyclic forces are potent stimuli for modulating postnatal sutural development, potentially by stimulating both osteogenesis and osteoclastogenesis. Cyclic loading may have clinical implications as novel mechanical stimuli for modulating craniofacial growth in patients suffering from craniofacial anomalies and dentofacial deformities.

Animals↗
PubMed2007

NMR analysis of G7-18NATE, a nonphosphorylated cyclic peptide inhibitor of the Grb7 adapter protein.

G7-18NATE is a nonphosphorylated, cyclic peptide that specifically inhibits the Grb7 adapter protein implicated in several pathways critical to cell proliferation and migration. It has been shown that G7-18NATE is able to compete with natural ligands for the Grb7 SH2 phosphotyrosine binding site, and to attenuate cell migration in a pancreatic cancer cell line. It is thus an important lead in the development of a selective inhibitor of Grb7 and potential novel anticancer therapeutics. The current study reports the solution properties of G7- 18NATE determined using NMR spectroscopy, in both water (pH 2-3) and phosphate buffer (pH 6.0), with 100 mM NaCl. The spectra reveal that G7-18NATE exists in two distinguishable conformational states on the NMR timescale, most likely due to cis-trans proline isomerization. In addition, the chemical shift data are consistent with a tendency of G7-18NATE to form a turn about the YDN motif, known to be important for binding, and suggest that this turn is stabilized in low salt and low pH conditions. Low NH temperature coefficients of Tyr-5 and Asn-7 amide protons may reflect their involvement in the formation of hydrogen bonds that stabilize such a turn. Overall, however, the peptide does not form a rigid structure, but exists in a highly flexible state in solution. Averaged 3JNH-H coupling constants and a lack of interresidue NOEs are characteristic of such peptide solution behavior. This suggests that there is scope for increasing the rigidity of the peptide that may enhance its binding affinity and specificity for Grb7.

Amino Acid Sequence↗
PubMed2006

QSAR analysis of antimicrobial and haemolytic effects of cyclic cationic antimicrobial peptides derived from protegrin-1.

In this paper we quantitatively analyse antimicrobial and haemolytic activities of porcine protegrin-1 (PG-1) mimetics-cyclic cationic peptides with beta-hairpin fold synthesised by Robinson et al. [Bioorg. Med. Chem.2005, 13, 2055]. The presented QSAR models, which use molecular properties related to possible mechanisms of cell membrane disruption that can be easily calculated from available data on amino acids, rationalize the relationships between sequences and antimicrobial and haemolytic potencies of the cyclic peptides. The best models obtained by application of genetic function approximation algorithm correlate antimicrobial potencies to the peptide's charge and amphipathicity index, while the haemolytic effect correlates well with the lipophilicity of residues forming the nonpolar face of the beta-hairpin. The models permit selection of site-directed residue substitutions leading to simultaneous optimization of antimicrobial and haemolytic potencies. Examples of such residue substitutions in the nonpolar face of a symmetric cyclic beta-hairpin PG-1 analogue with an ideal amphipathic structure are given.

Anti-Bacterial Agents↗
PubMed1994

Hairpin formation within the human enkephalin enhancer region. 1. Kinetic analysis.

The 3'-5' cyclic AMP inducible enhancer region of the human enkephalin gene is located within an imperfect palindrome of 23 base pairs, located from -106 to -84 base pairs upstream of the transcriptional start site. Recent evidence has indicated that hairpin formation within this region may be involved in transcriptional regulation of the human proenkephalin gene. A 23-bp synthetic oligonucleotide of this region has been shown to undergo a reversible conformational change from a duplex to a cruciform structure of two hairpins [McMurray, C.T., Wilson, W.D., & Douglass, J.O. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 666]. Our current studies explore the kinetics and activation energies of the hairpin to duplex transitions of synthetic oligonucleotides under a variety of conditions. Ultraviolet spectroscopic data collected over a range of pH values, ionic strengths, and temperatures are used to determine the reaction rates and activation energies of the hairpin to duplex reaction. The rate of formation of a duplex from two hairpins is a slow second-order process, dependent on both pH and ionic strength. The return from the hairpin state to the duplex state occurs with a high activation energy of 22-41 kcal/mol strand, depending on the conditions. Pseudo-first-order reaction conditions indicate that one of the hairpins, the AC hairpin, is the rate-limiting reactant. These results suggest a model by which the formation of a cruciform might regulate transcription.

Base Sequence↗
PubMed2002

Synthesis and conformational analysis of a coumarinic acid-based cyclic prodrug of an opioid peptide with modified sensitivity to esterase-catalyzed bioconversion.

The coumarinic acid-based cyclic DADLE (H-Tyr-D-Ala-Gly-Phe-D-Leu-OH) prodrug 1a exhibited more favorable physicochemical properties than did DADLE for permeation across the intestinal mucosa. However, prodrug 1a, whose bioconversion to DADLE was slow, was subject to extensive biliary clearance when administered to rats in vivo. To increase the rate of esterase-catalyzed bioconversion of prodrug 1a, thus decreasing its biliary clearance, the oxymethyl-modified prodrug 1, in which an aldehyde equivalent is inserted between the phenolic group of the promoiety and the carboxylic acid group of the peptide, was synthesized from benzofuran-2-carboxylic acid 16 via a nine-step procedure. Briefly, phenacyl-protected 3-(2-hydroxyphenyl)-propynoic acid 17 was coupled with Boc-d-Leu-OCH(2)I 5 to give the intermediate 18, which was further elaborated and conjugated with tetrapeptide 4 to give linear precursor 2. Precursor 2 was then deprotected and cyclized to obtain compound 1 using a high dilution technique. In an attempt to investigate the effect of the physicochemical properties and the conformation of prodrug 1 on its permeation characteristics, we calculated its physicochemical parameters and determined its solution conformation using spectroscopic techniques (CD and NMR) and molecular dynamics simulations. Prodrug 1 showed a cLogP value and a molecular size similar to that of prodrug 1a. The deconvoluted CD spectra indicated that prodrug 1 has more random component (71%) than prodrug 1a (42%). 2D-NMR studies of prodrug 1 showed no signals for amide-amide hydrogen interactions and few ROE cross-peaks in ROESY spectra. Using distance restraints constructed from ROESY spectra, molecular dynamics simulations of prodrug 1 generated five conformation families. One family satisfied most of the distance restraints and all of the dihedral angles measured by NMR coupling constants. In summary, prodrug 1 showed favorable physicochemical properties for permeation of the intestinal mucosa. Prodrug 1 adopted a more random conformation in solution than prodrug 1a. These differences in solution conformation could affect the permeation of the prodrugs across the intestinal mucosa by passive diffusion and/or their ability to interact with efflux transporter(s) that would limit their transcellular permeation.

Animals↗
PubMed1986

Importance of oscillations in alveolar gas concentrations in the analysis of rebreathing data.

Cyclic rebreathing of a soluble inert gas can be used to estimate lung tissue volume (Vt) and pulmonary blood flow (Qc). A recently proposed method for analyzing such cyclic data (Respir. Physiol. 48: 255-279, 1982) mathematically assumes that ventilation is a continuous process. However, neglecting the cyclic nature of ventilation may prevent the accurate estimation of Vt and Qc. We evaluated this possibility by simulating the uptake of soluble inert gases during rebreathing using a cyclic model of gas exchange. Under cyclic uptake conditions alveolar gases follow an oscillating time course, because gas concentrations tend to increase during inspiration and to decrease during expiration. We found that neglecting these alveolar gas oscillations leads to the underestimation of soluble gas uptake by blood, particularly during the early rebreathing breaths. When continuous ventilation is assumed Vt and Qc are overestimated unless rapid rebreathing rates, large tidal volumes, and gases of moderately low solubility are used. Under these conditions the amplitude of the cyclic oscillations is minimized, the alveolar time course more closely resembles that expected from continuous ventilation, and the resulting errors are minimized. Alternatively, when the effect of oscillating alveolar gas concentrations on mass transfer are considered, these estimation errors can be eliminated without restricting rebreathing rate or gas solubility. We conclude that failure to consider the effect of cyclic rebreathing on the time course of alveolar gas concentrations may result in significant errors when evaluating rebreathing data for Vt and Qc.

Lung Volume Measurements↗
PubMed1998

Structural polymorphism and raman conformation markers of cyclic deoxytriadenylic acid.

X-ray analysis of two different trigonal crystal forms (space groups R32 and P3 ) of cyclic deoxytriadenylic acid [c(dAp)3] indicates for each an asymmetric unit consisting of two conformationally similar c(dAp)3molecules. Raman spectroscopy supports the X-ray interpretation for the R32 crystal, but identifies another c(dAp)3conformation not revealed in the P3 X-ray structure. The results for the P3 crystal can be explained if an additional c(dAp)3conformer is present but not sufficiently ordered within the lattice to contribute to X-ray diffraction. The Raman signature of aqueous c(dAp)3, which differs from signatures of both the R32 and P3 crystals, exhibits backbone markers similar to those of thermally denatured DNA and indicates that c(dAp)3molecules in solution populate a wider range of phosphoester ring conformations than in R32 and P3 crystals. Thus, polymorphism is observed for both crystal and solution structures of c(dAp)3. The results imply a highly flexible phosphoester ring that may be relevant to the function of cyclic oligonucleotides as biological effectors. A novel Raman marker at 821 cm-1is demonstrated as diagnostic of phosphoester torsions alpha and zeta in the gauche+ range. Specific Raman markers are also identified for the S -type (C2'- endo) deoxyadenosine conformations that occur in R32 and P3 crystal structures of c(dAp)3.

Adenine Nucleotides↗
PubMed1988

Systemic effects of single hindlimb burn injury on skeletal muscle function and cyclic nucleotide levels in the murine model.

This study tested the hypothesis that a single hindlimb burn has both local and distant effects. Male CF1 anaesthetized mice were given a full thickness scald burn of 3 per cent total body surface area (BSA) by immersion of their left hindlimb in water at 95 degrees C for 5 s. Muscle tension was measured through twitch analysis. Levels of cyclic adenosine 3'-5' monophosphate (cAMP) and cyclic guanosine 3'-5' monophosphate (cGMP) were analysed by 125I-radioimmunoassay. Measurements were made in gastrocnemei of the ipsilateral burned and contralateral unburned limbs over a 28-day postburn period. Within 1 week the burned limb showed an increase in both tension and a 100-fold increase in levels of cAMP. However, by the end of the second week muscle tension in the burned limb dropped to one-seventh of control values despite persistence of high levels of cAMP. In contrast, the systemic effects were manifested in the unburned contralateral limb which showed tension to undergo a six-fold compensatory increase at the end of the second week with a 75-fold increase in cAMP. By the end of 4 weeks, tension levels of both burned and unburned limbs were attenuated to one-half control values indicating neuromuscular (NM) dysfunction. Nevertheless, cAMP levels remained elevated in both limbs. Levels of cGMP were reduced throughout the 4-week postburn period. Subsequent to the single hindlimb injury both ipsilateral and contralateral gastrocnemei muscles showed elevated levels of total protein content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Conformational analysis of amphotericin B molecule.

Conformational analysis of a cyclic molecule of a channel-forming antibiotic amphotericin B was conducted by the methods of molecular mechanics. A number of conformers differing in both hydroxyl group orientation and lactone ring conformation were obtained. The stable states of the conformers have close intrinsic energies. The conformational analysis supports the conclusion by Mazerski and Borowski (Biophys. Chem. 54:49-60 (1995)) on the flexibility of the amphotericin B lactone ring.

Amphotericin B↗
PubMed2006

Chronic snoring and sleep in children: a demonstration of sleep disruption.

OBJECTIVE: Chronic snoring that does not adhere to the criteria for a diagnosis of obstructive sleep apnea syndrome may be associated with learning and behavioral problems. We investigated the sleep structure of chronic snorers who had an apnea-hypopnea index of < 1 event per hour and analyzed the cyclic alternating pattern. METHODS: Fifteen successively seen chronic snorers (9.8 +/- 4 years) with an apnea-hypopnea index of <1 and 15 aged-matched control subjects (10.3 +/- 5 years) underwent an investigation of their sleep with the determination of non-apneic-hypopneic breathing abnormalities polysomnographic scoring using current criteria and analysis of the cyclic alternating pattern. RESULTS: Chronic snorers have evidence of flow limitations and tachypnea during sleep even if they do not present with apneas, hypopneas, and decrease in oxygen saturations. They also present with abnormal cyclic alternating pattern rates and changes in phase A of cyclic alternating pattern compared with control subjects. CONCLUSIONS: An apnea-hypopnea index value cannot be the sole determinant in evaluating sleep-disordered breathing in children. Children who have chronic snoring and do not respond to the criteria for obstructive sleep apnea syndrome can present with an abnormal sleep electroencephalogram as evidenced by a significant increase in cyclic alternating pattern rates, with a predominance of abnormalities in slow wave sleep.

Adolescent↗
PubMed1988

Control of light-sensitive current in salamander rods.

1. The exponential decline of light-sensitive current seen after switch from Na+ to Li+ in the presence of Ca2+ probably depends on the activity of the phosphodiesterase (PDE) which hydrolyses cyclic GMP. 2. This probability is supported by experiments with suction electrodes which show that in toad and salamander rods the rate constant, b, of the exponential decline of current was increased at least 10-fold by moderate light intensities and decreased about 10-fold by 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of PDE. 3. The rate constant b is about 3 times more sensitive to weak lights or to IBMX than the membrane current. This may be explained by a feed-back involving calcium ions which tends to hold current constant, perhaps by calcium inhibition of guanylate cyclase. 4. The time course of b, which probably represents the changes in PDE activity, was measured by switching from Na+ to Li+ at various times after a flash. The results suggest that a moderate flash (140 Rh) increased b about 7 times in 0.5 s and that b then declined with a time constant of 1.5-2 s. 5. Extrapolated values of the parameter b suggest that strong flashes (5000-10,000 Rh) increased b from 1 s-1 in the dark to perhaps 60 s-1 and that b continued to increase with flash strength for several log units after the current had reached saturation. 6. The observations in 4 and 5 fit well with the idea that b is related to PDE activity and that changes in the latter are sufficient to account for the rising phase of the flash response. 7. After a flash the light-sensitive current recovers much more rapidly than the time constant b-1, a discrepancy which is explained if a light flash causes a delayed increase in guanylate cyclase activity. 8. The apparent delayed increase in cyclase activation is consistent with an inhibitory effect of [Ca2+]i which is reduced when calcium is pumped out during the plateau of the response. 9. Experiments in which pulses of IBMX were applied at different times during a flash response support the idea that a flash causes a delayed increase in the rate of supply of cyclic GMP. Quantitative analysis of these and other tests with IBMX gave rate constants similar to those obtained by the Na+----Li+ method.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Cyclic homooligomers from sugar amino acids: synthesis, conformational analysis, and significance.

Sugar amino acids (SAAs) were designed as new building blocks carrying an amino group and a carboxyl group on a carbohydrate scaffold. By exploiting standard solid- and solution-phase coupling procedures, linear and cyclic homooligomers containing glucosyluronic acid methylamine (Gum) were synthesized. We achieved a high yield and a very short coupling time for the oligomerization and cyclization of sequences encompassing two, three, four, and six Gum units. The synthesis of cyclic oligomers containing only SAAs as repetitive units has not been reported before. The conformational preferences in aqueous solution of the cyclic derivatives and their applications as potential host molecules are described herein. Benzoic acid and p-nitrophenol were chosen as model guest molecules to study the formation of cyclodextrin-like inclusion complexes. The complexation behavior of the cyclic hexamer was proved from three different points of view: chemical shifts, longitudinal relaxations (T(1)), and diffusion coefficients. All of them showed different values for host and guest molecules measured independently and in the presence of each other.

Amino Acids↗