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At least 91 records · Page 5Linked to original sources
PubMed1994

Acute effect of corticosteroids on respiratory mechanics in mechanically ventilated patients with chronic airflow obstruction and acute respiratory failure.

We assessed the short-term effect of steroids on respiratory mechanics in eight mechanically ventilated patients with chronic airflow obstruction (CAO) and hypercapnic respiratory failure. Airflow (V), airway pressure (Paw), and changes in pulmonary volume were measured using a conventional ventilator. End-expiratory and end-inspiratory airway occlusions were performed to assess intrinsic PEEP (PEEPi), static compliance of total respiratory system (Cstrs), maximum inspiratory resistance (Rrsmax), and minimum inspiratory resistance (Rrsmin). These parameters were recorded at control, 30 min after saline, and 90 min after steroid (methylprednisolone 0.8 mg/kg intravenous) administration. No significant changes were found in respiratory mechanics after administration of saline. Steroids induced a significant decrease (p < 0.01) in inspiratory resistance (Rrsmax from 20.3 +/- 8.6 cm H2O/L/s (control) to 15.3 +/- 6.1 (90 min) and Rrsmin from 16.2 +/- 8.0 (control) to 11.9 +/- 6.5 (90 min), with no significant reduction in Paw and Cstrs. The PEEPi, reflecting pulmonary dynamic hyperinflation, was also significantly reduced (-16% from control). We conclude that in mechanically ventilated CAO patients, steroids may be useful in improving respiratory mechanics and therefore in providing better conditions for weaning from mechanical ventilation.

Female↗
PubMed2000

Molecular mechanism of mechanical stress-induced cardiac hypertrophy.

Mechanical stress is a major cause of cardiac hypertrophy. Although the mechanisms by which mechanical load induces cardiomyocyte hypertrophy have long been a subject of great interest for cardiologists, the lack of a good in vitro system has hampered the understanding of the biochemical mechanisms. For these past several years, however, an in vitro neonatal cardiocyte culture system has made it possible to examine the biochemical basis for the signal transduction of mechanical stress. Passive stretch of cardiac myocytes cultured on silicone membranes activates phosphorylation cascades of many protein kinases including protein kinase C, Raf-1 kinase and extracellular signal regulated kinases, and induces the expression of specific genes as well as an increase in protein synthesis. During that process, the secretion and production of vasoactive peptides such as angiotensin II and endothelin, are increased and they play critical roles in the induction of these hypertrophic responses. Although the involvement of vasoactive peptides in the development of cardiac hypertrophy is clinically important, the "mechanoreceptor" which receives the mechanical stress and converts it into intracellular biochemical signals remained unknown. We have recently obtained evidence suggesting that ion channels and integrins may be the "mechanoreceptor", the activation of which leads to cardiac hypertrophy.

Animals↗
PubMed2006

The role of interfacial mechanics in the prediction of global mechanical behavior of a bioactive composite: an in vitro study.

A bioactive bone-tissue substitute, hydroxyapatite (HA)-polymethylmethacrylate (PMMA) with the addition of a copolymer coupling agent, was examined in vitro to determine the influence of the coupling agent on the local mechanical properties of the system before and after simulated biologic conditions. Nano-indentation of the cross-sectional interface between the HA and PMMA of the composite was studied. The fracture mechanism and position of each indent mark were analyzed at up to 5000x magnification under field-emission, environmental-scanning electron microscopy. The local interfacial results were compared with global quasistatic compression test results. It was found that nano-indentation of the interface could predict changes in global mechanical behavior of the composite. Both interfacial and global Young's moduli were reduced after immersion in the simulated biologic media. Although the coupling agent improved the interfacial and global mechanical properties before and after 24 hours in in vitro immersion, it did not affect the surface bioactivity of the system, as shown in the measurement of calcium and phosphate concentration uptake. Thus, nano-indentation is a sensitive technique for examining interfacial mechanics and mechanical consequences of biologic reactivity of composite materials.

Biocompatible Materials↗
PubMed2005

The benefit of combining non-mechanical agents with mechanical loading: a perspective based on the Utah Paradigm of Skeletal Physiology.

The Utah Paradigm of Skeletal Physiology with its key component, the mechanostat hypothesis, suggest plausible explanations of some of the tissue-level changes occurring from combining selected non-mechanical agents (anabolic and anti-resorptive/( re)modeling agents) with mechanical loading (osteogenic exercise) to increase bone mass and strength. The evidence for combining selected anabolic agents like parathyroid hormone, prostaglandin E(2), growth hormone, etc. with mechanical loading can increase bone mass is strong. Anabolic agents influence loading-related bone formation changes in a permissive manner and modulate (increase) the responsiveness of bone tissue to mechanical loading by changing thresholds for bone formation and resorption. However, any beneficial effect of combining selected anti-resorptive/(re)modeling agents like estrogen with loading is marginal, especially in adult skeletons. Postulated changes in modeling and remodeling thresholds (set points) and known direct effects on bone cells by non-mechanical agents may explain the observed tissue-level changes associated with large and minor increases in bone mass. Although the pharmaceutical industry has avoided considering osteogenic loading in the treatment of osteoporosis, a methodical dose-response study of anabolic agents combined with loading should: (1) provide opportunities for therapeutic intervention to imitate or enhance the osteogenic response to loading in order to correct osteopenias; (2) provide the potential to diminish the dosage of drugs required to induce bone formation in ways that enhanced efficacy and reduced any side effects; and (3) improve the quality of life and reduce the risk of falls by improving balance, gait speed and muscle strength with a non-mechanical agent like GH that could improve both muscle and bone mass and strength. Lastly, more studies are needed which determine bone strength instead of only "mass" in aged skeletons so one can assess how effective such treatments would reduce the risk of fracture in the clinic.

Anabolic Agents↗
PubMed2006

[Dynamic change in respiratory mechanic dynamics and its clinical significance during mechanical ventilation in hyaline membrane disease of children].

OBJECTIVE: To explore the characteristics of changes in respiratory mechanic dynamics and clinical significance in hyaline membrane disease (HMD) under mechanical ventilation. METHODS: One hundred and twenty-six newborns with HMD undergoing mechanical ventilation were divided into two groups: complication group with 43 cases and no-complication group with 83 cases. The blood gases and indices of respiratory mechanic dynamics were monitored 2, 24, 48 and 72 hours after the first ventilation and before the first weaning from ventilation. RESULTS: Pulmonary compliance [(0.55+/-0.10) ml.cm H(2)O(-1).kg(-1), (0.43+/-0.10) ml.cm H(2)O(-1).kg(-1)] and minute volume [MV, (0.65+/-0.10) L/min, (0.62+/-0.30) L/min] were elevated compared with that after ventilation for 2-72 hours, however the oxygenation index [OI, (10.2+/-1.9)mm Hg vs. (13.6+/-4.3) mm Hg] significantly lower. The compliance and MV in no-complication group were higher than that in complication group 24 and 48 hours after ventilation. There were no differences in the airway resistance and lung inflation index between two groups. The pulmonary compliance was negatively correlated with OI (r=-0.208, P<0.01) and corrected with MV (r=0.218, P<0.01). In no-complication group, all cases ventilation was weaned successfully at once in all the patients,and their mean compliance and MV were (0.55+/-0.10) ml.cm H(2)O(-1).kg(-1) and (0.65+/-0.20) L/min respectively. However, in complication group, weaning failed 38 patients, their mean compliance and MV were (1.03+/-0.30) ml.cm H(2)O(-1).kg(-1) and (0. 33+/-0.30) L/min respectively. CONCLUSION: Respiratory mechanic dynamics monitoring is beneficial in evaluating the severity of hyaline membrane disease and complications, guiding mechanical ventilation management and weaning.

Female↗
PubMed2005

Molecular mechanisms of neuropathic pain-phenotypic switch and initiation mechanisms.

Many known painkillers are not always effective in the therapy of chronic neuropathic pain manifested by hyperalgesia and tactile allodynia. The mechanisms underlying neuropathic pain appear to be complicated and to differ from acute and inflammatory pain. Recent advances in pain research provide us with a clear picture for the molecular mechanisms of acute pain, and substantial information is available concerning the plasticity that occurs under conditions of neuropathic pain. The most important changes responsible for the mechanisms of neuropathic pain are found in the altered gene/protein expression in primary sensory neurons. After damage to peripheral sensory fibers, up-regulated expression of the Ca(v)alpha(2)delta-(1) channel subunit, the Na(v)1.3 sodium channel, and bradykinin (BK) B1 and capsaicin TRPV1 receptors in myelinated neurons contribute to hyperalgesia; while the down-regulation of the Na(v)1.8 sodium channel, B2 receptor, substance P (SP), and even mu-opioid receptors in unmyelinated neurons is responsible for the phenotypic switch in pain transmission. Clarification of the molecular mechanisms for such complicated plasticity would be extremely valuable when considering the therapeutic design of pain relieving drugs. Although many reports deal with the changes in expression of key molecules related to neuropathic pain, the initiation and the mechanisms that follow remain to be determined. The current study using lysophosphatidic acid (LPA) receptor knockout mice revealed that LPA produced by nerve injury initiates neuropathic pain and demyelination following partial sciatic nerve ligation (PSNL). A single injection of LPA was found to mimic PSNL in terms of neuropathic pain and its underlying mechanisms. This discovery may lead to the subsequent discovery of LPA-induced secondary genes, which would be therapeutic targets for neuropathic pain.

Animals↗
PubMed2002

Role of protein flexibility in enzymatic catalysis: quantum mechanical-molecular mechanical study of the deacylation reaction in class A beta-lactamases.

We present a theoretical study of a mechanism for the hydrolysis of the acyl-enzyme complex formed by a class A beta-lactamase (TEM1) and an antibiotic (penicillanate), as a part of the process of antibiotic's inactivation by this type of enzymes. In the presented mechanism the carboxylate group of a particular residue (Glu166) activates a water molecule, accepting one of its protons, and afterward transfers this proton directly to the acylated serine residue (Ser70). In our study we employed a quantum mechanics (AM1)-molecular mechanics partition scheme (QM/MM) where all the atoms of the system were allowed to relax. For this purpose we used the GRACE procedure in which part of the system is used to define the Hessian matrix while the rest is relaxed at each step of the stationary structures search. By use of this computational scheme, the hydrolysis of the acyl-enzyme is described as a three-step process: The first step corresponds to the proton transfer from the hydrolytic water molecule to the carboxylate group of Glu166 and the subsequent formation of a tetrahedral adduct as a consequence of the attack of this activated water molecule to the carbonyl carbon atom of the beta-lactam. In the second step, the acyl-enzyme bond is broken, obtaining a negatively charged Ser70. In the last step this residue is protonated by means of a direct proton transfer from Glu166. The large mobility of Glu166, a residue that is placed in a Ohms-loop, is essential to facilitate this mechanism. The geometry of the acyl-enzyme complex shows a large distance between Glu166 and Ser70 and thus, if protein coordinates were kept frozen during the reaction path, it would be difficult to get a direct proton transfer between these two residues. This computational study shows how a flexible treatment suggests the feasibility of a mechanism that could have been discounted on the basis of crystallographic positions.

Acylation↗
PubMed2005

Small-molecule dynamics and mechanisms underlying the macroscopic mechanical properties of coordinatively cross-linked polymer networks.

Specific metal-ligand coordination between bis-Pd(II) and Pt(II) organometallic cross-linkers and poly(4-vinylpyridine) in DMSO defines a three-dimensional associative polymer network. Frequency-dependent dynamic mechanical moduli of a series of four different bulk materials, measured across several decades of oscillatory strain rates, are found to be quantitatively related through the pyridine exchange rates measured on model Pd(II) and Pt(II) complexes. Importantly, the mechanism of ligand exchange in the networks is found to be the same solvent-assisted pathway observed in the model complexes, and so the bulk mechanical properties are determined by relaxations that occur when the cross-links are dissociated from the polymer backbone. It is how often the cross-links dissociate, independently of how long they remain dissociated, that determines the bulk mechanical properties. The quantitative relationship between bulk materials properties and the kinetics and mechanisms observed in model compounds holds promise for the rational, molecular design of materials with tailored mechanical properties.

Computer Simulation↗
PubMed1998

Prediction of the mechanisms of enzyme-catalysed reactions using hybrid quantum mechanical/molecular mechanical methods.

The use of hybrid methods, involving both quantum mechanics and molecular mechanics, to model the mechanism of enzyme-catalysed reactions, is discussed. Two alternative approaches to treating the electrostatic interactions between the quantum mechanical and molecular mechanical regions are studied, involving either the inclusion of this term in the electronic Hamiltonian (QM/MM), or evaluating it purely classically (MO + MM). In the latter scheme, possible problems of using force fields that are standard for macromolecular modelling are identified. The use of QM/MM schemes to investigate the mechanism of the enzymes thymidine phosphorylase (ThdPase) and protein tyrosine phosphatase (PTP) is described. For both systems, transition states have been identified using a PM3 Hamiltonian. For ThdPase, concerted motion of the enzyme during the course of the reaction is suggested and, for PTP, a two-step dephosphorylation reaction is indicated, both with quite low barriers.

Catalysis↗
PubMed2006

Molecular mechanisms of cellular mechanics.

Mechanical forces play an essential role in cellular processes as input, output, and signals. Various protein complexes in the cell are designed to handle, transform and use such forces. For instance, proteins of muscle and the extracellular matrix can withstand considerable stretching forces, hearing-related and mechanosensory proteins can transform weak mechanical stimuli into electrical signals, and regulatory proteins are suited to forcing DNA into loops to control gene expression. Here we review the structure-function relationship of four protein complexes with well defined and representative mechanical functions. The first example is titin, a protein that confers passive elasticity on muscle. The second system is the elastic extracellular matrix protein, fibronectin, and its cellular receptor integrin. The third protein system is the transduction apparatus in hearing and other mechanical senses, likely containing cadherin and ankyrin repeats. The last system is the lac repressor protein, which regulates gene expression by looping DNA. This review focuses on atomic level descriptions of the physical mechanisms underlying the various mechanical functions of the stated proteins.

Biomechanical Phenomena↗
PubMed2006

Bohmian mechanics with complex action: a new trajectory-based formulation of quantum mechanics.

In recent years there has been a resurgence of interest in Bohmian mechanics as a numerical tool because of its local dynamics, which suggest the possibility of significant computational advantages for the simulation of large quantum systems. However, closer inspection of the Bohmian formulation reveals that the nonlocality of quantum mechanics has not disappeared-it has simply been swept under the rug into the quantum force. In this paper we present a new formulation of Bohmian mechanics in which the quantum action, S, is taken to be complex. This leads to a single equation for complex S, and ultimately complex x and p but there is a reward for this complexification-a significantly higher degree of localization. The quantum force in the new approach vanishes for Gaussian wave packet dynamics, and its effect on barrier tunneling processes is orders of magnitude lower than that of the classical force. In fact, the current method is shown to be a rigorous extension of generalized Gaussian wave packet dynamics to give exact quantum mechanics. We demonstrate tunneling probabilities that are in virtually perfect agreement with the exact quantum mechanics down to 10(-7) calculated from strictly localized quantum trajectories that do not communicate with their neighbors. The new formulation may have significant implications for fundamental quantum mechanics, ranging from the interpretation of non-locality to measures of quantum complexity.

Journal Article↗
PubMed2002

The concerted mechanism of photo-induced biprotonic transfer in 7-azaindole dimers: a model for the secondary evolution of the classic C2h dimer and comparison of four mechanisms.

A mechanism is proposed for the formation in gas phase, during a short time, of the delicately symmetrical coplanar C(2h) classic 7-azaindole (7AI) doubly hydrogen-bonded dimer. Of the five card-pack or otherwise random geometry structures most likely to be formed in the supersonic jet expansion molecular beam, none would be an obvious precursor to the C(2h) dimer. One unstable dimer with dipole-dipole, van der Waals, and plane-to-plane hydrogen bonding is shown to be capable of unhinging about the hydrogen-bond pair as an axis, from 0 degrees to 90 degrees to 180 degrees, yielding a deep minimum for the C(2h) structure with its delicate geometry and symmetry. This relaxation mechanism is feasible in the 3-micros interval between the nozzle escape and the first laser pulse interception of the molecular beam. In the second part of the paper four published mechanisms are compared for concerted vs. two-step biprotonic phototransfer for the 7AI dimers. The dependence of the latter two models on H-atom instead of proton-transfer as an intermediate step negates the mechanism in a singlet (pi,pi*) electronic state by the valency repulsion, in the 3-electron orbital that would be generated. The concerted mechanism for biprotonic phototransfer is reaffirmed by the analysis of the quantum mechanical conditions set on the biprotonic transfer in the photo-excited molecular 7AI pair.

Dimerization↗