Relaxation Techniques

Relax Your Mind

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Couplings and from Cross Correlated Relaxation Application to Biomacromolecules 147

7.4 Cross-Correlated Relaxation for the Measurement of Projection Angles between Tensors 18 161 7.4.1 J-Resolved Constant Time Measurement of Cross-Correlated Relaxation Rates 165 7.4.2 Quantitative r Measurement of Cross-Correlated Relaxation Rates 168 7.4.4 Transferred Cross-Correlated Relaxation 173

Teaching Relaxation Skills

The goal of teaching relaxation skills is to enable patients to relax as much as is possible and appropriate both throughout the day and at times of particular stress. This contrasts with procedures such as meditation, which provide a period of deep relaxation and time out as sufficient in themselves. Relaxation skills are best learned through three phases learning basic relaxation skills using relaxation at times of stress. The first stage involves practice under optimal conditions such as a quiet room in a comfortable chair - where there are no distractions and it is relatively easy to relax. Initially, a trained practitioner should lead the individual through the process of deep relaxation. This is augmented by continued practice at home, typically using taped instructions. The relaxation process most commonly taught involves alternately tensing and relaxing muscle groups throughout the body in an ordered sequence. As the individual becomes more skilled, the emphasis of practice...

Relaxation and Stress Management

Techniques that may be used include relaxation training, breathing re-training, biofeedback, yoga, meditation, rapid relaxation and the identification (using questionnaires) of our own behavior and attitudes that lead to anger and stress. Each week one of the patients is asked to recall a recent event that had stressed them or made them very angry and the group is shown stress management techniques to avoid this. Patients are taught a rapid relaxation and distraction technique that they can

Magnetic Relaxation In Ferrofluids

Neel Brownian Relaxation

Ferromagnetic particles suspended in a liquid carrier are generally referred to as ferroflu-ids 19 . The dynamic behavior of these ferrofluids is governed by two very different magnetization relaxation pathways. Either the magnetization can change within each magnetic particle (Neel relaxation) or the whole particle can rotate in the liquid (Brow-nian relaxation). We will first discuss each mechanism individually and then turn to systems with size dispersions, where both relaxation mechanisms can be present simultaneously. 4.3.1 Internal Magnetic Relaxation In the following we will neglect magnetic interactions between magnetic particles, which may arise from dipolar coupling. This assumption is nontrivial, but in the case of biologically functionalized magnetic nanoparticles, the ligand coating helps to separate the individual particles independent of their concentration. The important parameter for assessing the importance of interactions is the ratio of interaction to thermal...

Nuclear Magnetic Relaxation

Where (n - n e)t is the displacement from equilibrium, ne, at time t, (n - ne)0 is the displacement from equilibrium, ne, at time zero, and T is the relaxation time. Two types of relaxation processes are known with possibly different relaxation times. These are known as T1 and T2. Looking at Figure 3.17, one can imagine a 180 pulse that inverts the magnetization. Following the end of the pulse, relaxation processes begin to return magnetization to its initial state. This process is called T1 or longitudinal relaxation because it takes place in the direction of B0. If one uses a 90 B1 pulse, the magnetization is moved to the xy plane (Mxy) as in the rotating frame figure, Figure 3.17. This transverse magnetization rotates at the nuclear Larmor frequency and because some nuclear spins are faster and some are slower, the xy magnetization starts to fan out and lose coherence, eventually resulting in Mxy 0. The characteristic time for this process is called transverse relaxation or T2. The...

Stress Relaxation and Strain Hardening

Subsequent to these original formulations a number of refinements to these relationships have been proposed. Observations of persistent deformations after micropipette aspiration for extended periods of time formed the basis for the development of a model for long-term stress relaxation Markle et al., 1983 . The characteristic times for these relaxations were on the order of 1-2 h, and these times were thought to correlate with permanent rearrangements of the membrane elastic network. Another type of stress relaxation is thought to occur over very short times ( 0.1 s) after rapid deformation of the membrane either by micropipette Chien et al., 1978 or in cell extension experiments (Waugh and Bisgrove, unpublished observations). This phenomenon is thought to be due to transient entanglements within the deforming network. Whether the phenomenon actually occurs remains controversial. The stresses relax rapidly, and it is difficult to account for inertial effects of the measuring system...

Relaxation of MT and MO Particles

As a rule, chromatin is reconstituted on a topoisomer of negative supercoiling sufficient to keep it out of the relaxation equilibrium (see Note 22, and Fig. 1). In practice, this implies to use topoisomers of ALk below -1.5 for MT and below -2.2 for MO (this criterion is met in Fig. 6). Moreover, reconstitution is made at a histone DNA ratio low enough for the amount of dimer particles to be negligible. tin relaxation buffer, add 2-3 U of DNA topoisomerase I, incubate for 30 min at 37 C, and put immediately on ice. 2. Dilute with 3-4 vol of ice-cold TE-BSA, load onto a chromatin gel (see Subheading 3.5.2.), and apply voltage as soon as possible after samples are loaded. Examples of relaxations are displayed in Fig. 6.

Isovolumic relaxation period

During relaxation, ventricular pressure is determined by two overlapping processes the decay of the pressure actively developed during the preceding systole and the build up of the passive filling pressure. Together, these two components result in the effective pressure of the isovolumic relaxation period. The rapid fall in pressure can be approximated by a mono-exponential curve and described by its time constant t.88 Maximal negative dP dt and the duration of the isovolumic relaxation period have been also used for the evaluation of ventricular relaxation. The rate of relaxation is modulated by sympathetic tone and circulating catecholamines. It increases with positive inotropic stimulation and increasing heart rate. Interventions causing an increase in the rate and extent of relaxation are called positive lusitropic effects. A delay of ventricular relaxation can be caused by pressure or volume overload, which primarily prolongs the contraction. The delayed relaxation can affect the...

Determination of Protein Dynamics Using 15N Relaxation Measurements

Multidimensional NMR methods, combined with isotope labeling, can provide access to virtually every atom in a molecule, unique for protein structural studies. This not only allows characterization of the structure and interaction of proteins in their native milieu, but also provides unparalleled possibilities to obtain a complete atomic-level resolution picture of protein dynamics in a time range from picoseconds up to seconds, the range where most motions relevant to protein function take place. A significant number of 15N and 13C relaxation studies have been performed on a large number of proteins in the last decade, initiated by the pioneering work of Refs. 1 and 2 . In this chapter we review some experimental and analytical approaches to protein dynamics by 15N relaxation measurements and outline the current picture of protein dynamics revealed by NMR.

Relaxation Editing

Vector away from the static field direction. Once perturbed, both a spinning gyroscope and a spinning nucleus tend to return to their original positions. The rate of return for a nucleus is on the order of seconds for small molecules in aqueous solution because nuclei are extremely weakly coupled to their environments. This return to equilibrium, or relaxation, of the polarized nuclear spin is often dominated by dipolar interactions with neighboring nuclei that have components of molecular motion at frequencies either near zero (transverse relaxation) or at the Larmor (NMR) frequency (longitudinal relaxation). The longitudinal relaxation time (rate) is termed T1 (R1 1 7 ), and the transverse relaxation time (rate) is T2 (R2 1 T2). For rotational motion of a nucleus characterized by a correlation time, t, in a fluid of low viscosity, such as water, the dipolar relaxation rates are given by

The movements of respiration

During inspiration the movements of the chest wall and diaphragm result in an increase in all diameters of the thorax. This, in turn, brings about an increase in the negative intrapleural pressure and an expansion of the lung tissue. Conversely, in expiration the relaxation of the respiratory muscles and the elastic recoil of the lung reduce the thoracic capacity and force air out of the lungs.

Ancient Greece And Rome

The narrative continues by explaining that the drug had been given to Helen by an Egyptian, For Egypt teems with drugs. There has been much speculation as to the identity of this substance some have suggested that it may have been cannabis (Singer and Underwood, 1962 Burton, 1894 edn a Walton, 1938). As the story continues the guests do not become sedated or start to hallucinate, and so presumably the nepenthe was given to promote relaxation and discourse rather than heavy intoxication, sedation or psychotomimetic effects. It has also been suggested that Greek warriors may have taken nepenthe as a courage-boosting intoxicant before charging into the violence of combat (Cooper, 1995). Others have speculated that the 'wine of the condemned' cited by the Greek writer Amos in about 700 BC as a method of reducing the pain of a slow death was also cannabis (Walker, 1954). In reality it is impossible to determine the identity of substances such as these from the vague descriptions given....

The structure of the book

This then leads to the study of other complementary or alternative approaches which can involve both physical and psycho-social measures. There are a variety of physical interventions, including electrical, heat and cold, massage and aromatics, and counter-irritation. However, there are also many interventions based on psychology that can help to prevent pain or to enable the sufferer to develop meanings for the pain that give him or her a greater sense of control over the situation. Other psychologically based approaches include relaxation and distraction.

Selective Protonation of Methyl Groups in 2HLabeled Proteins

As described in the introduction, deuteration is routinely used to reduce the rapid transverse relaxation rates characteristic of larger proteins, leading to improvements in peak line widths and experimental sensitivity. Deuteration of all the carbon-bound protons maximizes the sensitivity gains that can be obtained from this labeling strategy, and has thus proven useful for in the assignment of backbone XH, 15N, 13C and side-chain 13C chemical shifts of large proteins. However, the elimination of all but the exchangeable protons significantly impedes structural studies that rely on conventional NOE approaches. Although in some cases it is possible to use only backbone 1HN-1HN NOEs to obtain a protein global fold, the accuracy of these structures is very low because of the small proportion of distance restraints between protons from nonsequential residues. These global folds tend to be less compact than high-resolution structures, with the backbone pairwise root-mean-squared deviation...

Annexins And Heart Disease

Annexin 6 has been shown in vitro to be a modulator of the sarcoplasmic reticulum Ca2+ -release channel, the cardiac L-type channel and the Na+ Ca2+ exchanger (Diaz-Munoz et al., 1990). Cardiomyocytes derived from an annexin 6 null mutant mouse show increased contraction and relaxation amplitudes and reduced 'time to peak relaxation', (Song et al., 2002). Heart-specific annexin 6 overexpression in a mouse resulted in dilation of the heart, acute diffusive myocarditis, moderate to severe fibrosis throughout the heart and frequency-dependent reduced shortening and rates of contraction of isolated cardiomyocytes (Gunteski-Hamblin et al., 1996) consistent with a role in negative inotopic calcium handling.

Elaboration of Vasoactive Substances

One function of endothelium that may be important in vascular physiology is the ability to mediate relation of the underlying smooth muscle in response to appropriate stimuli. Endothelial-dependent relaxation is now recognized as resulting from release of nitric oxide, which is synthesized by endothelial cells in response to shear forces and various phar-macologic agents. Sjoberg and his co-investigators evaluated the ability of the transplanted aorta to mediate endothelial-dependent relaxation in the rat.22 This study used syngeneic donors and recipients, and the vascular grafts were transplanted with a mean ischemic time of 41 minutes. Thus, this study considered the best case situation of a graft transplanted with minimal possibility of immunologic response or adverse consequences of harvest, sterilization and storage. These grafts exhibited excellent preservation of endothelia-mediated relaxation at both three and 60 days after implant. Although this experimental protocol is...

Viscoelastic Properties

Cartilage Viscoelastic

Where Oj(t) and eH(x) are the time-dependent second rank stress and strain tensors, respectively, and Ciju(t - t) is the fourth-rank relaxation modulus tensor. This tensor has 36 independent elements for the lowest symmetry case and 12 nonzero independent elements for an orthotropic solid. Again, as for linear elasticity, a reduced notation is used, i.e., 11 1, 22 2, 33 3, 23 4, 31 5, and 12 6. If we apply Eq. (1.17) to the case of an orthotropic material, e.g., plexiform bone, in uniaxial tension (compression) in the 1 direction Lakes and Katz, 1974 , in this case using the reduced notation, we obtain Thus, for a more complete understanding of bone's response to applied loads, it is important to know its rheologic properties. There have been a number of early studies of the viscoelastic properties of various long bones Sedlin, 1965 Smith and Keiper, 1965 Laird and Kingsbury, 1973 Lugassy, 1968 Black and Korostoff, 1973 . However, none of these was performed over a wide enough range...

In Silico Dynamic Studies of Cis Trans Isomerization in Organic and Biological Systems

The reaction path of photochemical reactions is determined primarily by the topology of the excited singlet surfaces Sx (x 1, 2, ), along with the topology of the ground state S0 if no intersystem crossing to a triplet surface occurs. The most important characteristics of these potential energy surfaces (PESs) are the locations of minima, points of contact (e.g. conical intersections between S0 and S1), barriers and singlet-triplet intersection points. The shapes of the PESs are intimately tied to changes in the electronic wave function in relation to molecular geometry. Different approaches can help in the understanding of photoisomeriza-tion processes. Qualitative approaches are based on correlation diagrams expressed either in the valence bond (VB) or in the molecular orbital (MO) framework 1,2 . Although essential for the understanding of the nature and the symmetry of the electronic wave functions associated with the respective molecular geometries in the various electronic...

Myocardial Oxygen Consumption

Changes in stroke volume, whether caused by changes in preload, afterload, or inotropy, significantly alter the oxygen consumption of the heart. Changes in heart rate likewise affect myocardial oxygen consumption. The contracting heart consumes a considerable amount of oxygen because of its need to regenerate the large amount of ATP hydrolyzed during contraction and relaxation. Therefore, any change in myocardial function that affects either the generation of force by myocytes or

Prostate Cancer Stem Cells A Target for New Therapies

Deed, when AR mutations are observed, they frequently result in either enhanced androgen binding or a relaxation of the steroid specificity of the receptor, enabling it to activated gene expression after binding to other steroids, estrogens and even the commoner antagonists used for therapy (Culig et al. 1993 Linja and Visakorpi. 2004). Zero function mutations, such as those found in androgen insensitivity patients, are frequently toxic when re-expressed in prostate epithelial cells (Birnie and Maitland, unpublished data). However, the mechanism whereby the AR gene amplification arises remains unknown.

Neurohumoral control of coronary vascular tone

Substance P and CGRP immunoreactive nerve fibres are rare in the proximal region of epicardial coronary arteries and increase in number distally.83 Substance P and CGRP produce a marked relaxation of epicardial coronary arteries88 89 but exert only a weak vasodilatory effect on intramyocardial resistance vessels.89 90

Centriole Disorientation

Loss of orthogonal relationship between the centriole pair, observed during late Gj, is commonly said to be the leading event in centrosome reproduction (Figure 9.1b) 14-16 . Although this morphological change has been interpreted to mean a disjunction event, a proposition supported by the behavior of centrioles in Xenopus egg extracts 16 , it is not rigorously known if this represents the functional separation of the mother and daughter centrioles or rather a relaxation in their spatial association without loss of physical connection in somatic cells. Although the cen-trioles separate slightly at this time, the centrosome as a whole does not split until later in interphase.

Shear Stress And The Release Of Vasoactive Mediators

Furchgott and Zawadzki (1980) demonstrated that relaxation of vascular smooth muscle following acetylcholine administration was dependent on the integrity of the endothelium, which responded by upregulating the production of the free radical gas nitric oxide (NO), which was subsequently identified as the endothelium-derived smooth muscle relaxing factor. In the endothelium the isoform of nitric oxide synthase (eNOS) converts the amino acid L-arginine to L-citrulline and nitric oxide, shear stress being the most potent and direct regulatory factor of eNOS activity (Kuchan and Frangos, 1994) and gene expression (Noris et al., 1995), while low levels of shear stress and turbulent flow have the opposite effect. The sudden onset of flow induces a burst of nitric oxide production. This process is both calcium- and G protein-dependent. In contrast, steady shear stress induces a sustained release of nitric oxide that is calcium and G protein-independent (Kuchan and Frangos, 1994). Transient...

Oxygensensitive Mechanisms

Evidence that endothelial-derived adenosine is in part responsible for the dilation of rat femoral vessels during systemic hypoxia has been described above (Figure 9.4). Recently, evidence has been developed that the red cell itself may participate in the vascular response to lowered oxygen. It has been shown that hemoglobin deoxygenation in the passage of blood through the microcirculation causes release of ATP from the red blood cell (Sprague et al., 1996 Ellsworth, 2004), which may act on the arteriole. ATP could also act on the venular endothelium to cause release of prostaglandins, which could in turn diffuse to adjacent arterioles as reported by Hester and Hammer (2002), providing a feedback mechanism linked to HbO2 saturation in the microcirculation. The vascular network also possesses the capability of transmitting hyper- or depolarization, and it has been suggested that a vasodilator response is conducted upstream from the capillary network to the arterioles in contracting...

Morphine Onthe Central Nervous System

Morphine is the most generally useful high-efficacy opioid analgesic it eliminates pain and also allows subjects to tolerate pain, i.e. the sensation is felt but is no longer unpleasant. It both stimulates and depresses the central nervous system. It induces a state of relaxation, tranquillity, detachment and well-being (euphoria), or occasionally of unpleasantness (dysphoria), and causes sleepiness, inability to concentrate and lethargy, always supposing that this pleasant state is not destroyed by nausea and vomiting more common if the patient is ambulant. Excitement can occur but is unusual. Morphine excites cats and horses, though it is illegal to put this to practical use. Generally, morphine has useful hypnotic and tranquillising actions and there should be no hesitation in using it in full dose in appropriate circumstances, e.g. acute pain and fear, as in myocardial infarction or road traffic accidents.

Magnetic Resonance Imaging

In contrast to optical imaging, MRI has the advantages of a very high spatial resolution (25-100 im) and the ability to measure more than one physiological parameter at once using different radiofrequency pulse sequences (23). These features make MR very attractive for imaging reporter gene expression. The imaging signal is generated as a result of spin relaxation effects, which can be altered by atoms with high magnetic moments (e.g., gadolinium and iron). One particularly useful MR imaging signal amplification system is

Localizing Nanoparticle Concentrations

Magnetic resonance imaging has been shown to be very well suited for diagnostic cancer imaging as a result of the exceptional anatomical resolution of this modality 29,30 . The basis of molecular MRI is generally based on the assumption that antibodies, peptides, or other targeting molecules, tagged with a magnetic contrast agent, binds to the target and produces a local magnetic field perturbation that results in an increased proton relaxation rate that is detectable by magnetic resonance techniques. Magnetic nanoparticles are a form of magnetic contrast agent in MRI. Para- and superparamagnetic agents such as Gd(III) and various forms of iron oxide in both molecular and nanoparticle form have been used in a broad range of MRI applications to enhance image contrast. This approach is only limited by the inherent sensitivity of MRI, and the specific pulse sequence chosen, to the presence and distribution of the magnetic contrast agent 25,26,31,32 .

Stabilizing Proteins by Intein Mediated Backbone Cyclization

Limited protein stability often hampers successful structure elucidation by X-ray crystallography and or NMR spectroscopy. Relaxation properties are usually improved at elevated temperatures, and multidimensional NMR experiments require sample lifetimes to extend over several days to weeks in order to acquire all the necessary data. In addition, the activity of contaminating proteases that are sometimes present in purified samples can be significant at the experimental temperatures. Therefore, the stability of a target protein can be a concern, in particular for expensive isotope-labeled proteins.

Neuromuscular Blocking Drugs

That voluntary muscle tone and reflex contraction be inhibited. This can be attained by deep general anaesthesia, regional nerve blockade, or by using neuromuscular blocking drugs. Deep general anaesthesia causes cardiovascular depression, respiratory complications, and slow recovery. Regional nerve blocks may be difficult to do or contraindicated, for example if there is a haemostatic defect. Selective relaxation of voluntary muscle with neuromuscular blocking drugs allows surgery under light general anaesthesia with analgesia it also facilitates tracheal intubation, quick induction and quick recovery. But it requires mechanical ventilation and technical skill. Neuromuscular blocking agents should be given only after induction of anaesthesia.

Events in the Cardiac Cycle

The heart serves as a muscular pump that generates varying pressures as its chambers contract and relax. Systole is the period of ventricular contraction. In the diagram shown below, pressure in the left ventricle rises from less than 5 mm Hg in its resting state to a normal peak of 120 mm Hg. After the ventricle ejects much of its blood into the aorta, the pressure levels off and starts to fall. Diastole is the period of ventricular relaxation. Ventricular pressure falls further to below 5 mm Hg, and blood flows from atrium to ventricle. Late in diastole, ventricular pressure rises slightly during inflow of blood from atrial contraction.

Marine Invertebrates of the Andaman and Nicobar Islands

Several steroidal, terpenoids, and acetylenic compounds isolated from nudibranchs were also found in sponges which they feed upon.204 The bioactive nucleoside characterised as 1-methyl-isoguanosine has been found in the sponge Tedania digitata205,206 as well as in the nudibranch Anisodoris nobilis.207-209 Isoguanosine isolated from marine nudibranch Diaulula sandiegensis210 produced hypotension and relaxation of smooth muscles in mammals. Hexadecylglycerol isolated from Archidoris montereyensis 211 showed high order of activity in vitro against Staphylococcus aureus and Bacillus subtilis. Sea-hares accumulate large quantities of metabolites in their digestive gland and skin. These compounds are believed to originate from the algae which they take as food. Aplysiatoxin, a toxic metabolite has been isolated both from the Hawaiian sea-hare Stylocheilus longicauda and also from blue-green alga Lynbrya majusticula212 on which it feeds. Aplysistatin is a well known antileukemic metabolite...

Modulation of Pain by the Autonomic Nervous System

Perception of intestinal stimulation (61). Using brief distending stimuli in the intestine, the effect of sympathetic activation by LBNP on sympathetically mediated intestinal relaxation and on vagally mediated gastric relaxation was measured by corresponding barostats. The effect of LBNP on perception of duodenal distension was also compared to the perception of somatic stimulation. It was found that sympathetic activation significantly heightened perception of intestinal distension without modifying perception of somatic stimuli (perception scores increased by 41 and 2 , respectively). Also, the reflex responses to duodenal distension significantly increased during sympathetic activation both in the stomach and in the intestine (relaxation increased by 91 and 69 , respectively, with p < 0.05 for both).

Fluorescent probes in proteins and membranes

Membranes are more complex than the unrestricted rotational diffusion discussed above. To begin with, the fluorescent probe is no longer 'free' but is confined to some restricted geometry due to the local environment. The steady-state local orientational distribution of the fluorophore is no longer isotropic however the global orientational distribution of the larger host molecule is wholly random and the fluorescence anisotropy will tend towards zero. The two orientation relaxation processes can be separated by several orders of magnitude for tryptophan 214 in human serum albumin (HSA) the local tryptophan motion has a rotational lifetime on the order of 200 ps whilst HSA shows a rotational diffusion time of 20-30 ns depending on the biological molecules it transports. If the two orientational relaxation processes are independent, the fluorescence anisotropy is described by Two photon fluorescence anisotropy measurements yield anisotropy decays of a wholly equivalent form to Equation...

Regulation of Appetite in the Elderly

Adaptive Relaxation Stomach

During a meal, the fundus distends to accommodate food, a process termed adaptive relaxation. Food is then passed to the antrum after mixing with stomach secretions. Antral distension is the major signal for termination of a meal 1 . With aging, there appears to be impaired gastric fundal accommodation 6 due to impaired adaptive relaxation, which is caused by a decline in the local release of nitric oxide. Older mice have decreased nitric oxide synthase activity in their fundus 7 . The decline in adaptive relaxation that occurs with aging leads to more rapid antral filling. In addition, some studies suggested that large- Nitric Oxide, Adaptive Relaxation, and Appetite

Magnetic Resonance Imaging MRI and spectroscopy

Computed Tomography Fatty Liver

Of this macroscopic magnetisation, in a process called excitation. After switching off the RF waves, magnetisation returns to the thermal equilibrium in a time and direction dependent manner. This process is called relaxation and the changing macroscopic magnetisation induces an electrical signal in the receiver coil. Signal intensity in MRI is dependent not only on the proton density in the volume of interest, but also on the interaction between tissue protons and externally applied RF waves during the excitation, and on the interaction between nuclei within the tissue during the relaxation. The different physical properties of protons within water and fatty acid molecules result in strong differences in the time and phase dependent behaviours of these nuclei during the relaxation, producing a relaxation and phase dependent contrast for magnetic resonance imaging. T -relaxation based contrast can be used for volumetric measurements of subcutaneous and intra-abdominal fat...

Fluorescence Spectroscopy

Fluorescence is the emission of radiation that occurs when an excited molecule returns to the ground state (Lakowicz, 1999). The relaxation of the excited molecules back to the ground state may occur by the radiationless process. Its presence results in a quenching of the fluorescence intensity. Fluorescence involves two processes absorption and subsequent emission. The shape of the emission band is approximately a mirror image of the absorption band if the vibronic structures of the two states are similar. Each process occurs in the time scale given by the inverse of the transition frequency ( 10-15s), but there is a time lag of about 10-9 s when the molecule exists in the excited state. Fluorescence occurs at a lower frequency than that of the exciting light. Because the detection frequency is different from the incident frequency, the sensitivity in fluorescence spectroscopy is high (sample concentration in the 10-8M range). Therefore fluorescence spectroscopy is widely used in the...

Cardiac Cell Structure And Function

Cardiac Myocytes Syncytium

This results in a movement (ratcheting) between the myosin heads and the actin. The actin and myosin filaments slide past each other, thereby shortening the sarcomere length (this is referred to as the sliding filament theory of muscle contraction) (Fig. 3-4). Ratcheting cycles will occur as long as the cytosolic calcium remains elevated. Toward the end of the myocyte action potential, calcium entry into the cell diminishes and the sarcoplasmic reticulum sequesters calcium by an ATP-dependent calcium pump, sarco-endoplasmic reticulum calcium ATPase (SERCA see Fig. 3-3). As in-tracellular calcium concentration declines, calcium dissociates from TN-C, which causes a conformational change in the troponin-tropomyosin complex this again leads to tro-ponin-tropomyosin inhibition of the actin-binding site. At the end of the cycle, a new ATP binds to the myosin head, displacing the adenosine diphosphate (ADP), and the initial sarcomere length is restored. Thus, ATP is...

Coronary flow reserve

Tachycardia And Increased Contractility

Many studies have estimated CFR from the reactive myocardial hyperaemia that follows transient total coronary occlusion. If there is no hyperaemia, coronary vascular reserve is deemed to have been exhausted by having to compensate for a stenosis in the supply vessel, and the supply vessel is deemed to be critically constricted.164 Reactive hyperaemia is, however, the result of complex interactions between vasodilator metabolites, myogenic relaxation, and coronary capacitance.165 It is difficult to standardise because it varies with the duration of occlusion, basal coronaiy perfusion pressure, sympathetic tone, and

Pressure autoregulation

Autoregulation Coronary Hypertensive

A schematic diagram of the changes in blood flow to an organ over a wide range of perfusion pressures in the presence or absence of autoregulation is shown in Fig. 6.5. In the absence of autoregulation, pressure-flow relationships are linear, and increases in driving pressure lead to direct increases in perfusion. An autoregulatory curve is characterised by a large range of pressures during which flow remains relatively constant. vasodilation is achieved at lower perfusion pressures by relaxation of smooth muscle, and vascular smooth muscle constriction occurs at higher perfusion pressures to maintain constant flow. The ability to autoregulate assumes that a set point of basal vasomotor tone allows for this dilatation or constriction to occur. Flow varies directly with pressure when the limits of autoregulation are exceeded. In regional beds that are maximally vasodilated, for example by a drug such as dipyridamole, the process of autoregulation is eliminated and flow is directly...

Centriole Duplication

Shown as shaded barrels the appendages on the older centrioles represent sub-distal and distal appendages. The pericentriolar material is not shown in some cell types it surrounds both centrioles and in other types it is associated primarily with the older centriole. a. At the end of mitosis each daughter cell receives a single centrosome containing a pair of centrioles in close proximity. The centrioles are shown to be connected by a fibrous link. b. Centriole disorientation is seen as a relaxation of the tight orthogonal relationship between the older and younger centrioles in late G1. Although this is said to be the leading event of centrosome duplication, it is not known if this represents a disjunction event or the relaxation of a persistent connection. c. The start of centriole duplication is seen by the assembly of short pro-centrioles at right angles to the proximal ends of the two parental centrioles. The pro-centrioles elongate throughout the rest of interphase, reaching...

Structures Of The Cardiac Cytoskeleton Cell Adhesion And The Sarcomere

The major function of cardiomyocytes is in the cardiac contraction-relaxation cycle. The contractile proteins in cardiomyocytes constitute about 75 of the total volume of the myocardium, although only about one-third of the number of all the cells in the myocardium are cardiomyocytes. About half of each ventricular cell is occupied by myofibers, and about one-fourth to one-third by mitochondria. The major proteins involved in contraction and relaxation are the thin filament (composed of actin, tropomyosin, and C-, I-, and T-troponin) and the thick myosin filament. During contraction, the filaments slide over each other (A band) without the individual molecules of actin or myosin actually shortening, leading to a pulling together of the two ends of the fundamental contractile unit called the sarcomere (Fig. 1A,B). The sarcomere is limited on either side by the Z-disc (Z is an abbreviation for the German Zuckung, meaning contrac

Clinical features

Ischial Spine

Wall and guided by a finger to the ischial spine, which can be palpated per vaginam. Alternatively, the needle can be introduced just medial to the ischial tuberosity to a depth of 1 in (2.5 cm). When the procedure is carried out bilaterally there is loss of the anal reflex (which is a useful test that a successful block has been achieved), relaxation of the pelvic floor muscles and loss of sensation to the vulva and lower one third of the vagina (see Fig. 99b).

Distension of Hollow Viscera

Using fixed-pressure distensions, the result is quite different if the gut contracts, both intraluminal volume and perception decrease (12). Hence, using these methods, perception of gut distension depends on the muscular activity of the gut, and varies upon contraction and relaxation. To overcome these problems, a new methodological approach, the tensostat, has been developed (13). The tensostat is a computerized air pump that applies fixed tension levels on the gut wall. Based on intraluminal pressure and intraluminal volume, the system calculates wall tension, by applying Laplace's law (either for the sphere or for the cylinder) and drives in the pump to maintain the desired tension level on the gut wall. Applying fixed-tension distensions, if the gut contracts, intraluminal volume decreases and intraluminal pressure increases, but perception remains unaffected. These data indicate that perception of gut distension in healthy subjects depends on stimulation of...

Arterial Spasm from Subarachnoid Hemorrhage

It is not surprising that the exact biochemical mechanism underlying the prolonged vasoconstriction of vasospasm is unknown since the nature of normal vascular constriction-relaxation is so incompletely understood. Most current concepts of smooth muscle contraction were initially gained by physiologists working with other forms of muscle. More than 100 years ago, while studying ventricular cardiac muscle contraction Ringer found that Ca2+ was a requirement. Within a decade Fletcher and Hopkins showed that lactic acid was produced during Calcium ions (Ca2+) were shown to be the activator of the contractile system by Weber and Wincur (58). The concentration of Ca2+ controls contraction and relaxation by an allosteric mechanism in which the flow of information is from Ca2+ to troponin to actin to myosin. The rise and fall of sarcoplasmic free Ca2+ is the fundamental means of controlling smooth muscle contraction and relaxation (59). increased by phosphorylation of the regulatory light...

Histone Deacetylase Inhibitors

Histone deacetylases (HDAC) catalyse the deacetylation of lysine residues at the amino termini of core nucleosomal histones (42). This process is associated with chromatin relaxation and uncoiling, which permits the transcription of various genes including the key cyclin-dependent kinase inhibitor, p21 (42). By inhibiting HDAC, histone deacetylase inhibitors (HDI) cause hyperacetylation of histones. Hyperacetylation of histone H3 leads to transcriptional up regulation of p21, cell cycle arrest and apoptosis in tumor cells (42,43). The HDI acid SAHA induced p21 expression in one of the two CML cell lines and induced expression of p27, a key cell cycle regulator, in both of them (42). SAHA treatment was also associated with down regulation of p210Bcr-Abl protein. Combination treatment of CML cell lines with SAHA and imatinib resulted in a greater level of apoptosis than was achieved with either agent alone (42,44). This combination also produced synergis-tic induction of apoptosis in...

Interaction of Sensory and Reflex Dysfunctions

Normally, ingestion of a meal induces a relaxation of the proximal stomach to accommodate the meal volume, and the magnitude of the relaxation is regulated by a complex net of reflexes (61,62). Hence, this partial relaxation prevents wall tension increments and symptoms, but still the residual contraction of the proximal stomach gently forces gastric content distally into the antrum and initiates gastric emptying. As the relaxatory input decreases, the proximal stomach regains tone and emptying progresses. A gastric hyporeactivity to relaxatory reflexes would predictably result in a defective volume accommodation of the proximal stomach and antral overload. In patients with functional dyspepsia, gastric tone and compliance are normal during fasting (47,48,63,64). However, the reactivity of the stomach to regulatory reflexes is abnormal, and the proximal stomach does not relax properly in response to reflexes arising from the antrum and the small intestine (14,48,65). Consequently,...

Preventing Reinfarction

Other studies have shown positive gains following shorter and more general stress management interventions. Blumenthal and colleagues,8 for example, assigned patients to a 4-month program of exercise or stress management training or usual treatment control. Participants in the stress management group were significantly less likely to have a cardiac event over the follow-up period than participants in either other condition. Appels and colleagues9 used a simpler intervention program involving a relaxation and controlled breathing program following angioplasty. This resulted in a 50 lower risk of further intervention or a new coronary event than that of participants in a no treatment group in the following 18 months.

Sensing Applications Utilizing Rotational Brownian Motion

Rotational Brownian motion for the signal transduction of biochemical binding events. In one of the earliest measurements, the random rotational motion of a wire in a liquid was detected by light reflected from a mirror attached to the wire 9 . Obviously, the detection of rotational Brownian motion for spherical particles is more complicated and requires an anisotropy to break the spherical symmetry. Examples of symmetry-breaking are permanent electric dipole moments, whose motion can be detected with inelastic light scattering 10 , or anisotropic optical properties, which leave a distinct signature of the rotational motion in dynamical light-scattering experiments 11 . Clearly, a permanent magnetic moment will also break the spherical symmetry its use for the detection of rotational Brownian motion is discussed in Section 4.3.2. An alternative approach for the detection of Brownian relaxation is nuclear magnetic resonance, since the relaxation time for nuclear spins is modified by...

Mri Of Atherosclerosis Multi Contrast MRI of Atherosclerosis

Mri Atherosclerosis

The appearance of a thrombus or intraplaque hemorrhage, on MRI, largely depends on the state of hemoglobin contained in the hemorrhage or retained in the thrombus. Depending on the stage of the hemorrhage thrombus it may contain different oxidative and byproduct forms of hemoglobin such as hemosiderin, ferritin, oxyhemoglobin, deoxyhemoglobin, or met-hemoglobin. The different oxidative and byproduct forms of hemoglobin have particular magnetic resonance relaxation parameters that give them different signal intensities due to differences in their T1 and T2 (51-55). The progression of hemorrhage and subsequent thrombus and its appearance on MRI has been

The parasympathetic system

The parasympathetic nervous system is also controlled by the hypothalamus and is related to the activity of the pituitary-adrenal system. However, it is concerned with maintenance activity within the body. Thus digestion is aided by the production of saliva and the digestive enzymes, and peristalsis is maintained. The heart rate is reduced and the respiratory system also decreases in activity. The tissue-repair processes are stimulated and sugars are converted to fats and stored. The body enters a restful, peaceful stage. Sleep is easier during this phase and after a heavy meal the parasympathetic system is very active. The overall effect then is one of muscular and mental relaxation, while the restorative functions take place.

Interventricular Delay

Mitral Regurgitation Wigger

Events of the cardiac electrical cycle. Atrial contraction followed by relaxation produces a negative pressure gradient, causing a surge of blood in the LV at end diastole. Reversal of the atrioventricular pressure gradient initiates mitral valve (MV) closure because of a rapid decrease in pressure between the MV cusps pulling them into apposition. A brief period of isovolumetric contraction exists after MV closure and before AV opening during which the maximal rate of pressure change (peak + dP dt) occurs. Rapid ejection occurs during ventricular systole and is terminated when ventricular pressure falls below aortic pressure, closing the aortic valve (AV). A brief period of isovolu-mic relaxation follows during which the maximal rate of pressure decline (peak - dP dt) occurs. As the left ventricular (LV) pressure continues to decline and fall below atrial pressure, the MV opens and diastolic ventricular filling begins. Normal diastolic filling is characterized by an...

Variations in myocardial perfusion

Coronary Flow And Aortic Pressure

Blood supply to the heart is affected by ventricular contraction and relaxation. Any myocardial stress is expected to alter underlying myocardial geometry and, in turn, geometry of intramyocardial vessels. This may affect Isolated coronary venules dilate in response to an increase in flow.147 This flow-induced vasodilation is endothelium-dependent and mediated by the release of a nitrovasodilator. Endothelial disruption results in flow-induced constriction, suggesting that shear stress may directly act on the vascular smooth muscle.147 Whereas the additive effects of flow-induced dilatation and possibly myogenic relaxation of arterioles can maximise myocardial oxygen delivery during elevated the flow-induced venular dilatation may possibly

Mass Transfer Models

According to the polymer literature, mass transfer can be classified according to the governing mechanisms into three basic categories zero order, case I, and case II (51). Zero-order transport, termed constant-rate drying, refers to the case where the moisture content varies linearly with time, such as during the initial stages of drying, when the rate of moisture removal at the surface is equal to the rate of moisture transport to the surface. Zero-order transport is generally observed only during the initial stages of drying. Case I diffusion is characterized by a falling rate of moisture transport and is governed by Fick's law and Luikov's model. Luikov's model accounts for Soret and Dufour effects. Case II diffusion describes the case where material relaxation is important in moisture transport. Case II diffusion has been the subject of much research in the polymer field (5254) and has application to moisture transport in foods. Achanta et al. (55) developed a mechanistic model,...

Changes in ventricular performance related to ageing

On consideration of the high prevalence of clinically latent coronary artery disease and hypertension in elderly people, it is not easy to separate the effects of ageing from other pathological processes, and this may well explain some of the variations in the published data.122 Ageing is associated with increasing stiffness of the great arteries, which in turn leads to increases in arterial pulse wave velocity and pulse wave amplitude. The ejection of stroke volume into a stiffer arterial tree and the accelerated reflected pulse waves returning before the aortic valve closure result in higher systolic pressures.123 Thus, there is an increase in left ventricular systolic load manifesting itself as alterations in aortic input impedance. The characteristic impedance increases, there is increased fluctuation of the impedance moduli about the mean, and both the minimum modulus and the pressure-flow phase crossover shift to higher frequencies. The zero frequency impedance modulus,...

Isolated carpal dislocations

Carpal Dislocations

As for most dislocations, an attempt at reduction requires a sufficient amount of muscle relaxation. Ten pounds of traction is applied with finger traps to further fatigue the forearm musculature. The thumb of the dominant hand is placed over the volar aspect of the radius and moved distally until resting on the proximal pole of the scaphoid. The finger traps are then removed and traction is maintained by the opposite hand. A dorsally directed pressure is applied to the proximal pole of the scaphoid as the wrist is ulnarly deviated. With this maneuver a reduction of the scaphoid is usually achieved.

The Baking of Doughs

Imaging the baking of doughs is an attractive proposition because it provides real-time data on the changing moisture and fat distribution as well as the development of voids in the dough. Such information can assist in process optimization (3) and also affect product quality. Unfortunately, a number of factors combine to complicate this type of imaging experiment. To begin with, the low moisture content of the final product (typically less than 10 in a biscuit) shortens the water proton transverse relaxation time, and this eventually limits the liquid-type imaging experiments to moisture contents above ca. 10-15 . The relatively high fat content of biscuits (e.g., 5-15 ), which is characterized by a longer transverse relaxation time than the water protons, also contributes significant signal intensity and makes it necessary to devise ways of separating the fat and moisture contributions. A third complication is the increase in void formation and therefore of porosity during baking....

Extrusion Cooking of Cereals

During extrusion, the raw ingredients are fed into the barrel of the extruder, where they are subjected to shear stress by rotating screws to a pressure gradient, because the size of the die exit orifice is usually smaller than the barrel and to heating, both from external heat sources along the barrel and from internal heat generated by chemical reactions and friction. Under these conditions a complex series of physical and chemical changes take place, such as mixing, gelatiniza-tion, denaturization, evaporation, flavor production (and loss), and rheological changes. Not surprisingly, understanding and mathematically modeling these complex and rapid changes is a major challenge in cereal processing science. Magnetic resonance imaging can greatly assist in understanding this endeavor by providing real-time, noninvasive images of the flow within the extruder and, potentially, spatial maps of other NMR parameters, such as relaxation times, chemical shifts, and diffusion coefficients, as...

Normal Cardiac Presure

Heart Chambers Pressures

The seven phases of the cardiac cycle are (1) atrial systole (2) isovolumetric contraction (3) rapid ejection (4) reduced ejection (5), isovolumetric relaxation (6) rapid filling and (7) reduced filling. LV, left ventricle ECG, electrocardiogram a, a-wave c, c-wave y, v-wave AP, aortic pressure LVP, left ventricular pressure LAP, left atrial pressure LVEDV, left ventricular end-diastolic volume LVESV, left ventricular end-systolic volume, S1-S4, four heart sounds. In the following discussion, a complete cardiac cycle is defined as the cardiac events initiated by the P wave in the electrocardiogram (ECG) and continuing until the next P wave. The cardiac cycle is divided into two general categories systole and diastole. Systole refers to events associated with ventricular contraction and ejection. Diastole refers to the rest of the cardiac cycle, including ventricular relaxation and filling. The cardiac cycle is further divided into seven phases, beginning when...

The Rheology of Doughs and Batters The MRI Rheometer

One where the sample is placed between two concentric NMR tubes. By rotating the inner tube at a known angular velocity with a applied torque and imaging the radial velocity distribution in the sample it is possible to deduce the rheologi-cal flow curve in a model-independent way (17). The MRI rheometer has many potential advantages over conventional rheometers. By imaging the velocity field it is possible to see shear-induced phase transitions within the sample, induced, for example, by biopolymer aggregation. Combining flow imaging with measurements of relaxation times and diffusion coefficients provides additional insights into the microstructural and macromolecular origins of complex rheological behavior. Britton and Callaghan (17) have studied cornflour-water mixtures in this way and observed a shear-induced phase transition resulting from shear thickening. What was particularly surprising was the observation that the thickening process occurred at some distance from the shear...

Nitric oxide in the regulation of cerebral haemodynamics56

And requires Ca and tetrahydrobiopterin for its activity it differs from the inducible form of the enzyme, which is present in mononuclear blood cells and is activated by cytokines. Under basal conditions, endothelial cells synthesise NO which diffuses into the muscular layer and, via a cGMP-mediated mechanism, produces relaxation of vessels. There is strong evidence to suggest that NO exerts a tonic dilatory influence on cerebral vessels. It is important to emphasise that data on NO obtained from peripheral vessels cannot always be translated to the cerebral vasculature for example, some

Benefits and Side Effects of Nabilone and Cannabis

The adjuvant effects of improved sleep, pain compressing, pain distancing, anxiolysis, relaxation, euphoria, and relief of depression all have benefits on the patient's perception and management of pain. These will be mediated through cortical and limbic system mechanisms.

Inhibitory Effect Of Shosaikoto On Hepatic Fibrosis

Because of their anatomical location, their ultrastructural features, and similarities with peri-cytes that regulate blood flow in other organs, it has been proposed that HSCs function as liver-specific pericytes (Pinzani et al., 1992). Previous studies have shown that the contraction and relaxation of HSCs regulate hepatic sinusoidal blood flow (Pinzani et al., 1992 Bataller et al., 2000). Two vasoregulatory compounds with obvious effects on HSCs include endothelin (ET)-1

Answers To Review Questions

Both receptors are on smooth muscle cells. The receptor at which noradrenaline is most effective is coupled to phospholipase C and therefore causes an increase of cytosolic calcium concentration, leading to contraction and hence a closing of the blood vessel. The receptor at which adrenaline is most effective is coupled to adenylate cyclase and therefore causes an increase of cAMP concentration, leading to phosphorylation and therefore relaxation of the contractile machinery and

With cogwheel phenomenon

Fig. 21.5 a Testing of the muscle tone around the elbow joint by passive manipulation during maximal relaxation of the muscles. b Diagram of important pathological findings the pocketknife phenomenon (fading of resistance when under steady pressure), and cogwheeling (joint rigidity with repeated, brief, and uniform increases in tonus over the entire range of motion of the joint) in case of muscle rigidity in Parkinson's disease

Fundamentals Of Magnetic Resonance Imaging

To understand MR based contrast systems, a rudimentary appreciation of MR imaging and the nuclear magnetic resonance (NMR) phenomenon is required. The fundamental precept of NMR states that spins of protons (i.e., hydrogen nuclei) and electrons (6,7) when placed in a strong external magnetic field (B0) orientate themselves either parallel (i.e., spin-up) or antiparallel (i.e., spin-down) to the magnetic field (B0). Approximately, 1 106 to 1 107 protons adopt more spin-up than spin-down states per voxel. Although this is a trivial distribution imbalance, the overwhelming abundance of water in tissues magnifies this disparity and the impact is perceptible. Next, irradiating the magnetized sample with electromagnetic (radiofrequency) energy disturbs the thermal equilibrium distribution and increases the antiparallel or spin down level. The ensemble of spins exhibits a net magnetization vector tilted away from the direction of the main magnetic field (B0). The transition from this excited...

Endothelial control of coronary vascular tone

Muscle Endothelium Adenosine

Will depend on the net balance between released vasodilating and vasoconstricting factors. Decreased release of relaxing factors combined with an increased formation of contracting factors (as in ageing or hypertension) will attenuate endothelium-dependent relaxation. Vasoconstriction after platelet aggregation and damage is the result of smooth muscle cell activation by platelet-derived TXA2 (and serotonin). Normal coronary arteries exhibit endothelium-dependent dilatation in response to both local acetylcholine and increased flow. These physiological responses are lost in humans with advanced coronary artery disease.31 Oxidised low density lipoproteins and hypoxia or anoxia inhibit the release of EDRF. Ischaemia and reperfusion induce impairment in endothelium-dependent relaxation to most EDRF NO agonists.32 Although such studies underscore the potential clinical relevance of impaired release of EDRF NO in ischaemic syndromes, a potentially important role for endothelin is also...

Targets Of Cerebrovascular Gene Therapy

In contrast to the attempts to enhance NO-mediated vasorelaxation after SAH, gene transfer of calcitonin gene-related peptide (CGRP), a vasodilator neuropeptide, prevented vasospasm after SAH (55,56) (Fig. 2A). Gene transfer of CGRP increases the level of cAMP in the basilar artery (28), and this is thought to result in activation of K+ channels, such as adenosine triphosphate (ATP)-sensitive K+ channels (KATP channels), producing hyperpolarization of smooth muscle membrane and relaxation of cerebral arteries (57,58). This strategy has a good rationale, because the smooth muscle cell membrane is depolarized, and relaxation in response to activators of KATP channels is preserved or enhanced in cerebral arteries after experimental SAH (59-61). As a means for enhancement of cellular protection, gene transfer of superoxide dismutase (SOD) has also been tested. Elevated superoxide levels in the subarachnoid space may contribute to cerebral vasospasm (74-76). Superoxide impairs NO-mediated...

Control of the muscle circulation

Constriction of the muscle resistance vessels occurs solely by activation of the sympathetic noradrenergic nerves or muscle compression itself. On the other hand, neurogenic vasodilation can occur either by withdrawal of noradrenergic activity or by release of substances that lead to relaxation of vascular smooth muscle. The most important effectors of this type are sympathetic, cholinergic, and histaminergic systems. subtype. Activation of these receptors causes relaxation of the smooth muscle which can 5-HT receptors. In most animals, and most probably in humans, there is a cholinergic vasodilator pathway that originates in the motor cortex. The descending pathway has discrete relays in the hypothalamus and continues through the mesencephalon descending via the lateral spinothalamic tract. These cholinergic nerves run in the sympathetic nerves to the muscle vessels and they innervate almost exclusively the small arteries and arterioles. The acetylcholine released on activation of...

Coronary microcirculation

Of the more than 2000 capillaries mm , usually only 60-80 are open. The normal intercapillary distance is about 17 p,m (Table 4.1). During hypoxaemia, the intercapillary distance decreases to 14-5 m as a result of recruitment of additional capillaries. Recruitment occurs by relaxation of precapillary sphincter tone. During prolonged hypoxaemia, the intercapillary distance decreases even further to 11 p,m (Table 4.1).

Hypertrophic Cardiomyopathy

Pacing Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy is a disorder of the myocardium characterized by excessive myocardial hypertrophy, with a predilection for the interventricular septum. Although there may be obstructive (i.e., a demonstrable gradient across the left ventricular outflow tract) and nonobstructive forms, there might be little difference between them because the gradient is dynamic and affected by preload, afterload, and other factors. Difficulty with diastolic relaxation (and ventricular filling) of the thickened and noncompliant ventricular musculature is present in both forms of this disorder and may be an important determinant of the clinical presentation. Pacing is thought to exert a beneficial effect by inducing paradoxical septal motion and ventricular dyssynchrony and dilatation, thereby improving ventricular filling and reducing the outflow tract gradient.

Association Of Anticancer Drugs With Dna At The Chromatin Level

Dna Intercalation Bisanthracyclin

Ethidium also stabilizes the second nucleosome melting transition, but daunomycin does not. Dichroism and rotational relaxation time measurements indicated that daunomycin unfolds nucleosomes. The data favored an unfolded structure in which the nucleosome elongates along the DNA superhelical axis. Higher concentration of the drug at a ratio more than 0.15 per DNA base pair promotes nucleosome aggregation. The authors suggested that the activity of daunomycin as an antitumor agent arises out of its special intercalation geometry that strongly prefers free DNA regions to the bent helices found in nucleosomes and chromatin. As a result of this preference there is an increased local concentration of the drug in the genetically active regions of nuclear DNA in which nucleosomal structure is less prevalent. Presumably the abundance of such regions in tumor cells makes them especially sensitive to daunomycin. There have been many other reports, which aimed to quantitatively define the...

Anaesthesia and the cardiovascular system

The objective of anaesthesia is to provide analgesia, unconsciousness, suppression of reflex responses to surgical stimuli, and muscle relaxation, if required. In general, this goal is achieved by administering a combination of various agents, such as volatile and intravenous anaesthetic drugs, opioids, benzodiazepines, and muscle relaxants. In principle, all drugs used in anaesthetic practice affect the performance of the cardiovascular system, either by direct effects on the heart and the vascular system or indirectly by altering neurohumoral control of the circulation. It is very difficult to obtain a clear pharmacodynamic profile of an anaesthetic drug under in vivo conditions because both direct and indirect effects interact. Moreover, most anaesthetic drugs alter vascular tone and myocardial performance simultaneously. Thus, it is difficult to distinguish whether a decrease in blood pressure and or stroke volume is the result of changes in myocardial loading conditions or of a...

Transcapillary Fluid Exchange

Transcapillary Fluid Exchange

There are two routes by which fluid is returned to the blood. First, fluid reabsorption returns most of the filtered fluid to the blood at the venular end of capillaries or at postcapillary venules (see Fig. 8-3). The rate of reabsorption is less than filtration therefore a second mechanism is required to maintain fluid balance. This second mechanism involves lymphatic vessels. These specialized vessels, similar in size to venules, comprise an endothelium with intercellular gaps surrounded by a highly permeable basement membrane. Terminal lymphatics end as blind sacs within the tissue. The terminal lymphatics take up the excess fluid (including electrolytes and macromolecules) and transport it into larger lymphatics that leave the tissue. It is estimated that 5 to 10 of capillary filtration is transported out of tissues by the lymphatics. The larger lymphatics have smooth muscle cells that undergo spontaneous vaso-motion that serves to pump the lymph. Vasomotion is spontaneous...

Swelling and Solubility of Granular Starch

The current methodology for the determination of swelling and solubility patterns of starch was developed by Leach et al. (1959). It was postulated that bonding forces within the granule would influence the manner of swelling. The swelling, when plotted against the temperature of pasting, would give a curve representing progressive relaxation of the bonding forces within the granule, permitting comparison of the relative bonding strengths in various starches from the temperature (energy level) necessary to cause relaxation. The method involved making a suspension of starch in a known volume of water and gently stirring to keep it in suspension while incubating it at the desired temperature for 30 min, centrifuging it at 2200 rpm for 15 min, and obtaining the weight of the gel, which is expressed as sediment paste per gram (dry basis) of the starch. Solubility of the starch is obtained by drying the supernatant and is expressed as percentage soluble. This test has always been...

Changing Contours Of The Primigravid Abdomen

Hegar Sign

Relaxation of the lower esophageal sphincter allows stomach contents to back up into the lower esophagus. The decreased GI motility caused by pregnancy hormones slows peristalsis and causes constipation. Constipation may cause or aggravate existing hemorrhoids. Hormonally induced relaxation of joints and ligaments and the minor lordosis required to balance the growing uterus sometimes result in a lower backache. Pathologic causes must be ruled out.

Ronald T Brown Summary

This chapter reviews literature pertaining to the management of pain within the school setting. Etiological issues underlying obstacles to school attendance are reviewed, including issues pertaining to make-up work, concerns among many children pertaining to use of the bathroom at school, diet and eating habits at school, relationship with a teacher or peer, fear of pain episodes at school, learning problems, test or performance anxiety, separation anxiety, and familial reinforcement of sick behavior. Interventions to increase school attendance are reviewed these also include a careful assessment of the child and the family system, the use of behavioral interventions, as well as other treatment approaches, including the use of relaxation therapy and problem-solving therapy. Finally, specific directions for future research efforts and training also are provided.

The mechanism of deglutition

The cricopharyngeus then relaxes, allowing the bolus to cross the pharyngo-oesophageal junction. Fluids may shoot down the oesophagus passively under the initial impetus of the tongue action semi-solid or solid material is carried down by peristalsis. The oesophageal transit time is about 15 seconds, relaxation of the cardia occurring just before the peristaltic wave reaches it. Gravity has little effect on the transit of the bolus, which occurs just as rapidly in the lying as in the erect position. It is, of course, quite easy to swallow fluid or solids while standing on one's head, a well-known party trick here oesophageal transit is inevitably an active muscular process.

Fear of Pain Episodes at School

A primary goal in working with these children is to assist them in learning that they can cope with their pain (4). Walker recommended that children's initial return to school be brief, perhaps only 1-2 hours day. Most children will be able to attend school and even manage their pain for brief periods. The brief school attendance will assist children in building confidence so they may later be able to survive a pain episode at school. The child's health care provider and caregivers should have a plan in place in case the child experiences pain while at school. It is typically best if the child is allowed to lie down and rest until well enough to return to class or until it is time to leave school for the day. A child may also work with a school counselor to learn relaxation or distraction techniques (4,14). Walker cautioned it is often counterproductive for children to call home or be allowed to leave school early when a pain episode occurs as this reinforces complaining and passive...

CaMKII Function in Cardiomyocytes

Calcium is an important second messenger in cardiac cells. Upon membrane depolarization during the cardiac action potential, calcium enters the cy-tosol primarily through L-type calcium channels, which are concentrated in T-tubules in close proximity to SR ryanodine receptor (RyR) calcium release channels. Local elevation of calcium concentration triggers a much greater calcium release from SR stores via RyR channels, giving rise to the calcium transient and ultimately myofibril contraction. In addition to being the primary signal for myocardial contraction, intracellular calcium regulates the transduction of electrical activation to mechanical function (excitation-contraction coupling) (see Bers 2001 for review). Over a century ago, it was discovered that myocardial contraction is stronger at faster pacing rates (staircase phenomenon or positive force-frequency relationship Bowditch 1992). It has also been observed that the rate of muscle relaxation increases with pacing rate...

The Nuclear Overhauser Effect NOE

The number of nuclei in the upper energy state, N'+, is less than that in the lower energy state, N'_, and the probabilities of upwards and downwards transitions are different. The spin transitions are caused by the spins S of a nucleus, and the influence of these occurs directly through space. The transitions and their relaxations may be between the same or different type of nucleus, but in either case they are chemically shifted from the spin I. At equilibrium, some relative spin I populations exist and the fractional difference in populations between the two energy states can be written (remembering that ex is approximated by 1 + x) as Two factors contribute to zis. One is the ratio of the magnetogryric ratios of the two different spins, and the other depends on relaxation mechanisms. Provided that the relaxation mechanism is purely dipole-dipole, f has the value 1 2. If other relaxation mechanisms affect spin I, then f may approach zero. Assuming that the dipolar mechanism is...

Brain Responses To Emotional Stress Preliminary Evidence Of Sex Differences

Participants in this initial preliminary study were 7 men and 1 woman with a mean age of 33 years (SD 5.7) and educational level of 13.3 years (SD 2.3). Emotional stress was induced via a brief guided imagery and recall method, where subjects were exposed to individualized scripts of stressful life events and neutral relaxing life events. Three personalized stress and three neutral imagery scripts were developed prior to the fMRI session by obtaining specific stimulus and response information for separate stress and neutral events on scene construction questionnaires (for detailed procedures on script development, see Sinha et al., 2003). Subjects rated the level of distress experienced while reporting specific stress situations on a 10-point Likert scale, and only situations rated 8 or above were used for the development of stress scripts. The fMRI session included six scanning trials, with three stress and three neutral trials presented in random order. Each trial was 5.5 minutes...

Conclusions and Future Directions

Other therapeutic approaches like relaxation techniques and cognitive behavioral interventions given at school show promise. Such approaches may be applied to many children simultaneously. They are especially ecologically valid and generalizable and are cost-effective because they can be conducted by professionals already employed in the school system.

Descriptive Examples

An example utilizing two-dimensional NMR spectroscopy for a paramagnetic transition metal system is taken from Chapter 8 of reference 1. The chapter, entitled Nuclear Magnetic Resonance of Paramagnetic Metal Centers in Proteins and Synthetic Complexes,'' is written by Li-June Ming.20 The system to be analyzed is CuNiSOD (SOD superoxide dismutase) containing an antiferromag-netically coupled Cu2+-Ni2+ pair. The enzyme superoxide dismutase is discussed in Section 5.2.3. As discussed previously in this chapter, paramagnetic metal centers can extend the range of chemical shifts for nearby nuclei greatly, simplifying spectra by shifting important resonances away from congested regions of the spectrum. They also cause enhanced nuclear relaxation that may lead to significant increase in line width (line broadening). As with chemical shifts, paramagnetic centers cause great changes in nuclear relaxation rates. Longitudinal (T1), spinlattice, and transverse (T2), spin-spin, nuclear relaxations...

Magnetic Nanoparticles As Biosensors

When multivalent magnetic nanoparticles bind to multivalent targets in solution they form stable nanoassemblies, and associated with nanoassembly formation is an increase in R2 relaxivity and decrease in the spin-spin relaxation time (T2) of surrounding water molecules 23 , see Figure 8.3. Nanoassemblies can be disassembled and returned to their original dispersed state by a number of methods (heat, enzyme cleavage, disulfide bond reduction). Thus nanoparticles switch between a dispersed and nanoassembled states and are termed magnetic relaxation switches (MRSW). MRSW are unique as a biosensor system because they do not employ a biomolecule immobilized on a solid phase, and because they use radiofrequency radiation at the Larmour precession frequency of water protons rather than light. Therefore they are homogeneous type assays (no separation of bound and free), and can be performed in media that absorb, scatter or fluoresce when they interact with

Some Functions of the Endothelium

It has been observed in arteries and arterioles that increases in blood flow lead to vasodilation (flow-dependent dilation) Smiesko and Johnson, 1993 . This phenomenon appears to be mediated by NO release from the endothelium in those vessels. The sequence of events is (1) blood flow increases (2) shear stress at the vessel wall increases (thereby increasing the viscous drag on the endothelial lining of the vessel) (3) NO is released in response to the mechanical stimulus and (4) vascular smooth muscle relaxation (vasodilation) occurs in response to the elevated level of NO.

Other Magnetic Resonance Methods

By varying the image acquisition parameters, TR (pulse repetition time) and TE (echo time), it is possible to construct images of the proton relaxation times T1 and T2. The development of methods for echo planar imaging makes it possible to collect images with a large number of TR and or TE values quite rapidly and, thereby, to estimate localized T1 and T2 values very reliably. This relaxation time mapping is sometimes referred to as relaxometry. Changes in relaxation times may reflect anomalous cerebral development, as recently demonstrated in schizophrenia (Andreasen et al., 1991 Williamson et al., 1992 Yurgelun-Todd et al., 1995). Alternatively, alterations in cerebral perfusion may lead to small changes in T2 which can be detected using echo planar imaging (Teicher et al., 2000). In the area of substance abuse, relaxation time measurements have also been used to assess brain hydration. In general, as brain water content decreases, relaxation times become shorter. Within the brain,...

The Hypertensive Side Effect

All of the first-generation Hb-based blood substitutes cause some amount of blood pressure elevation (MAP) and gastrointestinal dysmotility (Conklin et al., 1995 Murray et al., 1995 Cullen et al., 1996 Hartman et al., 1998 Gulati et al., 1999 Hess, 1999 Winslow, 1999, 2003 Burhop and Estep, 2001 Konomi et al., 2001 Chang, 2003 Yeh and Alayash, 2003). These hypertensive and gastrointestinal dysmotility side effects clearly reflect interference with smooth muscle relaxation. With the exception of the Winslow and Intaglietta groups (Rohlfs et al., 1998 Winslow, 1998, 2002, 2003 McCarthy et al., 2001), most researchers interpret blood pressure elevation in Figure 31.3 Scheme for NO signaling in the endothelium, the roles of intracellular HbO2 and MbO2 in detoxifying NO that escapes into the blood stream and muscle tissue, and NO scavenging by extracellular HbO2 and its effects on smooth muscle function. This scheme is based on the ideas developed over the past 10 years on the...

NMR Structural Studies

Determine the overall structural dynamics of a target multidomain protein kinase. Subheading 3.3.1. describes the standard NMR approaches for determining the NMR solution structure of the regulatory domain, either in its isolated form or while ligated to its kinase domain. Subheading 3.3.2. describes the NMR relaxation experiments for determining the effects that placing the paramagnetic nitroxide spin label on the kinase domain has on the relaxation rates of the backbone amide protons of the regulatory domain, and how these effects can be converted into distance restraints between the site-directed spin label and each of the backbone amide protons. Subheading 3.3.3. describes methods for calculating the effective rotational correlation times, Tc, required for distance calculations. Subheading 3.3.4. describes methods for calculating the relative structures from distance restraints derived from the paramagnetic relaxation enhancement effects and assessing the relative degree of...

Laurel O Sillerud and Richard S Larson Summary

Nuclear magnetic resonance (NMR) techniques are widely used in the drug discovery process. The primary feature exploited in these investigations is the large difference in mass between drugs and receptors (usually proteins) and the effect that this has on the rotational or translational correlation times for drugs bound to their targets. Many NMR parameters, such as the diffusion coefficient, spin diffusion, nuclear Overhauser enhancement, and transverse and longitudinal relaxation times, are strong functions of either the overall tumbling or translation of molecules in solution. This has led to the development of a wide variety of NMR techniques applicable to the elucidation of protein and nucleic acid structure in solution, the screening of drug candidates for binding to a target of choice, and the study of the conformational changes that occur in a target on drug binding. High-throughput screening by NMR methods has recently received a boost from the introduction of sophisticated...

Brief overview of normal bladder function

To promote the storage function of the urinary bladder, sympathetic innervation plays two key roles. First, through a-adrenergic receptors, the neck and internal sphincter of the bladder are contracted to close the bladder outlet (Ek et al., 1977). Next, via b-adrenergic receptors, the body of the bladder relaxes. Normally, filling of the bladder occurs with minimal increases in pressure. Voiding the bladder is a coordinated process that involves contraction of the detrusor muscle with concomitant relaxation of the striated muscle of the urethra and pelvic floor and relaxation of internal and external sphincters. This requires integrated control from pontine centers in the brain and sacral spinal neurons (see de Groat and Yoshimura, 2001). When the bladder volume increases, sensory input from the bladder wall to the sacral spinal neurons increases until the threshold for the micturition reflex is reached and reflex voiding can be initiated. This process in the able-bodied person is...

E12 10e11 10e10 10e09 10e08 10e07

With distinct chemical shifts, irradiation of one nuclear resonance will result in changes in the intensity of the other, as long as the second nucleus is within range (< 6 A) so that dipolar coupling between the two will result in spin-lattice (7 ) relaxation. The NOE arises from the changes in populations of the nuclear spin states owing to enhanced relaxation of the observed state as a result of irradiation of the dipolar-coupled state. There is a strong dependence of the NOE on the rotational correlation time (Fig. 3). The fractional enhancement for the resonance integral of one proton on saturation of the resonance of a second, nearby proton is given by

Transferred NOE Spectroscopy

The binding of molecules to receptors is an equilibrium process in which there is chemical exchange between the free and bound forms of the ligand. Exchange results in the drug adopting the different physical properties of the receptor with attendent alterations in the correlation times and effective masses of the drugs. During the drug's residence in its receptor-binding site, it will adopt the bound configuration, which may bring remote groups into proximity. The resulting intramolecular NOEs in the NMR spectrum will give useful information about the distances between these groups in the bound state. Chemical exchange with drug molecules free in solution will transfer the bound NOE from the bound drug to the free drug, resulting in a trNOE. Protein-drug interactions cause significant relaxation enhancement even when the drug concentration is in excess by 10- to 100-fold over that of the receptor. In this way, the trNOE is amplified and visible in the narrow resonances of the drug in...

Inadequate detrusor function

Of the detrusor muscle is extremely variable between individuals. Clinical approaches to treat this problem include anticholinergic (anti-muscarinic) medication if excessive intravesical pressures prevail. If the detrusor muscle cannot be relaxed adequately with such medication to provide continence between intermittent catherizations, an indwelling catheter or attached device such as a condom catheter is necessary. If, due to lack of sensation, voiding cannot be managed effectively or conveniently, an external appliance (condom drainage) may be used in males. However similar devices are notoriously difficult to maintain in females, resulting, instead, in the use of an indwelling Foley or suprapubic (inserted through the lower abdominal wall) catheter. Decreasing de-trusor contractions may also be accomplished by chemically blocking C-fiber bladder afferent neurotransmission with intravesical vanilloids such as capsaicin or resiniferatoxin or by intravesical administration of...

Saturation Transfer Difference NMR

The foregoing discussion of NOE methods brought to light the concept of cross relaxation in which a given polarized nucleus can transfer its magnetization to a nearby nucleus, if the resonance frequencies for the two nuclei are similar. This leads to the concept of spin diffusion in which magnetization of a given site in, say, a protein receptor, would diffuse away from the initial site onto other adjacent protons. Spin diffusion is a highly efficient mechanism for magnetization transfer in proteins because there are large numbers of coresonant, nearby protons. Although this process must be taken into account in any quantitative analysis of internuclear distances based on NOE measurements, like many physical phenomena, it can also be exploited to provide useful information in other contexts.

Hemorrhagic shock study first entry into patients

The major drawback in the study was the difficulty in enrolling patients at those levels of shock. This resulted in a protocol amendment changing the inclusion criteria to include the less severe Class II hemorrhagic shock. Despite this relaxation of criteria and a large number of sites for a Phase II study, it still took almost 2 years to complete.

Heteronuclear Single Quantum Coherence

Transverse Relaxation Optimized Spectroscopy The direct observation of protein resonances has been traditionally limited to molecules with masses less than 50 kDa because the resonance line widths become too large owing to T2 relaxation. The advent of higher-field ( 21 T) superconducting magnets has increased the sensitivity and spectral resolution of NMR, and the applications to protein structure have followed in like fashion. Superconducting probes and preamplifiers have also been responsible for an additional increase in sensitivity. However, neither of these welcome developments has solved the basic problem of line width for large molecules. The discussion in Subheading 3.2. has shown that the transverse relaxation rate of a proton in a large protein is dominated, at moderate magnetic fields, by direct dipolar interactions with adjacent protons. One method for lowering R2 for amide protons is to deuterate all of the other hydrogen sites. The lower y of deuterium will then...

Hazel Y Stevens and John A Frangos 1 Introduction

In the absence of loading, interstitial fluid, originating from leaky venous sinusoids in the intramedullary cavity, is driven radially outward through intracortical pores, the direction being dictated by a transmural pressure gradient between the endosteal vasculature and the lymphatic drainage at the periosteal surface (5). Load-induced compression or bending of bone generates localized pressure gradients, which cause rapid fluid flow from areas of compression to areas where tension builds. After a loading event there is an associated relaxation phase, hence a pulsatile flow ensues. Changes in interstitial flow may be responsible for the induction of bone formation in regions of elevated intraosseous pressure, for example, hypertension whereas normal pressures may serve to maintain normal bone architecture (6).

Additional Technical Factors

Difficulties in quantification of metabolic information are complicated by a number of factors, including line-fitting algorithms, the use of area ratios vs absolute quantification, difference in metabolite relaxation, spin interaction, and overlap of resonant peaks. Peak parameters include frequency, height, and width at half-height. The width at half-height is proportional to 1 T2. MRS is prominently affected by inhomogeneity of the magnetic field, which increases peak width and reduces peak resolution.

Anatomy and innervation

The storage and periodic elimination of urine are regulated by the activity of two functional units in the lower urinary tract (1) a reservoir (the bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the pelvic floor). Under normal conditions, the urinary bladder and outlet exhibit a reciprocal relationship. During urine storage, the bladder neck and proximal urethra are closed and the bladder smooth muscle is quiescent, allowing intravesical pressure to remain low over a wide range of bladder volumes. During voluntary micturition, the initial event is a reduction of intraurethral pressure, which reflects a relaxation of the pelvic floor and the periurethral striated muscles, and an opening of the bladder neck (Chancellor and Yoshimura, 2002). The changes in the urethra are followed in a few seconds by a detrusor contraction and a rise in intravesical pressure that is maintained until the bladder empties. Reflex inhibition of the smooth and striated...

The Tissue Kallikreinkinin System Components

Tissue kallikreins (E.C. 3.4.21.35) belong to a subgroup of serine proteinases that process kininogen substrates and release vasoactive kinin peptides (1). The well-recognized function of tissue kallikrein is mediated by lysyl-bradykinin (Lys-BK or kallidin) and bradykinin (BK), which consist of 10 and 9 amino acid peptides, respectively. Kinins are then degraded by enzymes, such as kininases I and II and neutral endopeptidase to produce a number of kinin metabolites or inactive fragments. Intact kinins bind to BK B2 receptors, whereas kinin metabolites, such as Des-Arg9-BK or Des-Arg10-Lys-BK, bind to BK B1 receptors. The physiological functions of the tissue kallikrein-kinin system (KKS) are mediated by the constitutively expressed B2 receptor. Unlike the B2 receptor, the B1 receptor is expressed at low levels in the heart, vasculature, and kidney and is induced by trauma or inflammation (2). The binding of kinins to their respective receptors activates second messengers, such as...

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Relaxation Audio Sounds Dusk At The Oasis

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