Relaxation Techniques

Relax Your Mind

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Garnering Gating Information from Pre SteadyState Current Relaxations

In these types of experiments, kinetic constants for conformational changes of proteins are obtained by fast perturbation and measurement of the consequent relaxation to a new steady-state. This perturbation for example, a change of nucleotide concentration must be faster than the ensuing relaxation if rate-constant information is to be gained from the change. In the context of studying CFTR's gating (21) (Fig. 8), changes in ATP concentration can be achieved on the order of milliseconds, either through fast switching of the superfusing solution or by photolytic release of caged ATP (42,43). For these experiments, one requires many channels in a membrane patch. After a rapid concentration jump, the resulting change in channel activity will produce

Relaxation Enhancement

Biological tissues are associated with characteristic relaxation time constants T and T2, which reflect processes of longitudinal and transverse relaxation (often referred to as spin-lattice and spin-spin relaxation, respectively). These relaxation time-constants may indeed be directly interpreted as indicative of the nature of the microenvironment longitudinal relaxation is facilitated by (although not solely by) the presence of macromolecular or microstructural entities - hence water proton Tj may be short in white matter, and rather longer in cerebrospinal fluid in which such moieties are less prevalent. Similarly, spin-spin relaxation rates are facilitated by interactions between protons of water molecules. In the cerebrospinal fluid (CSF) environment, such interactions are brief in duration and so remain relatively ineffective (leading to a rather long T2 value). By comparison in more physically constrained biological tissues, in which interactions are more pronounced, the T2...

Fractons and Vibrational Relaxation in Proteins

In his book on random walks, Howard Berg makes the memorable statement Biology is wet and dynamic (Berg, 1983). Indeed, biochemical processes are inextricably linked to the solution chemistry of the aqueous milieu. One might anticipate a continuum description, as given in Chapter 5, as being the most appropriate for the diffusive processes of biochemistry. There is, nevertheless, considerable interest in discrete or jump transport processes. Such processes often provide a convenient mathematical limit for studying continuum events. However, discrete models are more than mathematical devices. The starting point for the formulation of vibrational relaxation in complex media are differential-difference equations. These equations have a rich phenomenology and can give rise to complex oscillatory and chaotic processes. The focus of the present chapter will be on vibrational processes in proteins. There are a number of other biological settings that are appropriately described by jump...

Impaired Relaxation

Transmitral Flow

Deceleration of mitral inflow is directly related to MV area and inversely related to ventricular compliance (as MV area or compliance decrease, E-wave deceleration time increases). Mitral inflow patterns are highly modulated by filling pressures and loading conditions, particularly LV preload. A rise in LA pressure is associated with an increase in peak E-wave velocity. Conversely, decreased LA pressure can be associated with a decrease in peak E-wave velocity as well as E-wave deceleration time, independently of the intrinsic relaxation properties of the LV. This dependence limits the clinical applicability of using MV inflow patterns to predict filling pressures and diastolic function (Fig. 6). Impaired Relaxation The Doppler pattern of impaired relaxation (Fig. 7) is characterized by E- to A-wave reversal (peak A-wave velocity > peak E-wave velocity, or E A < 1) and prolongation of E-wave deceleration time more than 220 ms. This pattern may...

Primary Nursing Diagnosis

Initially, the most important nursing interventions concentrate on pain management. Teach relaxation techniques, diversional activities, and position changes. Help promote the passage of renal calculi. Encourage the patient to walk, if possible. Offer the patient fruit juices to help acidify the urine. Teach the patient the importance of proper diet to help avoid a recurrence of the renal calculi, with particular emphasis on adequate hydration and avoiding excessive salt and protein intake.

Discharge And Home Healthcare Guidelines

Hypertrophic cardiomyopathy (HCM), also known as hypertrophic obstructive cardiomy-opathy or idiopathic hypertrophic subaortic stenosis, consists of ventricular hypertrophy, rapid contraction of the left ventricle, and impaired relaxation. It is commonly the result of hypertension or valvular heart disease. The process may go on for years with no or slowly progressive symptoms, or the first sign of the disease may be sudden cardiac death. Although the patient may live a normal life, deterioration usually occurs. The third form of cardiomyopathy, restricted cardiomyopathy, is the least common form. Both ventricles become rigid, which distorts the filling phase of the heart. The contraction phase remains normal. The result is that ventricular walls become fibrotic, cardiac filling diminishes, and cardiac output decreases. Restricted cardiomyopathy has a poor prognosis many patients die within 1 to 2 years after diagnosis.

Genesis of Hand Preference

Many cultures discourage the use of the left hand. Even in the United States and England, countries that are noted for their tolerance of diversity, the scientific term for left-handedness is sinistral, which means evil. In many other languages the terms used for left-handedness also have negative connotations. In the United States, children who write with their left hand are no longer trained to switch hands and to write with their nonpreferred right hand, but only a few generations ago this was a widespread practice. Despite the relaxation of cultural pressure in the United States, the percentage of people who are right handed has remained about 90 . Thus, although cultural factors might influence the overall prevalence of hand preference, cultural influences do not appear to play a critical role.

Indirect Methods Of Total Lipid Determination

Time domain low-resolution nuclear magnetic resonance (NMR) (referred to as wide-line NMR) and frequency domain NMR could be used to determine the total lipid content of foods. In time domain NMR, signals from the hydrogen nuclei (1H or protons) of different food components are distinguished by their different rates of decay or nuclear relaxation. Protons of solid phases relax (signal disappear) quickly, while protons in the liquid phase relax very slowly. Protons of water in the sample relax faster than protons of the lipid. The intensity of the signal is proportional to the number of protons and, therefore, to the hydrogen content. Thus, the intensity of the NMR signal can be converted to oil content of the sample using calibration curves or tables 57-60 . This method can be used to determine the contents of water, oil, and solid-fat and solid-to-liquid ratio of the sample. Time domain NMR has been used to analyze the fat content of foods, including butter, margarine, shortening,...

Frozen Tissue Sections

In this protocol, frozen tissue sections are mildly fixed in formaldehyde by using a short fixation time (e.g., < 15 min), as a means of reducing autofluorescence (see Strategic Planning). Proteolytic digestion is tuned so that the cells do not lose nuclear morphology through overdigestion. Compared to Basic Protocol 2, this protocol includes an extra acid dehydration step to avoid relaxation of the nuclei in the tissue section, which results in a loss of nuclear morphology. An optional fixation step prior to digestion with pepsin can also be performed to improve morphology and increase attachment of the cells to the slide.

Pharmacologic Highlights

Position the head of the bed at 30 to 45 degrees. Increase the patient's fluid intake, if possible, to assist in liquefying lung secretions. Provide humidified air. Suction the patient's airway if necessary. Assist the patient in controlling pain and managing dyspnea. Assist the patient with positioning and pursed-lip breathing. Allow extra time to accomplish the activities of daily living. Teach the patient to use guided imagery, diversional activities, and relaxation techniques. Provide periods of rest between activities.

Tcrb Allelic Exclusion

Upstream Vb segments (Sieh and Chen 2001). Thus, the current evidence suggests that stochastic association with pericentromeric heterochromatin limits Tcrb recombination to the other allele. Successful recombination and pre-TCR expression leads to feedback inhibition that triggers chromosomal relaxation and reverses V-DJ juxtaposition on the unrearranged allele in DP cells. Coupled with the sub-optimal recombination efficiency of Vb RSSs, these chromosomal constraints initiate an allelic exclusion process that is enforced by the loss of E47 and chromatin accessibility. However, numerous questions remain to be resolved. Dissection of the potential mechanisms for mediating Tcrb allelic exclusion is likely to remain a research focus for several years to come, as insights drive the need for increasingly robust, refined, and developmentally dynamic assay systems.

Distance Dependence Of Fret

Distance Dependence Fret

Fig. 1 A) General mechanisms of excited-state deactivation of a fluorophore. Up arrow represents transition from ground state (S0) to an Si excited state (thick line) or higher (thin lines) after photon absorption (wavy upward arrow). Down arrows represent relaxation, first from higher states down to Si (short arrow). Relaxation from S1 to S0 involves either fluorescence emission (F, wavy down arrow) or nonfluorescent mechanisms (NF, dashed down arrow). B) Mechanisms of excited state deactivation of a donor fluorophore in the presence of an acceptor. Same as A except that energy transfer (ET) is also displayed (longer dashed arrow) which results in less fluorescence emission from the donor excited state (D*) and activation of acceptor molecule from ground state (A) to excited state (A*). Excited state of A can also be depopulated via fluorescent (F) or nonfluorescent (NF) mechanisms. Fig. 1 A) General mechanisms of excited-state deactivation of a fluorophore. Up arrow represents...

Synthesis Biological Evaluation NMR Solution Structural Models of New Oxytocin Analogues

Structure For Nmr Spectra 184 And 186

NMR Spectroscopy ID NMR and 2D NMR spectra were recorded at the temperature of 298K on a BRUKER A VANCE 400 spectrometer operating at 400.13 MHz. ID spectra over the full spectral width (12 ppm) were acquired with and without presaturation of the H2O signal and a recycle delay of 0.8 s or 1.0 s. DQF-COSY 26 and TOCSY 27 experiments were performed in order to facilitate the identification of the spin-systems of each individual amino acid. TOCSY experiments were carried out by using the MLEV-17 spin-lock sequence and a mixing time of 80-100 ms in both temperatures, consisted by 2K data points in F2 dimension, 16-32 transients and 1024 complex increments in the F1 dimension. TPPI 28 NOESY spectra were recorded using the same as for ID spectra, spectral width. The mixing times varied from 200 ms to 800 ms. Spectra recorded with mixing times 400 ms or longer, were used in order to facilitate the resonance assignment. The NOE intensity volume-to-distance conversion was performed for the NMR...

Mitral Stenosis Murmurs Timing and Shape

ANS It begins just after the opening snap (OS). This means that there must be a pause between the A2 and the diastolic murmur, a pause due to isovolumic relaxation of the left ventricle (LV). Because of the pause that usually occurs after the S2, the MS murmur may be called an early delayed diastolic murmur.

Urinary frequency and urgency

Cystitis Symptoms Women

Urethral pressure profilometry may reveal urethral relaxation which will cause incontinence 254,255 . Unfortunately the clinical significance of urethral relaxation is poorly understood. In a series of 107 healthy female volunteers from a gynaecology clinic none of whom had previous urological complaints 16 had pressure variations greater than one-third of their maximum urethral pressures 256 but there was no association with symptoms of lower urinary tract dysfunction.

Peptides Bound to LPS

The bound conformation of PmB 31 and the preliminary structure of LALF-16 32 display an amphiphilic character caused by spatial separation of polar and non-polar residues. These structures have been determined from NMR structure refinement using data from transferred NOE experiments. The latter occurs in case of weak binding of a smaller ligand (in this case peptide) to a large molecule or assembly (in this case LPS aggregate) the cross-relaxation in the bound species is much larger than in the free ligand and is transferred to the latter through chemical exchange. The intra-molecular NOEs of the bound ligand therefore occur at the resonance frequencies of the free ligand and give structural insight to the bound conformation of the ligand 30 . The transferred NOE, however, is measured in conditions of approx. 10 1 peptide LPS molar ratio, and does not contain any information about the interactions with LPS. The model of the complex was therefore obtained using the bound conformation...

Pseudonormal Mv Inflow

Isovolumic Relaxation Time

AR, pulmonary venous peak atrial contraction reversal velocity EDT, early left ventricular filling deceleration time IVRT, isovolumic relaxation time S D, systolic-to-diastolic pulmonary venous flow ratio. AR, pulmonary venous peak atrial contraction reversal velocity EDT, early left ventricular filling deceleration time IVRT, isovolumic relaxation time S D, systolic-to-diastolic pulmonary venous flow ratio. If elevated intracardiac filling pressures are superimposed upon impaired LV relaxation, the Doppler pattern of mitral inflow can again appear normal, with an E A ratio greater than 1 and decreased E-wave deceleration time (Fig. 7). This occurs because increased LA pressure re-establishes a higher gradient between the LA and the LV, providing a larger pressure head to drive LV filling in early diastole. The result is a higher peak E-wave velocity and more rapid filling (decreased E-wave deceleration time). The fact that this apparently normal pattern occurs in the presence of...

Detrusor overactivity

Cystometrogram Picture

Relaxation of the urethra is known to precede contraction of the detrusor in a proportion of women with detrusor overactivity 159 . This may represent primary pathology in the urethra which triggers a detrusor contraction, or may merely be part of a complex sequence of events which originate elsewhere. It has been postulated that incompetence of the bladder neck, allowing passage of urine into the proximal urethra, may result in an uninhibited contraction of the detrusor. However, Sutherst and Brown 160 were unable to provoke a detrusor contraction in 50 women by rapidly infusing saline into the posterior urethra using modified urodynamic equipment.

Color M-mode Flow Propagation Velocity

Restrictive Physiology Cardiac Cath

With both constrictive pericardititis and restrictive cardiomyopathy, there is abnormal LV filling. With constrictive physiology, extrinsic factors (pericardial constraint) impede normal filling of the LV. In the case of restrictive cardiomyopathy, abnormal filling is secondary to factors intrinsic to the myocardium that cause impaired relaxation and decreased compliance. Ea velocities with constrictive pericarditis in the absence of coexistant myocardial pathology are typically normal. In contrast, Ea velocities in restrictive cardiomyopathy are typically reduced (see Chapter 9, Fig. 13). Approximately 2 of elite athletes may have an increased LV wall thickness, raising the potential diagnosis of HCM. It can be clinically challenging to discriminate the physiologic hypertrophy that results from intense athletic conditioning from pathological hypertrophy. Recent studies incorporating measurement of Ea velocities may be helpful in making this differentiation. Athletes typically have...

Midcavity Gradient On Echocardiography

Pictures Aortic Valve Mode

No clear relationship exists between the severity of hypertrophy and the severity of diastolic dysfunction. Asynchronous myocardial relaxation of the hypertrophied muscle can lead to complex patterns of intracavitary flow during diastole. Fig. 24. DUST discrete disproportionate upper septal hypertrophy in the elderly. Disproportionate upper septal hypertrophy is commonly seen in othewise normal elderly individuals. Note the relationship of the septal knuckle to the left ventricular outflow tract (A) with flow acceleration on color flow Doppler (B). Spectral Doppler envelope shows late-peaking velocities (C). The impaired relaxation pattern (E a ratio < 1) occurs in normal aging (D). Fig. 24. DUST discrete disproportionate upper septal hypertrophy in the elderly. Disproportionate upper septal hypertrophy is commonly seen in othewise normal elderly individuals. Note the relationship of the septal knuckle to the left ventricular outflow tract (A) with flow...

Urethral Pressure Profile

Rhabdosphincter

Profiles can be performed if the patient coughs repeatedly during the procedure. This enables the pressure transmission ratio (the increment in urethral pressure, on stress, as a percentage of the simultaneously recorded increment in intravesical pressure) to be calculated. Urethral instability or relaxation can also be identified. Although urethral pressure profilometry is not useful in the diagnosis of uro-dynamic stress incontinence 50,51 , it is helpful in women whose incontinence operations have failed and also in those with voiding difficulties.

Neoendemic And Paleoendemic Islands

Neoendemics typically form on isolated islands that have been created de novo and have abundant empty ecological space into which those few colonists can diversify. Besides Hawaii, other volcanic archipelagoes, including the Marquesas, Societies, and Galapagos in the Pacific and the Canaries in the Atlantic, have provided ideal conditions for the formation of neoendemics. However, species can also form on fragment islands, formed as a mass of land has broken away from a larger continental region. Examples of such islands include some of the Caribbean islands, and the islands of New Zealand and Madagascar. As these islands, formed upon losing connection with a continental source, become more isolated, gene flow between island and continental populations may become insufficient to overcome genetic divergence. Unlike volcanic islands that form in isolation, starting without any species and accumulating species through time, fragment islands are usually ecologically saturated at the time...

The V Wave and Y Descent

Most authors use the letter X to name both atrial relaxation and the fall in pressure due to the descent of the base, thus making the physiology of jugular contours difficult to understand. ANS Right ventricular relaxation allows RV pressure to fall below right atrial pressure, thus opening the tricuspid valve (at the end of isovolumic relaxation).

Renal Function In Heart Failure

About 20 of the cardiac output is normally delivered to the kidneys and virtually all of the renal blood flow (> 98 ) passes first through the glomeruli. Hydrostatic pressures within glomerular capillaries are regulated by constriction, or dilation, of preglomerular afferent arterioles and postglomerular efferent arterioles and by contraction or relaxation of periglomerular capillary mesangial cells. The hydrostatic pressures, surface area, and epithelial hydraulic permeability of glomerular capillaries determine the fraction of blood plasma perfusing the glomeruli which is filtered.

Suprasphincteric Dysfunction

Rectoanal inhibitory reflex (RAIR) enables rectal contents to come into contact with the epithelium of the upper anal canal, where there is a high concentration of free and organised sensory nerve endings 18 . The mechanism is guaranteed by concomitant rectal contraction and internal anal sphincter (IAS) relaxation. At the same time, there is a reflex external anal sphincter (EAS) contraction that prevents accidents. This sampling mechanism occurs several times per hour 19 and allows an accurate distinction between flatus, liquid and solid faces, and for these reasons it has a role in the fine adjustment of continence, allowing the individual to choose whether to retain or discharge their rectal contents. It is likely that minor degrees of sensory impairment are not by themselves causative of incontinence in patients with otherwise normal anorectal function 20 . However, if the sampling mechanism is defective and sphincter function is poor, the patient may ity, patients had a...

Neurophysiologic Investigations

Fibrillation potentials and positive sharp waves, and denervation of muscle fibers, (2) presence of muscle-fiber reinnervation 111-114 , (3) normal mild continuous tonic contraction in the EAS and puborectal-is muscles 115 and adequate contraction or relaxation during squeeze or straining, and (4) recruitment pattern and motor-unit-potential (MUP) waveform 116 . The most important parameters in the analysis of MUP are amplitude, duration, area, number of phases and turns, and firing rate that can be automatically evaluated by advanced EMG systems provided with special software analysis. Examination of the EAS muscle holds the central position in Podnar's and Vodusek's algorithm for electrodiagnostic evaluation of the sacral nervous system 104 . With the patient in a comfortable lateral position with knees and hips flexed, after grounded electrically at the thigh, a standard concentric needle EMG electrode is inserted into the subcutaneous portion of the EAS muscle to a depth of 3-5 mm...

Large Intestinal Motility

The myenteric plexus in the large intestine is concentrated underneath the teniae, that is, between the layers of longitudinal and circular muscle. The myenteric plexus receives input from local receptors and from both the parasympathetic and sympathetic systems. Parasympathetic fibers from the vagus innervate the cecum and ascending and transverse colons, and the descending and sigmoid colons and the rectum and anus are innervated by the pelvic nerves from the sacral region of the spinal cord. The pelvic nerves enter the colon near the rectosigmoid junction and project anteriorly and posteriorly along the myenteric plexus innervating it as well. Sympathetic innervation is supplied to the proximal colon via the superior mesen-teric ganglion, whereas the inferior mesenteric ganglion provides fibers to the distal colon. The rectum and anal canal receive sympathetic innervation from the hypogastric plexus. Within the autonomic system acetylcho-line, substance P, and tachykinins mediate...

Rectal Evacuatory Disorder

Scious contraction of the external anal sphincter occurs in response to rectal distension, thus preventing incontinence of stool during reflex relaxation of the internal anal sphincter (RAIR) 238 . This is crucially dependent on perception of rectal distension 255, 256 . However, the presence of diminished perception of rectal distension will allow faecal material to enter the rectum without conscious recognition, and thus conscious contraction of the external anal sphincter during reflex internal anal sphincter relaxation cannot occur 255,257 . This results in a reduction in anal canal pressure and allows stool to enter the anal canal, with the potential for passive leakage 250, 258 . Rectal hyposensitivity may also underlie dyssynergic defecation, exacerbating the retention of faeces in the rectum 243, 254 .

Clinical Uses Of Electrical Stimulation

Maintenance or increase in range of movement. Electrical muscle stimulation (EMS) is used to strengthen muscle and facilitate voluntary motor function. Although EMS devices are often advertised for muscle toning and weight reduction, they are authorized by the FDA only as prescription devices for maintaining or increasing range of motion, relaxation of muscle spasm, prevention or retardation of disuse atrophy, muscle reeducation, increasing local blood circulation, and postsurgical stimulation of calf muscles to prevent the formation of blood clots.

Functional Anatomy Of The Microcirculation

Blood enters the microcirculation through arterioles, which are surrounded by a thick, continuous layer of smooth muscle. Contraction of smooth muscle reduces the internal diameter of this microvessel and consequently increases the resistance to blood flow in the entire vascular bed. This feature makes the arteriole the major resistance element in the circulation and the principal determinant of the total peripheral resistance. Arteriolar smooth muscle tone also governs the amount of pressure transmitted from arteries to veins hence, capillary pressure falls when arterioles constrict and rises when arterioles dilate. Blood flows from arterioles into a narrower vessel, the metarteriole, which is surrounded by a discontinuous smooth muscle layer. Capillaries branch off from the metarteriole. The density of capillaries, which is an important determinant of the total area available for exchange between blood and tissue, varies significantly between organs,...

Movement Of Material Through The Esophagus

Decorticate Decerebrate Posturing

Esophageal motility is regulated by both central and peripheral mechanisms, all of which are not completely understood. Closure of the upper esophageal sphincter depends on the tone and elasticity of the cricophar-yngeal muscle. Relaxation of this muscle during a swallow is coordinated through the swallowing center, as previously discussed. The body of the esophagus receives innervation through the vagus nerves (see Fig. 4). Somatic motor nerves from the nucleus ambig-uus synapse directly with the striated muscle in the upper portion of the esophagus. Visceral motor nerves, arising from the dorsal motor nucleus, synapse with neurons of the myenteric plexus (between the circular and longitudinal layers of smooth muscle). These interneurons in turn innervate the smooth muscle layers (see Fig. 4). The interneurons also communicate signals with each other in other words, up and down the esophagus and relay input to the central nervous system (CNS) via afferent nerves in the vagus....

Marketing Insects In The Environment

Relatively low prices, and perceptions of relaxation, excitement, and even educational appeal. Ecotourism takes advantage of the attractiveness of adventure by offering the enticement and wonder of nature in an exotic setting. Insects, too, provide tourist attractions, and perhaps the best example involves the monarch butterfly, a popular insect in North America. A tropical species, it extends its range northward well into Canada during the growing season but cannot overwinter there. Individuals retreat southward for thousands of kilometers each autumn to take up residence in climes more amenable to their survival. These butterflies are attractive to ecotourism enterprises precisely because of this pattern of movement accompanying the remarkable biology of the insects. Almost anyone can view these beautiful butterflies flitting around meadows and parklands during the summer months. But as autumn approaches, they begin remarkable journeys southward and westward towards one of two...

Biological Implications

Over the last decade the devolepement on technology and methodology in NMR Spectroscopy was achieved in concert with the detailed analysis and exploitation of NMR data, especially these that can provide geometrical information (NOEs - Nuclear Overhausser Enhancement, paramagnetism, relaxation times, 3- HNHa couplings constants) in such a way that structural constrains could be extracted and used in the determination of 3D structures of biomolecules in solution. These structures are characterized by resolution comparable to that provided by X-ray in solid state. The assignment of 2D, 3D or even 4D NMR spectra is the stage where geometric information for the biomolecule becomes available. The main volume of the information is extracted from connectivities between protons close to each other in a distance up to 5.0-5.5 . The secondary structure could be identified through characteristic sequential NOE signals between HN, Ha and Hp protons, while tertiary structure is calculated through...

The Golgi Tendon Organ

In summary, the muscle spindle and the Golgi tendon organ provide counterbalanced systems for setting overall muscle tone. Group Ia and II afferents from muscle spindles carry information about the static length of the muscle and its rate of change during contraction and relaxation. Because the muscle spindle is connected to the main muscle fibers in parallel, passive stretching or relaxation lengthens the spindle, excites the sensory end organ, and increases the firing rate of Ia and II fibers. Through a monosynaptic feedback pathway (the myotac-tic reflex), Ia fibers excite alpha motor neurons and cause muscles to contract after they are passively stretched.

Gastrointestinal Smooth Muscle

FIGURE 2 Biochemical steps in the contraction of smooth muscle. Increased Ca2+ activates myosin light chain kinase, phosphorylating myosin. Myosin-P then binds to actin, resulting in contraction. As Ca2+ levels decrease, the kinase is inactivated, the phosphatase removes the phosphate from myosin-P, and relaxation occurs. (Modified from Johnson LR, ed., Gastrointestinal physiology, 6th ed. St. Louis CV Mosby, 2001.) FIGURE 2 Biochemical steps in the contraction of smooth muscle. Increased Ca2+ activates myosin light chain kinase, phosphorylating myosin. Myosin-P then binds to actin, resulting in contraction. As Ca2+ levels decrease, the kinase is inactivated, the phosphatase removes the phosphate from myosin-P, and relaxation occurs. (Modified from Johnson LR, ed., Gastrointestinal physiology, 6th ed. St. Louis CV Mosby, 2001.) one of the components of myosin. The phosphorylated form of myosin now interacts with actin to produce a contraction. The contraction is supported by the...

Potential preventive and therapeutic options Oral Hypoglycemic Agents

The cornerstone of DM therapy is optimal glycemic control, because hyperglycemia is the basis of all the metabolic disturbances that occurs in the disease. As shown previously, both in vivo and in vitro elevated glucose levels have been shown to cause abnormal endothelium-dependent relaxation. Lower glucose levels also result in a decrease in insulin levels, which consequently may also improve endothelial function. Therefore, therapy should be directed toward lowering glucose levels and increasing insulin sensitivity. The effect of oral hypoglycemic agents on endothelial function is controversial and probably relates to the agent and model of diabetes being evaluated. Metformin has been shown to improve endothelium-dependent function in the mesenteric arteries of insulin-resistant rats in vitro (165), and the ATP-dependent potassium channel blocker gliclazide ameliorated endothelium-dependent relaxation of the aortas of (alloxan-induced) diabetic rabbits (166). However, clinical...

Inhibitors of AGE Production

As discussed earlier, one possible mechanism of endothelial dysfunction in both type 1 and type 2 DM is the inactivation of NO by oxygen-derived free radicals. There is also a decrease in levels of endogenous antioxidants including superoxide dismutase and catalase in animal models of diabetes (172). Furthermore, several clinical studies have reported a decrease in endogenous vitamin C (173,174) and E (173,175) levels in both type 2 and type 1 DM. Any means of decreasing the oxidative stress has the potential to improve endothelium-dependent vasodilation. Timimi et al. (176) and Ting and coworkers (177) (Fig. 6) found that intra-arterial infusion of vitamin C improved endothelium-depen-dent (but not endothelium-independent) relaxation in patients with type 1 and type 2 diabetes, respectively. Furthermore, the intra-artrial infusion of ascorbic acid restored the impaired endothelial vasodilation in healthy subjects exposed to hyperglycemic clamp (178).

Calcium Activation Mechanisms

Various hormones and drugs activate plasma membrane receptors to elicit an increase in cytosolic calcium. Increases in cytosolic calcium occur through a combination of enhanced calcium entry from the extracellular environment and mobilization of calcium from internal stores however, the relative contributions of these two pathways can vary. Increases in calcium entry occur through a variety of pathways including receptor-operated channels, second messenger-operated channels, stretch activated channels, and voltage-dependent channels that are activated upon membrane depolarization. Depolarization results from influx of sodium and calcium following activation of receptor-operated cation channels, activation of chloride channels, or inacti-vation of potassium channels. Decreases in net calcium entry occur following dissociation of ligands from their receptors or as a consequence of membrane hyperpolarization, such as occurs when membrane potassium channels are activated. Several...

Measurement of Contrast Agent Concentration In Vivo

Spin-spin relaxation rates of tissues it should be possible to infer their distribution by observing the influence on the MR signal. Since the concentration of Gd ions is known to be directly proportional to the change in 1 T (Eq. 5.1), a series of measurements of the T of a tissue as a contrast agent distributes within it could, in principle, be used to monitor the changes in contrast agent concentration. Since the changes in T1 will also alter the signal intensity of a Trweighted imaging sequence, it should also be possible to monitor contrast agent concentration using signal intensity. It is preferable that two further criteria are met. The rate of measurement of contrast agent concentration should be sufficient to monitor the most rapid changes occurring within the tissue. Secondly, the relationship between concentration of contrast agent and the measuring function should be monotonic and minimally affected by small changes in the imaging parameters. In this way the concentration...

Principal Mechanisms Of Colloidal Stabilization And Destabilization

Bridging flocculation occurs when the loops and tails of a polymer adsorbed to one particle become attached to one or more other particles. The process is optimized for polymers which have several points of attachment on the colloidal surface and are large enough to have free segments (loops and tails) outside the zone of electrostatic repulsion and available to bind to other surfaces. The surface coverage of the adsorbed polymer appears to be a fundamental parameter controlling the probability of bridging65 with the half surface coverage postulated as the optimum condition for flocculation to occur.66 While flocculation can occur for polymers that are at equilibrium with the colloidal surface,67 nonequilibrium flocculation, occurring before the polymers are able to completely collapse on the colloidal surface, is thought to predominate.68 In that case, the dynamics of bridging flocculation are related to both the thermodynamics and kinetics of polymer adsorption, including transport...

Hepatobiliary Contrast Agents

Hepatobiliary contrast agents utilise hepatic excretion mechanisms to produce hepatocyte uptake and biliary excretion of paramagnetic ions by binding them to appropriate ligands. Two agents, Mangafo-dipir trisodium (Mn-DPDP, Teslascan) and Gado-benate dimeglumine (Gd-BOPTA, Multihance) are commercially available and a third, gadoxetic acid (Gd-EOB-DTPA, Eovist) is in phase III clinical trials (see Tables 14.1 and 14.2). Mangafodipir is the first manganese complex that has been used as contrast agent in clinical trials. The Mn2+ ion is a powerful T1 relaxation agent and the molecule demonstrates both biliary and renal excretion causing positive enhancement of normal liver tissue (Rofsky and Earls 1996 Morana et al. 2002). Its chemical similarity to vitamin B6 is cited as the reason for the hepatocyte uptake, but it is likely that some of the liver accumulation of paramagnetic manganese is due to the metabolism of the parent compound with release of free Mn2+ ions, which are known to...

Issues for Single Centre Trials

Be used as a reference for subsequent sequences (e.g. proton density sequences used as a reference for T1-weighted sequences, to allow rapid measurement of T1 relaxation times). Some manufacturers do not support this facility, and automatically reoptimise some or all of transmit amplifier attenuator settings, receiver amplifier attenuator settings, receive ADC set up and image scaling factors and filter factors each time a sequence is loaded.

Atrial Natriuretic Peptide and Related Peptides

Structure Natriuretic Peptides

ANP exhibits significant hypotensive, natriuretic, and diuretic effects (see Table 1). It lowers blood pressure by reducing cardiac output and peripheral vascular resistance 58 , ANP diminishes cardiac output by reducing preload and by blunting the hypotension-induced reflex rise in sympathetic efferent nerve activity and heart rate. ANP decreases preload by reducing intravascular volume, both by stimulating salt and water excretion and by stimulating redistribution of intravascular volume into the interstitial space. ANP either lowers peripheral vascular resistance or prevents a reflex rise in intravascular resistance (which would occur due to its hypotensive effect) by reducing renin secretion, thereby diminishing the circulating levels of the vasoconstrictor, angiotensin II. ANP can also effect relaxation of preconstricted vascular smooth muscle in vitro, but the importance of this effect in vivo has been difficult to establish. The importance of ANP in long-term blood pressure...

Parkinsons Disease and Parkinsonian Syndromes

Ing anal pressure, reduced voluntary anal contractility, and a paradoxical anal contraction or insufficient anal relaxation during straining the same impairments have been reported by Edwards et al. in PD patients 28 . Abnormal straining is an important cause of constipation in both PD and MSA patients and frequently is involved in the pathogenesis of outlet-type constipation. Therefore, anorectal mano-metric variables do not differentiate PD from MSA patients.

Gastroesophageal Reflux Disease GERD

Gastroesophageal reflux disease (GERD) is a syndrome that is caused by esophageal reflux, or the backward flow of gastroesophageal contents into the esophagus. Approximately 7 of the U.S. population has symptoms of heartburn each day. GERD occurs because of inappropriate relaxation of the lower esophageal sphincter (LES) in response to an unknown stimulus. Reflux occurs in most adults, but if it occurs regularly, the esophagus cannot resist the irritating effects of gastric acid and pepsin because the mucosal barrier of the esophagus breaks down. Without this protection, tissue injury, inflammation, hyperemia, and even erosion occur.

Physiological changes occurring in sleep stages

During sleep, air exchange decreases because of the loss of waking-related respiratory drive and a reduction in respiratory rate and minute ventilation. At the same time, the resistance in the upper airways increases as a result of muscle relaxation 21 . Reduced sensitivity of central chemoreceptors to higher levels of CO2 or to lower levels of O2 is also observed, especially during REM sleep 22 . These changes, usually present in normal sleep, contribute to sleep disorders such as sleep apnea 23 .

Genotype To Phenotype Correlations

Ventricular tachycardia observed with WPW is that of antegrade conduction through the AV node with retrograde conduction through the accessory pathway. The usual result is a regular supraventricular tachycardia with a rate of about 120 to 160 beats per minute. The overall configuration is a narrow QRS. The vectors of the QRS, however, may vary depending on the anatomical location of the accessory bundle. The most common anatomical bundle is that which goes from the left atrium to the left ventricle and occurs in about 50 a posteroseptal, right ventricular, or anteroseptal insertion of the AV pathway is found in approximately 30 , 13 , and 7 of patients, respectively. It is claimed that about 80 of the supraventricular arrhythmias associated with WPW have a regular supraventricular tachycardia with a narrow QRS. In the remaining 20 the arrhythmia is generally atrial fibrillation. The incidence of tachyarrhythmias in WPW syndrome is unknown. Reports from a variety of studies indicate...

Physiological Investigations

Loose Pelvic Floor Rectal Prolapse Gifs

Numeric value (i.e., mean or median) but also to consider pressure profiles, providing information on asymmetry in the anal canal due to a limited lesion of the internal anal sphincter (IAS) or the external anal sphincter (EAS) or decreased EAS endurance to muscle fatigue during prolonged squeeze. Based on a multichannel acquisition of resting-pressure profile, it is usually possible to visualize a vector manometry and identify segments of the anal canal with increased or decreased pressure (Fig. 2). Following the routine use of EAUS, clinical utility of vector manometry has progressively reduced 9 , even if, more recently, an inverted vector manometry has been suggested, giving good correlations with EAUS and providing combined functional and anatomic information 10 . On the other hand, in a number of incontinent patients, resting and or squeeze pressures could be normal, related to a nontraumatic pathophysiology of their incontinence. Although the rectoanal inhibitory reflex (RAIR)...

Characteristics Of Gastrointestinal Peptides

The GI peptides regulate many different functions water and electrolyte secretion from the stomach, pancreas, liver, and gut enzyme secretion of the stomach and pancreas and contraction and relaxation of the smooth muscle of the stomach, small and large bowel, various sphincters, and gall bladder. These peptides also regulate the release of GI peptides and some other endocrines, such as insulin, glucagon, and calcitonin. Some GI peptides have trophic effects, regulating the growth of the exocrine pancreas and the mucosa of the stomach, small and large intestine, and gall bladder. Many peptides have identical effects on an end organ. Others may produce opposite effects.

The A Wave X Descent C Wave and X Descent

Atrial relaxation produces the drop in pressure known as the X descent. Atrial relaxation produces the drop in pressure known as the X descent. Note Only a minority of cardiologists name this descent, and most of those who do name it call it X, i.e., they give it the same name as that given to atrial relaxation, thus leading to great confusion 1 .

Mechanisms of Continence and Defecation

Rectal curvatures, and the transverse rectal folds), recto anal sensation, and rectal compliance. Stool is often transferred into the rectum by colonic high-amplitude-propagated contractions, which often occur after awakening or meals 54 . Denny-Brown and Robertson observed that rectal distention evoked rectal contraction and anal sphincter relaxation, facilitating evacuation 28 . The pelvic floor, particularly the puborectalis, also generally relaxes during defecation (Fig. 3). Simultaneous assessments of intrarectal pressures and pelvic floor activity (by manometry, EMG, or imaging) reveal that increased intra rectal pressure and anal relaxation are required for normal defecation. However, the relative contributions of increased intra-abdominal pressure generated by voluntary effort 55 and rectal contraction 56 to the propulsive force during defecation are unclear, partly because a barostat rather than a manometry is necessary to optimally characterize rectal contractions, which are...

Functional Anatomy and Physiology

Posed of striated voluntary muscle closely related to the puborectalis (PR) muscle. The PR muscle originates at the pubis, wraps around the junction of the lower rectum and the anal canal, and plays an important role in fecal continence and in physiological defecation. Relaxation of the PR is, in fact, necessary for normal bowel emptying.

Sound Production And Reception

The organs of sound production are the tymbals, a pair of ribbed cuticular membranes located on either side of the first abdominal tergite (Fig. 3). In many species the tymbals are partly or entirely concealed by tymbal covers, platelike anterior projections of the second abdominal tergite. Contraction of internal tymbal muscles causes the tymbals to buckle inward, and relaxation of these muscles allows the tymbals to pop back to their original position. The sound produced is amplified by the substantially hollow abdomen, which acts as a resonator.

Predisposing factors for anaphylaxis

Alcohol is a clear example of a drug that may work in several ways. In amounts that are consumed socially, it impairs judgement and encourages risk taking and may therefore impair the intellectual response to being exposed to a food known to potentially contain an allergen that is unsafe for the subject (the classic example being the Indian takeaway). Alcohol also works physiologically by causing relaxation of blood vessels, leading to a fall in blood pressure. A fall in blood pressure may be more precipitous if an allergen is consumed during a meal in which alcohol is also consumed.

Antimicrobial C3a Biology Biophysics and Evolution

From investigations on the interaction between AMPs and model lipid membranes, it has been found that antimicrobial peptides in fact display a broad range of mechanisms of action. For a number of AMPs, formation of ordered helices is observed on lipid membrane incorporation, sometimes in an oligomerized form, resulting in structurally relatively well-defined pores. However, a number of other mechanisms have also been observed. One of these is membrane destabilization through thinning, caused by peptide adsorption in the lipid headgroup region, resulting in a lateral crowding in the headgroup region and in a structural relaxation of the phospholipid acyl chains (Lee, Hung, Chen and Huang 2005). For other peptides, yet other mechanisms have been observed, ranging from local packing defects and

Mechanism Of Action Of Pglycoprotein

Of ATP binding affinity showed only small changes upon drug binding.83 Senior et al. proposed that transport is driven by relaxation of a high-energy intermediate formed during ATP hydrolysis, which thus provides the power stroke.79 One molecule of ATP was proposed to drive the transport of one drug molecule. Sauna and Ambudkar have proposed an alternative model in which two molecules of ATP are hydrolyzed per cycle.185 In this model, drug and ATP binding do not influence each other hydrolysis of one ATP molecule drives drug transport, and hydrolysis of a second ATP molecule resets the transporter. This model is also unsatisfactory. There has been no independent verification of the proposed requirement for two rounds of ATP hydrolysis per drug molecule transported. Sauna et al. reported that Pgps with mutations in the Walker B Glu residues (E556Q and E1201Q) failed to undergo the second round of ATP hydrolysis required to reset the transport cycle.186 However, this was contradicted by...

Biochemical Interactions Of Actin And Myosin

As in striated muscle, contraction and relaxation of smooth muscle are regulated by changes in the amount of cytosolic calcium available to interact with the regulatory protein. In relaxed muscle, the level of free As in striated muscle, cytoplasmic free calcium must be decreased to allow for relaxation. In those cells with abundant SR, most of this calcium is pumped back into the SR via a calcium ATPase. However, in these cells, and especially in those cells with little SR, calcium must also be expelled from the cell across the cell membrane. Presumably, this is accomplished by a sodium-calcium exchange mechanism and perhaps by a membrane-bound calcium ATPase. Smooth muscles vary in the electrical events exhibited by their cell membranes. During relaxation, all are polarized, exhibiting resting membrane potentials of 40 to 80 mV. The basis for this potential is primarily the same as in striated muscle (Fig. 4). In many smooth muscles the membrane potential in relaxed cells is not...

Mechanical Response Of Smooth Muscle In Vitro

FIGURE 9 Recordings of isometric forces from a tonically active (A) and a phasically active (B) smooth muscle. The dashed lines indicate 0 force when the muscles are relaxed completely. Gm indicates that the force is measured in grams. Note that, during the time of these recordings, the tonic muscle never relaxed, while the phasic muscle went through two cycles of contraction and relaxation. FIGURE 9 Recordings of isometric forces from a tonically active (A) and a phasically active (B) smooth muscle. The dashed lines indicate 0 force when the muscles are relaxed completely. Gm indicates that the force is measured in grams. Note that, during the time of these recordings, the tonic muscle never relaxed, while the phasic muscle went through two cycles of contraction and relaxation.

Contrast Agent Relaxivity

Provided that the BMS shift is negligible, the relationship between relaxation rate (1 T and 1 T2) and contrast agent concentration can be predicted by the Solomon-Bloembergen equations (Gowland et al. 1992) where r1 and r2 are the spin-lattice and spin-spin relaxivity constants respectively and T10 and T20 are the spin-lattice and spin-spin relaxation times respectively in the absence of contrast material. These relationships have both been confirmed in vitro (Rosen et al. 1990 Donahue et al. 1994 Judd et al. 1995) and for T in vivo (Wedeking et al. 1992) across a range of concentrations. These expressions allow theoretical predictions to be made about the influence of a contrast agent, such as Gd-DTPA, on signal intensity. Relaxivity is dependent upon field strength and the chemical structure of the contrast agent (Springer 1994). While it is normally assumed that the physico-chemical nature of the tissue has little affect upon contrast agent relaxivity, there is strong evidence...

Categories of Contrast Agents

Some MRI applications have made use of the fact that ground state oxygen (O2), the redox state that we are constantly breathing, is paramagnetic and contains two unpaired electrons (Karczmar et al. 1994 Oikawa et al. 1997 Noseworthy et al. 1999 Rijpkema et al. 2002). However, high resolution image contrast rarely changes as O2 predominantly changes the T2* through change in the oxy deoxyHb ratio in the microvasculature. However, as a method, applied together with blood-oxygen level-dependent (BOLD) imaging, MRI with hyperoxia provides functional information on tumor biology such as whether a tumor may have greater probability of responding to radiation therapy (Rijpkema et al. 2002). The enhancement of T1 relaxation via molecular oxygen has also been used as a contrast mechanism for studying lung ventilation (wherein local partial pressure of oxygen gas influences parenchymal proton relax Metabolically activated agents have recently been developed for model systems in which a...

Medical Alcohol Drug Abuse or Dependence Detoxification or Other Symptom Treatment with CC

Most of the abused drugs fall into two main categories, CNS depressants and CNS stimulants. CNS depressants include narcotics, sedatives, barbiturates, tranquilizers, and inhalants. The desired effect by the user is a sense of increased self-esteem, euphoria, relaxation, and relief from pain and anxiety. CNS stimulants include amphetamines, hallucinogens, and cocaine. The desired effect by the user is a sense of well-being, alertness, excitation, overconfidence, and increased initiative.

Systemic Hemodynamic Responses And Conclusions

Many patients receiving diuretic therapy are hypertensive and a long-term goal of the therapy is to achieve sustained reductions in arterial pressure to normo-tensive levels. Indeed, monotherapy with diuretics has long been shown to be an effective treatment for many hypertensive patients. In more resistant cases, combinations of either ACE inhibitors or calcium antagonists with a diuretic have been effective in treating resistant patients. While the antihypertensive mechanisms for agents that directly elicit vascular smooth muscle relaxation are readily apparent, it is more difficult to explain the prompt antihypertensive effects of diuretics that primarily inhibit epithelial transport and do not have much direct effect on vascular smooth muscle to decrease peripheral vascular resistance. Studies in anephric subjects have shown that the direct systemic vasodilatory responses of most diuretics are rather modest. In addition, the immediate effects on arterial pressure of diuretics are...

Physiological adaptations to pregnancy labour and delivery

Blood volume starts to rise by the 5th week after conception secondary to oestrogen- and prostaglandin-induced relaxation of smooth muscle that increases the capacitance of the venous bed. Plasma volume increases and red cell mass rises, but to a lesser degree, thus explaining the physiological anaemia of pregnancy. Relaxation of smooth muscle on the arterial side results in a profound fall in systemic vascular resistance and together with the increase in blood volume, determines the early increase in cardiac output. Blood pressure falls slightly but by term has usually returned to the prepregnancy value. The increased cardiac output is achieved by an increase in stroke volume and a lesser increase in resting heart rate of 10-20 beats min. By the end of the second trimester the blood volume and stroke volume have risen by between 30 and 50 . This increase correlates with the size and weight of the products of conception and is therefore considerably greater in multiple pregnancies as...

Low Resolution Nuclear Magnetic Resonance

When a sample containing magnetic nuclei such as hydrogen protons is placed in a static magnetic field, B0, the nuclei align with the field and a bulk nuclear magnetisation develops. This process occurs exponentially in a characteristic time T1( the spin lattice relaxation time such that Variations in Bloc cause different nuclei to precess at different rates and the initial coherence of the nuclear magnetisation is lost. With the loss of coherence (dephasing) goes the loss of observed signal. For all but the very fastest decays which usually exhibit complex decay functions, this generally occurs exponentially in a characteristic time T2, the spin-spin relaxation time so that

Rehabilitative Techniques

The aim of sensory retraining is to increase the incontinent patient's ability to perceive the rectal distension induced by feces or flatus (rectal sensation) 20 . Impaired rectal sensation may be a cause of fecal incontinence. Reduced rectal sensation, with a higher than normal rectal distension conscious threshold, allows the stool to enter the anal canal and, due either to the absence or lateness of the external anal sphincter reflex contraction, incontinence may occur 4 . Conversely, an exaggerated rectal sensation, with a lower conscious threshold, may elicit fecal incontinence because it is associated with reduced rectal compliance, repetitive rectal contractions during rectal distention, and longer simultaneous sphincter relaxation 21 .

Inflammatory Bowel Disease

Increased frequencies of defecation (> 80 ), urgency (> 80 ), the sensation of incomplete evacuation (75 ) and tenesmus (63 ) were the most common symptoms reported in patients with active ulcerative colitis by Rao et al. 49 and more common in active rather than in quiescent disease but irrespective of proximal colonic involvement, suggesting that such symptoms related to an inflamed, irritable distal colon and rectum. In 1978, Farthing and Lennard-Jones reported lower rectal thresholds to balloon distension in patients with ulcerative colitis compared with controls, the difference being greater in those with active rather than inactive disease 50 . Rao et al. 51 confirmed these findings but also demonstrated lower rectal compliance in active disease and lower rectal volumes required to induce sustained internal sphincter relaxation.

Secondsite Binding Using Paramagnetic Probes

In steps 3 and 4 of SAR by NMR, it was necessary to saturate the first binding site and then screen for second-site ligands. While the traditional SAR by NMR strategy does this using chemical shift perturbations, one can also use paramagnetic probes 83, 84 . In this strategy, a first ligand is labeled with an organic nitr-oxide radical probe like TEMPO The location of the second ligand, relative to the first, is established based on the distance-dependant relaxation effect of the probe on the second ligand. The significant advantage offered by this method is that protein does not need to be labeled and sensitivity is quite high. The latter is true because the relaxation effect is dependant upon the gyromagnetic ratio of the electron, which is 658 times larger than that for protons. The relaxation rate enhancement is given by tron and nuclear spin, p is the Bohr magneton, fflH is the proton Larmor frequency and r is the distance between the probe and the proton on the second-site...

Subconscious Incubation

Many creative people have related that after discovering an unresolved problem, they are unable to immediately to solve this problem. After multiple attempts, they might become frustrated, give up trying to solve the problem, and then move on to other problems. Sometimes, after a few days, weeks, or months, suddenly the solution of this problem might come to them. As I mentioned, this experience has been termed illumination, or the aha experience, by Wallas (1926). The ability to suddenly understand the solution of a problem suggests that the brain has been actively manipulating stored knowledge. Wallas called this process of subconscious knowledge manipulation incubation. In his book Origins of Genius, Simonton (1999) quoted the famous French mathematician Poincare. As I mentioned in the relaxation section, Poincare wrote how he could not solve a mathematical problem and got his mind off this problem and then came up with the solution (i.e., I went to spend a few days at the seaside...

Pleiotropic Effects Of Creatine

Common denominators for many muscular, neuromuscular and neurodegener-ative diseases are (i) lowered energy status, that is decreased cellular energy reserves (PCr and ATP), (ii) accompanying chronic calcium overload, due to a misbalance in the energetics of calcium homeostasis, and (iii) concomitant formation of reactive oxygen species (ROS) (Rodriguez et al., 2007 Tarnopolsky and Beal, 2001). Incidentally, the most obvious phenotype of knockout mice lacking CK in muscle were difficulties with calcium sequestration and muscle relaxation (Steeghs et al., 1997). Accordingly, Cr supplementation was shown to improve calcium homeostasis in the mdx muscular dystrophy mouse model (Pulido et al., 1998) and muscle relaxation in humans (Hespel et al., 2002). These findings are easily explainable by the fact that the calcium pump ATPase of the SR is energetically very demanding and only works efficiently if a high local ATP ADP ratio is maintained by the action of CK functionally coupled to...

Longrange Changes in Locus Conformation

All antigen receptor loci, including Tcrb, undergo a dramatic contraction coincident with long-range recombination (V-to-DJ or V-to-J). Chromosome conformation capture (3C) and 3D-FISH studies demonstrate that Tcrb folds into contractive loops in DN thymocytes, bringing Vb elements into spatial proximity with DJb and Eb elements (Skok et al. 2007). Locus contraction on unrearranged alleles is reversed in DP cells where V-DJb recombination is prohibited by allelic exclusion. Looping that allows Tcrb to form an Igh-like rosette structure would overcome obvious spatial barriers to Vb DJb synapsis. The Krangel laboratory has shown that the Eb-proximal Vb31 segment (only 3 kb downstream of Eb) as well as Vb segments situated immediately upstream of a functionally rearranged V(D)Jb exon retain chromatin accessibility in DP cells, though they do not rearrange efficiently at this developmental stage. In contrast, more distal Vb segments on rearranged alleles are condensed into facultative...

The Crescendo Murmur to the Mt in Mitral Stenosis The Presystolic Murmur

There should be no mitral murmurs between the A2 and the OS, because this is isovolumic relaxation time. Note the slow Y descent of the left atrium due to the difficulty in emptying the left atrium through the stenotic valve. This accounts for the pressure gradient and murmur, both of which are decrescendo except for the very beginning and end.

And The Severity Of Mitral Stenosis

What are the major factors controlling the duration of isovolumic relaxation, or the 2-OS interval ANS a. Poor myocardial function due to either damage or aging. This causes prolongation of the isovolumic relaxation time. (Isovolumic relaxation time also increases strikingly with age.)

Might There Be Deleterious Consequences of Introducing DNA Hypomethylation in the Genome As a Cancer Therapy

Sullivan MJ, Taniguchi T, Jhee A et al. Relaxation of IGF2 imprinting in Wilms tumours associated with specific changes in IGF2 methylation. Oncogene 1999 18(52) 7527-34. 63. Malik K, Salpekar A, Hancock A et al. Identification of differential methylation of the WT1 antisense regulatory region and relaxation of imprinting in Wilms' tumor. Cancer Res 2000 60(9) 2356-60.

Are Protein Dynamics Fractal

While it is easy to describe a picture of polymer dynamics, putting this picture into a mathematical model is not so simple. The energy transfer modes within the polymer will depend on the nature of the bonding and internal connectivity of the polymer. This makes proteins a particularly challenging problem. Most work involves sorting through the phenomenology of protein dynamics and experimentally exploring the multitude of relaxation processes that are occurring. In the next section, an introductory discussion of protein dynamics is presented. The time, length, and energy scales of an array of different processes are discussed. Considering the complexity and range of protein dynamical processes, it is not surprising that protein dynamical processes often have a nonexponential time dependence. In Section 6.2 we examine a number of physically plausible and simple models that generate nonexponential behavior. We see that these models can be classified within two general schemes...

Fractal Aspects of Protein Structure

The scaling laws determined in this chapter will be of great utility when considering structural issues in later chapters. In Chapter 3, the configurational statistics of loop formation is considered. A number of different loop topologies exist and these will have characteristic scaling laws. These scaling laws are dependent on the mass fractal dimension of the polymer. Considering the complexity of protein structure, it is not surprising that protein dynamics are also quite complicated. Such issues will be taken up in Chapter 5 and 7. In Chapter 5, the surface fractal dimension of protein is used to develop a chemical kinetic model of hydrogen isotope exchange. The model relates structure and kinetics via a fractal dimension, known as a spectral dimension. Chapter 7 considers a similar connection for vibrational relaxation in proteins.

Other Neural Reflexes Involved With Blood Pressure Regulation

Endothelial cells contribute to the regulation of arterial blood pressure by regulating vascular tone through activation or inactivation of various circulating vasoactive substances, and by producing numerous agents that can act locally and or systemically to affect vascular tone. Nitric oxide (NO) is a potent vasodilator that is produced in endothelial cells via the oxidation of L-arginine by the enzyme NO synthase. Inhibitors of NO synthase elicit a reduction in blood flow to some tissues and a concomitant rise in arterial blood pressure, suggesting that NO produced by endothelial cells exerts a tonic inhibitory influence on arteriolar tone, thereby contributing to basal blood pressure. Nitric oxide also mediates the endothelium-dependent vasodilation that is elicited by a variety of agents, including acetylcholine and bradykinin. Patients with some forms of chronic arterial hypertension exhibit an impaired endothelium-dependent vascular relaxation, further supporting the...

The Heart Is An Example Of A Reciprocating Pump

The chamber's volume changes as the piston moves, causing the pressure within to rise and fall. In the heart, the change in volume is the result of contraction and relaxation of the cardiac muscle that makes up the ventricular walls. One complete rotation of the crankshaft in Fig. 1 will result in one pump cycle. Each cycle, in turn, consists of a filling phase and an ejection phase. The filling phase occurs as the pumping chamber's volume is increasing and drawing fluid through the input port. During the ejection phase, the pumping chamber's volume is decreasing and fluid is ejected through the output port. The volume of fluid ejected during one pump cycle is referred to as the stroke volume. The volume of fluid pumped each minute can be determined by simply multiplying the stroke volume times the number of pump cycles per minute.

Mechanical Response Of Smooth Muscle In Vivo

Quick or sustained stretch of many smooth muscles results in contraction of that muscle. In many instances, contraction occurs even in the absence of nerves thus, it is not due to activation of a neural reflex as in skeletal muscle. Contraction most likely results from membrane depolarization or from the opening of stretch-activated calcium channels. Such responsiveness may explain why organs such as the stomach, bladder, and small arte-rioles contract to oppose distension. In some smooth muscles, especially those of some larger blood vessels, a quick stretch is followed by a temporary increase in wall tension however, this increase is quickly followed by a relaxation toward the original wall tension referred to as stress relaxation (Fig. 11). The opposite, reverse stress relaxation, occurs when the muscle is allowed to shorten that is, if an external stress is removed, wall tension temporarily decreases. However, the decrease is followed quickly by muscle contraction to return to the...

Solidstate Properties

Thermal analyses in pharmaceutical analysis usually include DSC and TGA. Being widely used for preliminary characterization of a pharmaceutical solid, DSC can be a simple and rapid method of identifying the mixture of forms, understanding phase transitions, assessing thermodynamic stability of forms, and estimating the purity of materials.42 Figure 8.1 depicts a typical DSC thermogram of a pharmaceutical solid. Starting from an amorphous phase, the glass transition temperature Tg was evident as a small endothermic decrease in baseline and is represented by the midpoint of the decrease measured from extension of the pre- and post-transition baselines. The Tg was followed by an exothermic event, which was assigned to the recrystallization into a metastable crystal form. The metastable form then melted, and the melted compound was further recrystallized into a more stable crystal form, which eventually melted at a higher temperature. With the introduction of modulated DSC with improved...

Myotonic Muscular Dystrophy

Myotonic muscular dystrophy (DM, or dystrophia myotonica) is the most common adult-onset muscular dystrophy, having a frequency of one per twenty thousand persons in the general population. Myotonia, the delayed relaxation of a voluntary muscle after it is contracted, and muscle weakness are the hallmarks of the disorder. For example, a person with DM using a hammer will not immediately be able to release his grip on the handle when finished. It is an autosomal dominant disorder, but there is great variability in the disorder's severity and in the number of manifestations it leads to.

Pressures And Resistances In The Cardiovascular System

Although both length and radius of the vessel contribute to its resistance, it is the radius that is altered to modulate flow. Smooth muscle cells in the vessels, especially the arterioles, are arranged such that their contraction or relaxation results in reductions and increases in vessel radius, resp., causing major changes in the resistance to blood flow. Figure 16 illustrates the change in resistance in a single vascular bed that occurs during stimulation of its sympathetic nerves. The perfusion pressure is held constant. Note that at increasing stimulation rates the flow falls, indicating an increase in resistance. Now let's extrapolate this experiment to the intact body under two conditions. First, if there were generalized sympathetic stimulation to all the organs, and if cardiac output (CO) remained constant, then mean arterial blood pressure would increase. That is because the total peripheral resistance

TrWeighted Breast Cancer DCEMRI

Extracellular contrast media readily diffuse from the blood into the EES of tissues at a rate determined by the permeability of the capillaries and their surface area. Shortening of T1 relaxation rate caused by contrast medium is the mechanism of tissue enhancement. Most DCE-MRI studies employ gradient-echo sequences to monitor the tissue enhancing effects of contrast media. This is because gradient-echo sequences have good contrast medium sensitivity, yield images with high signal to noise ratio and enable data acquisition to be performed rapidly. The degree of signal enhancement seen on T1-weighted images is dependent on a number of physiological and physical factors. These include tissue perfusion, capillary permeability to contrast agent, volume of the extracellular leakage space, native T1-relaxation rate of the tissue, contrast agent dose, imaging sequence and parameters utilised and on-machine scaling factors (Roberts 1997). The relative effects of these factors on DCE-MRI are...

Gender Ethnicracial And Life Span Considerations

Assess the effects of a chronic illness on the patient and family if the patient does not get enough rest or relaxation, suggest lifestyle changes that might decrease stress. Heavy smokers may acquire certain hemoglobin abnormalities that can lead to secondary polycythemia.

Shoulder presentation

In early labour with the membranes intact, one could wait in anticipation of spontaneous or assisted correction to longitudinal lie while making all the preparation for CS. If the membranes rupture and the fetus is still in the transverse lie, CS should be performed to avoid injury to the fetus or the uterus. In cases where the diagnosis is made late the fetus may be impacted in the transverse lie and safe delivery may be only possible by a CS with a midline vertical incision. It may be possible to deliver the fetus through a lower segment transverse incision with acute uterine relaxation using a short acting drug (e.g. 0.25 mg terbutaline in 5 cc saline given IV over 5 min) 6 . Following this treatment if the uterus does not contract despite oxytocics, a small dose of beta blocker such as Propra-nolol 1 mg IV may be needed to contract the uterus and to avoid post-partum haemorrhage 7 . Labour and spontaneous vaginal delivery is possible in extreme preterm and macerated fetuses.

Rectal Compliance and Sensation

Distention of the rectum by stool is associated with several processes that serve to preserve continence, or if circumstances are appropriate, to proceed with defecation. Stool is often transferred into the rectum by colonic high-amplitude propagating contractions, which mostly occur after awakening or after meals 7 . It is likely that rectal contents are periodically sensed by the process of anorectal sampling 8, 9 . This process may be facilitated by transient relaxation of the internal anal sphincter, which allows the movement of stool or flatus from the rectum into the upper anal canal. Here they may come into contact with the specialized sensory end organs, such as the numerous Krause end-bulbs, Golgi-Mazzoni bodies and genital corpuscles, and the relatively sparse Meissner's corpuscles and pacinian corpuscles 10 . Specialized afferent nerves for touch, cold, tension, and friction subserves these organized nerve endings. An intact sampling reflex allows the individual to choose...

Future Directions Conclusion

Further understanding of the complex molecular mechanisms underlying cystic fibrosis disease pathology will impel not only the development of more effective gene therapy, but also the establishment of better endpoints to assess functional and clinical intervention (14). The establishment of animal models with complex genetic backgrounds and environmental exposures may provide for better determination of the safety and efficacy of various gene therapy protocols (24). An improved understanding of the cellular response to gene therapy vectors is also emerging. For example, methods to increase transduction efficiency by allowing transient and reversible relaxation of tight junctions (in order to allow access of vectors to the basolateral surface of target cells), or vector modifications that facilitate targeted binding to the apical cell mem

Using Channel Mutants Drugs and Other Probes to Dissect CFTR Gating

Another powerful tool for dissecting CFTR gating is the use of nucle-otide and phosphate analogs. As mentioned above, the use of the nonhydrolyzable ATP analog, AMPPNP, and the NBD2 mutant K1250A, implicated the involvement of ATP hydrolysis in channel opening and closing and established the presence of two functional sites for ATP (see above). These results from few channel patches were corroborated by macroscopic relaxation experiments using rapid solution changes. Switching from AMPPNP to ATP and then back to AMPPNP revealed that both opening and closing of CFTR are delayed (21) (Fig. 9). The delayed closing upon switching from ATP to AMPPNP is consistent with the above-mentioned binding of AMPPNP to a second binding site, where its binding inhibits channel closing. The delayed opening when changing from AMPPNP to ATP indicates the binding of AMPPNP to a nucleotide-binding site from which it must be released before ATP can open CFTR. These experiments also used ADP to elucidate...

Endotheliumderived relaxing factor

In 1980, Furchgott discovered that the endothelium is responsible for the vasodilator action of acetylcholine (10). This finding has fostered a great number of investigations on the role of the endothelium on the initiation and development of vascular disease and its subsequent clinical sequelae. Further research indicated that acetylcholine released a soluble factor from the endothelium termed EDRF and that this substance was released by other agents including bradykinin, substance P, serotonin, and adenosine triphosphate (ATP), and shear stress (11). Ignarro used spectral analysis of hemoglobin to prove that EDRF was identical to NO (12). Shortly thereafter, Palmer and colleagues concluded that NO was derived from the terminal guanidino nitrogen of the amino acid L-arginine. The production of NO is catalyzed by the family of enzymes known as NO synthase (NOS) (13). Three isoforms of NOS have been identified endothelial NOS (eNOS), neuronal NOS (nNOS), and cytokine-inducible NOS...

Effects of Estrogen on Endothelial Function

ERT also provides insights into NO regulation by estrogen. Thus, endothelium-depen-dent vasodilation of the branchial and coronary arteries is enhanced after ERT in postmenopausal women and levels of plasma NO and NO metabolites are increased (36,37). It is of interest that inclusion of progesterone in postmenopausal HRT may blunt the effects of estrogen on endothelial NO production (38). Similar effects of enhanced endot-helial function have been observed after ERT in young women with premature ovarian failure or following ovariectomy and in young women receiving oral contraception (33,39). Furthermore, a case has been reported of a young man with nonfunctional ERa as a result of mutation of the ER gene (40). The man was found to have impaired branchial endothelium-dependent relaxation and early coronary calcification supporting the view that ERa is important for endothelial NO release. environment, ultimately leading to eNOS stimulation (43-45). Additional mechanisms for nongenomic...

The Kallikrein Kinin Pathway

Bradykinin is generated by kallikreins from their precursor kininogens and it is a potent vasodilator that increases vascular permeability and plays a primary role in inflammation. In noninjured vessels, bradykinin causes relaxation of the VSMC through the synthesis and release of NO from the endothelium (42). In contrast, when the integrity of the endothelium is compromised, bradykinin will act directly in VSMCs promoting their vasoconstriction (43) and fibrosis. The direct action of bradykinin in VSMCs is mediated by its binding to its B2 receptors and subsequent activation and nuclear translocation of p42 and p44 mitogen-activated protein kinase (MAPK) that induces c-fos and c-jun mRNA levels and generation of reactive oxygen species (44,45). Activation of the MAPK pathway leads to an increase in ECM proteins, such as collagen I and fibronectin (45,46). Douillet and associates (46) have shown that activation of transforming growth factor (TGF)-P together with MAPK activation,...

Endothelium Dependent Vasodilation in Animal Models

Similarly, in an animal model of type 2 diabetes, the Zucker rat, which is characterized by hyperglycemia because of insulin resistance, abnormal endothelium-dependent va-sodilation is also seen (46). The early vascular dysfunction that occurs in type 1 diabetic animal models can be prevented by insulin therapy (50,51). The abnormal endothelial cell function that develops appears to be as a result of hyperglycemia rather than any other metabolic disturbance. This has been demonstrated by in vitro incubation experiments in which isolated arteries exposed to elevated glucose concentrations have similar decreases in endothelium-dependent vasodilation (52,53). This effect does not seem to be as a result of the hyperosmolarity because similar concentrations of mannitol have no effect on endothelium-dependent relaxation (52). The decreased endothelium-dependent vasodi-lation that occurs may be as a result of decreased synthesis or release of NO, decreased Early in the course of experimental...

Increased Nitric Oxide Inactivation Decreased Bioavailability andor Breakdown of Nitric Oxide

High glucose levels lead to increased NOS activity, making it likely that decreased NO bioavailability through either increased breakdown or other mechanisms is central to the overall decrease in NO activity in the diabetic state. One possible candidate that may modulate NO bioavailability is oxygen-derived free radicals (58,102). These increased free radicals are derived from either increased production or a decrease in the free radical scavenger system. In some animal models of diabetes, a decrease has been seen in levels of endogenous antioxidants including superoxide dismutase (SOD), catalase, and glutathionine peroxidase (103,104). If the aortas of diabetic rats are exposed to free radicals via xanthine and xanthine oxidase, endothelium-dependent relaxation is attenuated further (105). Furthermore, the addition of the free radical scavengers including SOD prevents the impairment of endothelium-dependent relaxation seen in aortic rings of diabetic rats (106). Normal rabbit aortas...

Vascular Contractility and Blood Flow

Changes in NO could also alter vascular contractility and blood flow. In the resistant vessels isolated from diabetic patients and animals, the relaxation phase after acetylcho-line stimulation appears to be delayed (134-137). These impaired vascular relaxation can be restored by PKC inhibitors and mimicked by phorbol ester in normal arteries (137). The inhibition of PKC increased mRNA expression of eNOS in aortic endothelial cells (138). We have observed reduced eNOS expression in microvasculature in Zucker fatty rats, which are the model of insulin resistance (33).

T2Weighted Perfusion

SE-based EPI techniques are predominantly based on the susceptibility effects rather than changes in the T2 relaxation rate. This is in fact a consequence of the relatively long sampling period of the EPI acquisition technique. The susceptibility contrast arising from compartmentalization of the contrast agent is therefore used to determine relative tissue and relative arterial concentration levels according to Eq. 3, allowing subsequent calculations of rCBV, rCBF, and MTT in the same manner as described in Chap. 4.2.1 (Fig. 7.1).

Preparation Of Dna Fibers From Fibroblasts By The Halo Technique

One of the oldest techniques used for DNA fiber-FISH mapping is called the halo preparation technique (Wiegant et al., 1992), a modified version of the technique described by Vogelstein et al. (1980). Cells growing on a glass slide are lysed in a buffer containing a detergent. This is then followed by high-salt washes to remove histones from the chromatin. The DNA in such nuclei consists of loops anchored to the nuclear matrix in a form having a high degree of negative supercoiling. Next, the nuclei are incubated in a high-salt buffer containing a DNA-intercalating dye to unwind the DNA loops by introducing positive supercoiling. This is then followed by UV irradiation to make nicks, which leads to relaxation of the DNA that has been looped out. Although in principle a true halo of DNA loops of 14 to 16 m can be obtained, for mapping purposes it is advantageous to produce much longer loops.

Human Studies of Endothelium Dependent Vasodilation

Human studies evaluating the effects of DM on endothelium-dependent vasodilation have yielded some conflicting results, although they generally corroborate those found in animal studies. Saenz de Tejada et al. (60) studied penile tissue excised from men with erectile dysfunction and found that endothelium-dependent relaxation is reduced in the corpus cavernosa of impotent men with diabetes relative to those who are nondiabetic. However, in vivo studies involving human subjects with insulin-dependent diabetes have demonstrated both blunted and normal vasodilatory responses to acetylcholine, methacholine, or carbachol (the latter two being acetylcholine analogs) in forearm resistance vessels in patients with DM (61-63). To evaluate in vivo endothelial function in these vessels, we and others have employed the venous occlusive plethysmography technique. Type 1 diabetic (61) individuals were shown to have impaired endothelium-dependent responses to methacholine in the forearm resistance...

HMG CoA Reductase Inhibitors

Large clinical trials have determined that hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) significantly reduce cardiovascular morbidity and mortality. Furthermore, lipid-lowering therapy has been shown to improve endothelial function in several studies (204,205). Attempts to ameliorate the impaired endothelium-dependent vascular relaxation that occurs in diabetic patients with dyslipidemia are few and the results mixed. Impaired endothelium-dependent vasodilation in patients with type 2 DM with dyslipidemia has been reported to improve with fibrate therapy (206) (which lowers the serum triglyceride level) but not with simvastatin (206,207).

Frequency dependence of g and g

This behavior was at first disappointing because no characteristic time scale was evident we were unable to identify a dominating relaxation process. The only characteristic time scale that falls out of the data is that associated with curvilinearity of the G data that becomes apparent in the neighborhood of 100 Hz (Fig. 3-4). As shown below, this curvilinearity is attributable to a small additive Newtonian viscosity that is entirely uncoupled from cytoskeletal dynamics. This additive viscosity is on the order of 1 Pa s, or about 1000-fold higher than that of water, and contributes to the energy dissipation (or friction) only above 100 Hz. Below 100 Hz, friction (G) remained a

Pyramid Evolution Integration of Crystallography and NMR

There are a number of NMR methods used to identify ligand binding to proteins, which can be divided into target-detected methods such as SAR by NMR 8 and li-gand-detected methods such as transverse relaxation NMR (T2) 48, 49 , saturation transfer difference NMR (STD-NMR) 50 , and water-ligand observed via gradient spectroscopy (Water-LOGSY) 51, 52 . In Water-LOGSY, the magnetisation of the bulk water is partially and selectively transferred to the free ligand via close protonproton contacts in the hydrated protein-ligand complex. The resonances of bound li-gands appear as positive peaks in the spectrum, whereas the peaks from the unbound hydrated ligands are negative and tend to be weaker 53 . In common with other li-gand-detected methods, Water-LOGSY has the advantage that it does not require isotope labeling of the protein, uses relatively small amounts of protein (approximately 1-50 M in a 0.5 ml sample) and can detect binding at ligand concentrations at or below the dissociation...

On Line Instrumentation

The required length of the magnet is determined by the speed of the production line and by the relaxation times Tj and T2. For a sample with a spin lattice relaxation time of 1.0 s and a production line moving at 0.2 m s, a polarising magnet 0.6 m long is needed in order to produce an initial magnetisation which is 95 (three decay constants) of maximum. If the sample T2 is 0.5 s then in order to see two decay constants of the FID the subsequent measurement magnet will need to be a further 0.2 m long. To this must be added the length of the product, say 0.2 m, giving a total length of 1 m. One large magnet may be used. If two separate magnets are used, the first can be of much lower homogeneity and can be set at a higher field strength so as to increase the magnetisation polarisation

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