Relaxation Techniques

Relaxation Audio Sounds Autumn In The Forest

Relaxation Audio Sounds Autumn In The Forest

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Brain Evolution System

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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...

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...

Nerve Supply to the Pelvic Floor Autonomic Innervation

Sacral parasympathetic pathways to the colon have excitatory and inhibitory components 14 . Excitatory pathways play an important role in colonic propulsive activity, especially during defecation. In other species (e.g., guinea pig), feces transport may be entirely organized by the enteric nervous system spinal and supraspinal reflexes are also involved in the process 15 . Inhibitory pathways allow colonic volume to adapt to its contents, and they also mediate descending inhibition that initiates colonic relaxation ahead of a fecal bolus.

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...

Crystallisation And Freezing

Decrease in mobility during freezing or crystallisation greatly attenuates MR signal amplitude, providing a means of following these related processes. Intensity of the MR signal depends on the relaxation rate of the interrogated nuclei the very fast relaxation rates found in solids prevent observation by use of liquid MR techniques. This inability to observe nuclei in a solid matrix presents a method for observation of kinetics of the liquid-solid phase transition. Disappearance of signal from a volume containing liquid may signify crystallisation or amorphous glass formation. Observation of the movement of the intensity interface dining solidification has provided kinetics information for crystallisation of fat water emulsions and freezing of meats and vegetables. Freezing, whether involving crystallisation or amorphous glass formation, decreases molecular mobility, thereby increasing relaxation rates and attenuating the MR signal. Movement of the freezing interface has been...

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...

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...

Dynamic Contrast Enhanced MRI

For both T1 and T2* approaches, it is possible that improvement in quantitation can be achieved by converting signal intensity changes observed directly on MRI into dynamic changes of contrast agent concentration to provide the source data for descriptive or kinetic modeling2 (Schwickert et al. 1995 Roberts 1997). In contrast to nuclear medicine and CT, signal changes in MRI are not directly related to tracer concentration, in vivo. Common practice is to convert observed signal intensities into local changes in the pertinent relaxation rate (1 T1, or 1 T2*). The implied assumption subsequently is that contrast agent potency (or relaxivity, r1 or r2* - the amount of relaxation enhancement per unit concentration of tracer) is the same across all tissues and compartments. This assumption is likely to be flawed in vivo, and may be especially inappropriate for transverse relaxivity, r2*, where local magnetic susceptibility field gradients are a function of local compartmentalized...

Additional Nursing Diagnoses Pain

Provide nonpharmacologic pain management strategies soothing baths massage therapy to painful areas education on possible (and encourage parent child to use) distraction techniques (i.e., music, aroma, humor, reading, journal writing, art work, pets, prayer, hypnosis, relaxation techniques. Specify).

Hirschsprungs Disease

Up to 50 of children following surgical treatment of Hirschsprung's disease (which affects 1 5,000 live births) suffer constipation or faecal incontinence 20 , although by adulthood, most have reasonable function 21, 22 . Physiologically, such disturbances may reside in loss of colonic length, a dysmotile residual colon with increased high-amplitude propagating contractile activity (HAPCs) resulting in rapid stool delivery to the neorectum, and rectal pressures exceeding external anal sphincter pressure, compounded by surgical interventions to relax the internal sphincter and disimpact the rectum, whereas loss of normal urge rectal sensation and failure of internal sphincter relaxation facilitate persistent constipation.

Length of the DHA Chain

These observations indicate that whatever DHA's conformation is, it must be compact. A second model, based on the ROS membrane, predicts a much different structure for DHA. A molecular spring model predicts a helical structure where DHA lengthens and shortens to accommodate conformation changes in rhodopsin (Dratz & Holte, 1992). Conformational energy calculations suggest DHA can lengthen or shorten over a range of 3-4 A with a small input of energy (Dratz et al., 1985). NMR order parameters and spin lattice relaxation times support the idea that DHA performs rapid structural transitions between extended and looped conformations (Holte et al., 1998 Koenig et al., 1997 Mitchell et al., 1998). It is therefore likely that whatever DHA's structural role in membranes is, it does not support a thick membrane in fact, DHA's conformation is quite compact.

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).

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.

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

Stages and Estimation of Age of Hemorrhage on MRI

Recognizing cerebral hemorrhage is critically important, and a knowledge of the complex parameters that influence the MRI appearance of an evolving hematoma is therefore essential. The MRI of a hematoma depends on whether Tl-shortening proton electron dipole - dipole (PEDD) interactions or T2-shortening preferential T2 proton relaxation enhancement (PT2-PRE) occur. The interaction that predominates thereafter depends on the particular heme moiety present (e.g., oxyhemoglo-bin, deoxyhemoglobin, methemoglobin, or hemosiderin), and on whether it is in free solution or compartmentalized into red blood cells or macrophages (Fig. 4).

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 .

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

Experimental findings in living cells

To study the rheology of cytoskeletal polymers requires a probe whose operative frequency range spans, insofar as possible, the internal molecular time scales of the rate processes in question. The expectation from such measurements is that the rheological behavior changes at characteristic relaxation frequencies, which in turn can be interpreted as the signature of underlying molecular interactions that dominate the response (Hill, 1965 Kawai and Brandt, 1980). Much of what follows in this chapter is an attempt to explain the failure to find such characteristic relaxation times in most cell types. The experimental findings of our laboratory, summarized below, are derived from single cell measurements using magnetic twisting cytometry (MTC) with optical detection of bead motion. Using this method, we were able to apply probing frequencies ranging from 0.01 Hz to 1 kHz. As shown by supporting evidence, these findings are not peculiar to the method rather they are consistent with those...

Role For Pkc Activation

The experimental evidence obtained with various PKC inhibitors as well as the dia-cylglycerol complexing agent cremophor by several groups (81,86-88) suggests the detrimental role of PKC activation in vasa nervorum. The PKC inhibitors, WAY151003, chelerythrine, and LY333531 as well as cremophor prevented or reversed NBF and conduction deficits (81,86,87), and the PKC inhibitor Ws-indolylmaleimide-1HCl corrected acetylcholine-mediated vascular relaxation in epineurial arterioles in the STZ-diabetic rat model (88). The role for neural PKC in the pathogenesis of PDN remains unclear. However, recent findings suggest that neuronal PKC might be related to diabetes-associated changes in expression, phosphorylation, and function of the vanilloid receptor 1, known to play an important role in diabetic neuropathic pain (89). The novel PKC-P isoform selective inhibitor JTT-010 was found to ameliorate nerve conduction deficits, hyperalgesia (formalin test in its first phase), and hypoalgesia...

Pivotal Role Of Calcium

FIGURE 5 Sarcoplasmic reticulum (SR) in skeletal muscle. The SR consists of two components. The terminal cisternae serve as reservoirs of calcium during relaxation. Upon stimulation, Ca2+ is released to interact with the troponin complex. Once released, Ca2+ is avidly taken up by the second component, the longitudinal SR. Uptake is mediated by a calcium ATPase. FIGURE 5 Sarcoplasmic reticulum (SR) in skeletal muscle. The SR consists of two components. The terminal cisternae serve as reservoirs of calcium during relaxation. Upon stimulation, Ca2+ is released to interact with the troponin complex. Once released, Ca2+ is avidly taken up by the second component, the longitudinal SR. Uptake is mediated by a calcium ATPase. In relaxed skeletal muscle, all the calcium that normally takes part in E-C coupling is stored inside the cell in the sarcoplasmic reticulum (SR) (Fig. 5). As might be expected, the SR of these cells is highly developed and extensive. Structurally, it is of two types the...

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.

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.

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...

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...

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.

Dynamic Contrast Enhanced Imaging

It has been shown that accurate characterisation of the AIF requires a temporal resolution in the order of a second (Henderson et al. 1998). Furthermore, following bolus injection of a typical clinical dose of contrast agent the T1 of the blood may decrease by more than an order of magnitude (Fritz-Hansen et al. 1996). Monitoring such large changes in relaxation rate requires an imaging sequence with a good dynamic range (Fig. 5.2). Competing directly with this requirement is the need to monitor much smaller changes in T1 at the level of the tissue. The location of the AIF, in relation to the tissue of interest, and the extent of that tissue dictates the requirements for spatial coverage. Finally, it is rare to identify a local feeding artery to provide an AIF but the closer the AIF is to the true tissue arterial supply the more accurate the subsequent modelling (Calamante et al. 2000). However, the spatial resolution of the images places a minimum diameter on the artery to be imaged....

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

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...

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.

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

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.

Dnabinding Cyanine Dyes

The fluorescence quantum yield of cyanine dyes increases when torsional motion around the methine bridge is restricted, which reduces the probability of nonradiative relaxation from the excited singlet state. 7,8 When the dyes bind DNA, internal rotation is likely to be strongly hindered, which causes the dramatic increase in fluorescence.

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...

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).

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...

Endothelium Dependent Vasodilatation

Both ACE inhibition and AT1 receptor antagonism improves acetylcholine-induced vasorelaxation in NIDDM subjects (127,128). Treatment of normotensive type 1 diabetics with an ACE inhibitor has also been shown to increase acetylcholine-induced vasorelaxation in (129,130). In these studies, no difference in vasodilatation induced by NO donors (sodium nitroprusside) was observed in diabetic vs control subjects, suggesting that the endothelium dysfunction was related to impairment in the generation of NO rather than an impaired response potential. ACE inhibition may improve endothelium-dependent relaxation by suppressing Ang II effects on vascular NADH NADPH oxidase production of superoxide anions and or vascular insulin signaling (131-133). Although ACE inhibition improves endothelium-dependent vasorelaxation induced by acute aceylcholine infusion (127,130) it did not improve endothelial function in response to flow-mediated dilation (134,135). Therefore, ACE inhibition appears to...

Experimental Erectile Dysfunction

Experimental erectile dysfunction in experimental diabetes and aging has been studied in the rat (40-42). Rat studies typically consist a measurement of intracavernous pressure in response to electrical stimulation of the cavernous nerve in normal and diabetic rats (43). The pathophysiology of erectile dysfunction in DAN appears to mimic the human condition wherein it is vasculogenic resulting in engorgement of corpora cavernosa and is because of a deficiency of nitric oxide (40,44-46). In the penile corpora cavernosa, nitric oxide is produced mainly by the activation of the neuronal nitric oxide synthase (NOS) in the nerve terminals and, to a lesser extent, by endothelial NOS in the lacunar and vascular endothelium (40,46). Nitric oxide stimulates guanylate cyclase cGMP activation of phosphokinase G reduction of intracellular Ca2+ relaxation of the smooth muscle cells penile engorgement. Support for this concept in the rat derives from a number of observations. Nitric oxide...

Other Blood Volumerelated Mechanisms Involved In Blood Pressure Regulation

The stress-relaxation mechanism represents an effort by the blood vessels to fit around the existing blood volume. This phenomenon is related to the intrinsic ability of smooth muscle to return to its original force of contraction after it has been elongated or shortened. Stress-relaxation is more pronounced in the visceral smooth muscle surrounding hollow organs like the urinary bladder, but it does occur to some extent in vascular smooth muscle. Hence, if blood volume and arterial pressure become too high, the blood vessels are stretched and then slowly relaxed as though to accommodate a larger intravascular volume. As a result, the pressure within the arterial tree will fall toward normal. With hemorrhage, on the other hand, a reverse stressrelaxation will cause blood vessels to contract around the reduced blood volume, thereby tending to buffer the fall in arterial pressure.

Techniques Combining T2 T2 or T1

Effect in the measurement of quantitative hemody-namic parameters, such as rCBV, rCBF, and MTT, combined techniques may be useful, involving simultaneous measurements of the changes in the T1, T2, or T2* relaxation rate. To be insensitive to T1 enhancement, a radiofre-quency-spoiled gradient echo sequence is preferred with dual echo acquisition. The change in the T2* relaxation rate, AR2*(t), can then be readily calculated from (Vonken et al. 2000),

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.

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.

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.

Critical Choice of an Effective Diagnostic Workup

Shows higher accuracy in detecting minor abnormalities in anal pressures and increased pressures in patients with abnormal sphincter relaxation and subsequent fecal seepage 47 . Only minimal attention has been dedicated to RAIR in FI patients a possible role of relaxation and contraction times needs to be elucidated in cases of mild continence disturbances. Concerning rectal sensations, even if they are frequently found to be altered (reduced or increased) in FI patients, in other cases, they can be normal 48,49 . The assessment of rectal sensation is preliminary in patients who are possible candidates for sensory retraining. Indeed, preservation of rectal sensation before therapy and its improvement determined by the therapy are suggested as major determinants of biofeedback success 50 .

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.

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 .

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...

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.)

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...

Vascular Effects of Estrogens

Vasoregulation occurs as a balance between the release of relaxing and constricting factors. The predominant relaxing factor is nitric oxide (NO), which is synthesized from the amino acid L-arginine. NO release activates SMC guanylate cyclase, leading to increased cyclic guanosine monophosphate production and vascular relaxation (25). Other relaxing factors include prostacyclin and hyperpolarizing factor, which act through cyclic adenosine monophosphate and potassium channels respectively. The major constricting factors are endothelin-1, thromboxane, and prostaglandin H2 (24).

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...

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.

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...

Prevention and Control

Prevention and control measures are applied to those orbiviruses that cause economically important disease in domesticated animals. The most significant of these measures are intended to prevent introduction of viruses not already present into areas that may contain both susceptible hosts and competent vector populations. The results of such introductions were illustrated in the Iberian peninsula in 1956-1960 with BTV and 1987-1991 with AHSV. The measures used to control the import of virus vary from country to country, involving restrictions on movement of animals and germline material (semen and ova) from infected areas. These restrictions, which may include quarantine periods, or even a complete ban on importation, are inevitably dependent on sensitive tests for both virus and antibodies. With the inability to confirm a carrier state for BTV in cattle, there is pressure for some relaxation of the current import export restrictions, particularly if coupled with adequate testing of...

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...

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.

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,...

Effects of HRT on Endothelial Function in Postmenopausal Women With Diabetes

Ation in a small cohort of postmenopausal women with diabetes before and 6 months after transdermal 17 -estradiol (80 mg twice weekly) in combination with oral nonethisterone (1 mg daily). The authors concluded that this particular HRT regimen had potentially beneficial effects on vascular relaxation. Data were consistent with improvements in endothelial function, vascular smooth muscle function, or both. Abnormal responses to endothelium-independent agonists have been reported in type 2 diabetes by other workers (165) but there have been no previous reports of augmented endothelium-independent responses after HRT in women with or without type 2 diabetes.

And Paraffin Embedded TissueProtocol

In formalin-fixed and paraffin-embedded tissue material, the DNA is trapped in a relatively strong matrix of cross-linked protein. If the tissue material is fixed at neutral pH for not longer than 24 hr, the DNA and proteins are internally cross-linked to a limited extent. This protocol describes such a cross-linking procedure. Incubation in formic acid H2O2 removes protein prior to permeabilization with pepsin, improving nuclear isolation and permeabilization. Following permeabilization, formalin-fixed nuclei are brought to pH 9, resulting in a three-fold increase in nuclear size. Compare this to the pH-driven swelling of fresh nuclei, which uses a change from acidic to neutral pH (see Basic Protocol 2). For formalin-fixed nuclei, a higher pH is needed for relaxation as a result of cross-linking of histone proteins during formalin fixation. The morphology of the nuclei isolated by this protocol will resemble that of methanol acetic acid-fixed cells with respect to size and efficiency...

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.

Metabonomics Data Acquisition Methods

Plasma and serum contain both low- and high-molecular weight components, and these give a wide range of signal line widths. Broad bands from protein and lipoprotein signals contribute strongly to the 1H NMR spectra, with sharp peaks from small molecules superimposed. Standard NMR pulse sequences can be used for spectral editing experiments. These are based on molecular diffusion coefficients or on NMR relaxation times and can be used to select only the contributions from macromolecules or the signals from the small molecule metabolites, respectively.

Pharmacologic Highlights

One of the most life-threatening complications of liver failure is airway compromise because of neurological or respiratory deterioration. Keep endotracheal intubation equipment and an oral airway at the bedside at all times. Elevate the head of the patient's bed to 30 degrees to ease respirations, and support the patient's arms on pillows to decrease the work of breathing. It is essential to be at the bedside and to perform serial assessments of all critical systems. Space all activities and limit visitors as needed so that the patient gets adequate rest. To encourage rest, consider nonpharmacologic methods such as diversionary activities and relaxation techniques.

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...

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.

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...

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...

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...

Topoisomerase Inhibitors

Topoisomerases temporarily break DNA strands and perform topological changes to selected regions of the genome available for transcription. Two main classes of topoisomerases are recognized to date topoisomerases I and II. Topoisomerase I catalyzes the ATP-independent relaxation of DNA supercoils by transiently breaking and religating single-stranded DNA. Topoisomerase II relaxes supercoiled DNA through catalysis of a transient breakage of double-stranded DNA in an ATP-dependent manner. Examples of topoisomerase inhibitors are etoposide and camptothecin, which form a stable ternary DNA-topoisomerase II drug complex that maintains a cleaved state of DNA and interferes with DNA replication, repair, and transcription of eukaryotic cells (Fig. 80).

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...

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.

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...

Reticuloendothelial System RES Contrast Agents

Kupffer cells in the normal liver will take up partic-ulate matter from the circulation and this property has been utilised to produce a group of RES-specific contrast agents. These consist of suspensions of superparamagnetic iron oxide particles (SPIO) or ultra-small superparamagnetic iron oxide particles (USPIO) (Fretz et al. 1989 Weissleder et al. 1989 Weissleder et al. 1990). These agents exhibit strong T1 relaxation properties, and due to susceptibility differences to their surroundings also produce a strongly varying local magnetic field, which enhances T2 relaxation. Pathological tissues which do not contain reticuloendothelial cells will maintain their normal signal intensity. Currently available agents include Endorem and Feridex Ferrumoxides. (USAN). SPIO. Ami-25, dextran-coated) , Resovist (Ferucarbotran, car-boxy-dextran coated iron oxide nanoparticles), Sinerem (USPIO) and Combidex (ferumoxtran-10, AMI-227) (for manufacturers' details see Table 14.1). There is...

Possible mechanisms of impaired endotheliumdependent vasodilation

Although the data are conflicting, overwhelming evidence presently suggests that DM is associated with an impairment of endothelial vasodilation. The mechanism(s) for this impairment is even less well understood. The most likely initial insult is hyperglycemia. Tesfamarian and colleagues took normal rabbit aortic rings and exposed them to high concentrations of glucose (up to 800 mg dL for 3 hours), resulting in a decrease in endothelium-dependent relaxation, in response to acetylcholine and ADP (52,53). This effect appears to be both concentration and time dependent. As stated earlier, this effect does not appear to be a result of the hyperosmolar effects of glucose because mannitol did not cause any such endothelium-dependent vasodilation (53). Bohlen and Lash (73) demonstrated that hyperglycemia at 300 and 500 mg dL suppressed the vasodilatory response to acetylcholine but not to nitroprusside. Similarly, Williams and colleagues (68) found that acute hyperglycemia attenuated...

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.

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...

Physiology And Behaviour

Hence the high energetic costs of having and maintaining heavy muscles and their associated skeletal support no longer have to be met. Thus many of the elaborately developed sensory systems supported by large brains and a well developed central nervous system, typical of many species in the upper mesopelagic and epipelagic zones, become a liability rather than an asset (Marshall, 1971). As a result many bathypelagic species are physiologically more akin to jellyfish than they are to their evolutionary closest relatives (Childress and Thuesen, 1992). In the many bathypelagic fishes that have larval stages that live and feed near the surface, as the maturing larvae migrate down into deep water many of their sensory systems such as eyes regress. There are also reductions in those parts of the central nervous system which become redundant as the sensory systems they previously supported become non-functional. Visual receptors are often replaced by elaborations...

Oxidative Phosphorylation

Further studies show that when PCr is absent, contractile properties are altered, such that relaxation is impaired and the kinetics of contraction are slowed (Ventura-Clapier et al., 1987c). Relaxation becomes greatly impeded owing to the decrease in Mg-ATP , thus leading to rigor tension development (tension without calcium). These findings suggest that there is restricted access of nucleotides to the intramyofibrillar space and that myofibrillar CK is necessary to ensure maximal activity of the myosin ATPase and a high local Mg-ATP Mg-ADP ratio. subcellular localization of CK in smooth muscle (Ishida et al., 1991 Clark et al., 1992,1993). Mitochondrial CK is found in the mitochondria while BB-CK binds to the contractile proteins (Clark et al., 1992, 1993), and Mi-CK can generate PCr via nascent ATP from oxidative phosphorylation (see Chapter 5). As described earlier, PCr is then able to diffuse out of the mitochondria to other cellular locations and serve as an energy source....

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...

How To Select Your Fertility Counselor

Start by talking with your own fertility specialist and medical staff at your fertility clinic. Fertility clinics may have counselors who are associated with the clinic and ready to help you, and if not, they likely have already compiled a list of good fertility counselors for your consideration. Some clinics also offer special relaxation and stress reduction programs to help you manage your overwhelming feelings. If these choices don't work, try the ASRM website They have a list of mental health professionals who specialize in fertility issues. Another alternative would be to contact a national support group such as RESOLVE ( or the American Fertility Association (

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...

Mechanisms of Faecal Incontinence in Diabetes

Patients with long-standing diabetes are apparently more likely to be affected by nocturnal faecal incontinence than are nondiabetics with faecal incontinence, which may reflect neuropathy involving the sympathetic nerve supply. The colon is normally relatively quiescent during sleep, probably as a result of tonic activity in the sympathetic efferent nerves to the colon 39 , which reduces propulsion, facilitates fermentation, and increases absorption. Damage of the sympathetic nerves supplying the colon by diabetic microvascular disease could result in mass movements at times when they would not normally occur. Therefore, events such as the delivery of meal contents into the caecum and the buildup of fermentation gases could readily generate colonic mass movements, which would rapidly distend the rectum, causing unrecognised relaxation of the internal anal sphincter and thus faecal incontinence. This is particularly important at night when there is no conscious augmentation of...

Insulin Resistance and Nitric Oxide

Insulin mediates NO production through specific pathway, which includes insulin receptor tyrosine, phosphatidyl inositol 3-kinase and its downstream effector, akt (118,119). This increase in NO release, in turn, results in vasodilation (120). This endot-helial-dependent relaxation is accompanied by an increase in glucose transport and metabolism (121,122) and may also potentially result in the removal of postprandial glucose. Therefore, endothelial dysfunction may lead to insulin resistance. This argument is further strengthened by the findings of Petrie and coworkers (123), which showed a correlation between basal endothelial function and insulin sensitivity in healthy controls. This relationship was not seen with either nitroprusside or acetylcholine, suggest

Diffuse Liver Diseases

Phology and signal characteristics which can be characterised by MRI. Although these do not represent malignant disease processes cirrhosis in particular is of importance since it is a common association with hepatocellular carcinoma. Cirrhosis does not significantly alter the T1 or T2 relaxation times of liver although it will produce the classic morphological changes of caudate and left hepatic lobe enlargement and distortion and compression of intrinsic hepatic vessels. Extrahepatic findings such as ascites, splenomegaly and enlargement of the hepatic portal vein and its tributaries may indicate portal hypertension and collateral varices are easily detected.

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.

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.

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).

Enhancement of nitric oxide synthase activity in endothelial cells

The term endothelium-derived relaxing factor was originally proposed by Robert Furchgott for a then unknown factor leading to relaxation of the smooth muscle of large arteries in response to acetylcholine. Nitric oxide NO, which is in fact a free radical, was later found to be the mediator of this response. Most of NO in the body is synthesized by the endothelial isoform of NO synthase (NOS) from its precursor L-arginine (Palmer et al., 1988a), which is inhibited by false substrates of NOS, e.g., L-NG-monomethyl arginine (L-NMMA) (Palmer et al., 1988b). NOS is a highly regulated protein and the endothelial form (eNOS) is predominantly found in endothelial cells. In them, two different isoenzymes can be expressed, depending on the activation state of these cells. In resting, non-activated endothelial cells a constitutive enzyme (ecNOS) is expressed (Moncada & Higgs, 1993) and after challenge with proinflammatory cytokines and or bacterial endotoxin a cytokine-inducible enzyme (iNOS)...

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.

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,...

Pharmaceutical Agents Used During Anaesthesia

General anaesthesia is accomplished by continuous administration of intravenous opiates (i.e. alfentanil 30-50 g kg h) and volatile anaesthetics (i.e. isoflu-rane) along with endotracheal intubation. Generally, additional muscle relaxation after intubation of the trachea is not necessary, except in the occasional case with increased lung compliance or if the surgeon requires it.

Role of Epidural Anesthesia

Regional anesthesia for the relief of labor pain has become more popular over the past 20 years. Some studies suggest that epidural analgesia, by enabling relaxation of the pelvic floor, leads to greater control of delivery of the fetal head and consequently fewer perineal lacerations 39 , but prolongation of the second stage of labor may also increase the incidence of pudendal nerve damage 40,41 . Robinson et al. 42 recently examined the relationship between epidural analgesia and perineal damage and found that the rate of significant perineal injury was higher with epidural analgesia (16.1 ) than with increased use of operative intervention.

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

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

DCEMRI in Comparison with Other Imaging Modalities

Conventional (non-contrast) MRI can provide measurements of parameters such as mobile proton density (PD), the relaxation times T2, T2 or T2* and the apparent self-diffusion coefficient of tissue water (ADC). These parameters have shown interesting responses to intervention in animal and human tumour studies. However, interpretation is difficult as they depend in a complex way on tumour oedema, necrosis, interstitial space and deoxyhaemoglobin, and for this reason they are probably insufficiently evaluated to use as a primary endpoint in a clinical trial. However, parameters such as T2* and ADC may be useful as secondary endpoints and it may be feasible to measure one or more of these parameters during the precontrast part of a DCE-MRI protocol.

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.