Relaxation Techniques

Relax Your Mind

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Active transport pumps in the sarcoplasmic reticulum (SR) begin to pump Ca2+ from the cytosol back into the cisternae. Here, the calcium binds to a protein called calsequestrin (CAL-see-QUES-trin) and is stored until the fiber is stimulated again. Since active transport requires ATP, you can see that ATP is needed for muscle relaxation as well as for muscle contraction (see insight 11.2).

Management options

The significance of this is disputed. Uterine relaxation has been achieved by using one or more of volatile agents, magnesium sulphate or glyceryl trinitrate. Fetal monitoring may be difficult but pulse oximetry, ultrasonography and cardio-tocography have been used. Bleeding may be excessive in prolonged open procedures.

Disruption of NO pathways

Impaired endothelium-dependent relaxation, or endothelial dysfunction, has been shown to be present after experimental SAH in animal and human cerebral arteries (47-50). Mechanisms that have been proposed for this well-documented finding include scavenging of NO and destruction of NO-releasing neurons by oxyhemoglobin (51). In addition, metabolites of hemoglobin, such as bilirubin-oxidized fragments, increase levels of the arginine metabolite asymmetric dimethylarginine, an endogenous inhibitor of eNOS (51). An alternative and even more intriguing hypothesis involves the reaction of NO with superoxide, which is formed during the spontaneous oxidation of oxyhemoglobin to methemoglobin (52 ). Superoxide reacts with NO at near diffusion-limited rates to form another potent free radical, peroxynitrite, which in turn oxidizes tetrahydrobiopterin, an essential coenzyme of NOS (53). Tetrahydrobi-opterin deficiency has been shown to uncouple NOS, thereby switching the vascular protective...

Management options Termination for maternal indications

An anaesthetic technique suitable for day-case anaesthesia should be employed, e.g. induction with propofol followed by nitrous oxide oxygen and maintenance with propofol or a volatile anaesthetic agent. There has been concern about concentrations of volatile anaesthetic agents greater than one minimum alveolar concentration causing uterine relaxation unresponsive to oxytocics. For a termination of pregnancy at less than 15 weeks, standard concentrations of volatile anaesthetic agents do not appear to pose a risk and may be used to maintain anaesthesia. Analgesia may be provided by intravenous fentanyl or alfentanil with rectal diclofenac 100 mg.

Oxyhemoglobin Saturation and Fluorescence

Oxygen is able to diffuse rapidly, and will react with many molecules. It can be detected by spectroscopic techniques because of its capacity for modifying the relaxation times of excited species. Spectroscopy (cryospectroscopy and near-infrared spectros-copy) is based on the spectral differences between oxygenated and deoxygenated hemo

Cortical Spreading Depression

Evidence favouring CSD as the basis of the migraine aura has gradually accumulated since Leao and Morison first suggested this 87 , and is reviewed in Migraine page 29. We can learn something of the mechanisms of CSD induction from descriptions from migraineurs (with aura) of the precipitating factors they implicate. Sometimes onset follows relaxation after a period of intense concentration or physical exercise. The onset is attributed to hunger by some migraineurs with aura, and we may speculate in the light of discussion below (page 25 Relationship of Cortical Glucose Availability with PID Frequency) that hypoglycaemia is responsible in these individuals. The various other precipitating factors do not at present appear relevant in this context.

Radicals Electrophiles and Other Reactive Species

Endothelial cells produce the weak radical nitric oxide (NO), which is a major regulator of vascular tone. it promotes relaxation of blood vessels, reduces monocyte and leukocyte adhesion to vascular endothelium, decreases platelet adhesion, and inhibits smooth muscle proliferation (H3, M4). Thus, it is potentially antiatherogenic (M3). Normally, NO levels are well regulated. But sustained production of NO by leukocytes and endothelial cells can be induced during inflammation (C1). As illustrated in Fig. 3A, under this situation NO may react with superoxide anion to produce the powerful RNS peroxynitrite. Peroxynitrite can directly promote oxidation of lipoproteins (H2) or give rise to hydroxyl (M5, R8) or longer-lived radicals, such as nitrogen dioxide (E2, R8) and carbonate radical, which can initiate oxidation at sites distant from its origin (R1). Myeloperoxidase from leukocytes can also generate RNS and other reactive species such as those illustrated in Fig. 3B (G1, H3, H11).

Problemsspecial considerations

Increased circulating progesterone associated with pregnancy relaxes smooth muscle and causes relaxation of the lower oesophageal sphincter, whereas placental gastrin increases the volume and decreases the pH of gastric contents. The enlarging uterus increases intragastric pressure and there is an increase in small and large bowel transit time. However, evidence suggests that gastric emptying per se is not affected by pregnancy though it may be decreased in labour if opioids are given.

Nmr Studies On Sugar Moieties Of Some New Triterpenoid Saponins From Aralia Spinifolia And Nothopanax Da Vidii

Abstract Nine new triterpeniod saponins with oligosaccharide linkages as sugar moieties were isolated from Aralia spinifolia and Nothopanax davidii. Their structures were elucidated on the basis of spectroscopic and chemical evidence. In this paper, we would like to report their NMR studies on the sugar moieties by modern NMR techniques ( COSY, RCT, NOESY, HMBC, DIFNOE, SINEPT and 13C-Ti relaxation times)._

Rationale For Drugs Treating Heart Failure

Atrial Natriuretic Peptides - During heart failure, atrial concentrations of atrial natriuretic peptides (ANPs) are increased (26). Atrial natriuretic peptides are synthesized and stored in specialized atrial cells, which are released into the circulation following atrial stretching (27). ANPs cause natriuresis and diuresis and promote vascular smooth muscle relaxation (28). They also reduce the production of renin, aldosterone and arginine vasopressin (29). All of these effects of the ANPs have the potential to decease blood pressure, blood volume and cardiac afterload. Atrial natriuretic peptides are inactivated by neutral endopeptidases. Thus, inhibition of these enzymes (NEP inhibitors) leads to an increase in the concentration of the ANPs, and this has been viewed as a new potential treatment of HF.

Ontic Openness And Emergence

Both uncertainty equations are related to the complex relation between the observer and the experiment. The first one deals with position and momentum, the second one deals with energy and relaxation time. Both equations assume time reversibility and are valid in a given instant the momentum is related to the derivative of space with respect to time and the relaxation time is related to the lifetime of the elementary particle in the excited state. Both equations are valid in the quantum physics paradigm and deal with conservative quantities (mass, energy), but not with living systems or evolutionary quantities.

Physical and Emotional Health How They Interact

There has been a recent surge of interest in the mind body connection by physicians to see if positive health effects can be obtained from relaxation techniques such as meditation. The increasing complexity and pace of life and the awareness that long-term stress has a negative physiological effect on the body have triggered the exploration of relaxation techniques. By combining knowledge of meditative techniques from Eastern cultures with Western scientific techniques, doctors have developed a form of meditation that may have positive effects on blood pressure and heart disease. Meditation appears to lower metabolism decreasing breathing rate, heart rate, and blood pressure. An understanding of the connection between the mind and the body becomes clearer as new techniques are found to examine and to measure the nervous system's subtle control over changes in the circulatory system. The positive response of the circulatory system to a variety of relaxation techniques, such as...

Treatment Of Upper Gastrointestinal Symptoms

Cisapride has been reported to accelerate gastric emptying in both normal patients and those with gastric motor abnormalities (3). Its role in stimulating gastric emptying and improving symptoms in patients with gastroparesis has been studied extensively. The motility effect is most likely due to its 5-HT4 agonist effects facilitating acetylcholine release. Along with its ability to increase antral contractility, cisapride has many other physiological effects in the stomach. It has been shown to relieve gastric outlet obstruction in patients with diabetic autonomic dysfunction, possibly through its ability to affect inhibitory nitrergic transmission (4). It can also affect fundic relaxation and accomodation in response to meals, and may counteract enteric negative feedback in response to intraduodenal lipids (4).

Lymphatic Circulation

A compression relaxation cycle causes the lymphatic vessels to suck up lymph. Lymph valves in lymphatic vessels make this possible. A volume of fluid equal to the total plasma volume in a single human is filtered from the blood to the tissues each day. It is critical that this fluid is returned to the venous system by lymph flow each day. The lymphatic vasculature collects approximately 3 L day of excess interstitial fluid and returns it to the blood. The lymph system is responsible for returning plasma proteins to the blood.

Discuss the hemodynamic profile of the phosphodiesterase III inhibitors amrinone and milrinone

Amrinone and milrinone are approximately equipotent to dopamine and dobutamine in increasing cardiac output through increased inotropy and improved lusitropy (myocardial relaxation). In addition to direct myocardial effects, vasodilation typically occurs, making it difficult to separate the relative contributions of these effects on enhanced cardiac output. Right ventricular function can be favorably impacted as these agents decrease pulmonary vascular resistance (comparable to 20 ppm of nitric oxide in cardiac surgery patients), thus improving forward flow. Coronary vessels and arterial bypass grafts (internal mammary and gastroepiploic arteries and radial artery grafts) become dilated furthermore, in the presence of these drugs they are less subject to the vasoconstrictive effects of concomitantly administered a-adrenergic agonists.

Phosphodiesterase 4 Inhibitors

Introduction - cAMP and cGMP are ubiquitous second messengers which mediate biological responses to a variety of hormones, neurotransmitters, autocoids and drugs (1). Increased concentration of these cyclic nucleotides results in activation of protein kinase A (PKA) and protein kinase G (PKG). These kinases phosphorylate a variety of substrates, including transcription factors and ion channels, which regulate a myriad of physiological functions, including the activation state of a variety of cell types. Phosphodiesterase (PDE) enzymes are responsible for the inactivation of cAMP and cGMP by hydrolysis to AMP and GMP, respectively. Inhibition of PDE enzymes results in an accumulation of cAMP and or cGMP, which has many biological consequences including smooth muscle relaxation and reduction in inflammatory cell activity. The classification of PDE enzymes into seven isozyme families, on the basis of substrate affinity and specificity, regulatory characteristics and inhibitor profile,...

Kallikreins in Normal Physiology

Little is known about the physiological functions of kallikreins in normal tissues. However, accumulating evidence indicates that kallikreins might have diverse functions, depending on the tissue and circumstances of expression. hK1 exerts its biological activity mainly through the release of lysyl-bradykinin (kallidin). It cleaves low-molecular weight kininogen to produce vasoactive kinin peptides. Intact kinin binds to bradykinin B2 receptor in target tissues and exerts a broad spectrum of biological effects including blood pressure reduction via vasodilatation, smooth muscle relaxation or contraction, pain induction, and mediation of the inflammatory response 177 . Low renal synthesis and urinary excretion of tissue kallikrein have been repeatedly linked to hypertension in animals and humans 178 . It has also been reported that tissue kallikrein cleaves kininogen substrate to produce vasoactive kinin peptides that have been implicated in the proliferation of vascular smooth muscle...

SUMO and Cancer Caretakers and Gatekeepers

Topo-I and -II play essential roles during DNA replication, transcription, recombination and mitosis by relaxation of negatively and positively super-coiled DNA 121 . Topo-II exists in two isoforms a and p, the a isoform being the predominant in proliferating cells 110 . Whereas Topo-I transiently cleaves only a single strand of duplex DNA, Topo-II cleaves both DNA strands simultaneously. Topoisomerases are found in multi-protein complexes that include RP-A, BLM and the RAD51 DMC-I complex among others 79,73 . Several studies have demonstrated an increased topoisomerase inhibitor sensitivity of cells defective in DNA damage repair proteins, replication checkpoints, or both. For this reason topoisomerases now constitute major cellular targets for numerous anti-cancer drugs, e.g. Topo-I for camptothecin (CPT) and its analogues or Topo-II for VP-16 63 . Recent results have implicated sumoylation in the regulation of Topo-I 46,49,78 and -II activity 4,5 . In the case of Topo-I, asimple...

Neurohumoral Control of the Circulation

Tion results in is rather potent vasodilation of all sized coronary microvessels, predominantly as a result of a release of endothelium-derived NO. -Adrenergic stimulation produces a potent relaxation of all coronary arteries, but especially small resistance vessels (62). In vitro, the p2-adrenergic receptor-subtype predominates in vessels less than 100 microns in diameter (62). In vivo, however, mixed pr or p2-adrenergic receptor population controls vascular resistance. Larger coronary vessels are regulated by a mixed pr and p2-adrenoceptor subtype population, or a predominant P1-adrenergic mechanism.

Endothelial Regulation of the Coronary Microcirculation

In smaller vessels of both the coronary and peripheral circulations, factors other than NO can modulate endothelium-dependent vascular relaxation. One such factor is the endothelium-derived hyperpolarizing factor (EDHF). Even before the endothelium was found to be critical in modulating vascular tone, it was known that certain relaxing substances would hyperpolarize vascular smooth muscle. It was subsequently shown that this phenomenon was endothelium-dependent (83). This hyperpolarizing effect occurs via opening of vascular smooth muscle potassium channels, and the channel type involved has been the subject of substantial interest. These have largely been characterized using pharmacological means. In cerebral vessels, a voltage-regulated potassium channel has been implicated in endothelium-dependent hyperpolarization (84), whereas others have suggested that the EDHF acts on large conductance potassium channels. When the vascular smooth muscle is hyperpolar-ized, voltage-sensitive...

Considerations regarding the coronary venules in modulation of overall coronary vascular responsiveness

Not only is vasomotor regulation differentially controlled between the venous and arterial microcirculations, but certain reactions to pathologic stimuli occur preferentially on one side of the capillary bed. For example, postcapillary venules are the initiating site of neutrophil adherence and transmigration (94), whereas arterioles seldom manifest these initial changes in the inflammatory response. In addition, complement fragment C5a causes neutophil adherence in venules but not in arteri-oles, suggesting that different mechanisms mediate neutrophil-endot-helial adherence in the two vessel types. The mechanism of C5a-induced neutrophil adherence has recently been shown to involve the activation of Src kinase, Src -catenin association, and P-catenin phosphorylation (95). Neutrophil adherence, in turn, causes dysfunction of the endothelial cell barrier leading to hyperpermeability which is seen in ischemia and other inflammatory disease states (96). While ischemia-reperfusion has...

Properties of the Coronary Microcirculation

The initial studies demonstrating abnormal endothelium-dependent vascular relaxation in various disease models were performed in larger vessels. Subsequent experiments have shown that most, if not all, of these disease processes also affect the coronary microcirculation in a similar fashion. This is of particular interest in the case of hypercholesterolemia and atherosclerosis. One of the first examples of an alteration in coronary microvessels in atherosclerosis was made in vessels from monkeys fed a high-cholesterol diet for 18 mo (131). These animals developed advanced atherosclerotic lesions in larger vessels, and had abnormal vasodilation in response to acetylcholine, the calcium iono-phore A23187, and thrombin in those vessels. On the other hand, coronary microvessels from the same animals had dramatically impaired relaxations to the same acetylcholine, bradykinin, and the calcium iono-phore A23187, and in some cases, these agents produced paradoxical constrictions (Fig. 5)....

Acute microvascular effects of growth factors

Microvascular reactivity studies after 4 wk of vascular endothelial growth factor (VEGF) treatment in a porcine model of myocardial ischemia with (B,C) or without (A) hypercholesterolemia-induced endothelial dysfunction. Graphs show percent relaxation to increasing concentrations of vasodilating agents following preconstriction with U46619. SNP, sodium nitroprusside ADP, adenosine diphosphate. From ref. 146. Fig. 7. Microvascular reactivity studies after 4 wk of vascular endothelial growth factor (VEGF) treatment in a porcine model of myocardial ischemia with (B,C) or without (A) hypercholesterolemia-induced endothelial dysfunction. Graphs show percent relaxation to increasing concentrations of vasodilating agents following preconstriction with U46619. SNP, sodium nitroprusside ADP, adenosine diphosphate. From ref. 146. eral vasodilation. The angiogenic potential of FGF-2 is largely independent of the release of NO, whereas VEGF-induced vessel formation is potently coupled to...

Are monitors available to assess the depth of anesthesia

Brain electrical activity monitoring can be used to assess depth of anesthesia and includes two categories processed electroencephalogram (pEEG) and evoked responses (e.g., auditory). No single monitor can provide a fail-safe answer to the question of depth of anesthesia. pEEG waveform technology of differing formats can be used and has entered the market to a greater extent then evoked responses. The most familiar technology is known as the bispectral index (BIS). The purpose of any of these forms of EEG analysis is to estimate the degree of hypnosis that the patient is experiencing. Raw data, collected by electrodes placed on the forehead and temporal area, are processed by the computer module to create a dimensionless numeric representation of the degree of sedation. Lower numbers correspond to a greater depth, whereas higher numbers are found in awake or lightly sedated patients. The incidence of awareness in high-risk cases was reduced by approximately 82 (0.91 to 0.17 ) when...

Oxidative Stress And Antioxidant Treatment Effects On Neurovascular Function In Experimental Diabetes

Defective endothelium-dependent relaxation has been found in diabetic animals and in type 1 and type 2 patients (39-47) and is an important target for antioxidant treatment. An example is shown in Figure 2, where the lipophilic ROS scavenger, a-tocopherol, protected rat aorta against a diabetic deficit in NO-mediated endothelium-dependent relaxation to acetylcholine (39). A similar protective effect of ROS scavengers has been noted for vasa nervorum blood flow and NCV. The magnitude of effects possible by this approach is illustrated in Figure 3, where a high dose of the probucol analogue, BM 150639, completely corrected motor NCV and blood flow deficits in diabetic rats. These effects were attenuated by cotreatment with a NO synthase inhibitor, emphasizing the importance of the vasa nervorum NO system (19). The effectiveness of a variety of scavengers has been assessed over the last 5 years, including lipophilic drugs like butylated hydroxytoluene, a-tocopherol (vitamin E),...

Interactions Between Antioxidants And Essential Fatty Acids

There are multiple defects of vasa nervorum endothelium and possibly smooth muscle in diabetes that cause reduced nerve blood flow and function. The NO deficit is compounded by diminished PGI2 synthesis and increases in endo-thelin-1 and angiotensin II. Recently, it was shown that relaxation mediated by endothelium-derived hyperpolarizing factor (EDHF) is also affected by diabetes. In the rat mesenteric vascular bed, EDHF was 76 reduced after 8 weeks of diabetes. In common with the NO defect, the EDHF deficit was attenuated by antioxidant treatment with a-lipoic acid (89). Vasodilator prostanoid synthesis is also deleteriously affected by oxidative stress high levels of lipid peroxides inhibit cyclooxygenase (90), and a-tocopherol treatment corrected the lowering of the PGI2 thromboxane A2 ratio found in diabetic rats (91).

In vitro and in vivo study of the modulation of basal forebrain neurons

Microinjection of transmitters or their agonists into the basal forebrain cholinergic cell area was performed in the rat using a remotely driven system that allowed insertion of the drug-filled cannulae (one each side) into permanently fixed outer cannulae ('Insert Cannulae to here') prior to the experiment and then lowering of the cannulae into the basal forebrain cholinergic cell area ('Lower Cannulae to here') immediately preceding the injection (see Fig. 7). This procedure allowed full relaxation of the animal following placement of the cannulae while preventing desensitization of receptors by drug leakage into the site prior to the injection. In addition to other substances described (see text), NA was injected into the basal forebrain to mimic the effect of that transmitter that is contained in fibers innervating the cholinergic neurons from the locus coeruleus (LC, see Fig. 7). The figure was adapted from Cape and Jones (1998). Fig. 6. Microinjection of transmitters or...

How does a normal pressurevolume loop appear

The AB segment is ventricular filling, BC is isovolumic contraction, CD is ejection, and DA is isovolumic relaxation. D point represents the aortic valve closing, A the mitral valve (MV) opening, B the MV closing, and C the aortic valve opening. Stroke volume through the aortic valve is the distance between C and D points. End-systolic volume can be measured at the D point, and end-diastolic volume can be measured at the B point. The end-systolic pressure-volume relationship slope is a measure of contractility. A horizontal-clockwise shift of the slope represents a decrease in contractility (Figure 35-1).

Discuss the pathophysiology of aortic stenosis

Aortic stenosis (AS) is classified as valvular, subvalvular, or supravalvular obstruction of the LV outflow tract. Concentric hypertrophy (thickened ventricular wall with normal chamber size) develops in response to the increased intraventricular systolic pressure and wall tension necessary to maintain forward flow. Ventricular relaxation decreases, causing diastolic dysfunction. Decreasing LV compliance accompanies elevated LV end-diastolic pressure. Contractility and ejection fraction are usually maintained until late in the disease process. Atrial contraction may account for up to 40 of ventricular filling (normally 20 ). In developing countries rheumatic valve disease is still the most common cause of AS. In North America and Europe AS is primarily caused by calcification of a native trileaflet or a congenital bicuspid valve. Patients often present with angina, syncope, or congestive heart failure. Angina with Figure 35-1. Pressure-volume loop In normal heart performance. AB,...

Discuss the pathophysiology of aortic insufficiency

Pressure-volume loops In aortic regurgitation compared to the normal loop. In acute aortic Insufficiency (AI) the end-diastolic and end-systolic volume is increasing. The stroke volume can be increased, normal or decreased, depending on the severity of AI. The left ventricular (LV) volume is increasing during the isovolumic relaxation period (DA segment). The end diastolic pressure (AB segment, B point) is high. Contractility is decreased because the myocardium is overstretched. In chronic AI the end-diastolic, end-systolic, and stroke volumes are enlarged. Cardiac output is normal, and the contractility is decreased. The LV volume is increasing during the isovolumic relaxation period also (DA segment), but the end diastolic pressure (AB segment, B point) is normal thus the heart has diastolic reserve to accommodate to limited volume or pressure load. LV, Left ventricular. Figure 35-3. Pressure-volume loops In aortic regurgitation compared to the normal loop. In acute...

Role of PARP1 and PARP2 in DNA repair

Several PARPs share a catalytic domain capable of catalyzing the transfer of ADP-ribose units using nicotinamide adenine dinucleotide (NAD+) to form long and branched poly(ADP)ribose (PAR) chains 2 . PARP-1 and the closely related PARP-2 are nuclear proteins and possess N-terminal DNA-binding domains 4 . These domains serve to localize and bind PARP to sites of DNA single- and double-strand breaks (SSB and DSB). A central automodification domain permits these enzymes to poly(ADP-ribosyl)ate themselves, while the C-terminus contains the catalytic active site, which is responsible for polymerizing the ADP-ribose. Upon DNA binding, the catalytic activity of these enzymes is stimulated more than 500-fold, resulting in the addition of PAR polymer chains to itself and to associated DNA repair proteins 5 . This leads to subsequent chromatin relaxation and fast recruitment of DNA repair factors, resulting in DNA break repair through a process known as base excision repair.

Cation Transport Systems

In addition to influencing signaling pathways associated with cell growth and inflammation, ROS modulate intracellular Ca2+ concentration ( Ca2+ .), a major determinant of vascular contraction. Superoxide and H2O2 increase Ca2+ i in VSMCs and endothelial cells.109 These effects have been attributed to redox-dependent inositol-trisphosphate-induced Ca2+ mobilization, increased Ca2+ influx, and decreased activation of Ca2+-ATPase.109110 Plasma membrane K+ channels in VSMCs that control a hyperpolarization-elicited relaxation are opened by mechanisms associated with thiol oxidation by ROS.99 100 110 These redox-regulated Ca2+ processes may be more important in stress responses than in receptor-mediated signaling by growth factors or cytokines and may play a role in altered vascular contractility in hypertension. In fact contractile responses to H2O2 are exaggerated in arteries from SHR compared with normotensive counterparts,111 suggesting that in addition to impaired...

Vascular Endothelial Growth Factors

The efficacy of periadventitial delivery of VEGF was tested in a porcine ameroid model (64,67). Treatment with VEGF was associated with better preservation of coronary flow in the ameroid zone during pacing. Magnetic resonance imaging (MRI) demonstrated not only significantly better perfusion of the compromised territory, but also a reduction in size of this territory in VEGF-treated animals (65). The number of collateral vessels were increased nearly fourfold in the VEGF-treated animals (66). Analysis of microvascular function demonstrated significantly better restoration of endothelium-mediated, receptor-dependent relaxation in VEGF-treated animals (66,68).

Oxidative Stress In Patients With Diabetes Mellitus

Lately, considerable effort has been devoted to gain insights into the role of oxidative stress in the development and progression of late micro-and macrovascular complications in diabetes (17,23,27,28,31-34). Although hyperglycemia is an acknowledged pathogenic factor in diabetic complications, it is not known through which mechanism an excess of glucose results in tissue damage. Accumulating data support the hypothesis that oxidative stress might play an important role in the pathogenesis of late diabetic complications. Several pathways are leading to oxidative stress associated with acute or chronic hyperglycemia, such as the polyol pathway, prostanoid synthesis, glucose autoxidation, and protein glycation by increasing the production of free radicals (35-39). A close relationship of oxidative stress with glycemic control has been described, showing a significant positive correlation between malondialdehyde (MDA) and both fasting blood sugar and glycosilated hemoglobin (40)....

Hypothesis Of Advanced Glycation End Products And Its Receptor

Increased levels of AGE-modified low-density lipoprotein (LDL) with a markedly impaired clearance have been found in the plasma of diabetic patients, suggesting a pathway for pathogenic modification of LDL (62). The mediating role of AGEs in development of late diabetic complications (Table 1) (49,63-70) has been studied in animal models by short- and long-term administration of AGEs. Short-term administration of AGEs led to increased vascular permeability and leakage, impaired endothelial relaxation, subendo-thelial mononuclear recruitment, activation of NF-kB, and subsequent VCAM-1 gene expression (71-73). Long-term administration of AGEs resulted in arteriolar basement thickening and complex vascular dysfunction (74) and in glomerular basement thickening, mesangial expansion, glomerulosclerosis, and proteinuria (68).

Discuss the properties of nitric oxide NO

NO is a small molecule produced by vascular endothelium. Formed from the action of NO synthetase on arginine, NO crosses into vascular smooth muscle and stimulates guanylate cyclase, resulting in formation of 3 ,5 -cGMP. Subsequently cGMP produces smooth muscle relaxation and vasodilation. NO is administered by inhalation and crosses the alveolar membrane to the vascular endothelium, producing smooth muscle relaxation. But when it crosses into the circulation, it is rapidly bound to hemoglobin (with an affinity 1500 times greater than carbon monoxide) and deactivated thus it has no systemic vasodilator effect. In addition, since it is only delivered to perfused alveoli, it may increase blood flow to ventilated alveoli. Dosage ranges can be quite wide, but 20 to 40 parts per million is not an atypical dose.

Tissue Characterization The Need for Multiple Contrast Weighting

Recent studies have shown that a combination of different contrast weightings is necessary for noninvasive characterization of plaque morphology 82, 102 . T1-, T2-, PD-, gradient echo, and other contrast schemes have all been evaluated for plaque tissue characterization. Different contrast weightings reveal different features of the plaque. For example, the MR signal intensity of hemorrhage is dependent on the structure of hemoglobin and its oxidation state 83 . Recent hemorrhage with short T1 and long T2 shows a hyperintensive signal intensity on all contrast weighted images, and is readily identified. Calcified tissues, which have very little water and appear dark on all contrast weightings, are easily detected. Calcification on the plaque surface or cal-cific nodules extending into the lumen is difficult to detect due to low signal intensity, which is easily masked on black-blood sequence (SE or FSE T1, PD-and T2-weighted) 73 but they are easily detected on bright-blood sequence...

Anatomy and Physiology of the Lower Urinary Tract

The storage and periodic elimination of urine are dependent on the reciprocal activity of two functional units in the lower urinary tract a reservoir, the bladder and an outlet represented by the bladder neck and the smooth and striated sphincter muscles of the urethra. During urine storage, the bladder outlet is closed and the bladder smooth muscle is quiescent, allowing intravesical pressure to remain low over a wide range of bladder volumes. During voluntary voiding, the initial event is a relaxation of the pelvic floor and striated urethral muscles, followed by a detrusor muscle contraction and opening of the bladder neck. This activity is mediated by three sets of peripheral nerves parasympathetic (pelvic), sympathetic (hypogastric) and somatic (pudendal) nerves (Fig. 1). These nerves also contain afferent axons terminating in the lower urinary tract which are involved in initiating micturition.

The Veins Always Come Last Right Before The Heart

A patient glance back at Figure 11.4 shows that the veins have the same three tunicas as do the arteries. As you can see, though, veins have wider lumens compared to arteries, but thinner walls, overall. In particular, veins have a thinner tunica media than arteries. This means that they are much less able to vasoconstrict or vasodilate by contraction-relaxation of smooth muscle in their walls. (This also means that veins in a cadaver are much less stiff to the touch than are arteries, and that their lumens are readily collapsible.)

Molecular Genetics of Muscle Disorders

SMILING, WRITING, RUNNING, drawing, walking, gripping, chewing, kissing, swallowing, breathing, and virtually any other activity that involves movement depend on one or more of the 650 different muscles in the human body. In general terms, muscles are responsible for locomotion, upright posture, balancing on two legs, support of internal organs, controlling valves and body openings, production of heat, and movement of materials, including blood, along internal tubes. There are three types of muscle tissue skeletal, cardiac, and smooth. Skeletal muscles, which make up about 40 of our body mass, are attached to the skeleton. They are responsible mainly for locomotion, and both contraction and relaxation are controlled voluntarily (i.e., consciously). Cardiac muscle, found only in the heart, pumps blood and functions involuntarily. Smooth muscle, which lines the walls of internal systems, is involuntary and propels material through internal passageways. The elasticity of muscle tissue...

Vascular Blood Flow

In the macrovessels, increases in contractility found in diabetes are due to a delay in the relaxation response after contraction induced by cholinergic agents (72-75). These abnormal responses can also be prevented by PKC inhibitors (76), suggesting that PKC activation plays a general role in causing abnormal peripheral hemodynamics in diabetes.

Personality and health

Although, as was seen in previous chapters, personality is reasonably settled, it is not set in stone. To some extent personality is modifiable and so it is with Type A behaviours. Generally, we can alter our perceptions and emotional reactions by working on our cognitions. So, someone who recognises Type A tendencies in himself or herself might set various life-style changes in place, ranging from taking more exercise and learning relaxation techniques to broadly changing typical reactions to stressful situations. An example might be learning to be relaxed when standing in a supermarket checkout queue behind someone who cannot find the correct money or who seems to have forgotten the pin number on their card. In this situation, the Type A person would be tense with frustration and impatience and even potentially hostile. The control of any such way of reacting can only be good for the immune system.

Increasing The Throughput Of Electrophysiological Assays

A series of naphthopyrans was found to relax precontracted aortic tissue, but the relaxation was not sensitive to a variety of K* channel blockers, including glibenclamide (KAtp), apamin (SK) or charybdotoxin (maxi-K). The relaxation property of naphthopyran 8 was attenuated by 4-aminopyridine, indicating that it was acting through opening of voltage-sensitive K+ channels (32). Cyclization of the oxygen and nitrogen of the chromokalim chemotype resulted in a series of benzopyranooxazines which may be of utility for the treatment of urinary incontinence. Sulfonamide 9 relaxed precontracted bladder tissue selectively as compared to porteal vein (33). The relaxation could be inhibited by the addition of glibenclamide, indicating that the relaxation was mediated by opening of Katp channels. relaxed bladder smooth muscle, but that the relaxation was not sensitive to glyburide (a Katp blocker). The activity could be reversed by the addition of iberiotoxin, indicating that the bladder...

A specific health problem smoking

1 to gain positive feelings such as relaxation The major techniques that can be used to help the cessation of smoking are hypnosis, relaxation, self-talk, nicotine patches and rapid smoking. The latter is an interesting technique based on making smoking become aversive by having the person smoke a large number of cigarettes in a very short time, in order to make them feel sick. This is straightforward classical conditioning, putting together the behaviour of smoking with an unconditioned, aversive response -being sick. Self-talk is like the converse of rapid smoking, helping the person stick to the decision to stop smoking by reinforcing for themselves the positive benefits of so doing.

Neurophysiological Correlate Of Parkinsonism

Rigidity in patients with parkinsonism manifests as a difficulty of complete muscle relaxation, with often permanent tonic background EMG activity (11). Several neurophysiological tests have been used to assess rigidity, although direct clinico-neurophysiological correlations have proven more difficult than with bradykinesia. Rigidity has been considered to be the cause of some neurophysi- Like with bradykinesia, most tests directed to the evaluation of rigidity have been proven in patients with IPD, and more scarcely in patients with APDs. However, it is not unreasonable to admit that when and where rigidity is present, patients with APDs would present similar abnormalities as those described for IPD. Direct surface electrophysiological recording of a muscle in rigid patients in resting conditions may be enough to notice that there is increased muscle activity with respect to normal subjects. Electrophysiological evidence for that can be found when testing the relaxation time after a...

How is preeclampsia managed

Antihypertensive agents should be titrated. Although hydralazine is the most commonly administered agent, it was recently compared to intravenous labetalol or oral nifedipine in a metaanalysis of trials. In the systematic review labetalol or nifedipine therapies were as effective as hydralazine in controlling blood pressure with fewer side effects. Labetalol is representative of a class of drugs that act as competitive antagonists at both a- and p-adrenergic receptors. Although systemic vascular resistance is reduced, cardiac output is maintained. Labetalol has also been shown to preserve uteroplacental perfusion. Hydralazine, an arteriolar vasodilator, remains a popular drug for patients with preeclampsia because it increases renal and uterine artery blood flow. The onset and duration are often unpredictable. Side effects include reflex tachycardia and ventricular dysrhythmias. Nifedipine is a calcium channel blocker that prevents the release of calcium, resulting in smooth muscle...

Post Operative Pain Management

- Relaxation training and withdrawal from interpersonal contact. Fear and anxiety are the major emotional concomitants of acute pain and are especially pronounced when associated with fear of death. Severe acute pain that remains unrelieved for days may lead to depression and helplessness as a result of patients experiencing a loss of control over their environment. It is now generally agreed that unrelieved severe acute pain exacerbates premorbid tendencies for anxiety, hostility, depression, or preoccupation with health. In a few cases, the inability to cope with pain may create an acute psychotic reaction. However, acute pain is one of the important factors contributing to the development of delirium in intensive care units. For all these reasons psychological approaches are an integral part of the medical care of the patient with pain (Box 5b). All patients can benefit from psychological assessment and support and some are good candidates for specific psychological therapy....

Management And Prognosis

Patients should be managed in an intensive care setting of a tertiary-care center whenever possible. Facilities and equipment that should be available include a quiet darkened room, suction equipment and oxygen, cardiac and respiratory monitors, a ventilator, and tracheostomy equipment. The patients must be managed by experienced caregivers skilled in ventilatory support and maintenance of cardiovascular stability. Minimizing external stimuli and maintaining intravenous hydration may be sufficient in the initial days of the illness. Sedation and muscle relaxation should be instituted, usually with diazepam (0.1-0.2 mg kg intravenously every four to six hours). Additional sedation with phenothiazines may be needed. If spasms are not adequately controlled, therapeutic paralysis may be necessary (4).

Emergy exergy and their joint use

According to Svirezhev (2000), this fact is normal, since this concept resembles that of a relaxation time, i.e., the time necessary to recover from disturbances, so that the exergy to empower ratio should be related with concepts like resilience and resistance of an ecosystem.

The Colon Our Large Intestine Brings Up the Rear

Fortunately for us, there is also a ring of voluntary striated (cross-striped) muscle, positioned in the lower portion of the rectum. This muscular ring is called the external anal sphincter. Its contraction and relaxation is very much under our conscious control (at least, ever since we were first ''potty-trained'') Therefore, we can usually choose the time and place where we will consciously relax this lower sphincter and carry out defecation (egestion).

Glossary of Pharmacological Terms

Fade, the time-dependent decrease in response upon prolonged exposure of a biological system to an agonist. Originally, this was defined as the characteristic peak contraction followed by relaxation produced by guinea pig vas deferentia, but the term has also been generalized to

Magnetic Resonance Imaging

Magnetic resonance (MR) imaging (MRI) is a noninvasive technique that uses the interaction between the magnetic properties of nuclei and radio waves to portray the structure of biological tissues (Damadian, 1971 Lauterbur, 1973). When placed in an external magnetic field and exposed to radio waves of proper frequency, the hydrogen nuclei within body tissues resonate i.e., can absorb energy from a tuned radio wave and then, after a delay (relaxation time) emit the energy back at the same frequency . The energy radiated back by the resonating nuclei, typically hydrogen nuclei (protons) for imaging, is the signal that is used for generating the MR image. The intrinsic differences in hydrogen density between the various components of body tissues (e.g., fat, blood, glandular tissue, muscle, etc.), as well as differences in magnetic relaxation times from voxel to voxel, determine the contrast of the MR image. Since these differences in MR characteristics are greater than differences in...

On Related Behaviours

We therefore hypothesized that the release of OXT within the brain has far-reaching behavioural consequences and beneficial effects for the male rat, i.e. reducing the level of anxiety and increasing risk-taking behaviour for several hours. Indeed, when exposing mated and non-mated males to the elevated plus-maze and light-dark box, a clear reduction in anxiety-related behaviour was found up to 4 h after mating (Waldherr and Neumann, 2007). This anxiolytic effect of sexual activity could be blocked by an OXTR antagonist administered i.c.v. immediately after mating. These results provide evidence that the activated brain OXT system, as a consequence of sexual activity, mediates the mating-induced anxiolytic effect. The mating-induced anxiolytic effect might enable an advantageous behavioural strategy for a polygamous male rodent, promoting the unsafe search for novel mating partners with the ultimate goal to optimize the distribution of its genes. In humans, there is anecdotal and...

Magnetic Resonance Imaging and Spectroscopy

The proton is the element responsible for the signal generation in proton MRI, and can be viewed as a minimagnet due to the spinning single electron. MRI utilizes two energies, a strong magnetic field and pulses of radio frequency (RF) electromagnetic energy. RF energy is not ionizing, and a trillion times less in magnitude than X-rays. The sensitivity of the technology is related to the large number of protons that are present in water and fat, the primary constituents of a human or animal. When protons are placed in a magnetic field, they become aligned with, or opposed to, the external field. Excitation with a precise resonance frequency (MHz) results in excited-state protons, all of which are in phase, but tilted away from the direction of the external magnetic field. The in-phase aspect is unique to the excited state, since ground-state protons are not in phase. Therefore, to summarize, absorption of a resonance RF energy by the proton results in an excited state, where all the...

How to Perform Right Ventricular Angiography in ARVCD

Angiography Calibration

The following recommendations have been proposed by Wichter et al. 12 for the core laboratory of RV angiography within the NIH-funded North American Multidisciplinary Study of ARVD 13 and the EU-funded European Registry of ARVC D 14 . The protocol was designed to perform RV an-giograms of best quality to assess structural and functional RV abnormalities in ARVC D and to allow quantitative measurements of RV volumes, ejection fraction, and regional contraction and relaxation.

Threshold Latent Period and Twitch

Frog Gastrocnemius Latent Period

A sufficiently weak electrical stimulus to a muscle causes no contraction. By gradually increasing the voltage and stimulating the muscle again, we can determine the threshold, or minimum voltage necessary to generate an action potential in the muscle fiber and produce a contraction. The action potential triggers the release of a pulse of Ca2+ into the cytoplasm and activates the sliding filament mechanism. At threshold or higher, a stimulus thus causes a quick cycle of contraction and relaxation called a twitch (fig. 11.13). Relaxation phase Relaxation phase What role does ATP play during the relaxation phase The contraction phase is short-lived, because the sacroplasmic reticulum quickly pumps Ca2+ back into itself before the muscle develops maximal force. As the Ca2+ level in the cytoplasm falls, myosin releases the thin filaments and muscle tension declines. This is seen in the myogram as the relaxation phase. The entire twitch lasts from about 7 to 100 msec.

Treatment Of Constipation

Prucalopride (10) (R093877), the first of a new chemical class of benzofurans, has specific agonist activity at 5-HT4 receptors. In vitro studies suggest it is less potent than cisapride, and approximately equivalent to tegaserod, in producing relaxation in isolated canine smooth muscle strips (38). In a rat model of postoperative ileus, prucalopride (1 and 5 mg kg) had a modest effect in promoting intestinal transit. The combination of prucalopride (1 mg kg) and the 5-HT3 antagonist, granisetron (9) (50 pg kg), significantly improved intestinal transit after laparotomy with or without mechanical stimulation of the intestine (39). In 50 healthy human volunteers, 0.5-4 mg prucalopride daily for 7 days accelerated colonic transit and increased proximal colonic emptying, but had to effect on gastric emptying or small intestinal transit (12).

Utilization of Composite Rhytidectomy to Correct the Unfavorable Outcomes Following Facelift Surgery

Esthetic Surgery Finger

If one judges the vectors of aging of patients in the standing position, they are the same for all humans and are predictable for every person after a certain age (Fig. 42.11a). Without question the conventional facelift can create an excellent jawline but in most cases the tension on the SMAS flap is a shorter, more vertical vector and tension on the upper portion of the conventional flap including the malar fat procedure is less vertical and more superior lateral in spite of claims of vertical malar fat repositioning. While malar fat techniques and deep plane facelifts have been an improvement over the subcutaneous procedures, the basic problem is still giving an unpredictable result to any patient undergoing conventional techniques. By omitting the surgery of the lower eyelid, the surgeon clearly can promise the patient an early return to social activity often within days. One must remember that a facelift cannot be judged over the first few months since the final results may...

Udenafil Erectile Dysfunction [111115

Animal Human Coupling

Udenafil is the fourth in a class of drugs targeting the inhibition of the enzyme phosphodiesterase 5 (PDE5) for the treatment of erectile dysfunction. Inhibition of PDE5 results in the increase in endogenous cyclic guanosine monophosphate (cGMP) concentrations in the penile corpus cavernosum. cGMP induces smooth muscle cell relaxation and subsequent increased blood flow leading to a sustainable erection. Udenafil is a potent antagonist of human PDE5 with an IC50 of 8.25 nM and a comparable selectivity profile as sildenafil for the other PDEs. Unlike ta-dalafil, it does not inhibit PDE11, which has been implicated in myalgia and testicular toxicity. The key steps in the synthesis of udenafil involve the coupling of

NADPH Oxidase and Plaque Formation in Coronary Artery Disease

The original hypothesis that atherosclerosis is an inflammatory disease centered on oxidized LDL as the main effector. It is clear, however, that oxidative stress plays a much broader role in the pathogenesis of this disease. Animal models of atherosclerosis have documented that all of the constituents of the plaque produce and use ROS 18, 20, 38, 39, 119 . Analysis of coronary arteries indicated that O2* is distributed homogeneously throughout normal vessels, whereas intense ROS production is found in the plaque shoulder of atherosclerotic arteries, suggesting that increased oxidative stress contributes to coronary atherosclerosis 71 . In cholesterol-fed rabbits, O2* is increased in the aorta 40 , and treatment with polyethyleneglycol SOD reverses the impaired endothelial-dependent relaxation 120 . In vessels from patients with CAD, expression of NOX2 and NOX4 is enhanced, which is consistent with a role of these oxidases in CAD 121 . During restenosis of carotid artery after balloon...

Theophylline Toxicity

Theophylline Toxicity Signs

Like its bronchodilator activity, adverse effects are related to the logarithm of the serum concentration. Hendeles and associates demonstrated a relationship between serum concentration and symptoms of theophylline toxicity. Few toxic symptoms were noted when the steady-state serum concentration was less than 14.6 g mL. Adverse effects appeared as the serum concentration rose beyond 20 g mL. These included gastrointestinal, CNS, and cardiovascular effects (Fig. 1). Of all adverse effects, those involving the gastrointestinal tract are most common. Vomiting, particularly if persistent, is very suggestive of theophylline toxicity. Hematemesis has been reported primarily in children its exact pathogenesis is not clear. Gastrointestinal symptoms occur most often as a result of a central effect of an excessive serum theophylline concentration on the medulla rather than because of a local irritative effect on the stomach. Relaxation of cardioesophageal smooth muscle may lead to reflux and...

Alcohol and substance abuse

Acute alcohol use may cause esophagitis, gastritis, and pancreatitis. Chronic alcohol use leads to delayed gastric emptying and relaxation of the lower esophageal sphincter, increasing the risk of aspiration. The liver undergoes transient and reversible fatty infiltration during acute alcohol use. Although such changes resolve with abstinence and the cycle can repeat itself many times, prolonged alcohol exposure leads to chronic infiltration of fat, which overtime progresses to necrosis and fibrosis of liver tissue. The initial presentation of fatty liver is hepatomegaly. When necrosis, fibrosis, and cirrhosis become apparent, the liver regresses in size. Chronic severe consumption of alcohol leads to irreversible cirrhosis and alcohol-induced hepatitis. Hepatic synthetic function is also impaired. Production of albumin and coagulation factors II, V, VII, X, and XIII is decreased. Reduction of albumin results in lower intravascular oncotic pressure and may lead to tissue edema. A...

Interaction Between Venous Sinus Hypertension and CSF Pressure

On a 0.15 Tesla magnet reported no signal change in 7 children with PTS. The same finding was reported by Silbergleit et al. 154 in 6 patients with PTS using a 0.35 Tesla magnet. Benefiting from improved technology, Moser et al. 120 used a heavily-weighted T2 MR technique (1.5 Tesla) to investigate the brain water content in 10 patients with PTS. They found an increase in the signal white matter free water content as reflected in prolongation of the T2 relaxation time. The authors concluded that this represents a diffuse low level of oedema. In addition, a triple-echo sodium MR technique was used to study 5 patients. Three demonstrated no change in their sodium signal. However, two patients who were clinically the most severely affected demonstrated increases in their sodium signal. As most sodium is extracellular, the authors concluded that the increase in brain water was likely to represent a vasogenic oedema. Sorenson et al. 161, 162 using diffusion sensitive sequences at 1.5 Tesla...

Atherosclerosis Arterial Stiffness and Antihypertensive Therapy

As shown earlier in this book, the links between atherosclerosis, arterial stiffness, age and high BP are often difficult to establish, particularly according to age. Many atherosclerotic alterations (AA) are subclinical and difficult to define in routine clinical investigations. On the other hand, many markers have been proposed, such as defects in vascular relaxation, alterations in endotheli-um-dependent flow dilatation and or presence of atherosclerotic plaques (see chapter by Baldewsing et al., pp 35-61, and chapter by Hayoz and Mazzolai, pp 62-75). Within the framework of antihypertensive drug therapy, it seems likely that the links between atherosclerosis and arterial stiffness should primarily be explored through a simple clinical description of CV events clearly related to AA. The principal AA are those responsible for peripheral arterial disease (see chapter by Safar, pp 199-211), coronary ischemic disease (see chapter by Kingwell and Ahimastos, pp 125-138) and carotid...

Voyage Through The Digestive System

It takes 12-48 h for ingested food to complete its voyage through the digestive system. The food first arrives in the mouth (pH 7) where it is chewed and exposed to its first set of enzymes, called salivary enzymes. Subsequently, the food travels down the esophagus to the stomach (pH 1-2), which undergoes receptive relaxation as it fills to a capacity of 2 L or more (Figure 1.1). The next stage in the digestive system is the small intestine where chemical digestion continues and most nutrients are absorbed. The small intestine is made up of three parts the duodenum where the contents of the stomach are neutralized to pH 6 by pancreatic secretions (NaHCO3), then the 2 m long jejunum (pH 7-8), and finally the ileum (3 m long). Those substances which are not digestible or not absorbed join the large intestine, where leftovers are formed into semisolid masses ready for disposal. When digested nutrients are absorbed

NADPH Oxidases in Hypertension

One of the key factors regulating blood pressure is endothelium-derived relaxation factor (also known as NO*), and the role of this molecule in vascular homoeostasis has been studied extensively 62 . Furthermore, reduced level of endothelial NO* causes endothelial dysfunction, which contributes to hypertension and other vascular diseases 56, 62 . Vitamin C has been shown to recover endothelial function by restoring the NO-mediated vasodilation of the endothelium in hypertensive patients 63 . Although a number of mechanisms have been suggested to explain decreased NO* in endothelial dysfunction, there is now a large body of data indicating that NO* bioavailability is reduced primarily by reaction with vascular ROS 56, 57 . Indeed, the reaction of NO* and O2* is one of the fastest known biochemical reactions, indicating that NO* would be consumed anytime it encounters O2* 1 . In support of this concept, Wang et al. 64 demonstrated that adventitial O2* inactivated endothelial NO* in...

Sarika Arora1 Richa Vaishyat PK Dabla and Bhawna Singht

Reactive oxygen species (ROS), especially superoxide anion and hydrogen peroxide, are important signaling molecules in cardiovascular cells. ROS participate in growth, apoptosis, and migration of vascular smooth muscle cells, in the modulation of endothelial function, including endothelium-dependent relaxation and expression of proinflammatory phenotype, and

The mechanism of GK activation by allostericsite binders

In hepatocytes, where the inhibitory regulatory protein GKRP is involved in the regulation of GK activity, the binding of a GKA prevents relaxation to the super-open form to which GKRP binds (vide supra). Since the binding of GKRP is necessary for the sequestration of GK into the nucleus, GKAs have the effect of restricting the localization of GK to the cytoplasm 4 .

Replication And Expression Of Genetic Information

Replication Factory Bacteria

Unwinding or relaxation of the chromosome's supercoiled DNA Relaxation of supercoiled chromosomal DNA is required so that enzymes and cofactors involved in replication can access the DNA molecule at the site where the replication process will originate (i.e origin of replication). On exposure of the replication site (a specific sequence of approximately 300 base pairs that is recognized by several initiation proteins), unzipping of the complementary strands of parental DNA begins. Each parental strand serves as a template for the synthesis of a new complementary daughter strand. The site of active replication is referred to as the replication fork there are two during the replication process. Each replication fork moves through the parent DNA molecule in opposite directions so that replication is a bidirectional process. Activity at each replication fork involves different cofactors and enzymes, with DNA polymerases playing a central role. Using each parental strand as a template, DNA...

What are some of the physiologic processes that occur as a patient becomes hypertensive

Often cardiac output temporarily increases, followed by sustained increases in systemic vascular resistance. Vascular smooth muscular hypertrophy is observed, and there is increased arteriolar tone. Extracellular fluid volume and renin activity have no consistent pattern, but usually intracellular sodium and calcium concentrations increase. Sustained HTN leads to concentric hypertrophy of the left ventricle and impaired ventricular relaxation, known as diastolic dysfunction. Diastolic dysfunction leads to increased end-diastolic pressures.

Why is rapidsequence induction preferred for airway management in trauma patients

Rapid-sequence induction is used because trauma patients are at riskfor pulmonary aspiration of gastric contents and it minimizes the time between loss of consciousness and airway protection with a cuffed endotracheal tube (ETT). The usual rapid-sequence induction begins with preoxygenation with 100 oxygen. A cardiostable induction agent (ketamine or etomidate) in reduced doses is chosen in the unstable patient. The moribund patient may require only paralysis. A rapid-acting relaxant, usually succinylcholine (SCh), is chosen. Before induction, pressure is applied firmly over the cricoid ring (Sellick maneuver) to prevent regurgitation of gastric contents. The patient is intubated as soon as adequate muscle relaxation is achieved (usually around 45 to 60 seconds). The presence of end-tidal CO2 is confirmed, and breath sounds are assessed before release of cricoid pressure.

Adipokines Inhibitory Yin and Stimulatory Yang Signals in Inflammation

In addition to their importance in lipid, glucose, and energy homeostasis, adipokines are pivotally involved in coordinating a variety of processes such as inflammation and immunity (8,9-11,29) and vascular biology-related processes including artery relaxation via perivascular adipose tissue-derived relaxing factor (30), arteriolar constriction and insulin resistance (31), and smooth muscle cell growth (32).

Temporomandibular Disorder

For some affected people, the discomfort of TMD will eventually go away on its own. Because many cases of TMD are temporary and do not get worse, doctors usually prescribe simple and conservative treatments for the disorder. Eating soft foods, applying heat or ice packs, and avoiding extreme jaw movements such as wide-mouthed yawning often produce favorable results. Stress-reducing relaxation techniques (see page 119) also can improve symptoms. Doctors sometimes enlist the help of a physical therapist, who can provide gentle muscle-stretching exercises. The doctor may recommend using nonsteroidal antiinflammatory drugs such as aspirin or ibuprofen for a short period. He or she may prescribe muscle relaxants. A dentist may recommend that you wear a plastic appliance called a splint or bite guard, which fits over your upper or lower teeth. This device can help prevent you from grinding your teeth at night.

Which perioperative events predispose a patient to hypothermia

Heat loss is common in all patients during general anesthesia because of peripheral vasodilation, altered thermoregulation, and the inability to generate heat by shivering. General anesthesia widens the interthreshold range and, since the thermoregulatory response is markedly less robust, body temperature changes passively with existing temperature gradients. Hypothermia is as common during neuraxial anesthesia as general anesthesia and is a result of sympathetic blockade, muscle relaxation, and a lack of afferent sensory input into central thermoregulatory centers.

What physiologic effects are related to change in body position

The supine position results in decreased functional residual capacity and total lung capacity secondary to the abdominal contents impinging on the diaphragm. Anesthesia and muscular relaxation further diminish these lung volumes. Trendelenburg and lithotomy positions result in further compression of the lung bases, with a subsequent decrease in pulmonary compliance. Although some improvement is achieved with positive-pressure ventilation, the diaphragm is not restored to the awake position. In the supine position spontaneous ventilation to the dependent lung areas increases. Matching of ventilation to perfusion improves because blood flow also increases to dependent areas.

What is considered a safe increase in intraabdominal pressure

The current recommendation for intra-abdominal pressure (IAP) during laparoscopy is less than 15 mm Hg, and most laparoscopic procedures are performed with IAPs in the 12-to 15-mm Hg range. In general IAPs less than 10 mm Hg have minimal physiologic effects. Insufflation pressures above 16 mm Hg result in undesirable physiologic changes (i.e., decreased CO, increased systemic vascular resistance SVR and decreased compliance of the lung and chest wall). At pressures greater than 20 mm Hg, renal blood flow (RBF), glomerular filtration rate, and urine output also decline. Insufflation pressures of 30 to 40 mm Hg have significant adverse hemodynamic effects and should be avoided. Many insufflation machines are set to alarm at 15 mm Hg. If the machine alarms when the surgeon is not insufflating with high pressure, the anesthesiologist should consider insufficient abdominal wall relaxation as one possible cause of the high-pressure alarm. Low-pressure pneumoperitoneum (7 mm Hg) and gasless...

What does the pressurevolume loop look like in acute and chronic aortic insufficiency

In acute AI the end-diastolic and end-systolic volume is increasing. The stroke volume can be increased, normal, or decreased, depending on the severity of AI. The LV volume is increasing during the isovolumic relaxation period. The end-diastolic pressure is high. End-diastolic pressure 25 to 30 mm Hg manifests as pulmonary edema. Contractility is decreased because the myocardium is overstretched. There is no diastolic reserve, thus the heart cannot increase the stroke volume with increasing preload or afterload (see Figure 35-3).

What concerns the practitioner when administering general anesthesia for cesarean section How is it performed

The obstetric population is at greater risk for difficult intubation, rapid oxygen desaturation, and aspiration of gastric contents. The goal is to minimize maternal risk and neonatal depression. This goal is accomplished by following certain guidelines. After monitors are placed, while the patient is being preoxygenated, the abdomen is prepared and draped. When the obstetricians are scrubbed in and ready to make their skin incision, rapid-sequence induction with cricoid pressure is performed, and incision occurs after correct endotracheal tube placement is verified. Frequently used induction agents include thiopental, ketamine, propofol, or etomidate. Succinylcholine is the muscle relaxant of choice for most patients (1 to 1.5 mg kg). To prevent maternal awareness until the neonate is delivered, a combination of 50 nitrous oxide in oxygen is used with a low end-tidal concentration of a halogenated agent (0.5 minimum alveolar concentration). Larger concentrations of a volatile agent...

What are the mechanism and sites of action of nitrovasodilators

Nitrates such as nitroglycerin and sodium nitroprusside are pro-drugs that penetrate the vascular endothelium and become reduced to nitric oxide (NO). Nitroglycerin requires intact endothelial enzymatic activity, which is not present in the smallest or damaged vessels, whereas nitroprusside nonenzymatically degrades into NO and cyanide (a compound highly toxic to the mitochondrial respiratory chain). NO then stimulates production of cyclic guanosine monophosphate (cGMP), resulting in decreased cellular calcium levels and thus vascular smooth muscle relaxation.

Review the alleged benefits and risks of garlic

Garlic decreases blood pressure and reduces plasma lipids. It may produce smooth muscle relaxation and vasodilation by activation of endothelium-derived relaxation factor. It has been shown to have antithrombotic properties by increasing thrombolytic activity secondary to plasminogen activation and decreasing platelet aggregation through inhibition of thromboxane B2 formation. Garlic may potentiate the effects of warfarin, heparin, nonsteroidal antiinflammatory drugs (NSAIDs), and aspirin. A spontaneous spinal epidural hematoma associated with excessive garlic ingestion has been reported. However, garlic taken in normal dietary doses does not impair platelet function.

Radiographic Indicators Of Progressing Stroke

Anatomia Cranio

MRI includes a variety of techniques that can be employed to predict outcome of progressing stroke and are described in detail in Chapter 18. Diffusion-weighted imaging (DWI) permits the in vivo measurement of the translational mobility of water in tissue and was first reported as a marker of acute ischemic brain injury in 1990 (13,14). The image intensity on DWI is dependent on the apparent diffusion coefficient (ADC), measuring the mobility of water molecules in tissue and the transverse relaxation time (T2) that might represent prior distortion of tissue architecture ( T2 shine-through ). In ischemic brain tissue, ADC values decline, leading to a region of hyperintensity on a gray-scale derived image. The ADC probably reflects the accumulation of intracellular water (cytotoxic edema) caused by disruption of energy metabolism and loss of ion homeostasis (15). These ADC changes do not occur uniformly throughout the ischemic lesion. Serial studies performed in experimental stroke...

What is diastolic dysfunction

Diastolic dysfunction can occur with normal LV EF in many patients. Impaired LV relaxation or compliance or both are the major characteristic features of LV diastolic dysfunction. Early diastolic filling depends on the rapidity of ventricular relaxation, characterized by an Figure 34-1. Left ventricular (LV) pressure-volume loops illustrating normal performance (loop 1), diastolic (loop 2), and systolic dysfunction (loop 3). AB, Diastolic filling BC, isovolumic contraction CD, ejection DA, isovolumic relaxation. In diastolic dysfunction one of the problems can be the impaired LV compliance, which manifests in high LV end-diastolic pressure. The stroke volume and ejection fraction are normal. This loop can represent diastolic dysfunction in hypertension or aortic stenosis with LV hypertrophy (loop 2). In systolic dysfunction the LV is dilated, the stroke volume is normal or less than normal the left ventricular end-diastolic and end-systolic volumes are enlarged. The end-diastolic...

Mediators of Inflammation

NO was originally discovered as a vasodilatation factor released from endothelial cells and hence was called as endothelium-derived relaxing factor 63 . It is a soluble gas produced not only by endothelial cells but also by a variety of cells including macrophages and brain neurons. It is now evident that many (if not all) cells produce NO and that NO also participates in inflammation. It acts in a paracrine manner on target cells through induction of cyclic guanosine monophosphate (cGMP) that, in turn, initiates a series of intracellular events leading to the desired response such as relaxation of vascular smooth muscle cells, neurotransmission, tumoricidal, cytotoxic,

Current Indications for Right Ventricular Angiography in ARVCD

As in every imaging technique, the diagnostic value of RV angiography depends on the experience of the investigator in the performance and interpretation of results of the study. In general, the an-giographic diagnosis of ARVC D is based on segmental abnormalities rather than global RV enlargement or hypokinesia. Dedicated computer software is currently under development and will provide a new convenient and reproducible method for quantitative assessment of global and (probably more importantly) regional RV contraction and relaxation in comparison to a database of normal control subjects.

ADVAntAgES of ArthroSCoPiC AnD EnDoSCoPiC DiSC Surg Ery

In an animal model, Hampton et al. (9) reported on the healing potential of a surgically induced defect in the annular fibers of 10 dogs. The dogs were sacrificed within 3-12 wk postoperatively. Dissection of the surgical site demonstrated that the defect was filled with a solid plug of fibrous structures. Postoperative imaging studies by my colleagues and I on patients who had undergone percutaneous posterolateral discectomy confirmed these findings. Markolf and Morris (10) reported a decrease in compressive stiffness and an increase in creep and the relaxation rate of the intervertebral disc in cadaveric specimens that were exposed to annular fenestration and then followed by exposure of the spinal unit to compressive forces. In younger specimens, extrusion of nuclear tissue had a tendency to seal off the annular defect and to restore normal function of the spinal unit.

Discovery Of The 5ht4 Receptor In The Gi Tract

In almost all tissues where 5-HT4 receptors are present, 5-HT or any other agonists increase intracellular cAMP synthesis 12 , as has been shown for hippocampus, atrium, esophagus, intestinal tissue and adrenal cortex. A number of processes can be triggered by an increase in intracellular cAMP. For instance in the intestine, an increase in intracellular cAMP concentrations following activation of 5-HT4 receptors can trigger a relaxation of the smooth muscle. However, activation of 5-HT4 receptors present on intestinal inter- and motor-neurons leads to a facilitation of acetylcholine release and, thereby, to increased contractions of intestinal smooth muscle 13 .

Bronchospasm and Severe Bronchitis A Real Chokehold on Ventilation

Although a mild-to-moderate degree of bronchoconstriction is a completely normal event, bronchospasm (BRAHNG-koh-spazm) is quite another matter A spasm in general is any ''convulsion'' - a powerful, sudden sequence of involuntary muscle contraction, then relaxation. Bronchospasm, then, is a powerful and sudden contraction of the circular smooth muscle in the bronchiole wall. If strong and sustained enough, bronchospasm can produce a deadly chokehold of complete bronchoconstriction of important airways.

Psychology in life

Fortunately, Charlie's new coach has had a great deal of experience with this sort of thing, something that he describes to himself as 'freezing'. He always deals with it in the same way, although suiting exactly what he says and does to the person he is dealing with. He has given Charlie some training in relaxation and has been getting him to visualise being on the putting green and making various putts while he is in the relaxed state. The moment that Charlie says that he is feeling anxious, the coach stops him from thinking about the putting and gently gets him to relax again.

Potassium Channels

Four types of potassium channels are expressed in the cell membranes of VSMCs in cerebral vessels, each with a different profile of functional characteristics and stimuli for activation (97). In general, activation, or opening, of potassium channels in VSMCs results in the efflux of potassium ions, membrane hyperpolarization, and, ultimately, vascular relaxation due to closure of voltage-gated calcium channels and reduced intracellular calcium concentration (39). Endothelium-derived hyperpolarizing factor, an important factor in endothelium-mediated vasodilation, produces relaxation by activating potassium channels (39). Further, vasoconstrictors, such as epinephrine, norepinephrine, angiotensin II, endothelin, and thromboxane A2 depolarize the muscle membrane and have been shown to inhibit K channels (98).

Magnetic Resonance

The effect of oxygen on relaxation time is a function of the diffusion coefficient and mostly of its concentration. For magnetic resonance, the measurement will depend on the field strength of the magnet and the probe relaxation time. This is a noninvasive procedure that can give an indirect assessment of tissue oxygenation through the evaluation of tumor metabolism (30,31). The most widely used techniques are 31P-MRS and XH-MRS (lactate). The latter techniques is promising because lactate production is markedly increased in tumor cells, compared to normal tissues (31).

Cervical Cancer

The International Federation of Gynecology and Obstetrics (Federation Internationale Gynecologique Obstetrique or FIGO) along with the World Health Organization last revised its staging system in 1995.4 The FIGO staging (Table 2.1) system is based upon a thorough clinical examination, chest X-ray, intravenous pyelogram, cystoscopy, proctoscopy and barium enema as indicated. The physical examination should include abdominal, pelvic, rectovaginal and lymph node examinations. Examination under anaesthesia is strongly recommended because of the added benefits of muscular relaxation and inter-examiner correlation.5 If up-to-date imaging methods are available such as magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning, an examination under anaesthesia EUA may not be needed for treatment planning.


The treatment strategy should allow the anesthesiologist to secure an adequate depth of anesthesia to sympathetic stimulation during every phase of surgery. The agents chosen should facilitate the anesthesiologist's ability to quickly manipulate blood pressure and intracellular water content of the brain (brain relaxation) at any time during the surgery. The maintenance strategy must also allow the anesthesiologist to be successful with his her plan for rapid postoperative neurologic evaluation in patients with favorable SAH grades (I II). It is important to note that, during the different phases of aneurysmal surgery, stimulation can vary significantly. Manipulation at the scalp, skull, and dura requires a deeper level of anesthesia than does aneurysmal dissection, which causes little to no stimulation. However, sudden changes in heart rate and blood pressure might occur when the brain stem or cranial nerves are retracted. Relaxation of the brain can be achieved by hyperventilation...


G. para, alongside of, + L. axis, axle. G. paresis, relaxation. G. pathos, disease, + logos, treatise. G. peri, around, + chondros, cartilage. G. peri, around, + mys, muscle. G. peri, around, + osteon, bone. G. phagein, to eat, + kytos, cell. G. phainein, to display, + typos, type. G. physikos, natural.


In the context of SAH, the term vasospasm refers to a condition that is much more complex than simply constriction of blood vessels. Additional contributing factors include pathologic changes in arterial walls, with narrowing of the lumen and impairing vascular relaxation, altered vascular reactivity, and hypovolemia. The term delayed ischemic deficit (DID) more aptly describes the situation in which these multiple factors conspire to result in cerebral ischemia.


If all of your smooth muscle cells relaxed instantaneously, you would faint immediately. Such relaxation would allow a large increase in volume of blood in the cardiovascular system, dropping blood pressure precipitously. In skeletal muscle and other tissues, a large number of capillaries can remain closed for long periods due to the contraction of the precapillary sphincter. This mechanism is a part of the regulation of vascular resistance.


In addition to ID proteins, the cytoskeleton of car-diomyocytes consists of a sarcomeric skeleton (e.g., titin, a-actinin), true cytoskeletal proteins (i.e., intermediate filaments, microtubules, and actin), and membrane-associated proteins (e.g., dystrophin, spec-trin, talin, vinculin) 26 . This complex network stabilizes cellular organelles, maintains cell size and shape, and plays an active role during contraction relaxation and intracellular signaling 27,28 . The perisarcomer cytoskeleton anchors to the lateral cell membrane in areas called costameres, which are composed of focal adhesion proteins. Therefore, the cytoskeleton responds to the physical and biochemical properties of the extracellular matrix.

Recent Developments

After the final draft of this manuscript was completed, a further report appeared on the ROCK2-selective series exemplified by compounds 17-19 (see Section 5.1). Inhibitor 47 was shown to be highly selective for ROCK2 (ROCK2 IC50 105 nM ROCK1 IC50 24,000 nM) and was shown to reduce the plaque burden in the ApoE(_ _) mouse model of atherosclerosis when administered once daily at doses of 30 or 100 mg kg 61 . Interestingly however, 47 had no effect on bp in rats (strain not reported) at doses up to 300 mg kg, nor did it block the bp reducing effect of 1 in rats. Moreover, while the unselective inhibitors 1 and 2 were shown to relax pre-contracted aortic tissue strips, 47 did not induce such relaxation at concentrations up to 25 p.M. Additional work is needed, but these data suggest that ROCK1 may be the isoform primarily responsible for maintaining vascular tone.

Dumping syndrome

The primary mechanisms leading to the dumping syndrome are loss of reservoir function of the stomach and the rapid emptying of hyperosmolar carbohydrates into the small intestine (Fig. 8). Decreased gastric reservoir is caused by a loss of proximal gastric receptive relaxation and accommodation with vagotomy and loss of gastric capacity with gastric resection. Ablation or bypass of the pylorus results in loss of the control of gastric emptying. In Billroth II reconstruction, loss of duodenal feedback with inhibition of gastric emptying also contributes to rapid gastric emptying.


Nitrates induce relaxation of vascular smooth cells in both arteries and veins. At low concentration venodilation predominates, but at higher concentrations arterial vasodilation is also produced. Hypotensive reaction may result from the combination of alcohol and nitroglycerin 25 , Unless the clinician is aware of this interaction, the hypotensive episode may be attributed to coronary insufficieny or occlusion 26 , Arterial pressure and ventricular wall stress tend to be lower in subjects taking both nitroglycerin and ethanol compared to either drug alone 27 ,


As originally described by Sellick, the assistant's forefinger is placed over the cricoid cartilage and firm pressure exerted posteriorly, with the thumb and middle finger supporting on either side. The optimal time to start exerting pressure is somewhat controversial since cricoid pressure is uncomfortable when the patient is awake, whereas regurgitation may occur if it is applied too late. As a compromise, many advocate gentle pressure until consciousness is lost, with firmer pressure thereafter (as Sellick originally described), although there is evidence that gentle pressure itself may cause relaxation of the lower oesophageal sphincter. Estimates of the force required to prevent regurgitation range from 20 N to over 40 N. Various devices have been described that apply the correct amount of force but they are not widely used.

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