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Beta Switch Program Summary


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Discharge And Home Healthcare Guidelines

Cortisol deficiency causes altered metabolism, decreased stress tolerance, and emotional lability. Aldosterone deficiency causes urinary loss of sodium, chloride, and water, resulting in dehydration and electrolyte imbalances. Androgen deficiency leads to the loss of secondary sex characteristics.

The Important Role Of Stress

That drug abuse patients are more vulnerable to stress than the general population is a clinical truism. Numerous preclinical studies have documented that physical stressors (e.g., foot shock or restraint stress) and psychological stressors can cause animals to reinstate drug use (e.g., Shaham, Erb, & Stewart, 2000). Furthermore, stressors can trigger drug craving in addicted humans (Sinha, Catapano, & O'Malley, 1999). One potential explanation for these observations is that abused drugs, including opiates and stimulants, raise levels of cortisol, a hormone that plays a primary role in stress responses cortisol, in turn, raises the level of activity in the mesolimbic reward system (Kreek & Koob, 1998). By these mechanisms, stress may contribute to the abuser's desire to take drugs in the first place, as well as to his or her subsequent compulsion to keep taking them.

Pharmacological Interventions And Treatment Implications

Methadone, a long-acting opioid medication with effects that last for days, causes dependence, but because of its sustained stimulation of the mu receptors, it alleviates craving and compulsive drug use. In addition, methadone therapy tends to normalize many aspects of the hormonal disruptions found in addicted individuals (Kling et al., 2000 Kreek, 2000 Schluger, Borg, Ho, & Kreek, 2001). For example, it moderates the exaggerated cortisol stress response (discussed earlier) that increases the danger of relapse in stressful situations.

Dehydroepiandrosterone DHEA

Glucagon is a linear polypeptide hormone with 29 amino acids synthesized in the a cells of the islets of Langerhans and secreted into the portal vein in response to fasting, starvation, glucogenic amino acids, CCK, gastrin, cortisol, exercise, infections, stress, beta-adrenergic stimulators, theophylline, or acetylcholine. Secretion is inhibited by glucose, insulin, somatostatin, secretin, free fatty acids, ketones, pheny-toin, alpha-adrenergic stimulators, GABA. It stimulates gluconeogenesis, glycogenolosis, lypolysis, and ketogenesis in the liver.

Adam W Carrico Michael H Antoni Lawrence Young and Jack M Gorman

Because HIV-positive persons endure a chronic disease that requires adaptation across a variety of domains, individual differences in the ways they adapt to these challenges may affect not only quality of life but also disease processes. Research in psychoneuro-immunology (PNI) has examined the potential bio-behavioral mechanisms whereby psychosocial factors such as stressors, stress responses, coping, and negative affective states influence disease progression (Antoni, 2003a). Psychosocial factors are thought to relate to immune-system function in humans via stress- or distress-induced changes in hormonal regulatory systems (Kiecolt-Glaser et al., 2002). Several adrenal hormones, including cortisol and catecholamines (norepinephrine and epinephrine), are altered as a function of an individual's appraisals of and coping responses to stressors (McEwen, 1998). What is particularly relevant to HIV AIDS research is the observation that a variety of neuroendocrine abnormalities occur in...

Stress Management And Psychiatric Interventions

Stress management techniques such as relaxation training, cognitive restructuring, and coping skills training may reduce negative mood states in HIV-positive persons by lowering physical tension and increasing self-efficacy (Antoni, 2003a). These affective changes are thought to be accompanied by an improved ability to regulate peripheral catecholamines and cortisol via decreases in ANS activation and improved regulation of the HPA axis, respectively. Neuroendocrine regulation may be associated with a partial normalization of immune system functions, providing more efficient surveillance of pathogens such as latent viruses that may increase HIV replication and enhance vulnerability to opportunistic infections or neoplasias. This normalization of stress-associated immune system decrements may ultimately forestall increases in viral load and the manifestation of clinical symptoms over extended periods. A relatively small number of controlled trials have examined the effects of...

The CRF hypothesis and stress

CRF is synthesized in the hypothalamus and elicits the release of adrenocorticotropic hormone (ACTH) from the pituitary. CRF was isolated from sheep hypothalamus and its structure as a 41-amino-acid peptide determined.96 The hypothalamic paraventricular nucleus (PVN) is the major region in the brain of CRF-containing cell bodies and through axonal projections to the capillaries of the median eminence can secrete CRF directly into the portal system where it acts at the pituitary to regulate ACTH secretion into the circulation. The principal role of ACTH is to stimulate the release of cortisol from the adrenal gland, thus completing the HPA axis, a primary component of the neuroendocrine response to stress. Similarly, projections from the PVN to the lower brainstem and spinal cord have been demonstrated to regulate autonomic function and help to further mediate the behavioral responses to stress. High densities of CRF-containing neurons are localized in particular to prefrontal,...

Plasma Ion Distribution

Sixty percent of all plasma protein ( B) is albumin (35-46 g L). Albumin serves as a vehicle for a number of substances in the blood. They are the main cause of colloidal osmotic pressure or, rather, oncotic pressure ( pp. 208, 378), and they provide a protein reserve in times of protein deficiency. The ai, a2 and globulins mainly serve to transport lipids (apolipoproteins), hemoglobin (haptoglobin), iron (apotransferrin), cortisol (transcortin), and cobalamins (transcobalamin). Most plasma factors for coagulation and fibrinolysis are also proteins. Most plasma immuno-globulins (Ig, D) belong to the group of y globulins and serve as defense proteins (antibodies). IgG, the most abundant immuno-globulin (7-15 g L), can cross the placental barrier(maternofetal transmission D). Each Ig consists of two group-specific, heavy protein chains (IgG y chain, IgA a chain, IgM chain, IgD 6 chain, IgE e chain) and two light protein chains (X or k chain) linked by disulfide bonds to yield a...

Step 5 Followup laboratory evaluation

A high serum androgen value may suggest the diagnosis of polycystic ovary syndrome or may suggest an androgen-secreting tumor of the ovary or adrenal gland. Further testing for a tumor might include a 24-hour urine collection for cortisol and 17-ketosteroids, determination of serum 17-hydroxyprogesterone after intravenous injection of corticotropin (ACTH), and a dexamethasone suppression test. Elevation of 17-ketosteroids, DHEA-S, or 17-hydroxyprogesterone is more consistent with an adrenal, rather than ovarian, source of excess androgen.

Risk Factors and Genetics

Breast cancer risk factors are related to prolonged exposure to estrogen. This is seen in women with early menarche and late menopause, older high estrogen dose oral contraceptives, and nulliparity. The highest risk involves a personal history of breast cancer or lobular carcinoma in situ. Family history in a premenopausal first degree relative is also an important risk factor.

General Mechanisms Whereby Biological Findings In Ptsd Might Reflect A Pathophysiology Of The Disorder

The possibility that the development of PTSD is facilitated by a failure to contain the normal stress response at the time of the trauma, resulting in a cascade of biological alterations that, eventually, underlie the enhanced recall, distress at reminders, avoidance, and hyperarousal symptoms that characterize PTSD. In contrast to the normal fear response, which is characterized by a series of biological reactions that help the body modulate, and gradually recover from stress (e.g., high cortisol levels), prospective biologic studies have shown that individuals who develop PTSD or PTSD-related symptoms appear to have more attenuated cortisol increases in the acute aftermath of a trauma than those who do not develop the disorder 37,38 . Moreover, persons who develop PTSD show elevated heart rates in the emergency room, and at one week post-trauma, compared to those who ultimately recover 39 , suggesting, if not a greater degree of sympathetic nervous system activation, one that is...

Physical and Emotional Health How They Interact

However, when a person is under constant stress, the body steadily releases a hormone called cortisol, which can cause long-term damage to the brain and other organs. The harmful effects of this hormone include an increased tendency for blood to clot, a surge in the pressure on coronary arteries, increased blood pressure, and other demands on the heart and blood vessels.

Early Mesodermal Events

The nuclear localization of Dorsal results in the transcriptional activation of two zygotic genes, twist (twi) and snail (sna). Genetic studies have established that mesoderm formation is dependent on the presence of twi, which takes its name from the twisted appearance of embryos that attempt to gas-trulate in its absence (Simpson, 1983 Grau et al., 1984). An abnormal ventral furrow is observed in these mutant embryos, but no mesoderm forms. By comparison, embryos mutant for sna exhibit no distinct furrow but do have subtle folds of cells that appear in the ventral region during gastru-lation. Similar to the situation in twi mutants, mesoderm does not form in sna mutant embryos. The twi gene, which encodes a basic helix-loop-helix (bHLH)-containing transcription factor, is initially expressed in mesodermal cells at Stage 5 (Thisse et al., 1988 Leptin, 1991). This expression generally begins to decline during Stage 11 but persists in a subset of mesodermal cells that are progenitors...

Segregation of the Visceral and Somatic Mesoderm

Figure 1 Positions of mesodermal subpopulations. The diagram shows the locations of mesodermal subpopulations relative to the units of subdivision used for the ectoderm (compartments and parasegments), the early mesoderm (A and P according to Azpiazu et al., 1996), later mesoderm (A and P according to Dunin-Borkowski et al., 1995), and the domains of eve and slp function in the mesoderm. The slp domain gives rise to the dorsally located heart precursors and to the majority of somatic muscles. Development of somatic muscles requires the maintenance of high levels of twist expression (Baylies and Bate, 1996). In the eve domain of each segment, the most dorsally located group of cells gives rise to the visceral musculature. The fat body primordium lies slightly more ventrally. The primordia of the visceral muscles and the fat body overlap the engrailed (en) and hedgehog (hh) expression domain, and these genes are necessary for their spatial determination (Azpiazu et al., 1996). The heart...

The scale of the problem

Ably around 106 neurons are in the hypothalamus, and this region controls a wide diversity of clearly definable functions that are much more amenable to experimental investigation. Different neuronal groups in the hypothalamus control the release of different hormones from the pituitary gland - oxytocin vasopressin prolactin growth hormone the gonadotrophic hormones adrenocorticotrophic hormone (that in turn controls steroid secretion from the adrenal glands) thyroid stimulating hormone (that controls the functions of the thyroid gland) and melanocyte-stimulating hormone. The hypothalamus also controls thirst, feeding behavior (including specific appetites such as sodium appetite), body composition, blood pressure, thermoregulation, and much instinctive or reflex behavior including male and female sexual behavior and maternal behavior. These functions involve highly specialised cells with specific properties cells for instance that have receptors or intrinsic properties that enable...

Glucocorticoid Therapy

The adrenal cortex (AC) produces the glucocorticoid cortisol (hydrocortisone) and the mine-ralocorticoid aldosterone. Both steroid hormones are vitally important in adaptation responses to stress situations, such as disease, trauma, or surgery. Cortisol secretion is stimulated by hypophyseal ACTH, aldosterone secretion by angiotensin II in particular (p. 124). In AC failure (primary AC insuffiency Addison's disease), both cortisol and aldosterone must be replaced when ACTH production is deficient (secondary AC insufficiency), cortisol alone needs to be replaced. Cortisol is effective when given orally (30 mg d, 2 3 a.m., 1 3 p.m.). In stress situations, the dose is raised by 5- to 10-fold. Aldosterone is poorly effective via the oral route instead, the mineralocorticoid fludrocortisone (0.1 mg d) is given. II. Pharmacodynamic therapy with glucocorticoids (A). In unphysio-logically high concentrations, cortisol or other glucocorticoids suppress all phases...

Measures for Attenuating or Preventing Drug Induced Cushings Syndrome

A) Use of Cortisol derivatives with less (e.g., prednisolone) or negligible miner-alocorticoid activity (e.g., triamcinolone, dexamethasone). Glucocorticoid activity of these congeners is more pronounced. Glucorticoid, anti-inflammatory and feedback inhibitory (p. 250) actions on the hypophysis are correlated. An exclusively anti-inflammatory congener does not exist. The glucocorti-coid related Cushingoid symptoms cannot be avoided. The table lists relative activity (potency) with reference to cortisol, whose mineralo- and glucocor-ticoid activities are assigned a value of 1.0. All listed glucocorticoids are effective orally.

Glucocorticoids principal and adverse effects

For long-term medication, a just sufficient dose should be given. However, in attempting to lower the dose to the minimal effective level, it is necessary to take into account that administration of exogenous glucocorticoids will suppress production of endogenous cortisol due to activation of an inhibitory feedback mechanism. In this manner, a very low dose could be buffered, so that un-physiologically high glucocorticoid activity and the anti-inflammatory effect are both prevented. Effect of glucocorticoid administration on adrenocortical cortisol production (A). Release of cortisol depends on stimulation by hypophyseal ACTH, which in turn is controlled by hypotha-lamic corticotropin-releasing hormone (CRH). In both the hypophysis and hypothalamus there are cortisol receptors through which cortisol can exert a feedback inhibition of ACTH or CRH release. By means of these cortisol sensors, the regulatory centers can monitor whether the actual blood level of...

What Is Blood Pressure

Carries angiotensin I to your lungs, it's converted to angiotensin II, a very potent constrictor of blood vessels. Angiotensin II also stimulates the adrenal cortex to produce yet another hormone, called aldosterone. This steroid hormone, closely related to cortisol, plays a major role in stimulating the kidney to excrete potassium and to retain sodium. In fact, in its absence, the body may retain potassium to a dangerous degree. (See Chapter 12.) But we now know that aldosterone also exerts a number of harmful effects, especially on the heart. This curious set of circumstances complicates treatment.

Effects of Estrogen on Hemostatic Factors

On the other hand, reduced fibrinolytic activity is associated with atherosclerosis and has been attributed to increased levels of the antifibrinolytic factor plasminogen activator inhibitor-1 (PAI-1) (53). Increased PAI-1 levels have been found in postmenopausal women, and a close relationship between low fibrinolytic activity, high PAI-1 and hyperinsulinemia has been observed in various populations (54). Even small doses of oral ERT activate the fibrinolytic system via a marked reduction in PAI-1 levels, with the greatest reduction occurring in women with the highest PAI-1 levels. Combination with progestogen does not appear to diminish this beneficial effect. In contrast to oral therapy, transdermal therapy does not seem to change PAI-1 levels (55,56). The activation of the fibrinolytic system by estrogens appears not to be dose-related, unlike the coagulatory activity that appears to be dose-dependent (53). On balance, therefore, HRT at low dosages may affect fibrinolytic activity...

Etiology of Metabolic Syndrome The Search for the Single Causal Mechanism

The other major focus in the search for the single causal mechanism underlying MetS has been the cause consequences of visceral obesity. These relate to both hormonal and metabolic consequences of obesity. The impact of several adipocytokines has been examined for their roles as etiological factors in MetS. These include leptin, adiponectin, and resistin as well as inflammatory hormones (TNF-a) and additionally nonesterified free fatty acids.36 The pattern of endothelial dysfunction and sympathoadrenal activation has been linked to these mediators as well as the inflammatory phenotype characteristic of patients with MetS.

Experimental Disease Models

Making them a suitable species for early preclinical research. Their relatively small size and body weight also make optimal use of precious peptides and small molecules that are being evaluated for their antiobesity effects. While there are many similarities in how animals control food intake, energy expenditure, adipose tissue physiology, and gastrointestinal function, there are many differences that limit the predictive validity of these models. For instance, rats have no gallbladder and are unable to store bile and therefore this changes the digestive process compared to humans. Also, there are many notable differences in hormonal regulation that need to be considered. For example, in rodents, leptin produced impressive reductions in food intake, increased metabolism, and reduced adiposity (see Section 6.18.7). In most human obese patients, leptin had very little effect on any of these parameters. With this in mind, these types of studies become important to facilitate...

New Research Areas Leptin The discovery of the peptide hormone leptin was a major advance in obesity research.17 Leptin is a 148-amino-acid protein that is primarily secreted from adipose tissue in proportion to fat mass. Structurally, it belongs to the type 1 cytokine superfamily and is characterized by a long-chain four-helical bundle structure similar to growth hormone (GH), prolactin, and interleukin-3. The leptin receptor (Ob-R) was originally cloned from mouse choroid plexus and is alternatively spliced, giving rise to six different forms of the receptor, known as Ob-Ra, Ob-Rb, Ob-Rc, Ob-Rd, Ob-Re, and Ob-Rf. Ob-R is a member of the class 1 cytokine receptor superfamily. Ob-Rb is expressed at high levels in the hypothalamus and is believed to mediate the central effects of peripherally secreted leptin. Natural mutation of the leptin gene is found in genetically obese (ob ob) mice, while the gene for the receptor is mutated in fatty (fa fa) rats and in diabetic (db db) mice. Chronic...

Dermatologic Physical Exam

When physical findings and history suggest a possible endocrinopathy, the patient should be appropriately tested. The most reliable screen is a dexamethasone suppression test. Alternative tests include 8 am and 4 pm serum cortisol determinations, or a 24-hour urinary free cortisol.

Very lowdensity lipoprotein chylomicrons and triglyceride transport

In the periphery, LpL acts on these particles to release the TG to adipose tissue for fat storage or to muscle tissue where they can be used for energy. The resulting TG-depleted and cholesteryl ester-enriched VLDL remnant particles can be recycled to the liver by the interaction of a specific hepatic LDL receptor (LDLr) with apoB and apolipoprotein-E (apoE). Alternatively, further remodeling of VLDL remnants produces cholesteryl ester-enriched particles first IDL and then LDL. In contrast to VLDL and chylomicrons, the smaller and denser LDL and HDL particles help move cholesterol to and from the periphery, respectively.

Dehydrogenases and reductases

ADH is a member of the family of medium-chain alcohol dehydrogenases.32 The major function of most short-chain alcohol dehydrogenases32 in mammals is steroid metabolism. Nevertheless, many of them play important roles in drug toxification and detoxification. The 3a-hydroxysteroid dehydrogenase (3a-HSD) of rat and man oxidizes vicinal dihydrodiols of polycyclic aromatic hydrocarbons to catechols and these to quinones.33 Hence, 3a-HSD is also called dihydrodiol dehydrogenase. This reaction sequesters the pre-bay dihydrodiols of polycyclic aromatic hydrocarbons away from their critical toxification pathway to the ultimate carcinogenic dihydrodiol bay-region epoxides to produce instead the much less toxic catechols33 (Figure 3). In addition, it inactivates the highly mutagenic and carcinogenic bay region diol epoxides.34 Both of these reactions are protective, but the formation of catechols, which are further oxidized to quinones, is on the other hand also a potential toxification, since...

Regulation Of The Jakstat Pathway Suppressors of Cytokine Signaling

Little is known about specificity within the SOCS family of proteins. To date, most studies of SOCS function have depended on the use of in vitro overexpression systems. These studies have shown that expression of SOCS-1 suppresses signaling in response to a variety of cytokines, including LIF, on-costatin M (OSM), IFNy, TPO, and growth hormone (GH) in addition to IL-6 (46,51,53,61-63). SOCS-3 expression also inhibits signaling in response to IL-6, LIF, GH, and IFN-y (54,61,63,64) in addition to blocking leptin-induced signal transduction (65). CIS expression suppresses cell proliferation in response to IL-3 and EPO cell proliferation (50). However, SOCS-2 has yet to be shown to inhibit cytokine signal transduction pathways.

Suketu Shah md Alina Gavrila md and Christos S Mantzoros md

Our understanding of the function of fat cells has changed dramatically with the realization of the endocrine function of adipose tissue. Initially thought to serve only as a repository for energy via storage of triglycerides, adipocytes are now known to secrete a variety of proteins with diverse metabolic functions. These proteins include leptin, TNF-a, plasminogen activator inhibitor-1, acylation-stimulating protein, resistin, and adiponectin (1,2). Adiponectin has received much attention for its putative role in diabetes and CVD. Besides being associated with the development of diabetes, it may also have a direct role in modulating inflammation and atherosclerosis and thereby be one of the factors that links obesity to CVD. Although its structure and source are known, the regulation of adiponectin remains to be determined. The various factors thought to be involved in controlling adiponectin production and secretion include obesity, nutritional status, hormones such as insulin,...

Carbonyl and quinone reductases

SDRs are enzymes of great functional diversity found throughout nature. In humans, cytosolic carbonyl reductase (CBR1) is a major member of the SDR superfamily that metabolizes a wide variety of xenobiotics, including the anticoagulant warfarin, anthracycline derivatives like daunorubicin, and aldehyde and ketone products of lipid peroxidation.74 A recent mouse knockout study demonstrated a critical role for CBR1 in the doxorubicin cardiotoxicity that is attributed to the reduced metabolite, doxorubicinol.75 CBR3 is a second member of the cytosolic human carbonyl reductases, but its substrate specificity is not well documented. The major human microsomal carbonyl reductase, 11 -hydroxysteroid dehydrogenase, also belongs to the SDR family. Each enzyme demonstrates a cofactor preference for NADPH, transferring the pro-S hydrogen to the substrate, i.e., the opposite of ADH. The AKRs perform oxidoreduction on a wide variety of natural and foreign substrates. A systematic nomenclature for...

Ketoconazole and Low Dose Prednisone

Ketoconazole inhibits the synthesis of cortisol, the main glucocorticoid hormone produced by the adrenal cortex. High rates of production of cortisol are associated with faster progression of chronic renal failure, while low rates of cortisol production are associated with slow progression or no progression. These observations led us to the hypothesis that ketoconazole administration on a long-term basis might slow the progression of renal failure. One problem with this concept is the well-known escape phenomenon When cortisol production is inhibited, adrenocorticotrophic hormone (ACTH), derived from the pituitary gland, increases and stimulates the adrenal gland to produce more cortisol. We have found that this escape can be prevented by administering a low dose (2.5 mg per day) of prednisone (a synthetic glucocorticoid) at the same time. ACTH levels do not rise, and the block in cortisol synthesis persists.

Diabetes and Insulin Resistance

The majority of data for animal studies thus far suggest that adiponectin acts as an insulin-sensitizing hormone. Adiponectin-knockout mice develop insulin resistance either independently of diet or only after high-fat and high-sucrose diet, and treating these mice with adiponectin ameliorates their insulin resistance (35,42). The insulin resistance in adiponectin-deficient lipoatrophic and obese mice can partially be reversed via adiponectin administration and fully restored with both leptin and adiponectin supplementation (29). Furthermore, in a longitudinal study analyzing the progression of type 2 diabetes in obese monkeys, decrease in adiponectin closely parallels the observed reduction in insulin sensitivity, and the obese monkeys with greater plasma levels of adiponectin had less severe insulin resistance (43).

Mechanisms of Renal Dysfunction

Recent studies have focused on exploring the mechanisms by which obesity increases sympathetic outflow. One of these is hyperleptinemia. Leptin can regulate energy balance by decreasing appetite and stimulating thermogenesis via sympathetic stimulation. Acute infusion of leptin increases sympathetic activity and the hypertensive effect of leptin was completely abolished by combined a- and -adrenoceptor blockade.22 Hyperinsulinemia also plays a role in the activation of the sympathetic nervous system associated with obesity. In rats, insulin causes an enhancement of sympathetic activity in different tissues such as the kidney.23 High circulating levels of free fatty acids in obese subjects may participate in the activation of the sympathetic nervous system. Collectively, these data suggest that leptin, hyperisulinemia, and increased plasma free fatty acids could contribute to the activation of sympathetic system in obese subjects.

Structural features

Indirect, i.e. tests of end-organ function plasma T4 (TSH) plasma cortisol (ACTH) Direct, dynamic TSH (ivTRH) LH, FSH (ivGnRH) ACTH (insulin hypoglycaemia) GH (stimulation sleep iv arginine insulin hypoglycaemia) PRL (iv TRH). Combined sequential stimuli testing with a triple intravenous bolus of hormones soluble insulin (0.15 unit kg) TRH (200 mg) and GnRH (100 mg). This involves venous blood sampling for glucose, cortisol, GH, LH, FSH, PRL and TSH prior to administration, and at 20, 30, 45, 60, 90 and 120 minutes thereafter.

Adrenocorticotrophic hormone ACTH

Adrenocorticotrophic hormone is a 39 amino acid peptide which is secreted by corticotroph cells of the anterior pituitary, being cleaved from a precursor molecule, pro-opiomelanocortin (POMC). It is secreted in a pulsatile fashion, with a diurnal rhythmicity. Peak secretion is in early morning, with a trough in late evening. Secretion of ACTH is controlled by closed loop feedback responsive to changes in serum cortisol, and by an open-loop component related to neurally mediated stimuli such as stress.

Gender Ethnicracial And Life Span Considerations

PE is a frequent cause of sudden death for approximately 50,000 people each year in the United States. PE in children is associated with cardiac conditions and coagulopathic diseases such as sickle cell anemia or cancer. Young women are at risk for PE during pregnancy or while they take high-estrogen-content birth control pills. Adults, particularly the elderly, are at risk for PE because of deep vein thrombosis (DVT), cardiac conditions, and increased blood coagulability. Both genders and all races and ethnicities are at risk for PE.

Topical Glucocorticosteroids

There are very few reports in the literature on the experience with topical GCS for the treatment of cutaneous lymphomas even though they probably are the most frequently used modality in early stages (29). Topical GCS of low to high potency twice daily resulted in complete remission in 63 of stage T1 patients and partial remission in 31 of patients, i.e., a total response rate of 94 . The comparable figures for stage T2 patients were 25, 57, and 82 , respectively. Reversible depression of serum cortisol levels occurred in 13 of patients (29).

Clinical disorders of external potassium balance

Primary adrenal insufficiency (Addison's disease) is now a rare cause of hyperkalemia. Diagnosis is indicated by the combination of hyperkalemia and hyponatremia and is confirmed by a low aldosterone and a low plasma cortisol level that does not respond to adrenocorticotropic hormone treatment.

Renal hyperkalemia

When urinary K excretion is low, yet blood urea nitrogen and creatinine levels are not elevated and urine volume is at least 1 L daily and renal sodium excretion is adequate (about 20 mEq day), then either a defect in the secretion of renin or aldosterone or tubular resistance to aldosterone is likely. Low plasma renin and aldosterone levels, will confirm the diagnosis of hyporeninemic hypoaldosteronism. Addison's disease is suggested by a low serum cortisol, and the diagnosis is confirmed with a ACTH (Cortrosyn) stimulation test.

Computer Assisted Drug Design CADD Applied to Nuclear Receptors Potential and Limits

Nam et al. applied MD and molecular mechanics generalized Born surface area (MMGBSA) to simulate the different biological activity of DES on two closely related receptors, ERa and ERRg. DES acts as an agonist ligand on ERa and as an antagonist on ERRg.102 Furthermore, van Lipzig et al. designed a model based on MD techniques and linear interaction methods to predict the binding affinity of xenoestrogen ER. Such a model could be helpful in identifying environmental estrogens that could represent a risk factor as endocrine disrupters.103 Other members of the steroid subgroup have been the subject of detailed studies, e.g., von Langen et al. analyzed the binding of five steroids to hGR. They measured the in vitro binding affinity of aldosterone, cortisol, estradiol, progesterone, and testosterone in competition with the ligand dexamethasone, and tried to predict the theoretical relative binding affinities of these ligands. They performed separate 4-ns MD simulations of these complexes...

Liposuction and Abdominoplasty

Liposuction, the most common cosmetic surgery procedure performed on men, is a procedure that can improve the contour of your body by removing stubborn pockets of fat that you have not been able to remove through exercise or diet. During the procedure, the plastic surgeon uses a vacuum device to suction these unwanted fat deposits from specific areas of the body. For men, these areas are usually the abdomen, the flanks ( love handles ), or the chest. Other possible neck. The best candidates for liposuction are men of normal weight with firm Cosmetic skin who have excess fat deposits in certain areas of the body. Liposuction is not Surgery a weight-loss method you should be at or near your ideal weight before surgery.

Specific Mechanisms Potentially Contributing To The Pathophysiology Of Ptsd

While the precise mechanisms whereby even well-established biological risk factors may influence a person's acute response to trauma have not yet been fully elaborated, it is important to consider the possibilities. With respect to the neuroendocrine alterations, for example, since cortisol inhibits its own release through negative feedback at the level of the pituitary and the hypothalamus, lower circulating cortisol levels may disrupt (or delay) the process of physiological stress recovery by failing to inhibit the activation of the hypothalamus pituitary. This failure of inhibition will result in increased corticotropin releasing factor (CRF) stimulation, in synergy with other neuropeptides, such as arginine vasopressin, resulting in a higher magnitude adrenocorticotropin hormone (ACTH) response, which in turn might further stimulate the sympathetic nervous system through a direct effect 42 . Moreover, since glucocorticoids inhibit norepinephrine release from sympathetic nerve...

Pyrethroid Insecticides Cypermethrin

To determine which component of this reduced immune response might be due to effects on the HPA axis, as opposed to the SNS-induced effects, corticosterone and prolactin concentrations were measured in these mice. Corticosterone can inhibit an immune response and prolacton, which is induced by dopamine, can enhance T cell function. Alaniz et al. (1999) found that corticosterone was elevated during a primary infection but not during a secondary infection, indicating that corticosterone may be only partly responsible for the observed T cell suppression. In addition, prolactin concentrations were similar in both groups. These findings provide direct evidence that the SNS has a dramatic influence on the development of Th1 cell responsiveness. Interestingly, leptin-deficient knockout mice with reduced sympathetic outflow, show similar T cell deficiencies (Lord et al. 1998). These mice may also offer a potential explanation for why malnourished animals have suboptimal immune responses. In...

Primary Nursing Diagnosis

The main focus is to find the primary cause of the cortisol excess and remove it if possible. In the case of iatrogenic Cushing's syndrome, care is focused on alleviating as many of the signs and symptoms as possible when the therapy cannot be discontinued. If the patient has primary Cushing's syndrome from an adrenal tumor, the tumor is removed surgically. Even if the tumor is unilateral, the patient is treated for adrenal insufficiency after the surgery because the high levels of cortisol from the tumor may have caused the unaffected adrenal gland to atrophy. Patients with adrenal carcinoma are treated postoperatively with mitotane to treat metastases. Throughout the patient's recovery, fluid, electrolyte, and nutritional assessment and balance are essential. For secondary Cushing's syndrome from a pituitary tumor, the preferred option is a transsphenoidal adenectomy, a procedure that explores the pituitary gland to find microadenomas. It is successful in 20 to 70 of patients. A...

Biological Mechanisms Of

Sensitization occurs as a result of repetitive activation by trauma reminders, which elevate sensitivity of limbic networks (Post, Weiss, & Smith, 1995), and that as time progresses these responses become increasingly conditioned to trauma-related stimuli (LeDoux, Iwata, Cicchetti, & Reis, 1988). In support of these proposals, there is evidence that people who eventually develop PTSD display elevated resting heart rates in the initial week after trauma (Bryant, Harvey, Guthrie, & Moulds, 2000b Shalev et al., 1998 see also Blanchard, Hickling, Gaslovski, & Veazey, 2002). There is also evidence that lower cortisol levels shortly after trauma predict subsequent PTSD (McFarlane, Atchison, & Yehuda, 1997 Delahanty, Raimonde, & Spoonster, 2000). Cortisol may act as an anti-stress hormone that restores equilibrium, and lower cortisol levels may reflect an incapacity to lower arousal following trauma (Yehuda, 1997). The importance of increased arousal in the acute phase is also indicated by...

Exogenous Sources of Advanced Glycoxidation End Products

Animal studies have demonstrated the close relationship between increased dietary AGE intake and development and or progression of many diabetes-related complications. Nephropathy, postinjury restenosis, accelerated atherosclerosis, and delayed wound healing were significantly inhibited by lowering dietary AGE intake (27-30). Sebekova and associates demonstrated in the remnant-kidney rat model that feeding an AGE-rich diet for 6 weeks increases kidney weight and causes proteinuria, independent of changes in glomerular filtration rate, pointing to the detrimental effect of such diet on the kidney (31). Of particular interest are studies showing that a low-glycotoxin environment can prevent or delay significantly autoimmune diabetes in successive generations of nonobese diabetic (NOD) mice (32) and to improve the insulin-resistant state in db db (+ +) mice (33). Reduction in exposure to exogenous AGEs of db db (+ +) mice, lacking in leptin receptor and thus prone to insulin resistance...

Peripherally Secreted Hormones

Cortisol and Other Glucocorticoid Hormones Stimulates angiotensinogen release and decreases the release of the vasodilator prostaglandin I2. Cortisol inhibits collagen formation, fibroblast activity, and formation of bone by osteoblasts with a decrease plasma calcium levels by inhibiting osteoclast formation and activity. It provides feedback inhibition of ACTH and CRH release in the anterior pituitary and hypothalamus, respectively

Why Inhibit Il1

Patients given 30-100 ng kg of IL-1p had a sharp increase in cortisol levels 2-3 h after the injection. Similar increases were noted in patients given IL-1 a. In 13 of 17 patients given IL-1p, there was a fall in serum glucose within the first hour of administration, and in 11 patients, glucose fell to 70 mg 100 mL or lower (14). In addition, there were increases in ACTH and thyroid-stimulating hormone but a decrease in testosterone (17). No changes were observed in coagulation parameters such as prothrombin time, partial thromboplastin, or fibrinogen degradation products. This latter finding is to be contrasted to TNF-a infusion into healthy humans which results in a distinct coagulopathy syndrome (19).


Dependence and addiction are most appropriately understood as chronic medical disorders, with frequent recurrences to be expected. The neurobiology of these disorders is becoming well understood, but much remains unknown about the genomic mechanisms that predispose to addictions and that are activated, perhaps irreversibly, by long-term drug use. The mesolimbic reward system appears to be central to the development of the direct clinical consequences of chronic abuse, including tolerance, dependence, and addiction. Other brain areas and neurochemicals, including cortisol, also are relevant to dependence and relapse. Pharmacological interventions for addiction are highly effective for opiates, and we have illustrated three different approaches using an agonist, an antagonist, or a partial agonist. However, given the complex biological, psycho

Negative Life Events

Some investigators have also examined relations between life events and clinical-disease outcomes in HIV-positive persons. In a series of studies conducted in the pre-HAART era, Leserman and colleagues demonstrated that cumulative negative life events are associated with faster disease progression in HIV-positive MSM through a 9-year follow-up. Specifically, their findings indicated that higher cumulative negative life events equivalent to one severe stressor doubled the risk of progression to AIDS over 7.5 years (Leserman et al., 1999, Leserman et al., 2000). These results remained unchanged after controlling for demographic variables, baseline CD4+ counts, baseline HIV viral load, number of antiretroviral medications, and serum cortisol. Using similar covariates, a subsequent investigation showed that greater cumulative negative life events (equivalent to one severe stressor) increased the risk of developing an AIDS clinical condition by threefold at 9-year follow-up (Leserman et...

Stress Reactivity

What physiologic changes that accompany a person's reaction to stressors could explain the association between life events and HIV disease progression There is some evidence that distress and other negative mood states may be related to dysregulated hypothalamic-pituitary-adrenal (HPA) activity (e.g., elevated cortisol) in HIV-positive men (Gorman etal., 1991). Alterations in peripheral levels of adrenal hormones could conceivably down-regulate important cellular immune functions. However, there are methodological difficulties inherent in tying physiological stress responses (which may be short-lived) to field stressors or In asymptomatic HIV-positive MSM, investigators have observed blunted adrenocorticotropin hormone (ACTH) responsiveness to a variety of behavioral challenges (Kumar et al., 1993), but no differences in cortisol increases over time compared with HIV-negative men (Starr et al., 1996). The lack of cortisol differences may be an artifact of the timing of blood draws...

Cognitive Appraisals

Individual differences in cognitive appraisals of stressors may moderate the association between stressful life events and health status in HIV-positive persons. Specifically, one research group has demonstrated that positive illusions and unrealistically optimistic appraisals may confer health-protective benefits (Taylor et al., 2000). Results from an investigation of bereaved HIV-positive men indicated that those who engaged in cognitive processing (deliberate, effortful, and long-lasting thinking) about the death of a close friend or partner were more likely to report a major shift in values, priorities, or perspectives (i.e., finding meaning) following the loss (Bower et al., 1998). For those who were classified as finding meaning, positive health effects appeared to follow. Finding meaning predicted slower CD4+ decline and greater longevity over a 2- to 3-year follow-up period (Bower et al., 1998). Decreased cortisol is one plausible mediator of the effects of finding meaning on...


Antoni MH, Wagner S, Cruess D, Kumar M, Lutgen-dorf S, Ironson G, et al. (2000b). Cognitive behavioral stress management reduces distress and 24-hour urinary free cortisol among symptomatic HIV-infected gay men. Ann Behav Med 22 29-37. Antoni MH, Cruess D, Klimas N, Carrico AW, Maher K, Cruess S, et al. (2005). Increases in a marker of immune system reconstitution are predated by decreases in 24-hour urinary cortisol output and depressed mood during a 10-week stress management intervention in symptomatic HIV-infected gay men. J Psychosom Res 58 3-13. effects of spirituality on depressive symptoms and 24-hour urinary-free Cortisol in HIV-positive persons. JPsychosom Res 61(1) 51-58. Cruess D, Antoni MH, Schneiderman N, Ironson G, Fletcher MA, and Kumar, M (1999). Cognitive behavioral stress management effects on DHEA-S and serum cortisol in HIV seropositive men. Psychoneu-roendocrinology 24 537 549. Cruess DG, Antoni MH, McGregor BA, Kilbourn KM, Boyers AE, Alferi SM, et al. (2000a)....

Case Study

As mentioned above, the mouse model of IBS consisted of exposing animals to a combination of stress and infection with the nematode N. brasiliensis, leading to a transient jejunitis.26 To assess inflammation at different time points after Nb infection IgE serum levels and jejunal mast cell counts as well as histological analysis were determined. At 3 weeks postinfection, the acute phase of inflammation was finished. Cortisol levels were significantly increased in stressed animals, regardless of infection, at 21 days postinfection. Based on these results, the assessment of mRNA expression levels in viscera-specific neurons was done at 21 days postinfection. At this time-point both NG and DRG visceral

Stress Management

Many connections between stress and chronic conditions are known. Stress increases blood levels of adrenaline and cortisol, two so-called stress hormones. Cortisol can suppress the immune system, making people more susceptible to infectious diseases such as colds and flu. The effects of stress on the circulatory system (a quicker pulse, narrowed blood vessels, and thickened blood) can make people more susceptible to heart rhythm irregularities, angina (chest pain), high blood pressure, and stroke.

Brown Adipose Tissue

In a narrow sense, adipose tissue consists of many adipocytes, which form small aggregates in the connective tissue of organs (cf. Figs. 173,174). The cell aggregates often form small lobules, sometimes also called fat lobules. Among other tasks, they serve a mechanical purpose. White fatty tissue forms cushions in the palms or on the soles, for example, which will dampen an impact (structural fat, fat cushion). Fat lobules are also an energy store, such as storage fat, which occurs under the skin, in the colon, the omentum and many other locations. These fat lobules are usually encased by a connec- tive tissue like capsule. Connective tissue septa extend into the inside of the capsule and subdivide it into several smaller lobes. At the heel cushion, structural fat accumulates in small compartments with rather tough walls. The adjacent figure shows a part of a fat lobule from the subcutaneous tissue of a fetus. Note the closely packed round or polygonal fat cells. In this preparation,...


Many of the reaction steps involved in gluco-neogenesis are catalyzed by the same enzymes that are used in glycolysis (see p. 150). Other enzymes are specific to gluco-neogenesis and are only synthesized, under the influence of cortisol and glucagon when needed (see p. 158). Glycolysis takes place exclusively when needed in the cytoplasm, but gluconeogenesis also involves the mitochondria and the endoplasmic reticulum (ER). Gluconeogenesis consumes 4 ATP (3 ATP + 1 GTP) per glucose i. e., twice as many as glycolysis produces.


When smokers, adolescents as well as adults, stop smoking, they may experience nicotine withdrawal as defined by DSM-IV-TR (American Psychiatric Association, 2000). About 50 of adults who attempt to stop smoking will meet DSM-IV criteria for nicotine dependence (American Psychiatric Association, 1996), and young smokers show signs of addiction within several months of taking up the habit (DiFranza et al., 2002). Diagnostic criteria for nicotine withdrawal are presented in DSM-IV-TR. Associated features include craving, a desire for sweets, and impaired performance on tasks requiring vigilance (American Psychiatric Association, 2000). Depression and difficulty sleeping are not uncommon. Associated laboratory findings include a slowing on elec-troencephalograph, decreases in catecholamine and cortisol levels, rapid eye movement (REM) changes, impairment on neuropsychological testing, and decreased metabolic rate (American Psychiatric Association, 2000). Nicotine withdrawal also may be...


Body size is determined by both genetic and environmental factors. Genetic background may explain 40 or more of the variance in body mass in humans. The genetics of obesity are complex and likely involve the interaction between multiple genes. Through a number of studies, over 250 genes, markers, and chromosomal regions have been identified and associated with human obesity. The clinical importance of these associations is still under investigation. In rare cases, monogenic causes of obesity have been identified in humans. These mutations include the genes for leptin, leptin receptor, prohormone convertase, proopiomelanocortin, melanocortin-4 receptor, and SIM1. While these rare mutations have not provided a solution to the obesity epidemic, they have been critical to enabling our understanding the etiology of the disorder.

Risk factors

Any characteristic that increases exposure to unopposed estrogen increases the risk for endometrial cancer. Conversely, decreasing exposure to estrogen limits the risk. Unopposed estrogen therapy, obesity, anovulatory cycles and estrogen-secreting neoplasms all increase the amount of unopposed estrogen and thereby increase the risk for endometrial cancer. Smoking seems to decrease estrogen exposure, thereby decreasing the cancer risk, and oral contraceptive use increases progestin levels, thus providing protection.


Normal changes in elderly slightly impaired immune response, visual (presbyopia) and hearing (presbycusis) impairment, decreased muscle mass, increased fat deposits, osteoporosis, brain changes (decreased weight, enlarged ventricles and sulci), and slightly decreased ability to learn new material.


Members in this family include growth hormone (GH), granulocyte colony-stimulating factor (G-CSF), erythro-poietin (EPO), leukemia inhibiting factor (LIF), IL-6, IL-12 a-chain, leptin, and ciliary neurotrophic factor. The four helices of this family are each 25-residues long (Fig. 17.1.5A and D).

Hormone Regulation

Leptin and glucocorticoids have also been thought to be involved in adiponectin regulation, because leptin is also secreted by adipose tissue and both hormones affect insulin sensitivity (28,29). Although a cross-sectional study reported a strong inverse relationship between serum adiponectin and leptin levels (30), leptin given exogenously to rodents or humans had no significant effect on the plasma concentration of adiponectin (18,19). In vitro studies show that dexamethasone suppresses adiponectin gene expression (24,25), but in human studies, cortisol was found to have no correlation with circulating levels of adiponectin (19). Further studies are necessary to evaluate if glucocorticoids have a local effect on adiponectin production not reflected by their serum concentrations.


Cortisol is the primary glucocorticoid in man. It is synthesised from cholesterol in the zona fasciculata of the adrenal cortex. Synthesis of cortisol involves the Zona fasciculata (70 ) 21 carbon glucocorticoids (Cortisol, dehydroepiandrosterone cytochrome P450 system. Secretion is episodic and variable, demonstrating a diurnal circadian rhythm. In the circulation, cortisol is largely bound to a specific glucocorticoid binding a2-globulin called corticosteroid-binding globulin, with the remainder being either bound to albumin (15 -20 ), or unbound (5 ). Stimuli to cortisol secretion include stress, hypoglycaemia, ACTH, haemorrhage.

Cushings syndrome

An increased cortisol secretion rate, with raised 24 hour urinary free cortisol Plasma steroids Cortisol (9 am and 11 pm levels) aldosterone. Plasma peptides ACTH angiotensin II. Urine 24 hour steroid metabolite excretion free Cortisol 17-hydroxycorticosteroids 17-ketosteroids. Loss of circadian rhythm of cortisol secretion, with raised midnight serum cortisol levels. Loss of negative feedback of increased glucocorticoid levels on the pituitary, with failure of inhibition of pituitary ACTH secretion and thence of serum cortisol by the administration of low-dose dexamethasone. High-dose dexa-methasone will significantly lower serum cortisol in pituitary-dependent Cushing's disease but not in ACTH-independent Cushing's syndrome. Highdose suppression has no effect on ectopic ACTH syndromes.

From Gonads To Brain

The simple hypothesis, then, is that testosterone is secreted by the testes, and this leads to a masculinized nervous system in male animals. A number of observations in birds and frogs suggest that other factors are involved (Wade and Arnold, 1996 Kelley, 1997). They raise the possibility that female and male brains differ from one another even in the absence of gonadal signals. First, the level of estradiol required to masculinize the nervous system of female birds is quite high, and even these high levels do not result in a fully masculinized phenotype. In frogs, the level of circulating androgen is quite similar in male and female animals during development. Second, it has not been possible to block masculine development of the nervous system in male birds by manipulations designed to decrease estrogen. Third, when genetic female zebra finches are pharmacologically engineered to develop with testes, and with little to no ovarian tissue, their vocal conrol nuclei continue to have a...

H524 E2

Derivatives, and were thus proposed to function as lipid sensors.58-60 PPARs bind PPREs in the promoter region of target genes as heterodimers with RXR and regulate the expression of numerous genes involved in lipid and glucose metabolism PPARa is involved in fatty acid catabolism and inflammation PPARg is a master regulator of adipocyte differentiation (and thus fat storage), and is also involved in insulin sensitization (and thus glucose storage) and in inflammation. Although the role of PPARb is less well known, its importance in lipid metabolism has been increasingly recognized and PPARb has recently emerged as a potential new target for the treatment of atherosclerosis and cardiovascular disease.61-63


Multiplex Pcr Principle

The hormones that influence carbohydrate metabolism include the pepti-des insulin and glucagon a glucocorticoid, cortisol and a catecholamine, epinephrine (see p. 380). Insulin activates glycogen synthase ( 1 see p. 388), and induces several enzymes involved in glycolysis 3, 5, 7 . At the same time, insulin inhibits the synthesis of enzymes involved in gluconeogenesis (repression 4, 6, 8, 9 ). Glucagon, the antagonist of insulin, has the opposite effect. It induces gluconeogenesis enzymes 4, 6, 8, 9 and represses pyruvate kinase 7 , a key enzyme of glycolysis. Additional effects of glu-cagon are based on the interconversion of enzymes and are mediated by the second messenger cAMP. This inhibits glycogen synthesis 1 and activates glycogenolysis 2 . Epinephrine acts in a similar fashion. The inhibition of pyruvate kinase 7 by glucagon is also due to interconversion. Glucocorticoids mainly cortisol (see p. 374) induce all of the key enzymes involved in gluconeogenesis 4, 6, 8,...

Sex Hormones

In addition, there is evidence that hormones such as androgens and estrogens might influence cognition, even postnatally. For example, Maki, Rich, and Rosenbaum (2002) studied 16 young women during two different stages of their menstrual cycle. During the follicular stage of the menstrual cycle, both estrogen and progesterone are low, and during the midluteal phase, both are high. These investigators found that whereas explicit memory was unchanged during the high estrogen phase, visuospatial functions were not as well-performed as during the low estrogen phase. Choi and Silverman (2002) studied the relationships between route-learning strategies and circulating testosterone and estrogen in a large population of students by obtaining salivary assays from the students. They found that testosterone levels were positively correlated with the use of route-learning strategies in men, but not in women. In addition, Wisniewski (1998) compared the spatial ability of hypogonadal men to normal...

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