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Epinephrine reviews

(80 References)

Akamatsu, T., T. Yokoyama, et al. (2003). "[Endoscopic hemostasis for bleeding peptic ulcers]." Nippon Naika Gakkai Zasshi 92(1): 73-8.

Al-Muhsen, S., A. E. Clarke, et al. (2003). "Peanut allergy: an overview." Cmaj 168(10): 1279-85.

            Peanut allergy accounts for the majority of severe food-related allergic reactions. It tends to present early in life, and affected individuals generally do not outgrow it. In highly sensitized people, trace quantities can induce an allergic reaction. In this review, we will discuss the prevalence, clinical characteristics, diagnosis, natural history and management of peanut allergy.

Andersson, K. E. (2003). "Erectile physiological and pathophysiological pathways involved in erectile dysfunction." J Urol 170(2 Pt 2): S6-13; discussion S13-4.

            PURPOSE: The importance of signaling pathways in penile smooth muscles involved in normal erection and erectile dysfunction (ED) is discussed based on a review of the literature. MATERIALS AND METHODS: Erection is basically a spinal reflex that can be initiated by recruitment of penile afferents but also by visual, olfactory and imaginary stimuli. The generated nervous signals will influence the balance between the contractant and relaxant factors, which control the degree of contraction of penile smooth muscles and, thus, determine the functional state of the penis. The different steps involved in neurotransmission, impulse propagation and intracellular transduction of neural signals may be changed in different types of erectile dysfunction. RESULTS: Recent findings have suggested an important role for RhoA/Rho kinase in the regulation of cavernosal smooth muscle tone and that changes in this pathway may contribute to ED in various patient subgroups, eg diabetes and vascular disease. Neurogenic nitric oxide is still considered the most important factor for immediate relaxation of penile vessels and corpus cavernosum. However, endothelially generated nitric oxide seems essential for maintaining erection. Endothelial dysfunction can contribute to ED in several patient subgroups. In addition, in conditions associated with reduced function of nerves and endothelium, such as aging, hypertension, smoking, hypercholesterolemia and diabetes, circulatory and structural changes in the penile tissues can result in arterial insufficiency and defect muscle relaxation. CONCLUSIONS: Different types of ED often have overlapping pathophysiologies but may also have common pathways contributing to ED. Such pathways may be potential treatment targets.

Babisch, W. (2003). "Stress hormones in the research on cardiovascular effects of noise." Noise Health 5(18): 1-11.

            In recent years, the measurement of stress hormones including adrenaline, noradrenaline and cortisol has been widely used to study the possible increase in cardiovascular risk of noise exposed subjects. Since endocrine changes manifesting in physiological disorders come first in the chain of cause-effect for perceived noise stress, noise effects in stress hormones may therefore be detected in populations after relatively short periods of noise exposure. This makes stress hormones a useful stress indicator, but regarding a risk assessment, the interpretation of endocrine noise effects is often a qualitative one rather than a quantitative one. Stress hormones can be used in noise studies to study mechanisms of physiological reactions to noise and to identify vulnerable groups. A review is given about findings in stress hormones from laboratory, occupational and environmental studies.

Barbeau, H. and K. E. Norman (2003). "The effect of noradrenergic drugs on the recovery of walking after spinal cord injury." Spinal Cord 41(3): 137-43.

            Clonidine, a noradrenergic agonist has been associated with improved walking in both spinal cat and spinal cord injured (SCI) subjects.OBJECTIVES: The objective of this brief review is to compare the effects of clonidine on walking capabilities in SCI subjects with functionally complete and incomplete spinal cord injuries. STUDY DESIGN/METHODS: Both oral administration and intrathecal injection of clonidine were investigated. A motorized treadmill was used and harness support provided in most of the SCI subjects as no walking capabilities could be observed overground. A single subject design was used in these chronic SCI subjects. SETTING: Canada and France. RESULTS: In complete SCI subjects while receiving clonidine, none of the subjects was able to initiate independent stepping. In contrast, the greatest effects were found in SCI subjects with injuries that are incomplete but still severely disabling while minimal effects could be observed in the more functional SCI subjects. These effects on walking are observed in measures of walking speed, and electromyographic and kinematic patterns. Regardless of effects on walking, however, a consistent decrease of the flexor reflex amplitude could be observed in all SCI subjects independent of the severity of the lesion. CONCLUSION: This review demonstrated that clonidine could be a powerful anti-spasmodic drug in addition to improving locomotion in a limited number of SCI subjects. The mechanism, significance and implications of these results will be discussed.

Baurand, A. and C. Gachet (2003). "The P2Y(1) receptor as a target for new antithrombotic drugs: a review of the P2Y(1) antagonist MRS-2179." Cardiovasc Drug Rev 21(1): 67-76.

            MRS-2179 is a selective P2Y(1) receptor antagonist, a strong inhibitor of ADP-induced platelet aggregation in vitro and ex vivo. By i.v. administration to mice MRS-2179 increases resistance to thromboembolism induced by a mixture of collagen and epinephrine or by a tissue factor. Likewise, it significantly increases the time to thrombus formation in a ferric chloride-induced model of localized arterial thrombosis. MRS-2179 also confers resistance to localized venous thrombosis, which is dependent on thrombin generation and in which platelets play a relatively minor role as compared to stasis or activation of coagulation. These data provide considerable encouragement for the development of new P2Y(1) receptor antagonists. Nevertheless, the properties of MRS-2179 indicate that new compounds should be optimized in order to increase the half-life of the molecule in vivo and its selectivity and potency at the P2Y(1) receptor. Further directions include the synthesis of molecules with modifications of the nucleotide structure which replace the fragile moiety by a stable bond and should lead to a non-hydrolysable structure. In conclusion, P2Y(1) antagonists have been shown to be efficient antithrombotic agents. MRS-2179 is the first P2Y(1) antagonist with antithrombotic action. Its effectiveness demonstrates that the P2Y(1) receptor is a potentially promising target for drugs designed to treat thrombotic syndromes.

Ben-Abraham, R., E. Hadad, et al. (2003). "Vasopressin in cardiac arrest and vasodilatory shock: a forgotten drug for new indications." Isr Med Assoc J 5(4): 272-6.

            Vasopressin is a potent endogenous vasoconstrictor that increases blood pressure and systemic vascular resistance. The administration of exogenous vasopressin during closed and open cardiopulmonary resuscitation in humans was shown to be more effective than optimal doses of epinephrine in several clinical studies. We summarize here the recent experimental and clinical data on the use of vasopressin in cardiopulmonary resuscitation and septic shock. As the use of vasopressin in human resuscitation is now in its early stages, it is expected that accumulated future experience will shed more light regarding the risk-benefit aspects of its use.

Benavides, S., K. Nicol, et al. (2003). "Yersinia septic shock following an autologous transfusion in a pediatric patient." Transfus Apheresis Sci 28(1): 19-23.

            Although the literature on infections transmitted via transfused blood focuses on viruses, Yersinia enterocolitica can also cause severe infections in patients receiving transfusions. A 13-year-old patient developed severe sepsis after an autologous blood transfusion contaminated with Y. enterocolitica. The patient was an otherwise healthy female undergoing posterior spinal fusion for congenital scoliosis. Prior to surgery, the patient donated blood for perioperative and postoperative use. A few days before the donation, she had complained of abdominal pain and was experiencing mild diarrhea. The patient received four units of packed red blood cells (PRBCs) during the surgery. Intraoperatively, the patient developed fever up to 103.6 degrees F, became hypotensive requiring epinephrine and dopamine, and developed metabolic acidosis with serum bicarbonate concentration dropping to 16 mmol/l. The surgery team believed the patient was experiencing malignant hyperthermia and attempted to cool patient during the procedure. Postoperatively, the patient was transferred to the pediatric intensive care unit and treated for severe shock of unknown etiology. The patient further developed disseminated intravascular coagulation. The patient received supportive care and was started on ampicillin/sulbactam on postoperative day (POD) one which was changed to clindamycin, ciprofloxacin and tobramycin on POD two when blood cultures grew gram-negative bacilli. On POD three, cultures were identified as Y. enterocolitica and antibiotics were changed to tobramycin and cefotaxime based on susceptibility data. Sequelae of the shock included adult respiratory distress syndrome requiring intubation and a tracheostomy and multiple intracranial hemorrhagic infarcts with subsequent seizure disorder. Due to severe lower extremity ischemia, she required a bilateral below the knee amputation. The cultures of the snippets from the bags of blood transfused to the patient also grew Y. enterocolitica. This case illustrates the importance of considering transfusion related bacterial infections in patients receiving PRBCs. All patients in shock following any type of transfusion may require aggressive antibiotic therapy, until the diagnosis and etiology are known.

Berridge, C. W. and B. D. Waterhouse (2003). "The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes." Brain Res Brain Res Rev 42(1): 33-84.

            Through a widespread efferent projection system, the locus coeruleus-noradrenergic system supplies norepinephrine throughout the central nervous system. Initial studies provided critical insight into the basic organization and properties of this system. More recent work identifies a complicated array of behavioral and electrophysiological actions that have in common the facilitation of processing of relevant, or salient, information. This involves two basic levels of action. First, the system contributes to the initiation and maintenance of behavioral and forebrain neuronal activity states appropriate for the collection of sensory information (e.g. waking). Second, within the waking state, this system modulates the collection and processing of salient sensory information through a diversity of concentration-dependent actions within cortical and subcortical sensory, attention, and memory circuits. Norepinephrine-dependent modulation of long-term alterations in synaptic strength, gene transcription and other processes suggest a potentially critical role of this neurotransmitter system in experience-dependent alterations in neural function and behavior. The ability of a given stimulus to increase locus coeruleus discharge activity appears independent of affective valence (appetitive vs. aversive). Combined, these observations suggest that the locus coeruleus-noradrenergic system is a critical component of the neural architecture supporting interaction with, and navigation through, a complex world. These observations further suggest that dysregulation of locus coeruleus-noradrenergic neurotransmission may contribute to cognitive and/or arousal dysfunction associated with a variety of psychiatric disorders, including attention-deficit hyperactivity disorder, sleep and arousal disorders, as well as certain affective disorders, including post-traumatic stress disorder. Independent of an etiological role in these disorders, the locus coeruleus-noradrenergic system represents an appropriate target for pharmacological treatment of specific attention, memory and/or arousal dysfunction associated with a variety of behavioral/cognitive disorders.

Bhave, G. and R. W. t. Gereau (2003). "Growing pains: the cytoskeleton as a critical regulator of pain plasticity." Neuron 39(4): 577-9.

            Inflammatory mediators act on peripheral sensory neurons to produce pain and hypersensitivity after tissue injury. In this issue of Neuron, Dina et al. report that inflammatory mediators, such as epinephrine and prostaglandins, appear to couple to specific G protein-coupled receptor signaling pathways through plastic interactions with the cytoskeleton.

Black, C. P. (2003). "Systematic review of the biology and medical management of respiratory syncytial virus infection." Respir Care 48(3): 209-31; discussion 231-3.

            Respiratory syncytial virus, the leading cause of serious upper and lower respiratory tract infection in infants and children, accounts for 125,000 hospitalizations and 450 deaths annually in the United States. It also may predispose to development of asthma later in life. Annual epidemics occur from November to April, and virtually all infants are infected by age 2. Immunity is not durable; hence, reinfection occurs throughout life, although subsequent infections are nearly always mild. Certain populations (eg, premature infants, infants with chronic lung disease, and immunocompromised individuals) are at risk for severe morbidity and have higher risk of mortality. Infection is spread to the nose and eyes by large droplets and direct contact with secretions, and fomites may remain infectious for up to 12 hours. Nosocomial infection is common. The virus infects airway ciliated epithelial cells, spreading by the formation of syncytia. Cellular debris and inflammation cause airway obstruction, hyperinflation, localized atelectasis, wheezing, and impaired gas exchange. Both humoral and cellular immune response are critical to ending the acute infection, but wheezing and reactive airways may persist for as long as 5-10 years after acute infection. No cure exists for respiratory syncytial virus infection, but commonly employed palliative treatments include oxygen, inhaled beta(2) agonists, racemic epinephrine, dornase alfa, systemic and inhaled corticosteroids, inhaled ribavirin, and nasopharyngeal suctioning. Infants suffering severe lower airways disease may require mechanical ventilation. Prophylactic measures include rigorous infection control and administration of polyclonal (RSV-IGIV [respiratory syncytial virus - immunoglobulin intravenous]) and monoclonal (palivizumab) antibodies. The cost of the prophylactic antibody treatment is high; it is cost-effective for only the highest risk patients. Development of a vaccine remains far in the future. Application of evidence-based clinical practice guidelines is making both out-patient and in-patient therapy as effective and economical as possible.

Brubaker, R. F. (2003). "Targeting outflow facility in glaucoma management." Surv Ophthalmol 48 Suppl 1: S17-20.

            Glaucoma is often characterized by decreased pressure-sensitive aqueous outflow through the trabecular meshwork. This defect in pressure-sensitive aqueous outflow is evident from the low tonographic facility of outflow ("C") measured in many patients. The impairment in outflow facility causes the high intraocular pressure (IOP) and large diurnal IOP fluctuations often found in glaucoma. Because large diurnal IOP fluctuations have been shown to be a risk factor for glaucomatous progression, IOP-lowering therapy should aim to achieve a low, stable IOP. Pressure-sensitive aqueous outflow helps prevent and dampen pressure spikes; thus, drugs that enhance outflow facility, in particular, may stabilize as well as lower IOP. Outflow facility is an attractive target for glaucoma treatment because enhancing outflow facility tends to restore the self-regulating tendency of IOP. Older drugs such as the cholinergic pilocarpine and the catecholamine epinephrine act primarily by improving outflow facility. This action is also important for the recently introduced prostamide, bimatoprost, as well as for the prostaglandin prodrug, latanoprost. Realization of the importance of facility of outflow in lowering and stabilizing IOP will stimulate additional research into the mechanism of action of ocular hypotensive agents and will help optimize the medical treatment of glaucoma.

Cao, L., M. H. Weil, et al. (2003). "Vasopressor agents for cardiopulmonary resuscitation." J Cardiovasc Pharmacol Ther 8(2): 115-21.

            The primary goal of cardiopulmonary resuscitation is to reestablish blood flow to vital organs until spontaneous circulation is restored. Adrenergic vasopressor agents produce systemic vasoconstriction. This increases aortic diastolic pressure, and consequently, coronary and cerebral perfusion pressures. The pharmacologic responses to the adrenergic agents are mediated by a group of receptors that are classified as alpha (alpha), including alpha1 and alpha2, and beta (beta), including beta1 and beta2. Epinephrine, which has each of these adrenergic actions, has been the preferred adrenergic agent for the management of cardiac arrest for almost 40 years. Its primary efficacy is due to its alpha-adrenergic vasopressor effects. This contrasts with its beta-adrenergic actions, which are inotropic, chronotropic, and vasodilator. Accordingly, beta-adrenergic actions prompt increases in myocardial oxygen consumption, ectopic ventricular arrhythmias, and transient hypoxemia due to pulmonary arteriovenous shunting. This may account for the failure to demonstrate that epinephrine improves ultimate outcomes in human victims of cardiac arrest. Major interest has more recently been focused on selective alpha-adrenergic agonists. Both alpha1-agonists and alpha2-agonists are peripheral vasopressors. However, rapid desensitization of alpha1-adrenergic receptors occurs during cardiopulmonary resuscitation. Moreover, alpha1-adrenergic receptors are present in the myocardium, and beta1-agonists, like beta-adrenergic agonists, increase myocardial oxygen consumption. If they cross the blood-brain barrier, alpha2-adrenoceptor agonists also have centrally acting vasodilator effects. In the absence of central nervous system access, alpha2-adrenergic agonists have selective peripheral vasoconstrictor effects. Under experimental conditions of cardiopulmonary resuscitation, selective alpha2-agonists, which do not gain entrance into the brain, produce only systemic vasoconstriction. Experimentally, these selective alpha2-agonists are as effective as epinephrine for initial cardiac resuscitation and have the additional advantage of minimizing myocardial oxygen consumption during the global myocardial ischemia of cardiac arrest. Accordingly, myocardial ischemic injury during cardiopulmonary resuscitation is minimized, and postresuscitation myocardial function is preserved with improved survival.

Chung, S. C. (2003). "Current management of acute gastrointestinal bleeding." Scand J Gastroenterol Suppl(237): 9-12.

            Endoscopic therapy is now the first-line treatment for the management of acute ulcer bleeding. Of the many endoscopic methods available, combination treatment using adrenaline injection to arrest the active bleeding, followed by thermal or electrical coagulation to seal the vessel, is currently the most popular. Endoscopic ulcer haemostasis is technically demanding, and indiscriminate extrapolation of results of published trials without reference to the expertise available locally may be dangerous. The cost-effectiveness of a routine second-look endoscopy has not been established, but repeat treatment in those who have rebled has shown good results in experienced hands. Current evidence supports the use of a proton-pump inhibitor to prevent acid-pepsin digestion of the blood clot plugging the eroded blood vessel. Interplay between acid, Helicobacter, NSAID and 'stress' results in peptic ulceration. Eradication of Helicobacter is an important measure in the secondary prevention of ulcer bleeding. The inability to measure blood flow in the eroded artery before and after treatment, to reliably seal a large blood vessel and to detect rebleeding before significant blood loss are limiting factors in the current management of ulcer bleeding.

Church, N. I. and K. R. Palmer (2003). "Ulcers and nonvariceal bleeding." Endoscopy 35(1): 22-6.

            Peptic ulcer remains the commonest and most significant cause of nonvariceal upper gastrointestinal bleeding. The incidence of peptic ulcer bleeding is rising in elderly patients, particularly for duodenal ulcer. Patients presenting with upper gastrointestinal bleeding who have low Rockall scores are at low risk of rebleeding and death. These patients currently utilize considerable health-care resources, but could safely be managed at home. The Rockall score can be used to predict the risk of rebleeding and death following variceal bleeding, but for patients with ulcer bleeding, its ability to predict death is questioned. Acid suppression is effective in preventing rebleeding from peptic ulcer. Standard doses of intravenous omeprazole may be as effective as high-dose regimens. Oral omeprazole also reduces rebleeding following endoscopic therapy for peptic ulcer. Mallory-Weiss tears result in significant bleeding in 23 % of cases. Endoscopic therapy may only be required in cases in which active bleeding is present. Endoscopic therapy is effective and safe in patients with major peptic ulcer bleeding who are over 80 years old. For peptic ulcer, injection of larger volumes of epinephrine (adrenaline; mean 16.5 ml) are more effective than small volumes (mean 8 ml). Injection of normal saline alone is less effective than bipolar electrocoagulation. The addition of fibrin glue to epinephrine injection does not confer an additional benefit over epinephrine alone. Argon plasma coagulation can be used to treat a range of lesions in the gastrointestinal tract. It is also effective for treatment of bleeding ulcer, but is no better than established methods. Haemoclips may be useful in bleeding Mallory-Weiss tears, but their use is difficult in patients bleeding from peptic ulcer. The presence of a large ulcer and active bleeding at the time of endoscopy are independent predictors of failure of endoscopic therapy.

Crandall, C. G., J. Cui, et al. (2003). "Effects of heat stress on baroreflex function in humans." Acta Physiol Scand 177(3): 321-8.

            INTRODUCTION: Heat stress significantly reduces orthostatic tolerance in humans. The mechanism(s) causing this response remain unknown. The purpose of this review article is to present data pertaining to the hypothesis that reduced orthostatic tolerance in heat stressed individuals is a result of heat stress induced alterations in baroflex function. METHODS: In both normothermic and heat stressed conditions baroreflex responsiveness was assessed via pharmacological and non-pharmacological methods. In addition, the effects of heat stress on post-synaptic vasoconstrictor responsiveness were assessed. RESULTS: Generally, whole body heating did not alter baroreflex sensitivity defined as the gain of the linear portion of the baroreflex curve around the operating point. However, whole body heating shifted the baroreflex curve to the prevailing (i.e. elevated) heart rate and muscle sympathetic nerve activity. Finally, the heat stress impaired vasoconstrictor responses to exogenous administration of adrenergic agonists. CONCLUSION: Current data do not support the hypothesis that reduced orthostatic tolerance associated with heat stress in humans is due to impaired baroreflex responsiveness. This phenomenon may be partially due to the effects of heat stress on reducing vasoconstrictor responsiveness.

Cros, A. M. and Y. Herve (2003). "[Acute laryngeal dyspnea]." Rev Prat 53(9): 985-8.

            Laryngeal dyspnea is a life-threatening emergency situation. The diagnosis is clinical and made from the association of: inspiratory bradypnea, intercostal and sus-sternal inspiratory depression, with or without stridor. The aetiologies are most often laryngeal tumours or inflammatory oedema; incidence of epiglottitis has decreased due to vaccine against Haemophilus influenzae. Airway obstruction due to foreign body includes acute laryngeal dyspnea and reflex paroxysmal coughing without fever. Management of a laryngeal dyspnea depends on the aetiology and the severity of clinical symptoms. Medical treatment associates racemic epinephrine aerosol, steroids, and oxygenation. In the presence of severe dyspnea, intubation after anaesthetising the patient and positive pressure ventilation is required.

Dhabhar, F. S. (2003). "Stress, leukocyte trafficking, and the augmentation of skin immune function." Ann N Y Acad Sci 992: 205-17.

            Delayed type hypersensitivity (DTH) reactions represent cell-mediated immune responses that exert important immunoprotective (resistance to viruses, bacteria, and fungi) or immunopathologic (allergic or autoimmune hypersensitivity) effects. We have used the skin DTH response as an in vivo model to study neuro-endocrine-immune interactions. We hypothesized that just as an acute stress response prepares the cardiovascular and musculoskeletal systems for fight or flight, it may also prepare the immune system for challenges (e.g., wounding) that may be imposed by a stressor (e.g., an aggressor). Studies showed that acute (2 hours) stress experienced before primary or secondary cutaneous antigen exposure induces significantly enhanced skin DTH. This enhancement involves innate as well as adaptive immune mechanisms. Adrenalectomy eliminates the stress-induced enhancement of DTH. Acute administration of physiological concentrations of corticosterone and/or epinephrine to adrenalectomized animals enhances skin DTH. Compared with those in controls, DTH sites from acutely stressed or hormone-injected animals show significantly greater erythema and induration, numbers of infiltrating leukocytes, and levels of cytokine gene expression. In contrast to acute stress, chronic stress is immunosuppressive. Chronic exposure to corticosterone or acute exposure to dexamethasone significantly suppresses skin DTH. These results suggest that during acute stress, endogenous stress hormones enhance skin immunity by increasing leukocyte trafficking and cytokine gene expression at the site of antigen entry. Elucidation of mechanisms mediating a stress-induced enhancement of skin immune function is important because such immunoenhancement can have protective (wound healing, resistance to infection) or pathological (allergic or autoimmune hypersensitivity) consequences.

Dobson, H., S. Ghuman, et al. (2003). "A conceptual model of the influence of stress on female reproduction." Reproduction 125(2): 151-63.

            Intriguingly, similar neurotransmitters and nuclei within the hypothalamus control stress and reproduction. GnRH neurone recruitment and activity is regulated by a balance between stimulation, suppression and permissiveness controlled by noradrenaline, neuropeptide Y and serotonin from the brain stem, impact from glutamate in the medial preoptic area and neuropeptide Y in the arcuate nucleus, in opposition to the restraining influences of gamma-aminobenzoic acid within the medial preoptic area and opioids from the arcuate nucleus. Stress also activates neuropeptide Y perikarya in the arcuate nucleus and brain stem noradrenaline neurones. The latter project either indirectly, via the medial preoptic area, or directly to the paraventricular nucleus to release corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP). Within the medial preoptic area, GnRH neurones synapse with CRH and AVP axons. Stimulation of CRH neurones in the paraventricular nucleus also activates gamma-aminobenzoic acid and opioid neurones in the medial preoptic area and reduces GnRH cell recruitment, thereby decreasing GnRH pulse frequency. Oestradiol enhances stress-induced noradrenaline suppression of LH pulse frequency but when applied in the paraventricular nucleus or brain stem, and not in the medial preoptic area or arcuate nucleus. The importance of CRH and AVP in the medial preoptic area needs confirming in a species other than the rat, which uses adrenal activation to time the onset of the GnRH surge. Another stress-activated pathway involves the amygdala and bed of the nucleus stria terminalis, which contain CRH neurones and accumulate gamma-aminobenzoic acid during stress.

Dodt, C., P. Lonnroth, et al. (2003). "Sympathetic control of white adipose tissue in lean and obese humans." Acta Physiol Scand 177(3): 351-7.

            AIM: To induce lipolysis, catecholamines could reach the adipocyte via the blood stream after being released from the adrenal medulla or, alternatively, via neuronal release in the vicinity of the fat cell. Sympatho-neuronal effects on fat tissue lipolysis have been demonstrated in experimental animal models. However, the role of sympathetic nerves in the control of lipolysis in human white adipose tissue, which is sparsely innervated, has not been clarified. CONCLUSION: The present review summarizes evidence for a direct neuronal influence on lipolysis in humans.

Dragon, S. and R. Baumann (2003). "Hypoxia, hormones, and red blood cell function in chick embryos." News Physiol Sci 18: 77-82.

            The red blood cell function of avian embryos is regulated by cAMP. Adenosine A(2A) and beta-adrenergic receptor activation during hypoxic conditions cause changes in the hemoglobin oxygen affinity and CO(2) transport. Furthermore, experimental evidence suggests a general involvement of cAMP in terminal differentiation of avian erythroblasts.

Eckberg, D. L. (2003). "Bursting into space: alterations of sympathetic control by space travel." Acta Physiol Scand 177(3): 299-311.

            AIM: Astronauts return to Earth with reduced red cell masses and hypovolaemia. Not surprisingly, when they stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied autonomic function in six male astronauts (average +/- SEM age: 40 +/- 2 years) before, during, and after the 16-day Neurolab space shuttle mission. METHOD: We recorded electrocardiograms, finger photoplethysmographic arterial pressures, respiration, peroneal nerve muscle sympathetic activity, plasma noradrenaline and noradrenaline kinetics, and cardiac output, and we calculated stroke volume and total peripheral resistance. We perturbed autonomic function before and during spaceflight with graded Valsalva manoeuvres and lower body suction, and before and after the mission with passive upright tilt. RESULTS: In-flight baseline sympathetic nerve activity was increased above pre-flight levels (by 10-33%) in three subjects, in whom noradrenaline spillover and clearance also were increased. Valsalva straining provoked greater reductions of arterial pressure, and proportionally greater sympathetic responses in space than on Earth. Lower body suction elicited greater increases of sympathetic nerve activity, plasma noradrenaline, and noradrenaline spillover in space than on Earth. After the Neurolab mission, left ventricular stroke volume was lower and heart rate was higher during tilt, than before spaceflight. No astronaut experienced orthostatic hypotension or pre-syncope during 10 min of post-flight tilting. CONCLUSION: We conclude that baseline sympathetic outflow, however measured, is higher in space than on earth, and that augmented sympathetic nerve responses to Valsalva straining, lower body suction, and post-flight upright tilt represent normal adjustments to greater haemodynamic stresses associated with hypovolaemia.

Eisenhofer, G. (2003). "Editorial: biochemical diagnosis of pheochromocytoma--is it time to switch to plasma-free metanephrines?" J Clin Endocrinol Metab 88(2): 550-2.

Ellis, A. K. and J. H. Day (2003). "Diagnosis and management of anaphylaxis." Cmaj 169(4): 307-11.

            Anaphylaxis is a severe systemic allergic reaction that is potentially fatal. It requires prompt recognition and immediate management. Anaphylaxis has a rapid onset with multiple organ-system involvement and is mostly caused by specific antigens in sensitized individuals. Reactions typically follow a uniphasic course, however, 20% will be biphasic in nature. The second phase usually occurs after an asymptomatic period of 1-8 hours, but there may be a 24-hour delay. Protracted anaphylaxis may persist beyond 24 hours. Concurrent beta-blocker therapy may adversely affect the response to management. Epinephrine is the treatment of choice and should be administered immediately. Secondary measures include circulatory support, H(1) and H(2) antagonists, corticosteroids and, occasionally, bronchodilators. Post-treatment observation of these patients is necessary, and they should remain within ready access of emergency care for the following 48 hours.

Ellis, A. K. and J. H. Day (2003). "The role of epinephrine in the treatment of anaphylaxis." Curr Allergy Asthma Rep 3(1): 11-4.

            Epinephrine is the cornerstone of anaphylaxis management. Its administration should be immediate upon evidence of the occurrence of anaphylaxis. Delays in administration may be fatal. The most appropriate administration is 0.3 to 0.5 mL of 1:1000 dilution intramuscularly for adults and 0.01 mg/kg for children, given in the lateral thigh. Patients with known anaphylactic reactivity should be prescribed an epinephrine auto-injector to be carried at all times for treatment of potential recurrences. Education of the patient or parent regarding the proper use of this tool is paramount.

Esler, M., G. Lambert, et al. (2003). "Sympathetic nerve activity and neurotransmitter release in humans: translation from pathophysiology into clinical practice." Acta Physiol Scand 177(3): 275-84.

            AIM: There has been a revolution in cardiovascular neuroscience in recent years with, in some cases, translation into clinical practice of the knowledge of pathophysiology gained through application of sympathetic nerve recording and catecholamine isotope dilution methodology. OBESITY-RELATED HYPERTENSION: An earlier hypothesis, based on findings in most models, was that weight gain in obesity is due in part to sympathetic nervous underactivity reducing thermogenesis. Microneurography and regional noradrenaline spillover measurements in human obesity have disproven this hypothesis, weakening the case for the use of beta3-adrenergic agonists to stimulate thermogenesis. Sympathetic nerve firing rates in post-ganglionic fibres directed to the skeletal muscle vasculature are increased, as is renal sympathetic tone, with a doubling of the spillover rate of noradrenaline from the kidneys. Given these findings, antiadrenergic antihypertensive drugs may be the preferred agents for obesity-related hypertension, but this has not been adequately tested. ESSENTIAL HYPERTENSION: Whether stress causes high blood pressure, previously hotly debated, has been under recent review by an Australian Government body, the Specialist Medical Review Council. Despite medicolegal implications, the ruling was that stress is one proven cause of hypertension. The judgment was reached after consideration of the epidemiological evidence, but in particular the described neural pathophysiology of essential hypertension: (a) persistent sympathetic nervous stimulation is commonly present, (b) suprabulbar projections of noradrenergic brainstem neurones are activated and (c) adrenaline is released as a cotransmitter in sympathetic nerves. These were taken to be biological markers of stress. CARDIAC FAILURE: At one time, the failing heart was thought to be sympathetically denervated. Longterm administration of inotropic adrenergic agonists, to provide the cardiac catecholamine stimulation thought to be lacking, increased mortality. Noradrenaline isotope dilution methodology subsequently demonstrated that the sympathetic outflow to the heart was preferentially activated, cardiac noradrenaline spillover being increased as much as 50-fold. The level of stimulation of the cardiac sympathetic nerves was the most powerful predictor of death. These observations provide the theoretical foundation for the very successful introduction of beta-adrenergic blockers for treatment of heart failure.

Faghihi, G. and A. H. Siadat (2003). "Cutaneous anthrax associated with facial palsy: case report and literature review." J Dermatolog Treat 14(1): 51-3.

            BACKGROUND: Anthrax is primarily an animal disease. Bacillus anthracis, the causal agent in anthrax, is a Gram-positive rod. Humans can acquire anthrax by industrial exposure to infected animals or animal products. METHODS: Reported here is the case of a 48-year-old male farm worker from Iran with a history of direct contact with herds. He presented after 6 days of fever with toxicity and a crusted ulcer on the face that was later confirmed bacteriologically to be cutaneous anthrax. He was treated with large doses of intravenous penicillin and corticosteroids along with multiple subcutaneous epinephrine injections that were used to control the infection and massive facial edema. RESULTS: After 14 days, he partially recovered; however, ipsilateral facial nerve palsy developed and persisted despite therapeutic efforts. CONCLUSION: It is not possible to conclude whether early diagnosis and treatment of anthrax results in a lower risk of complications. Facial palsy can be added to the list of variable complications of the cutaneous effects of anthrax.

Floras, J. S. (2003). "Sympathetic activation in human heart failure: diverse mechanisms, therapeutic opportunities." Acta Physiol Scand 177(3): 391-8.

            Plasma noradrenaline (NA) concentrations relate both to the severity of heart failure, and to its impact on survival, but have shortcomings that limit their usefulness as measures of sympathetic discharge. Neural recordings and the isotopic dilution method for determining organ-specific rates of NA spillover into plasma have enhanced our understanding of mechanisms responsible for sympathetic activation. Because the arterial baroreceptor reflex control of heart rate is impaired in heart failure, a parallel reduction in the reflex inhibition of sympathetic outflow has been assumed. However, human heart failure is characterized by rapidly responsive arterial baroreflex regulation of muscle sympathetic nerve activity (MSNA), attenuated cardiopulmonary reflex modulation of MSNA, and activation of a cardiac-specific sympatho-excitatory reflex related to increased cardiopulmonary filling pressures. Together, these baroreceptor mediated mechanisms account only, in part, for the time course and magnitude of adrenergic activation in heart failure. Non-baroreflex sympatho-excitatory mechanisms include: a metaboreflex arising from exercising skeletal muscle, mediated, in part, by adenosine, co-existing sleep apnoea, and pre-junctional facilitation of NA release. Thus, sympathetic activation in the setting of impaired systolic function reflects the net balance and interaction between augmented excitatory and diminished inhibitory influences. Variation, between patients, in the dynamics, magnitude and progression of sympathetic activation mandates an individualized approach to investigation and therapy. Excessive sympathetic outflow to the heart and periphery can be addressed by several complimentary strategies: attenuating these sympatho-excitatory stimuli, modulating the neural regulation of NA release, and blocking the actions of catecholamines at post-junctional receptors.

Forsyth, R. and B. Jayamoni (2003). "Noradrenergic agonists for acute traumatic brain injury." Cochrane Database Syst Rev(1): CD003984.

            BACKGROUND: Although there have been considerable gains in understanding the cascade of events that lead to secondary injury after traumatic brain injury (TBI), efforts to translate this understanding into new therapeutic, so-called neuroprotective, approaches have so far proven disappointing. Animal models suggest an alternative strategy: agents enhancing monoaminergic transmission, particularly amphetamines, have been shown to promote motor recovery from focal brain injury and it has been suggested that this might represent a complementary means of therapeutic intervention in the later post-injury phase. OBJECTIVES: To evaluate the evidence that amphetamines improve final outcome after traumatic brain injury. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Science Citation Index, Cochrane Controlled Trials Register and the Cochrane Injuries Group's Specialised Register of Controlled Trials. Researchers and authors of published trials were also contacted. SELECTION CRITERIA: Randomised controlled trials comparing the use of a noradrenergic agonist (together with conventional non-pharmacological rehabilitative therapy) versus conventional non-pharmacological rehabilitative therapy alone. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened records, extracted data and assessed trial quality. MAIN RESULTS: Although there is a limited clinical literature addressing this topic, none of the studies identified fully meets inclusion criteria for this review. REVIEWER'S CONCLUSIONS: At present there is insufficient evidence to support the routine use of methylphenidate or other amphetamines to promote recovery from TBI.

Frenkel, E. P. and E. F. Mammen (2003). "Sticky platelet syndrome and thrombocythemia." Hematol Oncol Clin North Am 17(1): 63-83.

            Platelets are intimately involved in the pathogenesis of thromboembolic disorders, especially arterial forms of thrombosis. Although most arterial thromboses develop on the basis of endothelial injuries, some do not. In these instances "hyperactive" platelets could be the cause. Hyperaggregable platelets have been described in association with a number of acquired disease entities whereby the cause-and-effect relationship is unclear. In contrast, the sticky platelet syndrome is a congenital, autosomal dominant disorder, characterized by hyperaggregable platelets in response to ADP, epinephrine, or both. Patients usually seek treatment for transient or permanent arterial vascular occlusions. These are often precipitated by stressful events. Treatment with low-dose aspirin (81 mg/day) reverses clinical symptoms and hyperaggregability in the laboratory.

Frieri, M. (2003). "Neuroimmunology and inflammation: implications for therapy of allergic and autoimmune diseases." Ann Allergy Asthma Immunol 90(6 Suppl 3): 34-40.

            OBJECTIVES: To review concepts of neuroendocrinoimmunology and provide an overview of the role of immune dysregulation, stress, and the understanding of the pathogenesis and treatment of allergic and autoimmune diseases. DATA SOURCES: Articles include original research papers, review articles, and references identified from the bibliographies of pertinent articles. RESULTS: Neuroendocrine hormones triggered during stress may lead to immune dysregulation or altered or amplified cytokine production, resulting in atopic, autoimmune diseases or decreased host defense. Various types of transmitter substances of the neuroendocrine-immune (NEI) network include epinephrine, norepinephrine, acetylcholine, substance P, vasoactive intestinal peptide, glucagon, insulin, cytokines, growth factors, and numerous other mediators. The stress response and induction of a dysregulation of cytokine balance can trigger the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Disorders in which abnormalities in immune function are mediated by the NEI network include allergic diseases: allergic rhinitis, atopic dermatitis, and gastro-intestinal allergies and asthma through overproduction of neuropeptides and cytokines. The multiple roles of Th2 cells in maintaining allergic inflammation and altering the balance between Th1 and Th2 responses are important mechanisms for allergic inflammation and tissue damage. In addition, several autoimmune diseases mediated by NEI network such as rheumatoid arthritis, systemic lupus erythematosus, and diabetes mellitus can be attributable to immune dysregulation. CONCLUSIONS: Understanding the NEI network will contribute to novel treatments for immediate and late allergic reactions. Chronic stress or depression could lead to decreased host defenses, decreased response to vaccines, viral susceptibility, or malignancy. Treatment of allergic, autoimmune diseases and asthma should include stress management and behavioral intervention to prevent stress-related immune imbalances.

Garcia Sanchez, M. V., P. Lopez Vallejos, et al. (2003). "[Factors associated with failure of endoscopic therapy in gastric ulcer bleeding]." Gastroenterol Hepatol 26(4): 227-33.

            INTRODUCTION: Endoscopic therapy is an effective technique in the control of bleeding due to peptic ulcer. However, bleeding persists or recurs in as many as 10-30% of patients. Gastric and duodenal ulcers present different clinical and endoscopic features and consequently the efficacy of endoscopic therapy and the factors associated with its failure should be studied separately.Objectives: To analyze the efficacy of endoscopic therapy in patients at high risk of persistent or recurrent bleeding due to gastric ulcer and to identify the factors associated with the failure of this technique. PATIENTS AND METHODS: We performed a retrospective study based on a clinical intervention protocol. Two hundred eight patients admitted for bleeding secondary to gastric ulcer with active bleeding or stigmas of recent bleeding who received endoscopic therapy between January 1992 and December 2001 were analyzed. Clinical, laboratory and endoscopic variables on admission, as well as the medical treatment and endoscopic procedure applied, were registered. Endoscopy was performed within 12 hours of admission. Patients were classified according to their response to endoscopic therapy: a) patients with limited bleeding, and b) patients with persistent or recurrent bleeding due to therapeutic failure. Intervention in patients with therapeutic failure was performed according to a previously established protocol. Variables that were statistically significant in the univariate analysis were included in a logistic regression model to identify those with an independent predictive value for failure of endoscopic therapy. RESULTS: Definitive hemostasis was achieved after initial therapy in 181 patients (87%). The efficacy of a second procedure increased the percentage of hemostasis to 91% of the patients. In the logistic regression model, the only variables that were independently associated with initial therapeutic failure were: hemodynamic status on admission (p = 0.016; OR = 3.99), the need for transfusion of blood products prior to endoscopy (p = 0.025; OR = 3.48), upper localization of the gastric ulcer (p = 0.050; OR = 3.08) and unsatisfactory endoscopic therapy (p = 0.009; OR = 17.39). CONCLUSION: These variables could contribute to the early identification of a subgroup of patients, which would enable us to increase medical-surgical surveillance and offer them other therapeutic alternatives.

Garcia-Poblete, E., H. Fernandez-Garcia, et al. (2003). "Sympathetic sprouting in dorsal root ganglia (DRG): a recent histological finding?" Histol Histopathol 18(2): 575-86.

            During the nineties it was described, as an original finding, the existence of afferent amyelinic nerve endings in animal dorsal root ganglia (DRG) caused by diverse experimental lesions. These works do not take into account the historical studies carried out by Ehrlich (1886), Ramon y Cajal (1890) and Dogiel (1885) among others. Ramon y Cajal (1899) confirmed the existence of these nerve endings naming them after their discoverer as "Dogiel's arborisations". Ramon y Cajal claims that these endings originate from fibres of sympathetic nature, something supported by later authors devoted to this topic. In any case, the same authors remarked already a possible relationship with pathological phenomena, nonetheless always referring to the frequent occasions in which the same images appeared in healthy animals. In this work we review the bibliography about the classically named "Terminal Dogiel's nests" which in modern literature have been referred to as sprouting of sympathetic axons in dorsal root ganglia likely related with sympathetically maintained pain. Furthermore, we present the finding, not described up to date, of multiple afferent amyelinic nervous endings related with the "Terminal Dogiel's nests" observed in different DRG from young adult healthy rabbits.

Golden, D. B. (2003). "Stinging insect allergy." Am Fam Physician 67(12): 2541-6.

            Systemic allergic reactions to insect stings are estimated to occur in about 1 percent of children and 3 percent of adults. In children, these reactions usually are limited to cutaneous signs, with urticaria and angioedema; adults more commonly have airway obstruction or hypotension. Epinephrine is the treatment of choice for acute anaphylaxis, and self-injection devices should be prescribed to patients at risk for this allergic reaction. Stinging insect allergy can be confirmed by measurement of venom-specific IgE antibodies using venom skin tests or a radioallergosorbent test. Patients with previous large local reactions have a 5 to 10 percent risk of experiencing systemic reactions to future stings. Patients with previous systemic reactions have a variable risk of future reactions: the risk is as low as 10 to 15 percent in those with the mildest reactions and in some children, but as high as 70 percent in adults with the most severe recent reactions. Because of demonstrated efficacy (98 percent), venom immunotherapy is recommended for use in patients who are at risk for severe systemic reactions to future insect stings. Venom immunotherapy is administered every four to eight weeks for at least five years. Immunotherapy may be needed indefinitely in patients at higher risk for recurrence of anaphylaxis after treatment is stopped.

Goldstein, L. B. (2003). "Neuropharmacology of TBI-induced plasticity." Brain Inj 17(8): 685-94.

            PRIMARY OBJECTIVE: The purpose of this report is to review both fundamental studies in laboratory animals and preliminary clinical data suggesting that certain drugs may affect behavioural recovery after brain injury. MAIN OUTCOMES AND RESULTS: Laboratory studies show that systemically-administered drugs that affect specific central neurotransmitters including norepinephrine and GABA influence affect recovery in a predictable manner. Although some drugs such as d-amphetamine have the potential to enhance recovery, others such as neuroleptics and other central dopamine receptor antagonists, benzodiazepines and the anti-convulsants phenytoin and phenobarbital may be detrimental. In one study, 72% of patients with traumatic brain injury received one or a combination of the drugs that may impair recovery based on both animal experiments and studies in recovering stroke patients. CONCLUSIONS: Until the true impact of these classes of drugs are better understood, care should be exercised in the use of medications that may interfere with the recovery process in patients with traumatic brain injury. Additional research needs to be completed before the clinical efficacy of drugs that may enhance recovery can be established.

Goldstein, D. S., G. Eisenhofer, et al. (2003). "Sources and significance of plasma levels of catechols and their metabolites in humans." J Pharmacol Exp Ther 305(3): 800-11.

            Human plasma contains several catechols, including the catecholamines norepinephrine, epinephrine, and dopamine, their precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), and their deaminated metabolites, dihydroxyphenylglycol, the main neuronal metabolite of norepinephrine, and dihydroxyphenylacetic acid, a deaminated metabolite of dopamine. Products of metabolism of catechols include 3-methoxytyrosine (from L-DOPA), homovanillic acid and dopamine sulfate (from dopamine), normetanephrine, vanillylmandelic acid, and methoxyhydroxyphenylglycol (from norepinephrine), and metanephrine (from epinephrine). Plasma levels of catechols and their metabolites have related but distinct sources and therefore reflect different functions of catecholamine systems. This article provides an update about plasma levels of catechols and their metabolites and the relevance of those levels to some issues in human health and disease.

Gorman, J. M. (2003). "New molecular targets for antianxiety interventions." J Clin Psychiatry 64 Suppl 3: 28-35.

            Recent advances in neuroscience and understanding in the etiology of anxiety have led researchers to new targets for treatments that are proving to be at least as effective as benzodiazepines, which have been the traditional treatment for anxiety for over 40 years. The gamma-aminobutyric acid (GABA) system has long been targeted in anxiety interventions via benzodiazepines, but better understanding of its role in anxiety disorders has led to the development of partial benzodiazepine-GABA receptor antagonists and agents that target specific subunits of the GABA-A receptor and that manipulate GABA levels. The recognition that antidepressants are effective in anxiety even in nondepressed patients has caused researchers to develop antianxiety agents that affect the serotonin and norepinephrine systems. Other neurotransmitter systems such as corticotropin-releasing factor and substance P appear to be abnormally regulated in patients with anxiety disorders, so antagonists of these neurotransmitters may prove to be beneficial anxiolytics. Meanwhile, antistress and antianxiety effects through neurogenesis may be possible with the use of agents that decrease glutamate neurotransmission, such as metabotropic glutamate receptor agonists. Finally, the stimulation of neurotrophic factors, such as brain-derived neurotrophic factor, which appears to enhance neurogenesis, may also prove to have anxiolytic effects.

Gothert, M. (2003). "Modulation of noradrenaline release in human cardiovascular tissues." Pharmacol Toxicol 92(4): 156-9.

Greden, J. F. (2003). "Physical symptoms of depression: unmet needs." J Clin Psychiatry 64 Suppl 7: 5-11.

            The burden of depression on society is sizable. Innate to this burden are underdiagnosis and under-treatment of unipolar and bipolar major depressive disorder in all parts of the health care system in part due to underrecognition of the physical symptoms that commonly are core components of major depressive disorder. Physical pains especially complicate the diagnosis of depression. Many patients de-emphasize psychosocial symptoms while emphasizing pains as their primary or sole complaints. There is a high correlation between the number of physical symptoms reported and the presence of depression. Additionally, patients with residual physical and emotional symptoms following treatment for depression appear to be at higher risk of relapse compared with those who have no residual symptoms. Complex genetic vulnerabilities underlie the depressive diathesis, and stress appears to be an accentuation for the gene expression that sets off episodes of depression in persons with these predispositions. If underdiagnosis interferes and acute treatment is not implemented early and effectively for initial episodes of depression and maintained after remission, individuals with genetic vulnerabilities may experience a pattern of recurrences, cycle acceleration, and increased severity. Serotonin and norepinephrine may be shared neurochemical links that tie depression and physical symptoms together. Thus, it is reasonable to hypothesize that antidepressants that incorporate both serotonin and norepinephrine reuptake inhibition might be a more efficacious treatment approach for patients with physical symptoms of depression.

Guimaraes, S., M. Morato, et al. (2003). "Hypertension due to blockade of adenosine receptors." Pharmacol Toxicol 92(4): 160-2.

            Chronic treatment of rats with 90 microg/kg/day DPSPX (1,3-dipropyl-8-sulphophenylxanthine) during seven days leads to a hypertensive state which is characterized by marked morphological changes of the blood vessel walls as well as by important functional alterations. While the angiotensin-converting enzyme (ACE) inhibitor captopril and the antagonist of angiotensin II AT 1 receptors losartan prevent the development of both hypertension and morphological changes, the selective beta1-adrenoceptor antagonist atenolol could prevent only the increase in blood pressure. It is concluded that at least two factors are involved in the development of the hypertensive state.

Inoue, T., Y. Kitaichi, et al. (2003). "[Treatment strategy of refractory depression and its presynaptic mechanism of action]." Nihon Shinkei Seishin Yakurigaku Zasshi 23(1): 11-20.

            Most antidepressants used in Japan are reuptake inhibitors of monoamine, such as noradrenaline and serotonin. Incidence of refractory depression, which is resistant to at least two monoamine reuptake inhibitors, is 10-20%. ECT and the addition of lithium, thyroid hormones or dopamine agonists is used for the treatment of refractory depression. Bupropion and MAO inhibitors are also effective for refractory depression but not approved in Japan. The presynaptic mechanism of action of these antidepressants has been studied by in vivo microdialysis studies. Serotonin reuptake inhibitors increase extracellular serotonin concentrations in the brain. Noradrenaline reuptake inhibitors increase extracellular noradrenaline concentrations in the brain, and increase extracellular dopamine concentrations in the frontal cortex, but not in the nucleus accumbens or striatum. ECT and MAO inhibitors increase extracellular serotonin concentrations in the brain, and ECT, bupropion and MAO inhibitors increase extracellular noradrenaline concentrations in the brain. In contrast to monoamine reuptake inhibitors, ECT, bupropion and MAO inhibitors increase extracellular dopamine concentrations not only in the frontal cortex but also in the nucleus accumbens and striatum. The facilitation of mesolimbic or nigrostriatal dopamine neurotransmission may be the mechanism of action behind these treatments' efficacies for refractory depression. Although there are only a few studies concerning the mechanism of action of augmentation therapy, recent studies demonstrated that subchronic lithium treatment increases basal concentrations of extracellular serotonin in the frontal cortex and hippocampus. Subchronic lithium further increases SSRI-induced increases in extracellular serotonin concentrations, and this effect is suggested to be the mechanism of action for lithium augmentation of antidepressants.

Kafka, M. P. (2003). "The monoamine hypothesis for the pathophysiology of paraphilic disorders: an update." Ann N Y Acad Sci 989: 86-94; discussion 144-53.

            A monoamine hypothesis for the pathophysiology of paraphilic disorders was first articulated in 1997 by Kafka. This hypothesis was based on four converging lines of empirical evidence. First, the monoamine neurotransmitters, dopamine, norepinephrine, and serotonin serve a modulatory role in human and mammalian sexual motivation, appetitive, and consummatory behavior. Second, the sexual effects of pharmacological agents that affect monoamine neurotransmitters can have both significant facilitative and inhibitory effects on sexual behavior. Third, paraphilic disorders appear to have Axis I comorbid associations with nonsexual psychopathologies that are associated with monoaminergic dysregulation. Last, pharmacological agents that enhance central serotonergic function in particular, have been reported to ameliorate paraphilic sexual arousal and behavior. Contemporary data supporting or refuting a monoaminergic hypothesis as a biological component associated with paraphilic sex offending behaviors will be reviewed. Particular attention will be given to pharmacological-metabolic probe studies, reports of Axis I comorbidity, the proposed role of disinhibited sexual motivation or sexual appetitive behavior, and cumulative pharmacological treatment data sets.

Kagan, R. S. (2003). "Food allergy: an overview." Environ Health Perspect 111(2): 223-5.

            Food allergy affects between 5% and 7.5% of children and between 1% and 2% of adults. The greater prevalence of food allergy in children reflects both the increased predisposition of children to develop food allergies and the development of immunologic tolerance to certain foods over time. Immunoglobulin (Ig) E-mediated food allergies can be classified as those that persist indefinitely and those that are predominantly transient. Although there is overlap between the two groups, certain foods are more likely than others to be tolerated in late childhood and adulthood. The diagnosis of food allergy rests with the detection of food-specific IgE in the context of a convincing history of type I hypersensitivity-mediated symptoms after ingestion of the suspected food or by eliciting IgE-mediated symptoms after controlled administration of the suspected food. Presently, the only available treatment of food allergies is dietary vigilance and administration of self-injectable epinephrine.

Klein, D. C., S. Ganguly, et al. (2003). "14-3-3 proteins in pineal photoneuroendocrine transduction: how many roles?" J Neuroendocrinol 15(4): 370-7.

            Recent studies suggest that a common theme links the diverse elements of pineal photoneuroendocrine transduction--regulation via binding to 14-3-3 proteins. The elements include photoreception, neurotransmission, signal transduction and the synthesis of melatonin from tryptophan. We review general aspects of 14-3-3 proteins and their biological function as binding partners, and also focus on their roles in pineal photoneuroendocrine transduction.

Langfort, J., M. Donsmark, et al. (2003). "Hormone-sensitive lipase in skeletal muscle: regulatory mechanisms." Acta Physiol Scand 178(4): 397-403.

            AIM: The enzymatic regulation of intramuscular triacylglycerol (TG) breakdown has until recently not been well understood. Our aim was to elucidate the role of hormone-sensitive lipase (HSL), which controls TG breakdown in adipose tissue. METHODS: Isolated rat muscle as well as exercising humans were studied. RESULTS: The presence of HSL was demonstrated in all muscle fibre types by Western blotting of muscle fibres isolated by collagenase treatment or after freeze-drying. The content of HSL varies between fibre types, being higher in oxidative than in glycolytic fibres. Analysed under conditions optimal for HSL, neutral lipase activity in muscle can be stimulated by adrenaline as well as by contractions. These increases are abolished by presence of anti-HSL antibody during analysis. Moreover, immunoprecipitation with affinity-purified anti-HSL antibody causes similar reductions in muscle HSL protein concentration and in measured neutral lipase responses to contractions. The immunoreactive HSL in muscle is stimulated by adrenaline via beta-adrenergic activation of protein kinase A (PKA). From findings in adipocytes it is likely that PKA phosphorylates HSL at residues Ser563, Ser659 and Ser660. Contraction probably also enhances muscle-HSL activity by phosphorylation, because the contraction-induced increase in HSL activity is increased by the protein phosphatase inhibitor okadaic acid and reversed by alkaline phosphatase. A novel signalling pathway in muscle by which HSL activity may be stimulated by protein kinase C (PKC) via extracellular signal regulated kinase (ERK) has been demonstrated. In contrast to previous findings in adipocytes, in muscle activation of ERK is not necessary for stimulation of HSL by adrenaline. However, contraction-induced HSL activation is mediated by PKC, at least partly via the ERK pathway. In fat cells ERK is known to phosphorylate HSL at Ser600. So, phosphorylation of different sites may explain that in muscle the effects of contractions and adrenaline on HSL activity are partially additive. In line with the view that the two stimuli act by different mechanisms, training increases the contraction-mediated, but diminishes the adrenaline mediated HSL activation in muscle. CONCLUSION: The existence and regulation of HSL in skeletal muscle indicate a role of HSL in muscle TG metabolism.

Leclerc, K. M. and W. C. Levy (2003). "The role of norepinephrine in exercise impairment in congestive heart failure." Congest Heart Fail 9(1): 25-8.

            Congestive heart failure is a disorder that includes a multitude of neurohormonal responses that become maladaptive over time. Chronic sympathetic stimulation adversely affects the well-being and survival of heart failure patients and contributes to the exercise intolerance frequently seen in these patients. Norepinephrine levels have been correlated with poorer survival in heart failure patients. Administration of norepinephrine has been shown to impair exercise responses in those with congestive heart failure, and the recent effort to incorporate beta blocker therapy into the standard management of heart failure patients addresses this abnormal neurohormonal process. Studies with central-acting sympatholytics have shown mixed results. The use of drugs such as clonidine has been suggested as potentially useful therapy in the long-term management of patients with heart failure, but definitive conclusions await further study. Regular exercise has been shown to reduce resting norepinephrine levels in heart failure subjects. This may serve as an additional rationale to recommend chronic exercise for these patients.

Lopez, R., F. Roig, et al. (2003). "Role of cyclooxygenase-2 in the control of renal haemodynamics and excretory function." Acta Physiol Scand 177(4): 429-35.

            AIM: The available evidence supporting the importance of cyclooxygenase-2 (COX-2) in the regulation of renal haemodynamics and excretory function is summarized. Cyclooxygenase-2-derived metabolites play a very important role in regulating renal haemodynamics when sodium intake is low whereas it plays a minor role in the control of cortical blood flow when sodium intake is normal or elevated. The importance of COX-2 in the regulation of renal haemodynamics seems to be dependent on the endogenous production of other vasoactive products such as nitric oxide (NO) or noradrenaline. The activation of COX-2 in response to a decrease in NO may represent a mechanism aimed at defending the renal vasculature in the face of a decrease in NO levels. CONCLUSION: Contrary to the important role of COX-2 in the long-term regulation of renal haemodynamics, the metabolites derived from COX-2 seem to be only involved in the acute regulation of renal excretory function.

Maheu, F. S. and S. J. Lupien (2003). "[Memory in the grip of emotions and stress: a necessarily harmful impact?]." Med Sci (Paris) 19(1): 118-24.

            While intense negative events are vividly recalled, information learned during stressful situations is poorly remembered. These differential effects of emotions and stress on memory have been attributed to the physiological manifestations generated during those affective states. Intense emotional and stressful events trigger the secretion of catecholamines and of glucocorticoids, in particular. These hormones would be modulatory agents of memory functions. In the first part of this paper, we review the specific effects emotions and stress have on memory. We then summarize the psychological and biological determinants responsible for these effects. Finally, we discuss different methodological issues that could explain the discrepancy found between the impact of emotions and stress on memory. Defining more precisely the effects emotion and stress have on memory will lead to a better comprehension of the cognitive problems that characterize patients dealing with emotional turmoil, such as patients suffering from depression or post-traumatic stress disorder.

Mark, A. L., K. Rahmouni, et al. (2003). "A leptin-sympathetic-leptin feedback loop: potential implications for regulation of arterial pressure and body fat." Acta Physiol Scand 177(3): 345-9.

            AIM: This manuscript briefly reviews evidence and potential implications of a leptin-sympathetic-leptin feedback loop. RESULTS: Leptin increases sympathetic nerve activity to brown adipose tissue, kidney and other tissues. This action has implications for regulation of arterial pressure. In turn, there is evidence that sympathoadrenal stimulation inhibits leptin mRNA expression and secretion from white adipose tissue through beta adrenergic mechanisms. CONCLUSION: This sympathetic modulation of leptin expression has potential implications for regulation of body fat.

Mazzeo, R. S. and J. T. Reeves (2003). "Adrenergic contribution during acclimatization to high altitude: perspectives from Pikes Peak." Exerc Sport Sci Rev 31(1): 13-8.

            We have examined the sympathoadrenal responses to both acute and chronic high-altitude exposure at the summit of Pikes Peak, CO, in both men and women. A dissociation between the adrenal medullary response (acute) with that of the sympathetic nervous system (chronic) is observed. Both alpha- and beta-adrenergic contributions to key metabolic and physiologic adjustments to high-altitude exposure are evident.

McIntyre, C. K., A. E. Power, et al. (2003). "Role of the basolateral amygdala in memory consolidation." Ann N Y Acad Sci 985: 273-93.

            Memories of emotionally arousing events tend to be more vivid and to persist longer than do memories of neutral or trivial events. Moreover, memories of emotionally influenced information may endure after a single experience. Recent findings strongly suggest that the influence of emotional arousal on memory consolidation is mediated by the release of adrenal stress hormones (epinephrine and glucocorticoids) and neurotransmitters that converge in modulating the noradrenergic system within the amygdala. Considerable evidence also indicates that amygdala activation influences memory by regulating consolidation in other brain regions. The findings suggest further that this memory-modulatory system may be involved in the formation of traumatic memories and posttraumatic stress disorder in human subjects.

Miseviciene, V. and J. Bojarskas (2003). "[Current treatment options for acute bronchiolitis in children]." Medicina (Kaunas) 39(3): 217-20.

            Bronchiolitis is the most common lower respiratory tract infection in infants and is responsible for the majority of pediatric hospital admissions in winter. Respiratory syncytial virus has been identified as the main causative agent, causing 50-90% of the cases of bronchiolitis. Despite significant advances in pharmacotherapy, the management of infants with bronchiolitis has changed little over the years from supplemental oxygen and good fluid management. Approaches to therapy vary widely all over the world and are controversial. This paper reviews current treatment options for bronchiolitis, including the use of bronchodilators, epinephrine, steroids and ribavirin. Most recent advances, including immunotherapy and intensive care, are discussed.

Morilak, D. A., M. Cecchi, et al. (2003). "Interactions of norepinephrine and galanin in the central amygdala and lateral bed nucleus of the stria terminalis modulate the behavioral response to acute stress." Life Sci 73(6): 715-26.

            Many aspects of drug abuse and addiction share neurobiological substrates with the modulatory processes underlying the response and adaptation to acute stress. In particular, the ascending noradrenergic system has been implicated in facilitating the response to stress, and in stress-induced reinstatement of drug seeking behavior. Thus, to better understand the link between stress and addictive behaviors, it would be informative to understand better the modulatory function of the ascending noradrenergic system, and its interaction with other neurotransmitters with which it is closely associated or co-localized, such as the neuropeptide galanin. In this paper, we review a series of studies investigating the functional interactions of norepinephrine and galanin in modulating the behavioral response to acute stress in two components of the extended amygdala, the central nucleus of the amygdala and the lateral bed nucleus of the stria terminalis. We showed that norepinephrine facilitates behavioral reactivity to stress on the elevated plus-maze and social interaction tests. However, when stress-induced activation of the noradrenergic system was enhanced by blocking inhibitory adrenergic autoreceptors, galanin release was recruited in the central amygdala, acting to attenuate the behavioral response to stress. By contrast, stress-induced galanin release in the lateral bed nucleus appeared to be independent of enhanced noradrenergic activation, and unlike the central amygdala, both galanin and norepinephrine facilitated behavioral stress reactivity in the bed nucleus. The different modes of interaction and differential region- and response-specificity of galanin and norepinephrine suggest that a complex neural circuit interconnecting these two regions is involved in the modulatory effects of norepinephrine and galanin on the behavioral response to stress. Such complexity may allow for flexibility and plasticity in stress adaptation, and may also contribute to behavioral changes induced by chronic drug administration. Thus, the interaction of galanin and norepinephrine may be a viable target for the future development of novel therapeutic strategies for treating behavioral disorders related to stress or drug abuse.

Muller, W. E. (2003). "Current St John's wort research from mode of action to clinical efficacy." Pharmacol Res 47(2): 101-9.

            Preparations from St. John's wort extracts are used in the treatment of depression in many countries and represent an accepted alternative to synthetic antidepressants or behavioural therapy. St. John's wort extracts are therefore used in a therapeutic area which extends well beyond the traditional field of herbal medicine. The current status of preclinical and clinical research is summarised. St. John's wort extract has a clear inhibitory effect on the neuronal uptake not only of serotonin, noradrenaline, and dopamine but also of gamma-aminobutyric acid (GABA) and L-glutamate. No other antidepressant shows an approximately equally broad inhibitory profile. In good agreement with the effects in various biochemical models of antidepressant action, many effects in a number of behavioural pharmacology models of antidepressant efficacy could also be demonstrated for St. John's wort extract. Similar doses of John's wort also cause changes in the above-mentioned neurotransmitter systems in the brain. Out of all individual substances of St. John's wort only hyperforin and its structural analogue adhyperforin inhibit the re-uptake of the investigated neurotransmitters. However, hyperforin does not act as a competitive inhibitor at the transmitter binding sites of the transporter proteins but it affects the sodium gradient which then leads to an inhibition of uptake. The broad spectrum of action which characterises St. John's wort extracts has only been described for the pure substance hyperforin. Over the past year a number of good clinical studies have been carried out which confirm the efficacy and tolerability of St. John's wort extracts in mild depressive disorders, even if the therapeutic efficacy has recently been questioned by an American study. All studies have confirmed the good tolerability of St. John's wort extract and the very low frequency of adverse events. However, some drug interactions have been found to occur with St. John's wort extract, a number of which are of clinical relevance. In summary, pharmacological activity and therapeutic efficacy of St. John's wort extract as an antidepressant are supported by a large number of scientific publications. Within the wide range of components in St. John's wort extract, hyperforin plays an important, if not an outstanding role.

Neal, J. M. (2003). "Effects of epinephrine in local anesthetics on the central and peripheral nervous systems: Neurotoxicity and neural blood flow." Reg Anesth Pain Med 28(2): 124-34.

Norbury, R., W. J. Cutter, et al. (2003). "The neuroprotective effects of estrogen on the aging brain." Exp Gerontol 38(1-2): 109-17.

            The population of the western world is ageing. This increase in the elderly population will inevitably mean a rise in the prevalence of age-related cognitive decline and late-onset neuropsychiatric disorder, such as Alzheimer's disease (AD). There are sex differences in the incidence and age of onset of these disorders. Sex steroids and sex chromosomes are therefore implicated in their pathophysiology. We have identified relevant past and current literature using a Medline search and from the references of relevant papers. These were then reviewed and relevant articles have been summarized and included in the review. Evidence is presented for the wide-ranging actions of estrogen in the brain at the cellular, metabolic and neurotransmitter levels as well as from the cognitive, AD, depression and cerebrovascular perspectives. The authors conclude that it is unlikely that estrogen will become a stand-alone treatment for any of these disorders, although there may still be a role as an adjunctive treatment and as a prophylactic measure.

Orhan, F. and B. E. Sekerel (2003). "Beef allergy: a review of 12 cases." Allergy 58(2): 127-31.

            BACKGROUND: Although beef allergy has long been considered a rare condition, the number of studies regarding the nature, epidemiology, and symptoms of beef allergy has been increasing. We aimed to describe the results of allergy work-up of 12 patients who have a convincing history of acute allergic symptoms following beef ingestion. METHODS: Detailed histories of 10 children and two adult relatives were obtained and patients underwent skin prick tests with commercial beef extract, raw beef and cooked beef. Serum total and beef-specific IgE were measured. Labial, and in selected cases, open food challenges were undertaken. RESULTS: Interestingly, the rate of family history of beef allergy was 67% (8/12). Three patients (two with commercial extract, and one with cooked beef) had positive skin test responses to beef. Ten (83%) patients had elevated serum IgE concentrations (median 316.5 kU/l, range 9-1321 kU/l) and the beef-specific IgE was positive in all patients (median 6.23 kUA/l, range 0.83-36.6 kUA/l). Labial food challenge was positive in four (30%) patients. Of the five patients who underwent open food challenges, three were positive and two tolerated the beef administered. CONCLUSIONS: We conclude that skin prick tests do not accurately diagnose IgE-mediated sensitization to beef. Thus, patients with suspected beef allergy should be screened additionally for beef-specific IgE antibodies, and in selected cases oral food challenge should be carried out to verify the diagnosis.

Otani, T. and T. Kato (2003). "[Posttraumatic stress disorder]." Ryoikibetsu Shokogun Shirizu(38): 481-6.

Rajput, A. and M. Rajput (2003). "Essential tremor and parkinsonism." Adv Neurol 91: 397-9.

Rance, F., P. Micheau, et al. (2003). "[Food allergy and asthma in children]." Rev Pneumol Clin 59(2 Pt 1): 109-13.

            The links between food allergy and asthma are becoming more clear. The association of food allergy and asthma in the same child is unusual (less than 10% in atopic subjects). This association is however a sign of gravity leading to more severe manifestations of food allergy in asthmatic children. Compared with the non-asthmatic child, the asthmatic child has a 14-fold higher risk of developing a severe allergic reaction to the ingestion of food. The most commonly cited foods are fruits with a rind, cow's milk and, of course, nuts. Epidemiological data established from methodologically sound studies should enable a definition of the current allergic environment. Formal diagnosis is established with standardized tests. Treatment is oriented towards prevention associating a restricted diet, asthma control, patient education, and prescription of an emergency first aid kit with epinephrine. Supplementary inquiries are needed to determine the outcome in children with food allergy and respiratory symptoms.

Richmond, R. and N. Zwar (2003). "Review of bupropion for smoking cessation." Drug Alcohol Rev 22(2): 203-20.

            The advent of bupropion hydrochloride sustained release (Zyban) has heralded a major change in the options available for smoking cessation pharmacotherapy. Bupropion is a selective re-uptake inhibitor of dopamine and noradrenalin which prevents or reduces cravings and other features of nicotine withdrawal. Bupropion is a useful oral and non-nicotine form of pharmacotherapy for smoking cessation. For this review a total of 221 papers were reviewed plus poster presentations. This review examines in detail original clinical trials on efficacy, categorised according to whether they were acute treatment trials in healthy smokers; studies in specific populations such as people with depression, chronic obstructive pulmonary disease (COPD) or cardiovascular disease; or relapse prevention studies. Overall, these studies in varying populations comprising over four thousand subjects, showed bupropion consistently produces a positive effect on smoking cessation outcomes. The evidence highlights the major public health role that bupropion has in smoking cessation. The methodological issues of published clinical trials reporting one year outcomes were examined in detail including: completeness of follow-up; loss to follow-up; intention to treat analysis; blindness of assessment; and validation of smoking status. The review discusses contraindications, adverse effects, dose and overdose, addictive potential, and the role of bupropion in reducing cessation-related weight gain. Bupropion combined with or compared to other pharmacotherapies (nicotine patch; nortriptyline) is considered. Impressive evidence exists for the use of bupropion in smoking cessation among difficult patients who are hard-core smokers such as those with cardiovascular disease, chronic obstructive pulmonary disease (COPD) and depression. Bupropion reduces withdrawal symptoms as well as weight gain and is effective for smoking cessation for people with and without a history of depression or alcoholism. Serious side effects of bupropion use are rare. The major safety issue with bupropion is risk of seizures (estimated at approximately 0.1%) and it should not be prescribed to patients with a current seizure disorder or any history of seizures. In clinical trials of bupropion for smoking cessation no seizures were reported. Allergic reactions occur at a rate of approximately 3% and minor adverse effects are common including dry mouth and insomnia.

Romano, M. C. (2003). "[The Individualized Welcome Project and its adaptation to the food allergy field]." Allerg Immunol (Paris) 35(1): 17-21.

            Allergy to food in childhood becomes today a real public health problem. Setting up some "Projets d'accueil Individualises" (i.e. a management project at school for each allergic patient) has allowed to protect the high risk pupils in the best way since 1999. Allergy adapted meals are proposed and emergency treatments they need are organized. In this field, net working seems to be essential more than everywhere else.

Romano, A., C. Mondino, et al. (2003). "Immediate allergic reactions to beta-lactams: diagnosis and therapy." Int J Immunopathol Pharmacol 16(1): 19-23.

            Beta-lactams are the antibiotics which most frequently provoke adverse reactions mediated by specific immunological mechanisms. These reactions, classifiable as immediate or non-immediate, can be produced by the four classes of beta-lactams (penicillins, cephalosporins, carbapenems and monobactams) currently available, which share a common beta-lactam ring structure. Immediate reactions occur within the first hour after drug administration and are characterized by urticaria, angioedema, rhinitis, bronchospasm, and anaphylactic shock. Immediate reading skin tests are the quickest and most reliable method for demonstrating the presence of beta-lactam specific IgE antibodies. It is crucial to use in diagnosis the suspected beta-lactams themselves, particularly cephalosporins, in addition to penicillin determinants. Serum specific IgE assays can be used as complementary tests. Negative test results should be interpreted in light of the time elapsed from the last exposure to the responsible beta-lactam. In fact, both in vivo and in vitro test sensitivity is known to decrease over time. In some diagnostic work-ups, patients with a positive history and negative skin and in vitro tests with classic reagents undergo a controlled administration of the suspected beta-lactam. The management of immediate allergic reactions should take into consideration their severity and type. Adrenaline is the drug of choice in the treatment of anaphylactic shock. In addition to adrenaline, corticosteroids and antihistamines should be administered. Histamine H(1) receptor antagonists are the mainstay of the treatment of immediate allergic reactions such as urticaria, rhinitis and conjunctivitis.

Sampson, H. A. (2003). "Anaphylaxis and emergency treatment." Pediatrics 111(6 Pt 3): 1601-8.

            Food anaphylaxis is now the leading known cause of anaphylactic reactions treated in emergency departments in the United States. It is estimated that there are 30 000 anaphylactic reactions to foods treated in emergency departments and 150 to 200 deaths each year. Peanuts, tree nuts, fish, and shellfish account for most severe food anaphylactic reactions. Although clearly a form of immunoglobulin E-mediated hypersensitivity, the mechanistic details responsible for symptoms of food-induced anaphylaxis are not completely understood, and in some cases, symptoms are not seen unless the patient exercises within a few hours of the ingestion. At the present time, the mainstays of therapy include educating patients and their caregivers to strictly avoid food allergens, to recognize early symptoms of anaphylaxis, and to self-administer injectable epinephrine. However, clinical trials are now under way for the treatment of patients with peanut anaphylaxis using recombinant humanized anti-immunoglobulin E antibody therapy, and novel immunomodulatory therapies are being tested in animal models of peanut-induced anaphylaxis.

Sicherer, S. H. (2003). "Advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insect venom." J Allergy Clin Immunol 111(3 Suppl): S829-34.

            This review highlights some of the research advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insect venom that were reported primarily in this Journal from 2001 to 2002. Among the topics highlighted: Epinephrine injected intramuscularly into the thigh provides the most efficient absorption profile for adults and children; determination of serum IgE antibody-specific food allergen concentrations and atopy patch tests with foods show promise for enhanced diagnostic accuracy; numerous food allergens are now characterized on the molecular level, allowing for improved diagnostic and treatment modalities; the complex immunologic mechanisms underlying drug hypersensitivity reactions are being elucidated; venom immunotherapy improves quality of life for sufferers, and increased venom immunotherapy doses are useful in recalcitrant cases.

Simonneaux, V. and C. Ribelayga (2003). "Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters." Pharmacol Rev 55(2): 325-95.

            Melatonin, the major hormone produced by the pineal gland, displays characteristic daily and seasonal patterns of secretion. These robust and predictable rhythms in circulating melatonin are strong synchronizers for the expression of numerous physiological processes in photoperiodic species. In mammals, the nighttime production of melatonin is mainly driven by the circadian clock, situated in the suprachiasmatic nucleus of the hypothalamus, which controls the release of norepinephrine from the dense pineal sympathetic afferents. The pivotal role of norepinephrine in the nocturnal stimulation of melatonin synthesis has been extensively dissected at the cellular and molecular levels. Besides the noradrenergic input, the presence of numerous other transmitters originating from various sources has been reported in the pineal gland. Many of these are neuropeptides and appear to contribute to the regulation of melatonin synthesis by modulating the effects of norepinephrine on pineal biochemistry. The aim of this review is firstly to update our knowledge of the cellular and molecular events underlying the noradrenergic control of melatonin synthesis; and secondly to gather together early and recent data on the effects of the nonadrenergic transmitters on modulation of melatonin synthesis. This information reveals the variety of inputs that can be integrated by the pineal gland; what elements are crucial to deliver the very precise timing information to the organism. This also clarifies the role of these various inputs in the seasonal variation of melatonin synthesis and their subsequent physiological function.

Small, K. M., D. W. McGraw, et al. (2003). "Pharmacology and physiology of human adrenergic receptor polymorphisms." Annu Rev Pharmacol Toxicol 43: 381-411.

            Adrenergic receptors are expressed on virtually every cell type in the body and are the receptors for epinephrine and norepinephrine within the sympathetic nervous system. They serve critical roles in maintaining homeostasis in normal physiologic settings as well as pathologic states. These receptors are also targets for therapeutically administered agonists and antagonists. Recent studies have shown that at least seven adrenergic receptor subtypes display variation in amino acid sequence in the human population due to common genetic polymorphisms. Variations in potential regulatory domains in noncoding sequence are also present. Here, we review the consequences of these polymorphisms in terms of signaling, human physiology and disease, and response to therapy.

Stewart, J. (2003). "Stress and relapse to drug seeking: studies in laboratory animals shed light on mechanisms and sources of long-term vulnerability." Am J Addict 12(1): 1-17.

            Relapse is a major characteristic of drug addiction disorders and remains the primary problem for treatment. Recently, there has been hope that these disorders may be amenable to pharmacological treatments that have successfully treated other psychopathological disorders. Pharmacological approaches to drug abuse have tended to be guided by the primary drug used by the individual, though substitution has been the guiding principle in some instances, as in the case of methadone maintenance in opioid addiction. Alternatively, blockade or antagonism of the effects of the primary drug being abused has been tried, as in the case of using naltrexone to treat opioid or alcohol addiction. Though reportedly successful in some populations, it is not clear that these approaches effectively control craving for 'highs' or euphoric experiences or a return to drug use as a response to stressful life experiences. Recent experimental studies of the factors that induce craving and relapse to drug use in both humans and laboratory animals, such as drug-related cues, re-exposure to the drug itself, or exposure to stressful events, have shown that the effects of these different events are mediated by dissociable neurochemical circuitry. Another finding that emerges from these studies is that the motivation underlying drug seeking induced by events that precipitate relapse is intensified by the duration and amount of pre-exposure to a drug and the passage of time since withdrawal of the drug. One implication of such findings for the treatment of addiction is that whatever approach is taken, treatment will have to be multifaceted and maintained over an extended period of time after the initial termination of drug use.

Stone, E. A., Y. Lin, et al. (2003). "Emerging evidence for a central epinephrine-innervated alpha 1-adrenergic system that regulates behavioral activation and is impaired in depression." Neuropsychopharmacology 28(8): 1387-99.

            Currently, most basic and clinical research on depression is focused on either central serotonergic, noradrenergic, or dopaminergic neurotransmission as affected by various etiological and predisposing factors. Recent evidence suggests that there is another system that consists of a subset of brain alpha(1B)-adrenoceptors innervated primarily by brain epinephrine (EPI) that potentially modulates the above three monoamine systems in parallel and plays a critical role in depression. The present review covers the evidence for this system and includes findings that brain alpha(1)-adrenoceptors are instrumental in behavioral activation, are located near the major monoamine cell groups or target areas, receive EPI as their neurotransmitter, are impaired or inhibited in depressed patients or after stress in animal models, and are restored by a number of antidepressants. This "EPI-alpha(1) system" may therefore represent a new target system for this disorder.

Tada, K. (2003). "[Pharmacology of anxiolytics and their therapeutic use]." Ryoikibetsu Shokogun Shirizu(38): 608-11.

Takeguchi, Y., Y. Miyamoto, et al. (2003). "[Severe hypotension during anesthesia in a patient on long-term antidepressant therapy]." Masui 52(3): 284-7.

            A 71-year-old woman on chronic therapy with mianserine and amantadine was scheduled to undergo abdominal hysterectomy under spinal anesthesia. Following spinal anesthesia she developed hypotension refractory to continuous intravenous fluid infusion as well as multiple boluses of ephedrine. Because the maximum level of analgesia was T 8, general anesthesia was added using laryngeal mask airway. Immediately after anesthetic induction, a marked hypotension occurred. Blood pressure again did not respond to ephedrine but went up excessively to a small dose of epinephrine without any changes in heart rate. Epinephrine infusion at a low dose rate was needed to sustain the blood pressure during surgery. Both depletion of presynaptic norepinephrine store and down-regulation of postsynaptic beta-receptor may have led to abnormal response to catecholamines in this case.

Teuber, S. S., S. S. Comstock, et al.