RESUMEN
Although circulating catecholamines and free serotonin in the plasma (f-5-HT) were found to be increased during asthma attacks, only f-5-HT levels correlated positively with bronchoconstriction and clinical severity. Tianeptine, a drug that enhances serotonin uptake by platelets and serotonergic axons at the central nervous system (CNS), provoked an abrupt disappearance of asthma attacks. This fact explains why tianeptine has proven to be a powerful therapeutic tool in controlling asthma. Its success has been demonstrated not only in two double-blind placebo, cross-over trials, but through an open study lasting more than seven years that included over 25,000 asthmatic patients. In the present article, we discuss the peripheral and central nervous system mechanisms that may explain the therapeutic success of tianeptine. These are summarized below. F-5-HT is taken up by pulmonary endocrine cells (PNEC) located at the parasympathetic terminals. A presynaptic element, these cells release serotonin and potentiate acetylcholine (ACh)-induced contraction of bronchial muscle. This effect is mediated by 5-HT(3) and 5-HT(4) postsynaptic receptors located at the bronchial muscle. According to the above, the increased f-5-HT plasma level, triggered by both platelet aggregation and nocturnal and/or diurnal hyperparasympathetic activity, potentiates ACh-induced bronchoconstriction. The fact that serotonin released by medullary serotonergic axons stimulates the medullary vagal cardiorespiratory neurons obliges us to think that serotonin-induced CNS mechanisms are also involved. Furthermore, the finding that drugs that interfere with serotonin uptake, by both platelets and 5-HT-terminals, worsen asthma symptoms and are able to provoke asthma attacks gives additional support to the above peripheral and CNS mechanisms.
Asunto(s)
Asma/tratamiento farmacológico , Tiazepinas/uso terapéutico , Animales , Antiasmáticos/química , Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Asma/epidemiología , Asma/inmunología , Ensayos Clínicos como Asunto , Estudios Cruzados , Método Doble Ciego , Humanos , Tiazepinas/farmacologíaRESUMEN
Neurochemical, neuroautonomic and neuropharmacological assessments carried out on all our myasthenia gravis (MG) patients showed that they presented a neural sympathetic deficit plus excessive adrenal-sympathetic activity. These abnormalities were registered during the basal (supine-resting) state, as well as after several stress tests (orthostasis, exercise, oral glucose and buspirone). In addition, MG patients showed increased levels of free-serotonin (f5HT) in the plasma, supposedly associated with the increased platelet aggregability which we found in all MG patients. As the above trio of neurochemical disorders (low noradrenergic-activity + high adrenergic-activity + increased f-5HT plasma levels) is known to favor Th-1 immunosuppression + Th-2 predominance, we outlined a neuropharmacological strategy for reverting the above neurochemical disorder. This treatment provoked sudden (acute), and late sustained improvements. Acute effects have been attributed to the increase of alpha-1 activity at the spinal motoneuron level. Late improvements always paralleled a significant normalization of immunological disorders. Complete normalization was registered only in non-thymectomized MG patients.
Asunto(s)
Epinefrina/sangre , Miastenia Gravis/tratamiento farmacológico , Neurotransmisores/uso terapéutico , Norepinefrina/sangre , Sistema Nervioso Simpático/efectos de los fármacos , Adolescente , Inhibidores de Captación Adrenérgica/uso terapéutico , Agonistas alfa-Adrenérgicos/uso terapéutico , Antagonistas Adrenérgicos beta/uso terapéutico , Adulto , Anciano , Compuestos de Bencidrilo/uso terapéutico , Buspirona/uso terapéutico , Desipramina/uso terapéutico , Quimioterapia Combinada , Electromiografía , Femenino , Humanos , Ácidos Hidroxámicos/uso terapéutico , Masculino , Persona de Mediana Edad , Modafinilo , Miastenia Gravis/inmunología , Miastenia Gravis/fisiopatología , Fármacos Neuroprotectores/uso terapéutico , Fenilalanina/uso terapéutico , Agregación Plaquetaria , Propranolol/uso terapéutico , Serotonina/sangre , Agonistas de Receptores de Serotonina/uso terapéutico , Sistema Nervioso Simpático/fisiología , Tirosina/uso terapéuticoRESUMEN
Studies have shown that levels of free serotonin in plasma are increased in symptomatic patients with asthma. In addition, the concentration of free serotonin in symptomatic patients with asthma correlates positively with clinical status and negatively with pulmonary function. Thus, reducing the concentration of free serotonin in plasma might be useful in treating patients with asthma. We studied the effectiveness of tianeptine in treating patients with asthma. Tianeptine is the only drug known to be able to reduce levels of free serotonin in plasma and to enhance uptake by platelets. In this study, 69 children with asthma were assigned in randomized fashion to receive tianeptine and/or placebo in a double-blind crossover trial that lasted 52 weeks. Tianeptine provoked a dramatic and sudden decrease in both clinical rating and free serotonin plasma levels and an increase in pulmonary function.
Asunto(s)
Antidepresivos Tricíclicos/uso terapéutico , Asma/tratamiento farmacológico , Tiazepinas/uso terapéutico , Adolescente , Análisis de Varianza , Asma/sangre , Asma/fisiopatología , Niño , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Serotonina/sangre , Índice de Severidad de la EnfermedadRESUMEN
Buspirone is an anxiolytic drug which exerts several central effects. It antagonizes presynaptic inhibitory DA2 autoreceptors at dopaminergic neurons and acts as an agonist for 5-HT1A inhibitor autoreceptors at serotonergic cells. Thus, buspirone respectively enhances and depresses the firing rates of both type of neurons. At doses which correlate with dopaminergic stimulation, but not 5-HT inhibition, buspirone also increases the firing rates of the central noradrenergic cells. We measured levels of circulating neurotransmitters before and up to 240 minutes after the oral administration of 20 mg of buspirone in 32 healthy volunteers. Buspirone significantly increased levels of noradrenaline, dopamine, and free serotonin but did not affect levels of adrenaline, tryptophane, or platelet serotonin. Small but significant drops in systolic blood pressure and heart rate were observed after buspirone ingestion. Atropine administration before buspirone ingestion annulled the free serotonin increase as well as systolic blood pressure-heart rate decrease. We found significant positive correlations between noradrenaline and dopamine levels. The strength and significance of these correlations were increased by using the noradrenaline/adrenaline ratio instead of noradrenaline absolute values. This finding indicates that increases in both noradrenaline and dopamine arise from sympathetic nerves rather than the adrenal glands. We also found significant negative correlations between free serotonin increases and systolic blood pressure-heart rate decreases. Our results indicate that buspirone stimulates central sympathetic activity. These acute effects of buspirone are reflected in an increased peripheral neural sympathetic activity, but not adrenal sympathetic activity in healthy individuals. In addition, buspirone increases free serotonin plasma concentrations and decreases systolic blood pressure plus heart rate levels through mechanisms associated with parasympathetic activation.
Asunto(s)
Ansiolíticos/farmacología , Buspirona/farmacología , Neurotransmisores/sangre , Adulto , Dopamina/sangre , Femenino , Humanos , Masculino , Norepinefrina/sangre , Concentración Osmolar , Valores de Referencia , Serotonina/sangreRESUMEN
Studies have shown the levels of free serotonin in plasma are increased in symptomatic patients with asthma. In addition, the concentration of free serotonin in symptomatic children with asthma correlates positively with clinical status and negatively with pulmonary function (forced expiratory volume in 1 second [FEV1]). Thus, reducing the concentration of free serotonin in plasma may be useful in treating children with asthma. We studied the effectiveness of tianeptine in treating these patients. Tianeptine is the only drug known to be able to reduce the level of free serotonin in plasma and to enhance the uptake by platelets. Sixty-nine of the 82 children with asthma initially enrolled participated in this study. Children were randomized to receive tianeptine or placebo or both in a double-blind crossover trial. The trial lasted 52 weeks. Tianeptine provoked a dramatic and sudden decrease of both clinical rating and free serotonin plasma levels and an increase in pulmonary function.
Asunto(s)
Antiasmáticos/uso terapéutico , Asma/sangre , Asma/tratamiento farmacológico , Serotonina/sangre , Tiazepinas/uso terapéutico , Adolescente , Análisis de Varianza , Antiasmáticos/sangre , Niño , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Espirometría , Tiazepinas/sangreRESUMEN
BACKGROUND: Previous research has shown that symptomatic asthmatic patients have increased levels of norepinephrine, epinephrine, dopamine, free serotonin, and cortisol in plasma when compared with asymptomatic patients. OBJECTIVE: We investigated the relationship between plasma levels of catecholamines, free serotonin, and cortisol and clinical status and pulmonary function in symptomatic and asymptomatic patients with asthma. METHODS: We compared clinical severity, spirometry, and neuroendocrine factors at weeks 0, 1, 2, 3, and 4 in 57 symptomatic (forced expiratory volume in one second [FEV1] < 70%) and 72 asymptomatic (FEV1 > 80%) asthmatic patients. We used multiple analyses of variance (repeated measures) to interpret the data. In addition, we used the Pearson Product Moment Test to investigate correlations among the different variables. RESULTS: The clinical severity rating and levels of free serotonin, norepinephrine, epinephrine, dopamine, and cortisol were significantly higher in symptomatic asthmatic patients than those in asymptomatic patients (P < .001, in all cases). FEV1 was significantly lower in symptomatic patients than in asymptomatic patients. In symptomatic patients, the level of free serotonin correlated positively with the clinical severity rating (r = .564, P < .01) and negatively with FEV1 (r = -.959, P < .001). In addition, the clinical severity rating showed a negative correlation with FEV1 (r = -.359, P < .01). No significant correlations were found in asymptomatic patients. CONCLUSION: Our finding that free serotonin was the only neuroendocrine factor closely associated with clinical severity and pulmonary function suggests that this factor plays an important role in the pathophysiology of acute asthma.
Asunto(s)
Asma/sangre , Serotonina/sangre , Adolescente , Adulto , Niño , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Agregación PlaquetariaRESUMEN
1. Exhaustive evidence is quoted showing that uncontrollable (uncoping) stress provoked in experimental mammals leads to depletion of central noradrenergic activity+ adrenomedullary-cortical gland hyperactivity. These physiological disorders cause the typical neuroendocrine peripheral profile: a) raised catecholamines (CA) in plasma [noradrenaline (NA)+adrenaline (Ad)+dopamine (DA), b) reduced NA/Ad ratio in plasma and c) raised plasma cortisol. 2. Exhaustive evidence is quoted which indicates that severely ill humans show peripheral neuroendocrine profile similar to that found in mammals submitted to uncontrollable stress situation. Further, the NA/Ad ratio does not increase but decreases during orthostasis and exercise stress challenges, as well as oral glucose stress (tolerance) test. 3. Exhaustive evidence is quoted which indicates that endogenous depressed subjects show a neuroendocrine profile opposite to that observed in stressed mammals and severely ill humans. This profile consists of central NA (neural sympathetic) hyperactivity+ adrenomedullary glands hyporresponsivity. These disorders are reflected in a three to ten fold increase of the NA/Ad ratio in plasma. 4. Exhaustive evidence is also quoted showing that dysthymic depressed patients show low plasma catecholamines+low NA/Ad plasma ratio (< 2) during supine-resting condition, it is normalized at orthostasis and exercise periods. 5. It is quoted evidence showing that whereas platelet serotonin is increased in dysthymics, the same is reduced in both endogenous depressed and stressed mammals as well as severely ill humans. 6. It is quoted evidence showing that free serotonin in plasma is greatly raised in uncoping stressed mammals and severely ill humans. The same parameter is normal or slightly increased in dysthymic and endogenous depressed humans. These findings are consistent with the increased platelet aggregability observed in "uncontrollable" stressed mammals and in severely ill, but not depressed patients. 7. It is also quoted evidence showing that whereas parasympathetic activity is absent in uncontrollable stressed mammals and severely ill humans, the same is increased in both types of depressed humans. 8. According to the above, the authors postulate the existence of 3 distinct central+ peripheral neuroendocrine profiles for endogenous depression, dysthymic depression and maladaptation to stress syndrome. These different profiles should lead researchers to attempt different therapeutical approach. 9. In view of the fact that the authors found much clinical overlap among the three syndromes (endogenous depression, dysthymic depression and severely ill patients), they believe that a differential diagnosis should be based on neurochemical, neuroendocrine, physiologic, metabolic and neuropharmacological grounds. 10. The experimentally induced uncontrollable stress (behavioral despair) syndrome in mammals should not be used as a valid model of human depressive syndrome.
Asunto(s)
Trastorno Depresivo/metabolismo , Trastorno Depresivo/psicología , Neurotransmisores/metabolismo , Estrés Fisiológico/metabolismo , Estrés Fisiológico/psicología , Humanos , Modelos PsicológicosRESUMEN
BACKGROUND: Previous clinical research has shown that severely ill (somatic) as well as many psychosomatic patients show raised noradrenaline (NA), adrenaline (AD), cortisol, free serotonin (f5HT) and platelet aggregability. Conversely, they show reduced NA/AD plasma ratio and platelet serotonin (p5HT). They also show adrenal hyperresponsiveness to an oral glucose load. These findings are opposed to those observed in depressed patients who show adrenal gland sympathetic hyporesponsiveness and neural sympathetic hyperactivity. OBJECTIVE: To investigate adrenal gland and neural sympathetic systems as well as the other parameters in nondrepressed severely ill patients through the orthostasis exercise stress test which in normals triggers NA but no AD rise. METHODS: We investigated 35 severely ill patients and their age- and sex-paired controls. Systolic, diastolic pulse pressure (PP), heart rate and neuroendocrine parameters were measured supine (0 min), at orthostasis (1 min) and exercise (5 min). A second test was performed 2 weeks later, after atropine injection. Multivariate analysis of variance, paired t test and Pearson product-moment test were employed. RESULTS: The normal PP orthostasis fall was not observed in patients. At this period, an abnormal AD peak substituted the normal NA peak. The normal p5HT-f5HT orthostasis-exercise peaks were absent in patients. Cortisol and platelet aggregability were raised in patients. CONCLUSIONS: Severely ill (somatic) patients responded to the orthostasis-exercise stress test with adrenal and corticosuprarenal but not neural sympathetic activity. They did not show the normal parasympathetic activity at orthostasis. This adrenal gland sympathetic hyperactivity registered in somatic patients is similar to that observed in mammals which fail to cope with stress and contrary to the profile registered in depressed subjects who show NA but not AD rise.
Asunto(s)
Presión Sanguínea/fisiología , Neurotransmisores/sangre , Estrés Fisiológico/sangre , Estrés Fisiológico/fisiopatología , Adolescente , Adulto , Análisis de Varianza , Plaquetas/química , Plaquetas/fisiología , Estudios de Casos y Controles , Enfermedad Crónica , Depresión/fisiopatología , Dopamina/sangre , Epinefrina/sangre , Prueba de Esfuerzo , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Norepinefrina/sangre , Serotonina/sangre , Posición Supina/fisiologíaRESUMEN
Aging is a physiological process that shares many behavioral, biochemical and neuroendocrine phenomena with the pathophysiological situation of unresolved stress, as well as with a pharmacologically induced syndrome resulting from chronic benzodiazepine (BZ) consumption. Behavioral findings include symptoms such as drowsiness, ataxia, fatigue, confusion, weakness, dizziness, vertigo, syncope, reversible dementia, depression, impairment of intellectual, psychomotor and sexual function, agitation, auditory and visual hallucinations, paranoid ideation, panic, delirium, depersonalization, sleepwalking, aggressivity, orthostatic hypotension, and insomnia. Neuroendocrine findings include: central depletion of noradrenaline (NA), dopamine, adrenaline (AD), and serotonin (5-HT); reduction in the ratio of circulating NA/AD as well as platelet 5-HT and increase of AD, plasma free 5-HT and cortisol. These disturbances together with the increased platelet aggregability observed in the three groups are typical of unresolved-stress situations. Immunological findings include significant reduction of peripheral T lymphocytes (CD3, CD4, CD8) and the CD4/CD8 ratio, CD16 and gamma-delta cells. On the other hand, the three groups (elderly subjects, subjects faced with unresolved stress, and BZ consumers) show increase of the CD57 lymphocyte subset as well as natural killer cytotoxicity. Alterations of several biological markers have also been found, specifically in the oral glucose tolerance test, the intramuscular clonidine test, and the supine/orthostasis/exercise test. From a clinical point of view, the three groups appear to be more susceptible to the appearance and progression of many acute and chronic diseases (infectious and malignant diseases). As a result, chronic consumption of BZs should be avoided in both the elderly and subjects in unresolved-stress situations.
Asunto(s)
Envejecimiento/fisiología , Benzodiazepinas/efectos adversos , Estrés Psicológico/fisiopatología , Adulto , Anciano , Biomarcadores , Sistema Nervioso Central/fisiopatología , Trastornos del Conocimiento/etiología , Contraindicaciones , Humanos , Hipotensión/etiología , Enfermedades del Sistema Inmune/etiología , Trastornos Mentales/etiología , Sistemas Neurosecretores/fisiopatología , Neurotransmisores/fisiología , Trastornos del Sueño-Vigilia/etiologíaRESUMEN
Although the concept of functional illness has blurred boundaries, some consensus exists on its understanding among clinicians. In short, it is easier to conceive than to define functional illness. Semantic and conceptual discussion concerning this issue have been endless. Many links exist that connect brain and body (mind and organs, psyche and soma). Amongst them, neurotransmitters, released by peripheral neurons and some glandular cells (adrenal, enterochromaffin cells, mast cells), are diverted into the bloodstream. Although neurotransmitters cannot cross the blood-brain barrier, basic and clinical research has progressively established the relationship between central and peripheral neurochemical activities. Hence, it is possible to obtain some approach to the central profile through the measurement of circulating neurotransmitters. However, this approach is more reliable if we can measure all circulating factors and, in addition, test the responses to different kinds of challenges (stressors, drugs, etc.). All diseases (somatic, psychiatric and psychosomatic) present some kind of plasma neurotransmitter disturbance; however, only in some has the whole abnormal profile been established. Technical difficulties as well as expensive procedures have interfered with the generalization of this research area. In the present review article, we summarize data quoted from current scientific literature reporting exhaustive research in this area.
Asunto(s)
Neurotransmisores/sangre , Trastornos Psicofisiológicos/fisiopatología , Trastornos Somatomorfos/fisiopatología , Trastornos de Alimentación y de la Ingestión de Alimentos/sangre , Trastornos de Alimentación y de la Ingestión de Alimentos/fisiopatología , Femenino , Enfermedades Gastrointestinales/sangre , Enfermedades Gastrointestinales/fisiopatología , Enfermedades de los Genitales Femeninos/sangre , Enfermedades de los Genitales Femeninos/fisiopatología , Cefalea/sangre , Cefalea/fisiopatología , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Hipoglucemia/sangre , Hipoglucemia/fisiopatología , Hipotensión/sangre , Hipotensión/fisiopatología , Trastornos Psicofisiológicos/sangre , Enfermedades Respiratorias/sangre , Enfermedades Respiratorias/fisiopatología , Trastornos Somatomorfos/sangre , Terminología como AsuntoRESUMEN
Major depressed patients showed greater heart rate, noradrenaline, and free-serotonin values than normal. Conversely, platelet-serotonin values in major depressed patients were significantly lower than normal. Patients registered the normal differential blood pressure reduction during orthostasis. They also revealed progressive and significantly higher heart rate rises during orthostasis and exercise periods, when compared to normals. Whereas noradrenaline showed maximal rises during the two last periods, adrenaline only showed small but significant increase during exercise. The analysis of correlations, together with the above data, suggests that major depressed patients register maximal neural sympathetic activity as well as adrenal glands sympathetic hypoactivity. In addition, these patients show hyperparasympathetic activity, as reflected by the free-serotonin profile. Finally, the fact that both the Hamilton Depression Rating Scale and the self-rating Beck Depression Inventory correlated positively with noradrenaline/adrenaline ratio and free-serotonin values strongly suggests that both neural sympathetic and cholinergic mechanisms are involved in major depression.
Asunto(s)
Nivel de Alerta/fisiología , Presión Sanguínea/fisiología , Depresión/fisiopatología , Ejercicio Físico/fisiología , Frecuencia Cardíaca/fisiología , Neurotransmisores/sangre , Postura/fisiología , Glándulas Suprarrenales/inervación , Adulto , Depresión/diagnóstico , Depresión/psicología , Epinefrina/sangre , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Norepinefrina/sangre , Sistema Nervioso Parasimpático/fisiopatología , Inventario de Personalidad , Serotonina/sangre , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
Dysthymic depressed patients showed platelet-serotonin (pS) + plasma-free serotonin values greater than normal as well as plasma noradrenaline values lower than normal during supine resting period (0'). Conversely, no significant differences were observed in the 0' values of any other of the measured parameters: systolic, diastolic and differential blood pressure (SBP, DBP, DP), heart rate (HR), adrenaline (Ad), dopamine (DA), cortisol, and platelet aggregability between patients and controls. Although patients showed then normal DP reduction at orthostasis (1'), this was not prevented by atropine as it does in controls. Patients but not normals showed significant rises of DBP at orthostasis and exercise (5') periods, which were positively correlated with NA rises. On the contrary, the abnormally raised resting fS values registered in patients showed progressive and significant reductions throughout the test that were negatively correlated with DBP-NA values. Adrenaline did not show the normal 5'-fS peak. The above findings suggest that dysthymics show hypoactivity of the two branches of the sympathetic system (neural + adrenal) along with hyperparasympathetic activity. Furthermore, their low NA + high pS values contrast with the high NA + low pS registered in major depressed subjects.
Asunto(s)
Monoaminas Biogénicas/sangre , Presión Sanguínea/fisiología , Trastorno Depresivo/fisiopatología , Ejercicio Físico/fisiología , Frecuencia Cardíaca/fisiología , Hipotensión Ortostática/fisiopatología , Descanso/fisiología , Adolescente , Adulto , Trastorno Depresivo/sangre , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/fisiología , Escalas de Valoración PsiquiátricaRESUMEN
Immunodeficiency is frequently invoked as an ethiopathogenetic factor for many somatic diseases. On the other hand, stress, depression, and psychotic disturbances are associated with severe immunological disorders. Taking into account that the benzodiazepines (BZ) are the psychoactive drugs more widely used than any other to treat psychological disturbances, it seems important to elucidate the immuno-enhancing or immunosuppressant potential of such drugs. Our goal was easily reached, since 69% of the outpatients visiting our Institute are chronic BZ consumers and because neurochemical, hormonal, immunological, and psychiatric investigations are routinely performed on all of our patients. In the present study, immune function was investigated on two occasions: while the patient was on active medication and 15 days after discontinuation. We concluded that chronic consumption of BZ provokes significant immunological disorders that should be further investigated. Said disorders could not be linked to a pre-existing affective disease or psychosis, since we only selected those BZ users in whom psychiatric investigations ruled out a past or present history of major psychiatric disease.
Asunto(s)
Ansiolíticos/efectos adversos , Tolerancia Inmunológica/efectos de los fármacos , Adulto , Ansiolíticos/uso terapéutico , Benzodiazepinas , Femenino , Humanos , Síndromes de Inmunodeficiencia/inducido químicamente , Recuento de Leucocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Trastornos del Humor/tratamiento farmacológico , Trastornos Psicóticos/tratamiento farmacológico , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunologíaRESUMEN
We routinely measured plasma neurotransmitters and hormone levels in order to investigate the role of stress on many types of diseases. In this study, we present results obtained from patients with severe chronic diseases. The study sample consisted of 88 patients (asthmatics, ulcerative colitis, Crohn's disease, chronic active hepatitis, chronic relapsing hepatitis, multiple sclerosis, trigeminal neuralgia, systemic lupus erithematous, and rheumatoid arthritis), and their respective controls. Noradrenaline (NA), adrenaline (Ad), dopamine (DA), platelet-serotonin (pS), free-serotonin (fS), growth hormone (GH) and cortisol (CRT) were determined during both exacerbation and improvement periods. A profile compatible with uncoping stress disorder (raised NA-Ad-DA + fS + CRT as well as low pS and NA/Ad ratio) was found during exacerbation periods when compared with improvement, as seen in controls. However, during improvement periods the neurochemical profile remained significantly different from that of normal controls. The neurochemical plus hormonal plasma profiles registered in chronic illness, both during exacerbation and improvement periods, strongly suggest that an uncoping stress mechanism underlies diseases of these patients.
Asunto(s)
Catecolaminas/sangre , Enfermedad Crónica , Hidrocortisona/sangre , Serotonina/sangre , Estrés Fisiológico/sangre , Adolescente , Adulto , Anciano , Femenino , Hormona del Crecimiento/sangre , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The oral glucose tolerance test (OGTT) with plasma neurotransmitter assays and blood pressure measurements were performed on 68 hypertensive (A and B) and 68 paired normal controls (group C). Those patients who failed to show significant or persistent blood pressure reductions throughout OGTT constitute group A (37 subjects); and those who did show significant and persistent reductions constitute group B (31 subjects). The purpose of this study was to assess if there were any significant differences between those patients whose blood pressure levels normalized throughout OGTT and those who didn't and, further, compare them to their controls. In group A, noradrenaline (NA) was high at the 0' (fasting) period, increasing further at 60' and 90'; however, circulating serotonin (p5HT) did not vary throughout OGTT. Group B, although showing high NA at 0', did not show rises afterwards; whereas, significant and sustained p5HT rises registered throughout postprandial periods. In group C, both p5HT and plasma NA showed significant and sustained increases. Therefore, the NA/p5HT ratio is higher in A, than in B and C. Group A patients were awake and alert throughout. Group B patients were mostly drowsy and many slept light and intermittently. Group C subjects slept throughout, dreaming and showing rapid eye movements. Our findings suggest that the hypertensive syndrome is most severe in those patients who do not show a rise in postprandial circulating serotonin (parasympathetic activity), group A, than those who do exhibit such a rise, group B.
Asunto(s)
Hipertensión/sangre , Neurotransmisores/sangre , Adulto , Presión Sanguínea/fisiología , Dopamina/sangre , Epinefrina/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Hipertensión/fisiopatología , Hipertensión/psicología , Masculino , Persona de Mediana Edad , Norepinefrina/sangre , Serotonina/sangre , Factores de TiempoRESUMEN
We report five consecutive cases of patients with acute pancreatitis resistant to conventional treatment who improved dramatically with clonidine. All patients showed greatly elevated noradrenaline, adrenaline and cortisol plasma levels (physiological indicators of stress) which fell abruptly upon initiation of clonidine therapy. The clonidine test performed in the patients showed a hyper-response in all, a reaction consistent with uncoping stress situation. Therefore, we postulate that stress might play a role in the pathogenesis of these patients pancreatic inflammatory disease.
Asunto(s)
Clonidina/uso terapéutico , Pancreatitis/tratamiento farmacológico , Enfermedad Aguda , Adulto , Presión Sanguínea , Epinefrina/sangre , Femenino , Estudios de Seguimiento , Hormona del Crecimiento/sangre , Humanos , Hidrocortisona/sangre , Masculino , Norepinefrina/sangre , Pancreatitis/sangreRESUMEN
We report five cases of patients with acute pancreatitis (AP) resistant to conventional treatment who improved dramatically with clonidine. All patients showed greatly elevated plasma levels of noradrenaline (norepinephrine) (NA), adrenalin (epinephrine) (Ad) and cortisol (CRT), physiologic indicators of stress, which decreased abruptly upon initiation of clonidine therapy. The clonidine test performed in the patients showed a hyper-response in all, a reaction consistent with uncoping stress situations. Therefore, we postulate that stress might play a role in the pathogenesis of pancreatic inflammatory disease in these patients.
Asunto(s)
Clonidina/uso terapéutico , Pancreatitis/tratamiento farmacológico , Enfermedad Aguda , Adulto , Catecolaminas/sangre , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Pancreatitis/sangreRESUMEN
Plasma noradrenaline (NA), adrenaline (Ad), dopamine (DA), platelet serotonin (p5HT), free serotonin (f5HT), glucose, heart rate (HR) and blood pressure (BP) were measured before and after an oral load of glucose (OGTT) in 100 normal humans. One sham-feeding test was performed in every subject 2-3 weeks before OGTT. Aside from glucose rise, significant increases in NA, p5HT and the NA/Ad ratio were registered. No significant changes were observed in Ad, DA, f5HT, HR and BP mean +/- SE values. Significant reductions in the NA/p5HT, Ad/p5HT and DA/p5HT ratios' mean values were registered at 90 and 180 min. Several significant correlations were found amongst plasma neurotransmitters. Very high positive correlations were obtained when NA, Ad and DA were plotted against the ratio of each one of them over p5HT; however, they (r = 0.99) decreased significantly at 90 and 180 min. Upon evaluation of these results we infer that quiescence of adrenal glands occurs during OGTT. Under such circumstances, plasma neurotransmitters are left under the control of a central bipolar system: noradrenergic-parasympathetic. All numerical data strongly suggest that the noradrenergic system predominates at 60, 120 and 210 min, whereas parasympathetic predominance occurs at 90 and 180 min. The fact that the latter is interfered by atropine reinforces this hypothesis. Analyses of correlations also suggest that DA and p5HT probably act as a buffer and modulate the excessive increase in NA plasma levels registered during OGTT.