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Biomedical subjects

B Orozco

Publications and source records attributed to B Orozco.

At least 19 recordsLinked to original sources

Enhancement of noradrenergic neural transmission: an effective therapy of myasthenia gravis: a report on 52 consecutive patients.

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.

Adolescent↗

The serotonin uptake-enhancing drug tianeptine suppresses asthmatic symptoms in children: a double-blind, crossover, placebo-controlled study.

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.

Adolescent↗

Effects of buspirone on plasma neurotransmitters in healthy subjects.

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.

Adult↗

Neuropharmacologic treatment of bronchial asthma with the antidepressant tianeptine: a double-blind, crossover placebo-controlled study.

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.

Adolescent↗

Increased levels of free serotonin in plasma of symptomatic asthmatic patients.

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.

Adolescent↗

Plasma neurotransmitters, blood pressure and heart rate during supine resting, orthostasis and moderate exercise in severely ill patients: a model of failing to cope with stress.

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.

Adolescent↗

DRD2, DRD3 and 5HT2A receptor genes polymorphisms in obsessive-compulsive disorder.

We performed an association analysis of the DRD2, DRD3 and 5HT2A genes polymorphisms in 67 Obsessive-Compulsive Disorder (OCD) patients and 54 healthy controls. There were no statistically significant differences in genotype or allele frequencies for any of the polymorphisms studied between OCD subjects and controls. For the subgrouped analysis, no results were significant after correction for multiple testing, although homozygosity of DRD2/A2A2 in subjects displaying vocal or motor tics approached significance compared to controls (Fisher exact test, P = 0.008). Our results may follow the notion that OCD patients with tics represent a different genetic subtype of the disease.

Adolescent↗

Plasma neurotransmitters, blood pressure, and heart rate during supine-resting, orthostasis, and moderate exercise conditions in major depressed patients.

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.

Adrenal Glands↗

Plasma neurotransmitters, blood pressure, and heart rate during supine resting, orthostasis, and moderate exercise in dysthymic depressed patients.

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.

Adolescent↗

Peripheral blood immunological parameters in long-term benzodiazepine users.

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.

Adult↗

Plasma neurotransmitters and cortisol in chronic illness: role of stress.

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.

Adolescent↗

Plasma neurotransmitters throughout an oral glucose tolerance test in non-depressed essential hypertension patients.

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.

Adult↗

Effects of an oral glucose load on plasma neurotransmitters in humans: involvement of REM sleep?

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.

Adult↗

Clonidine treatment of acute pancreatitis: report of five cases.

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.

Acute Disease↗

Dramatic improvement with clonidine in acute pancreatitis with elevated catecholamine and cortisol plasma levels: report of five cases.

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.

Acute Disease↗

[Risk factors for infection among the patrons of an HIV Control Program, Antioquia, Colombia].

A review is presented of the characteristics of 432 users of the Human Immunodeficiency Virus (HIV) Control Program sponsored by the Public Health Departmental Laboratory of Antioquia, Colombia, who were seen between July 1988 and June 1989. The prevalence of seropositivity to HIV was 29.4%, while that of AIDS was 6.7%. Eight of the seropositive subjects were women. The average age on entrance into the Program was 28.7 +/- 7.9, and it was significantly higher among the seropositive subjects. The study sample was divided into four subgroups: women, bisexual men, homosexual men, and heterosexual men. In all the subgroups the prevalence of high-risk sexual practices was high and the percentage of condom utilization was low. Frequency of exposure to different risk factors, such as injections, transfusions of blood or other fluids, surgical interventions, tattoos, consumption of alcohol and other psychoactive substances, acupuncture, and sexual preference and practices, was determined. HIV seropositivity for the group as a whole was associated with sexual relations with infected persons (OR = 3.96), active anal coitus (OR = 3.81), sexual relations with men (OR = 3.69), passive anal coitus (OR = 3.35), and sexual relations abroad (OR = 2.24). In men, HIV seropositivity was associated with anal coitus (OR = 4.0), homosexual relations (OR = 3.96), sexual relations with infected persons (OR = 3.75), and sexual relations abroad (OR = 1.88); in women there was an association with intravenous drug use (chi 2 = 10.72) and with sexual relations abroad (OR = 12.67).

Acquired Immunodeficiency Syndrome↗

Paracoccidioidomycosis and AIDS: report of the first two Colombian cases.

The records of the first two Colombian patients with AIDS and paracoccidioidomycosis are presented. Both patients were males and had no known risk factors for HIV although in the past they had worked in the field where they could have been infected with the fungus. They exhibited the juvenile type of disease with multiple organ system involvement and symptoms of short duration. They were deeply immunodepressed as indicated by less than 100 CD4 T lymphocytes per mL; however, serologic tests revealed circulating anti-Paracoccidioides brasiliensis antibodies and in one patient the first diagnostic clue came from such tests. In one case, the mycosis preceded the AIDS diagnosis while in the other, both pathologies were discovered simultaneously. Antimycotic therapy with itraconazole was administered for over 10 months, with an initial dose of 200 mg/day followed by 100 mg/day; marked improvement of the mycotic signs and symptoms was soon noticed an there have been no signs of relapse. The patients improvement was also due to the combined retroviral treatment that was instituted. In spite of the rarity of the AIDS-paracoccidioidomycosis association, physicians practicing in endemic areas should consider the presence of the mycosis in immunosuppressed patients, since a prompt diagnosis and institution of combined antimycotic-anti-retroviral treatments would result in patient improvement and survival. It appears possible that the longer survival time of today's AIDS patients would give the quiescent fungus the opportunity to revive, multiply and cause overt disease.

Acquired Immunodeficiency Syndrome↗