Immunological features beyond CD4/CD8 ratio values in older individuals.

The CD4/CD8 T-cell ratio is emerging as a relevant marker of evolution for many pathologies and therapies. We aimed to explore immunological features beyond CD4/CD8 ratio values in older subjects (>65 years old) who were classified as having lower (<1.4), intermediate (1.

Effect of homeostatic T-cell proliferation in the vaccine responsiveness against influenza in elderly people.

Background: Seasonal influenza virus infection is a significant cause of morbimortality in the elderly. However, there is poor vaccine efficacy in this population due to immunosenescence. We aimed to explore several homeostatic parameters in the elderly that could impact influenza vaccine responsiveness.

Phenotype and Polyfunctional Deregulation Involving Interleukin 6 (IL-6)- and IL-10-Producing Monocytes in HIV-Infected Patients Receiving Combination Antiretroviral Therapy Differ From Those in Healthy Older Individuals.

Background: Despite the relevance of monocytes as promoters of the inflammatory response, whether human immunodeficiency virus (HIV) infection induces premature age-related changes to the phenotype and function of monocytes or whether these alterations are different and/or specifically driven by HIV remains to be mechanistically determined.

Methods: We assayed the activation phenotype and the responsiveness in vitro to Toll-like receptor (TLR) agonists in classical, intermediate, and nonclassical subsets of monocytes by assessing intracellular interleukin 1α (IL-1α), IL-1β, interleukin 6 (IL-6), interleukin 8, tumor necrosis factor α, and interleukin 10 (IL-10) production in 20 HIV-infected patients receiving combination antiretroviral therapy (cART) and 2 groups of uninfected controls (20 age-matched young individuals and 20 older individuals aged >65 years).

Results: HIV-infected patients showed a more activated phenotype of monocytes than older controls.

Monocyte Phenotype and Polyfunctionality Are Associated With Elevated Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional and Cognitive Decline in Elderly Adults.

Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (α), IL1-beta (β), IL-6, IL-8, TNF-α, and IL-10 of elderly adults (median 83 [67-90] years old;n= 20) compared with young controls (median 35 [27-40] years old;n= 20).

In vitro effects on monoamine uptake and release by the reversible monoamine oxidase-B inhibitors lazabemide and N-(2-aminoethyl)-p-chlorobenzamide: a comparison with L-deprenyl.

To investigate whether the reversible monoamine oxidase-B (MAO-B) inhibitors lazabemide and Ro 16-6491 have any additional effect on monoamine uptake and release, in vitro experiments were performed on rat forebrain synaptosomes and blood platelets. The effects of the two drugs were compared with those of L-deprenyl, the well-known irreversible MAO-B inhibitor which is reported to affect amine uptake. Both lazabemide and Ro 16-6491 behaved as weak inhibitors of [3H]monoamine uptake by synaptosomes, with a similar rank order of potency for amine uptake inhibition (noradrenaline (NA) > or = 5-hydroxytryptamine (5 HT) > dopamine (DA)).

Effect of aging on lazabemide binding, monoamine oxidase activity and monoamine metabolites in human frontal cortex.

Age-related modifications of monoamine oxidase-A and -B (MAO-A and MAO-B) and amine metabolite concentrations were studied in human frontal cortex taken postmortem from 22 subjects of various ages (21-75 years). Qualitative and quantitative analysis for MAO-B was provided by kinetic studies with a specific radioligand, [3H]lazabemide. The data demonstrated a significant (P < 0.

Characterization of the binding of [3H]Ro 41-1049 to the active site of human monoamine oxidase-A.

The novel reversible and selective inhibitor of monoamine oxidase-A (MAO-A) Ro 41-1049 [N-(2-aminoethyl)-5-(m-fluorophenyl)-4-thiazole carboxamide HCl] shows inhibition characteristics similar to those of the structurally related reversible MAO-B inhibitors Ro 16-6491 and Ro 19-6327. In the present study, tritiated Ro 41-1049 was used as a high affinity ligand to study the binding characteristics of this inhibitor to MAO-A and its interactions with the enzyme. An homogeneous population of high affinity binding sites for [3H]Ro 41-1049 was found in membrane preparations from human frontal cortex and placenta (Kd = 16.

[3H]Ro 19-6327: a reversible ligand and affinity labelling probe for monoamine oxidase-B.

This study demonstrated the existence of specific binding sites for [3H]Ro 19-6327 in human platelet membranes. This compound is a novel, time-dependent inhibitor of monoamine oxidase type B (MAO-B) and is structurally closely related to [3H]Ro 16-6491. The density of the sites labelled with high affinity by [3H]Ro 19-6327 was similar to that observed in previous studies with [3H]Ro 16-6491 as ligand.

[3H]Ro 16-6491, a selective probe for affinity labelling of monoamine oxidase type B in human brain and platelet membranes.

[3H]Ro 16-6491 [N-(2-aminoethyl)-p-chlorobenzamide HCl], a reversible "mechanism-based" inhibitor of monoamine oxidase (MAO) type B, binds selectively and with high affinity to the active site of MAO-B in brain and platelet membranes. Under normal conditions, the binding of [3H]Ro 16-6491 is fully reversible. However, [3H]Ro 16-6491 could be irreversibly bound (covalently) to membranes by the addition of the reducing agent NaBH3CN to the sample and adjusting to pH 4.

Serotonin and noradrenaline concentrations and serotonin uptake in platelets from hyperphenylalaninaemic patients.

In three untreated patients with phenylketonuria (PKU), three PKU and six hyperphenylalaninaemic (HPA) patients in good metabolic control, the kinetic constants of platelet in vitro uptake of [14C]serotonin (5HT) did not significantly differ from those in 12 control subjects matched for age. The platelet concentrations of endogenous 5HT and noradrenaline (NA), taken as long-term indices of the amount of these amines circulating in plasma, were lower than normal in PKU and HPA patients, whether or not they were kept on a diet. However, a reduction in plasma NA concentrations at the moment of blood collection was seen only in untreated PKU patients.

Alcohol impairs age-dependent adaptation of human lymphocyte beta-adrenergic receptors.

Lymphocyte beta-adrenergic receptor function and norepinephrine (NE) plasma concentration have been compared in normal subjects and in ethanol-addicted patients of different ages. Direct measurement of the density and properties of beta-adrenoceptors in membrane fractions was performed using the radioligand 125I-Iodocyanopindolol (ICYP). In normal subjects beta-receptor density decreased and norepinephrine plasma concentration increased with age.

Binding of [3H]Ro 16-6491, a reversible inhibitor of monoamine oxidase type B, to human brain mitochondria and platelet membranes.

The reversible inhibitor of monoamine oxidase type B (MAO-B) [3H]Ro 16-6491 binds specifically and with high affinity to a single population of binding sites in human frontal cortex crude mitochondria and platelet membranes. In both tissues binding equilibrium was reached after 1 h incubation at 20 degrees C. Dissociation of bound radioactivity was relatively fast at 20 degrees C (t1/2 = 90-120 min) whereas at 0 degrees C [3H]Ro 16-6491 showed the characteristics of a slowly dissociating ligand.

Regulation of left ventricular mass by endogenous catecholamines in hypertensive progeny.

In 10 normotensives with both parents hypertensive, the relationship between changes in echocardiographic parameters of left ventricular anatomy and those in circulating catecholamine levels induced by three 3-week periods of different sodium and potassium intakes were examined. A high-sodium normal-potassium regimen reduced upright plasma norepinephrine (P less than 0.01), posterior wall thickness (PWT) and interventricular septal thickness (IVST) as well as the left ventricular mass index (LVMi).

Participation of endogenous catecholamines in the regulation of left ventricular mass in progeny of hypertensive parents.

To investigate whether adrenergic activity is a determinant of left ventricular hypertrophy in human hypertension, in each of 10 normotensive subjects with two hypertensive parents we have examined the relationship between changes in echocardiographic parameters of left ventricular anatomy and those in circulating catecholamine levels induced by three, 3 week periods of different sodium and potassium intakes. A high sodium-normal potassium regimen induced a significant reduction in upright plasma norepinephrine (from 599 +/- 89 to 379 +/- 45 pg/ml, p less than .01) and in posterior wall (PWT) and interventricular septal (IVST) thickness, as well as in the left ventricular mass index (LVMi).

Alterations in plasma noradrenaline in response to reflex modulation of sympathetic vasoconstrictor tone to skeletal muscles.

In man, stimulation and deactivation of carotid baroreceptors are accompanied by sympathetically-induced reduction and increase in total peripheral resistance, but not by alterations in plasma noradrenaline. This has been explained by the inability of arterial baroreflexes to sustainedly modulate sympathetic tone to skeletal muscle vessels on which plasma noradrenaline has been assumed largely to depend. In the present study nine subjects were submitted to procedures that cause a sustained alteration in muscle sympathetic vasoconstrictor tone, i.

Platelet met-enkephalin immunoreactivity and 5-hydroxytryptamine concentrations in migraine patients: effects of 5-hydroxytryptophan, amitriptyline and chlorimipramine treatment.

In thirty patients with common migraine the platelet concentrations of met-enkephalin immunoreactivity (ME) (76 +/- 9 pg/mg protein) were similar to those in 23 healthy volunteers (77 +/- 5), suggesting that there is no alteration in the ME pool in this biochemical compartment in migraine. Chronic treatment (4 weeks) with drugs that interfere with 5-hydroxytryptamine (5-HT) synthesis or uptake induced the expected changes in platelet 5-HT levels, i.e.

Different rebound rise in plasma prolactin during the postdopamine infusion phase in puerperal women and patients with pathological hyperprolactinemia.

Dopamine infused at a rate of 4 micrograms/kg . min for 120 min induced at the end of the infusion period a clear-cut and similar suppression of circulating PRL levels in normal and puerperal women as well as in patients with hyperprolactinemia either due to a tumor or of unknown etiology. At the discontinuation of the infusion there was a marked PRL rebound above baseline levels in normal subjects and a rapid return to basal levels in subjects with pathological hyperprolactinemia.

Studies of the mechanisms underlying impairment of beta-adrenoceptor-mediated effects in human hypertension.

To investigate the impairment of beta-adrenoceptor responsiveness in human hypertension, we evaluated the effect of an oral salt load (400 mEq/day of NaCl for 7 days) on plasma catecholamine concentrations and beta-adrenoceptor-mediated effects in 11 young patients with mild essential hypertension. Responses of heart rate and plasma cAMP to isoproterenol administration were used as indices of beta-adrenoceptor responsiveness. Salt loading induced a significant reduction in the dose of isoproterenol required to raise the heart rate by 25 bpm (CD25) (from 7.

Sequential changes in plasma renin activity and plasma catecholamines in mildly hypertensive patients during acute, furosemide-induced body-fluid loss.

To evaluate the role of adrenergic mechanisms in the acute response of renin to furosemide, plasma renin activity (PRA) and plasma catecholamine concentrations were measured for 3 h after i.v. administration of furosemide 1 mg/kg to 8 patients with mild essential hypertension.

Plasma adrenaline and noradrenaline concentrations in diabetic patients with and without autonomic neuropathy at rest and during sympathetic stimulation.

Plasma concentrations of adrenaline and noradrenaline were measured radio-enzymatically in nine patients with diabetic autonomic neuropathy, seven diabetic patients without autonomic neuropathy and nine normal subjects, in the recumbent position and after standing. Furthermore, in six patients with autonomic neuropathy and in the normal subjects, plasma noradrenaline and adrenaline concentrations were determined during and after cyclo-ergometer exercise. No differences in plasma adrenaline concentrations were found at any time in the study.

Effects of oral chlordemethyldiazepam on plasma adrenaline and noradrenaline and cardiovascular reactivity in preoperative patients.

In 11 preoperative women, plasma adrenaline (A) concentrations were lower after oral administration of an antianxiety dose (19.25 micrograms/kg) of chlordemethyldiazepam (Cl-DMDZ) than the predrug values, or those in 12 patients given placebo. No significant differences in supine plasma noradrenaline (NA), blood pressure (BP) and heart rate values were observed.

Plasma catecholamines in rats exposed to cold: effects of ganglionic and adrenoreceptor blockade.

Exposure to cold (4 degrees C) of catheterized rats acclimated to 20 degrees C resulted in a progressive increase in plasma noradrenaline (NA) concentrations which reached values consistently more than twice the basal ones (20 degrees C) by about 30 min. No further increase in plasma NA levels were detected when the cold exposure was continued for 24 h. Plasma adrenaline (A) and dopamine levels did not change at any time studied.

Plasma catecholamine response to postural stimulation in normotensive and dialysis hypotension-prone uremic patients.

The neurosympathetic responsiveness of two groups of uremics, each group treated for the same mean time by dialysis, categorized as normotensive, mean age 28.3 +/- (SE) 3 years, or dialysis hypotension-prone, mean age 49.6 +/- 5 years, was studied by determining plasma norepinephrine and epinephrine before and after postural activation of the sympathetic reflex arc.