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ABSTRACT: It has been observed that a distinct blood pressure (BP) response to prolonged and forced hyperventilation in adult patients
with essential hypertension is associated with significant changes in plasma catecholamine and β-endorphin levels. This paper
investigated whether hemodynamic and neuro-endocrine responses to hyperventilation in elderly patients with essential hypertension
(n = 39, mean age 81 ± 3 years) differ from those in elderly patients with secondary hypertension (isolated systolic hypertension,
bilateral chronic nephropathy, nephroangiosclerosis, diabetic nephropathy and hyperparathyroidism) (n = 39, mean age 80 ±
1 years). Plasma β-endorphin levels were normal in patients with essential hypertension and increased in patients with secondary
hypertension. Plasma norepinephrine levels were normal in both populations. Hyperventilation decreased BP and norepinephrine
levels and increased β-endorphin levels in essential hypertensive patients, whereas it did not significantly change BP or
neuro-hormonal levels in secondary hypertensive patients. Hierarchical cluster analysis based on BP response to hyperventilation
disclosed a sub-group of essential hypertensive patients with the highest basal levels of norepinephrine and the lowest β-endorphin
levels, in whom the BP decrease following hyperventilation was correlated with the decrease in norepinephrine and increase
in β-endorphin levels. This suggests that b-endorphin may be involved in modulating sympatho-adrenergic activity in elderly
patients with essential hypertension.
Central European Journal of Medicine 05/2012; 3(1):55-63. · 0.31 Impact Factor
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Roberta Budriesi,
Pierfranco Ioan,
Alessandra Locatelli,
Sandro Cosconati,
Alberto Leoni,
Maria P Ugenti,
Aldo Andreani, Rosanna Di Toro,
Andrea Bedini,
Santi Spampinato,
Luciana Marinelli,
Ettore Novellino,
Alberto Chiarini
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ABSTRACT: The synthesis, characterization, and functional in vitro assays in cardiac tissues and smooth muscle (vascular and nonvascular) of a number of 4-imidazo[2,1- b]thiazole-1,4-dihydropyridines are reported. The binding properties for the novel compounds have been investigated and the interaction with the binding site common to other aryl-dihydropyridines has been demonstrated. Interestingly, the novel 4-aryl-dihydropyridines are L-type calcium channel blockers with a peculiar pharmacological behavior. Indeed, the imidazo[2,1- b]thiazole system is found to confer to the dihydropyridine scaffold an inotropic and/or chronotropic cardiovascular activity with a high selectivity toward the nonvascular tissue. Finally, molecular modeling studies were undertaken for the most representative compounds with the aim of describing the binding properties of the new ligands at molecular level and to rationalize the found structure-activity relationship data. Due to the observed pharmacological behavior of our compounds, they might be promising agents for the treatment of specific cardiovascular pathologies such as cardiac hypertrophy and ischemia.
Journal of Medicinal Chemistry 04/2008; 51(6):1592-600. · 5.25 Impact Factor
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ABSTRACT: We studied circulating levels of endothelin-1, catecholamines and nitric oxide after a mental arithmetic test in 14 patients with early ischemic lesions of the extremities due to systemic sclerosis and slightly impaired peripheral vascular flow. The test induced an increase (P<0.01) in blood pressure, heart rate, endothelin-1 and catecholamine levels, whereas it did not change the low basal levels of nitric oxide. In healthy subjects (n=20) the test significantly (P<0.01) decreased endothelin-1 without affecting nitric oxide. The low basal levels of nitric oxide and the high plasma concentration of endothelin-1 after psychological stress cannot be explained by an impaired release from the limited ischemic lesions alone. This suggests a diffuse microvascular derangement that aggravates the course of peripheral microvascular ischemic lesions.
Peptides 12/2005; 26(12):2487-90. · 2.43 Impact Factor
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ABSTRACT: The repressor element-1 (RE-1) silencing transcription factor (REST) interacts with an RE-1 cis element and represses the transcription of neuron-specific genes in neuronal progenitors but is down-regulated in post-mitotic neurons. We report that REST expression is modified, in a time-dependent manner, in SH-SY5Y neuroblastoma cells exposed to insulin-like growth factor I (IGF-I), a polypeptide hormone affecting various aspects of neuronal induction and maturation. REST is increased in cells treated with IGF-I for 2 days and then declines in 5-day-treated cells concomitant with a progressive neurite extension. To investigate any role played by REST in neurodifferentiation by IGF-I, we employed an antisense oligonucleotide (AS-ODN) complementary to REST mRNA. In AS-ODN-treated cells, the effects elicited by IGF-I on cell proliferation are not influenced whereas a marked decrease of REST significantly increases neurite elongation without any gross perturbation of neurogenesis. Synapsin I and betaIII-tubulin gene promoters contain an RE-1 motif and their transcription is repressed by REST; both of them are increased in cells exposed to IGF-I for 5 days and further elevated by AS-ODN treatment. A parallel increase of growth cone-associated protein 43, a protein chosen as a neuronal marker not directly regulated by REST, is also observed. Therefore, REST is elevated during early steps of neural induction by IGF-I and could contribute to down-regulate genes not yet required by the differentiation program while it declines later for the acquisition of neural phenotypes. These results suggest a model in which differentiating neuroblastoma cells determine their extent of neurite outgrowth on the basis of REST disappearance.
European Journal of Neuroscience 02/2005; 21(1):46-58. · 3.63 Impact Factor
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ABSTRACT: Twelve patients with chronic critical limb ischemia in whom a spinal cord stimulation (SCS) system had been implanted for at least one year had increased microvascular flow and achieved healing of trophic acral lesions. After switching off the system, the clinical improvement persisted for 10 days and the neurohormonal pattern showed high plasma values of beta-endorphin and Met-enkephalin, normal dynorphin B, endothelin-1 and catecholamines, and low nitric oxide. Met-enkephalin levels were further increased (P < 0.01) immediately after switching on the electrical stimulation again. The persistence of high plasma opioid levels after switching off the spinal cord stimulation explains the absence of subjective complaints and suggests an involvement of opioids in the regulation and improvement of the microcirculation.
Peptides 04/2004; 25(4):571-5. · 2.43 Impact Factor
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ABSTRACT: The biocompatibility of polylactic acid (PLA) and polyglycolic acid (PGA) copolymers, employed in manufacturing bone-graft substitutes, is affected by their chemical composition, molecular weight and cell environment, and by the methods of polymerization and processing. Their in vitro bioactivity on human osteoblasts has been investigated very little. We first evaluated the behavior of primary human osteoblasts cultured in close contact with 75:25 and 50:50 PLA-PGA copolymers for 14 days adopting a cell culture system that allowed us to evaluate the influence of direct contact, and of factors released from polymers. The copolymers had no negative influence on cell morphology, cell viability and proliferation. Alkaline phosphatase (ALP) activity and osteocalcin production were also not affected. The initial adhesion of osteoblasts on implant surfaces requires the contribution of integrins, acting as a primary mechanism regulating cell-extracellular matrix (ECM) interactions. We observed that adhesion of osteoblasts to PLA-PGA copolymers, 2h after plating, was reduced by approximately 70% by antibodies capable to block integrin beta(1) and alpha(5)beta(1) complex and only by approximately 30% by an anti-integrin alpha(v) antibody. Therefore, beta(1) integrins may represent a predominant adhesion receptor subfamily utilized by osteoblasts to adhere to PLA-PGA copolymers. These materials do not show any negative influence on cell proliferation and differentiation.
European Journal of Pharmaceutical Sciences 03/2004; 21(2-3):161-9. · 3.21 Impact Factor
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ABSTRACT: After hyperventilation, systolic and diastolic blood pressure (BP) significantly decreased in 14 hypertensive patients (group 1), did not change in 9 (group 2) and increased in 8 (group 3). Basal BP, norepinephrine and dynorphin B levels were higher in group 1 than in groups 2 and 3. The decrease in BP after hyperventilation was associated with a decrease in plasma norepinephrine, Met-enkephalin and dynorphin B and an increase in beta-endorphin. Naloxone abolished the hyperventilation-induced BP and norepinephrine decreases. Our findings indicate that hyperventilation may select hypertensive patients with different sympatho-adrenergic activity and that the increase in beta-endorphin reduces BP response to hyperventilation in patients with high sympatho-adrenergic tone.
Peptides 06/2002; 23(5):911-8. · 2.43 Impact Factor
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ABSTRACT: The action of FeCl(3) on 3-(alkylsulfanyl)thiophenes (3-(alkylthio)thiophenes) leads to the one-step formation of regioregular alpha-conjugated oligothiophenes, from trimer to octamer, depending on the solvent used and on the length of the alkyl chain. The regiochemistry of these oligomers is characterized by one inner head-to-head linkage between adjacent rings and by a variable number of lateral head-to-tail junctions. The reaction of ferric chloride with the head-to-head and head-to-tail bis(methylsulfanyl)-2,2'-bithiophenes gives the corresponding tetramers, while the reaction with the tail-to-tail counterpart affords a high molecular weight insoluble material. With the aid of theoretical calculations, these results are interpreted on the basis of the joint effects of the orienting power of the substituents and of the stability of the radical cations formed during the oxidative process.
The Journal of Organic Chemistry 12/1996; 61(23):8285-8292. · 4.45 Impact Factor
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ABSTRACT: After hyperventilation, systolic and diastolic blood pressure (BP) significantly decreased in 14 hypertensive patients (group 1), did not change in 9 (group 2) and increased in 8 (group 3). Basal BP, norepinephrine and dynorphin B levels were higher in group 1 than in groups 2 and 3. The decrease in BP after hyperventilation was associated with a decrease in plasma norepinephrine, Met-enkephalin and dynorphin B and an increase in β-endorphin. Naloxone abolished the hyperventilation-induced BP and norepinephrine decreases. Our findings indicate that hyperventilation may select hypertensive patients with different sympatho-adrenergic activity and that the increase in β-endorphin reduces BP response to hyperventilation in patients with high sympatho-adrenergic tone.
Peptides.
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ABSTRACT: This study investigated plasma brain natriuretic peptide (BNP) levels in normotensive and hypertensive patients with suspected coronary artery disease during radionuclide pharmacological stress testing. Twenty-seven normotensive patients (15 males, aged 63.0 ± 4.5 years and 12 females, aged 63.0 ± 4.1 years) and 38 essential hypertensive patients (25 males, aged 63.3 ± 3.3 years and 13 females, aged 64.6 ± 2.6 years) with chest pain and exercise stress testing inconclusive for coronary artery disease underwent myocardial perfusion single-photon emission computed tomography (SPECT) using adenosine infusion. SPECT identified patients without (16 normotensive and 22 hypertensive) and patients with (11 normotensive and 16 hypertensive) transient perfusion defects. Basal BNP levels in normotensive patients without transient myocardial ischemia (3.1 ± 1.2 fmol/ml) were significantly (P < 0.01) lower than those observed in normotensive patients with transient ischemia (8.2 ± 1.2 fmol/ml), whereas BNP levels in hypertensive patients without transient ischemia (8.2 ± 1.0 fmol/ml) did not significantly differ from those in hypertensive patients with transient ischemia (8.1 ± 2.0 fmol/ml). No significant difference was found in BNP levels between males or females either in normotensive or hypertensive patients without or with ischemia. Adenosine infusion did not significantly change BNP levels in any subject group without or with myocardial perfusion defects. Our findings show that increases in BNP allow early detection of myocardial ischemia in normotensive patients, but not in hypertensive patients with suspected coronary artery disease. Adenosine-induced myocardial ischemia does not affect BNP production already activated by coronary artery disease in normotensive patients and by hemodynamic changes in hypertensive patients.
Peptides.
