Variations of plasma leptin and adiponectin levels in autistic patients.

Autism is a neurodevelopmental disorder with pathogenesis not completely understood. Although a genetic origin has been recognized, it has been hypothesized a role for environmental factors, immune dysfunctions, and alterations of neurotransmitter systems. In young autistic patients we investigated plasma leptin and adiponectin levels over a year period.

Effects of spa therapy on serum leptin and adiponectin levels in patients with knee osteoarthritis.

Adipocytokine, including leptin and adiponectin, may play an important role in the pathophysiology of osteoarthritis (OA). Spa therapy is one of the most commonly used non-pharmacological approaches for OA, but its mechanisms of action are not completely known. The aim of the present study was to assess whether spa therapy modified plasma levels of leptin and adiponectin in thirty patients with knee OA treated with a cycle of a combination of daily locally applied mud-packs and bicarbonate-sulphate mineral bath water.

Long-term plasma levels of leptin and adiponectin in Rett syndrome.

Objective: Rett syndrome is a progressive neurological disorder affecting almost exclusively females after age 6 months and characterised by acquired microcephaly, psychomotor retardation, growth failure, purposeless hand movements, autistic-like behaviour and wide-based and stiff legged gait. Leptin and adiponectin, peptides secreted by adipose tissue, are involved in the regulation of body weight and energy expenditure.

Design And Patients: We investigated in patients with Rett syndrome the variations of plasma leptin and adiponectin and their relation over a 2-year period.

Rett syndrome and plasma leptin levels.

Objective: To describe in patients with Rett syndrome (classic and preserved-speech variant) plasma leptin levels and their relationship to BMI (body mass index) and age.

Study Design: Female patients (n = 48; age range 3-20 years) affected by classic Rett syndrome were enrolled into the study. Eleven female patients, age range 3 to 20 years, with preserved-speech variant Rett syndrome were included in the study.

Effect of iloprost on plasma asymmetric dimethylarginine and plasma and platelet serotonin in patients with peripheral arterial occlusive disease.

Background: Iloprost, a prostacyclin analogue, is used in the treatment of peripheral arterial occlusive disease at Leriche-Fontaine stages III-IV, through intravenous infusion for at least 21 days. Recently, iloprost has been shown to be safe and effective in critical limb ischemia patients when administered per 7 days. We investigated in patients at Leriche-Fontaine stages III-IV the effect of 1-week treatment with iloprost on plasma asymmetric dimethylarginine (ADMA), plasma and platelet serotonin, and on clinical response.

Changes of peripheral A2A adenosine receptors in chronic heart failure and cardiac transplantation.

Peripheral blood mononuclear cells of chronic heart failure (CHF) patients produce great amounts of pro-inflammatory cytokines, indicating that circulating cells are activated and could mirror changes occurring in inflammatory cells infiltrating the failing heart. Adenosine is a regulatory metabolite acting through four membrane receptors that are linked to adenylyl cyclase: activation of the A2A receptor subtype has been reported to inhibit cytokine release. Changes of the adenosinergic system may play a role in CHF development.

Experimental model of short-time exercise-induced preconditioning in POAD patients.

Regular physical exercise improves walking performance in patients affected with peripheral obliterative arterial disease (POAD). The mechanisms underlying the phenomenon are still controversial. In order to verify the hypothesis that physical conditioning of lower limbs on a treadmill and ischemic preconditioning of the heart could share some biological aspects, 14 POAD subjects underwent a training program on the treadmill consisting of five repeated submaximal exercises at five-minute and two-hour intervals preceding the maximal tolerance test.

Modulation of venous endothelial activity and transcellular calcium transport by defibrotide: the adenosine hypothesis.

Defibrotide is a polydeoxyribonucleotide that possesses profibrinolytic and cytoprotective activities. These properties have been associated with its capacity to induce the release of prostacyclin and tissue plasminogen activator (t-PA) from endothelial cells. In the present study, the bolus administration of defibrotide in humans was able to induce (100-800 mg) a dose-dependent decrease in plasminogen activator inhibitor (PAI) (from 19.

Pharmacokinetics and pharmacodynamics of neutrophil-associated ciprofloxacin in humans.

Objective: To study the possibility that the penetration of the antibiotic ciprofloxacin into polymorphonuclear leukocytes (PMN) may be associated with some changes in cell reactivity.

Design: Superoxide anion and chemiluminescence generation induced by formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) were studied ex vivo in 12 healthy volunteers (mean age, 53.15 +/- 16.

Inhibition of neutrophil function in vitro by nimesulide. Preliminary evidence of an adenosine-mediated mechanism.

Nimesulide (CAS 51803-78-2) is a methane sulphoanilide derivative provided with specific anti-inflammatory activity. In human polymorphonuclear leucocytes (PMNs), the activity of nimesulide has been suggested to be based on the inhibition of the oxidative burst. However, the effect of the compound on PMNs function seems to be very complex.

Isradipine inhibits PMN leukocyte function. A possible interference with the adenosine system.

The dihydropyridine derivative isradipine is able to inhibit PMN leukocyte function, such as enzyme release and free radical generation, following the activation with specific stimuli. Moreover, the drug prevents calcium influx into the cells as detected by the specific fluorescent dye FURA 2/acetoxymethylester. The specific adenosine receptor antagonist theophylline is able to partially remove the inhibiting activity, thus suggesting a possible interference of isradipine with the adenosine system.

Inhibition of neutrophil function in vitro by heparan sulfate.

The profibrinolytic and antithrombotic glycosaminoglycan heparan sulfate (HS) was tested in vitro on some neutrophil functions induced by several stimuli. HS 1-500 micrograms/ml was able to significantly inhibit, in a dose-dependent fashion, superoxide anion generation, lysozyme and beta-glucuronidase release from neutrophils stimulated with the formylated oligopeptide fMLP, the ionophore A23187, and Platelet Activating Factor. Such an effect could represent an additional therapeutical benefit in those pathological conditions in which neutrophil activation contributes to tissue injury and vascular damage.

Pharmacodynamics of salmon calcitonin in humans: new markers of pharmacological activity.

In order to define the pharmacodynamic profile of salmon calcitonin (sCT) in humans, several markers of the biological activity of the drug have been studied, namely cAMP, adenosine and pO2 in venous blood, and the cytosolic free calcium level in circulating cells. Different dosages and routes of administration (1.5 IU.

Defibrotide inhibits Ca2+ dependent neutrophil activation: implications for its pharmacological activity in vascular disorders.

Defibrotide (DEF) is a polydeoxyribonucleotide agent provided with profibrinolytic and antithrombotic properties. Moreover, an antiischemic, cardioprotective effect of the drug has recently been demonstrated in experimental animals. Increasing evidence exists of the important role played by neutrophils in the development of tissue damage during chronic and acute ischemia and in the early phases of reperfusion.

Nitroprusside in vitro inhibits platelet aggregation and intracellular calcium translocation. Effect of haemoglobin.

The biologically final active compound of nitrovasodilators is now supposed to be nitric oxide (NO), a labile substance identical to EDRF. The effects of nitroprusside on platelet functions were studied in vitro. Platelet aggregation induced by several stimuli (ADP, collagen, arachidonic acid and PAF) was inhibited by increasing concentrations of the drug (1-50 uM); interestingly, the potency of nitroprusside is higher when PAF is employed as stimulating agent in comparison with the other agonists (ED50 = 2 uM for ADP, 2.

Adenosine system and cell calcium translocation: interference of calcium channel blockers.

Adenosine is able to inhibit in vitro neutrophil functions induced by formyl-methionyl-leucyl-phenylalanine (FMLP) and A23187, but not phorbol 12-myristate 13-acetate (PMA). The inhibiting activity on A23187 is reversed by increasing extracellular Ca2++ concentration. The calcium entry blocker flunarizine shows an activity very similar to that of adenosine.

Adenosine blocks calcium entry in activated neutrophils and binds to flunarizine-sensitive calcium channels.

Adenosine is able to prevent Ca+(+) influx into activated neutrophils as detected by the specific fluorescent indicator Quin 2. Such an effect is shown in a similar fashion by the calcium entry blocker flunarizine. The binding interaction between flunarizine and the neutrophil membrane as well as the flunarizine-adenosine antagonism are shown by the 1H-NMR technique, thus supporting evidence of a competition between the agents at the same or a nearby site on the cell membrane.

New in vivo model to assess venous endothelial cell functions. Effect of defibrotide.

In the past few years there has been increasing interest in the role of the vascular endothelium as an active modulator of biological responses. Endothelial cells exert antithrombotic activity by the release of prostacyclin [23] and adenine nucleotides [16], the availability on the cell surface of heparin-like substances [3], and thrombomodulin-mediated activation of protein C [8]. In addition, endothelium is involved in the regulation of fibrinolysis by releasing soluble factors, such as tissue plasminogen activator (tPA; [10]) and plasminogen activator inhibitor (PAI; [22, 11]), as well as in the control of vascular responsiveness by the production of smooth muscle relaxing and contracting factors.

Allopurinol prevents ischaemia-dependent haemorheological changes.

Pre-treatment with allopurinol is able markedly to attenuate the deterioration in blood viscosity (BV) and whole blood filterability (WBF) that occurs after ischaemia during exercise. It also reduces the exercise-induced increase in serum oxidase activity, although this action is slightly less effective in peripheral obliterative arterial disease (POAD) patients. Conversely, allopurinol is completely ineffective in modifying haemorheological parameters in vitro, and it does not affect superoxide anion generation or enzyme release from neutrophils stimulated in vitro with formyl-methionyl-leucyl-phenylalanine (FMLP).

Defibrotide in vitro inhibits neutrophil activation by a Ca++-involving mechanism.

Defibrotide, a polydeoxyribonucleotide provided with a pro-fibrinolytic and prostacyclin-like activity, was studied as an inhibitor of polymorphonuclear leucocyte activation in vitro. It was found capable of dose-dependently (1-8 X 10(-5) M) inhibiting FMLP-induced activation, as shown by a decrease of enzyme release and free-radical formation (superoxide anion generation and chemiluminescence). A similar inhibiting activity was observed on A23187-induced activation.