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Relaxation of the isolated human internal anal sphincter by sildenafil.
2007
Abstract Background Hypertonicity of the internal anal sphincter (IAS) appears to be involved in the pathogenesis of anal fissure. The relaxant effects of sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, on isolated human IAS were investigated. Methods The efficacy (maximal effect, Emax) and potency (−log IC50, where IC50 is half-maximal inhibitory concentration) of the PDE5 inhibitors, sildenafil and zaprinast, and of nitric oxide donors, sodium nitroprusside and glyceryl trinitrate, as relaxants of histamine (0·1 mmol/l)-induced tone were examined in IAS strips under isometric contraction. The presence of PDE5 isoenzymes and changes in intracellular calcium and cyclic nucleot…
Prostaglandin E2 activates the ciliary beat frequency of cultured human nasal mucosa via the second messenger cyclic adenosine monophosphate.
2001
Prostaglandins influence the ciliary beat frequency (CBF) of ciliated nasal epithelial cells and a stimulatory effect has been described for prostaglandin E2 (PGE2). Until now, it is not known whether PGE2 has direct ciliostimulatory properties or acts through a second messenger. In this study we investigated whether cyclic adenosine monophosphate (cAMP) is implicated in the signal transduction pathway of PGE2-induced activation of CBF. Ciliated cells of the nasal mucosa were cultured for up to 5 days whereafter the culture medium was removed and the cells were incubated with different concentrations of test solutions. The ciliated cells were recorded under a phase-contrast microscope and v…
Comparative effects of dilator drugs on human penile dorsal artery and deep dorsal vein
1998
The present study was designed to characterize the response of human penile dorsal artery and deep dorsal vein to dilator drugs used in the diagnosis and treatment of erectile dysfunction with special emphasis on the effects on sympathetic neurotransmission. Ring segments of penile dorsal artery and deep dorsal vein were obtained from 20 multi-organ donors during procurement of organs for transplantation. The rings (3 ;mm long) were suspended in organ bath chambers for isometric recording of tension. We then studied the relaxant responses to prostaglandin E1 (PGE1), vasoactive intestinal peptide (VIP), papaverine (PV), sodium nitroprusside (SNP) and linsidomine chlorhydrate (SIN-1), and ana…
Clonidine induces nitric oxide- and prostaglandin-mediated vasodilation in healthy human skin
2005
Sustained sympathetic activation not only leads to vasoconstriction but also might induce paradox vasodilation. This study was performed to explore whether and how alpha(2)-receptor stimulation mediates this vasodilation. We investigated 11 healthy subjects in 33 dermal microdialysis (MD) sessions. After nerve trunk blockade, MD fibers were inserted and perfused with physiological saline until skin trauma-related vasodilation subsided. Thereafter, fibers were perfused with either clonidine solutions (10(-3), 5 x 10(-4), 10(-4) mol/l), N(G)-monomethyl-l-arginine (L-NMMA; nitric oxide synthase blocker), acetylsalicylic acid (ASA; cyclooxygenase blocker), or combinations of these. Laser-Dopple…
Inhibition of thromboxane biosynthesis by triflusal in type 2 diabetes mellitus.
2004
Abstract Triflusal is an antiplatelet drug related to aspirin, with different pharmacological properties and a lower haemorrhagic risk. We aimed at comparing their effects on platelet and endothelial activation in type 2 diabetes mellitus (T2DM). In a randomized, double-blind, parallel group study, we compared the effects of three daily regimens (300, 600, and 900mg) of triflusal, and aspirin (100mg/day) on urinary 11-dehydro-thromboxane (TX)B 2 , index of in vivo platelet activation, ex vivo platelet function using the analyzer PFA-100, plasma von Willebrand factor (vWF), P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and serum nitrite a…
Consensus interferon and ribavirin for patients with chronic hepatitis C and failure of previous interferon-alpha therapy.
2006
BACKGROUND The efficacy of consensus interferon (CIFN), a synthetic IFN with optimised in vitro activity, was assessed in chronic hepatitis C virus (HCV) patients who had failed the pretreatment with interferon-alpha (IFNalpha) and ribavirin. METHODS One hundred and three patients after non-response (n=69) or relapse (n=34) to IFNalpha+/-ribavirin were randomly assigned to high-dose induction (CIFN 27-->9 microg daily for 24 weeks, 9 microg t.i.w. for 24 weeks) or low-dose treatment (CIFN 18 microg t.i.w. for 12 weeks, 9 microg t.i.w. for 36 weeks); each with ribavirin 800 mg/day. Follow-up was 24 weeks. RESULTS Non-responder patients treated with high-dose induction had higher early virolo…
Improved Responses to Pegylated Interferon Alfa-2b and Ribavirin by Individualizing Treatment for 24–72 Weeks
2011
Guidelines recommend that patients with chronic hepatitis C virus (HCV) infection be treated with pegylated interferon and ribavirin for 24, 48, or 72 weeks, based on their virologic response to treatment. We investigated the effects of treating patients for individualized durations.We treated 398 treatment-naïve patients who had HCV genotype 1 infections with pegylated interferon alfa-2b and ribavirin for 24, 30, 36, 42, 48, 60, or 72 weeks (mean of 39 weeks, termed individualized therapy); the duration of therapy was determined based on baseline viral load and the time point at which HCV RNA levels became undetectable (measured at weeks 4, 6, 8, 12, 24, and 30). Results were compared with…
Effect of Cabergoline on Metabolism in Prolactinomas.
2013
<b><i>Introduction:</i></b> Hyperprolactinemia has been implicated in the pathogenesis of obesity and glucose intolerance and is reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of 12- and 60-month treatment with cabergoline (CAB) on metabolic syndrome (MetS) in patients with prolactinomas. <b><i>Patients and Methods:</i></b> 61 patients with prolactinomas (13 men, 48 women, 41 with microadenoma, 20 with macroadenoma), aged 34.4 ± 10.3 years, entered the study. In all patients, prolactin (PRL) and metabolic parameters were assessed at diagnosis and after 12 and 60 months of continuo…
Urinary metabolites of histamine and leukotrienes before and after placebo-controlled challenge with ASA and food additives in chronic urticaria pati…
2002
Background: The recovery of mediator metabolites from urine has the potential to provide a rapid, safe, and easily available index of release of mediators. We aimed to determine urinary metabolites of both histamine and leukotrienes (LTs) in patients affected by chronic urticaria (CU). Methods: Twenty patients with CU were studied. They were selected on the basis of double-blind placebo-controlled challenge (DBPC) with acetyl salicylic acid (ASA) and food additives. Ten patients (group B) were negative to both challenges. Ten patients (group C) presented urticaria and/or the appearance of angioedema during or 24 h after challenge, with reactions to ASA (five patients) or food additives (fiv…
Iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis and the quality of life: a new therapeutic protocol
2006
Objectives: to evaluate the clinical efficacy and the effects on the quality of life of Iloprost, a prostacyclin analogue, used, according to a new protocol, in patients with Raynaud’s phenomenon secondary to Systemic Sclerosis. Methods: in this randomized study we treated 30 patients with Iloprost given by intravenous infusion, at progressively increasing doses (starting from 0.5 ng/Kg/min up 2 ng/Kg/min) over a period of 6 hours a day for ten days in two consecutive weeks, with repeated cycles at regular intervals of three months for 18 months. The results were compared with those obtained in 30 other patients, who had received the same drug but with different posologic schemes. Results: …