Further evidence that melanocortins prevent myocardial reperfusion injury by activating melanocortin MC3 receptors.

In rats subjected to myocardial ischemia/reperfusion, melanocortin peptides, including gamma(1)-melanocyte-stimulating hormone (gamma(1)-MSH), are able to exert a protective effect by stimulating brain melanocortin MC(3) receptors. A non-melanocortin receptor belonging to a group of receptors for Phe-Met-Arg-Phe-NH(2) (FMRFamide)-like peptides may be involved in some of the cardiovascular effects of the gamma-MSHs. FMRFamide-like peptides and gamma(1)-/gamma(2)-MSH share, among other things, the C-terminal Arg-Phe sequence, which seems to be essential for cardiovascular effects in normal animals.

Effect of gamma-hydroxybutyrate in two rat models of focal cerebral damage.

Gamma-hydroxybutyrate (GHB) and its lactone, gamma-butyrolactone (GBL) have been previously shown to produce a protective effect in animal models of cerebral ischaemia/hypoxia, as well as in human conditions of head injury-induced coma. The aim of the present research was to study the effect of GHB in experimental conditions of focal cerebral damage, either induced by ischaemia or excitotoxicity. Under general anaesthesia, rats were injected into the right striatum with either endothelin-1 (ET-1, 0.

[Laparoscopic liver resection using a radiofrequency dissector. Initial experience].

Laparoscopic liver surgery, especially when resective, requires both the skill of an expert laparoscopist and the experience of a liver surgeon. The aims of the study were to assess the feasibility of minor laparoscopic liver resection by means of a radiofrequency dissector and to evaluate the laparoscopic approach. From January 1993 to November 2002 we carried out 7 laparoscopic liver resections (3 men, 4 women), 5 of which for benign diseases and 2 for metastases from colorectal cancer.

Emerging problems in the pharmacology of migraine: interactions between triptans and drugs for prophylaxis.

Patients suffering from migraine take drugs for many years in order either to relieve or to prevent recurrent migraine attacks. When two or more drugs are co-administered, there is always the possibility of drug-drug interaction. Interactions can be either kinetic or dynamic.

Selective COX-2 inhibitors and dual acting anti-inflammatory drugs: critical remarks.

Non steroidal anti-inflammatory drugs (NSAIDs) are still the most commonly used remedies for rheumatic diseases. But NSAIDs produce serious adverse effects, the most important being gastric injury up to gastric ulceration and renal damage. Several strategies have been adopted in order to avoid these shortcomings, especially gastrointestinal toxicity.

Treatment of chronic overmedicated headache patients.

The effective treatment for chronic headache with analgesic overuse is examined in this review. The first step of treatment is how to stop daily use of the analgesic, supporting the withdrawal syndrome and the worsening headache. In this phase there are different strategies from no treatment to antimigraine drugs.

Lack of dendritic cell mobilization into the peripheral blood of cancer patients following standard- or high-dose chemotherapy plus granulocyte-colony stimulating factor.

Background: Dendritic cells (DC), the most specialized antigen-presenting cells, can be detected in the peripheral blood (PB) and divided into two subsets of populations, DC1 and DC2, endowed with different functions. The aim of this study was to evaluate the effect on DC release and on their subsets of three regimens utilized to mobilize CD34+ cells into the PB in cancer patients and in normal CD34+ cell donors.

Patients And Methods: The mobilizing sequences were: standard-dose epirubicin+taxol+granulocyte-colony-stimulating factor (G-CSF; 15 patients with advanced breast cancer), high-dose cyclophosphamide (CTX)+G-CSF (10 patients with breast cancer patients and 7 with non-Hodgkin's lymphoma, NHL), and G-CSF alone (5 normal donors of CD34+ cells for allogeneic transplantation).

Efferent vagal fibre stimulation blunts nuclear factor-kappaB activation and protects against hypovolemic hemorrhagic shock.

Background: We investigated whether electrical stimulation (STIM) of efferent vagus nerves may suppress nuclear factor (NF)-kappaB activation and the inflammatory cascade in hemorrhagic (Hem) shock.

Methods And Results: Rats were subjected to bilateral cervical vagotomy (VGX) or sham surgical procedures. Hem shock was induced by intermittent withdrawing of blood until mean arterial pressure stabilized within the range of 35 to 40 mm Hg.

Effect of repeated administration of prolactin releasing peptide on feeding behavior in rats.

Prolactin releasing peptide (PrRP) has been reported to reduce food intake in rats. We tested the effect of i.c.

Portal biliopathy.

Herein we describe a case of obstructive jaundice and cholangitis originating from choledochal lithiasis secondary to a stricture of the common bile duct in a patient with cavernous transformation of the portal vein. In fact, portal cavernous transformation gives rise to many dilated pericholedochal and periportal collaterals that bypass the portal vein obstruction. Extrinsic compression of the common duct by dilated venous collaterals together with pericholedochal fibrosis from the inflammatory process causing portal thrombosis may lead to biliary stricture and dilatation of the proximal biliary tree.

Aldosterone antagonist improves diastolic function in essential hypertension.

Experimental studies demonstrated that mineralocorticoid antagonists prevent or reverse myocardial fibrosis. Therefore, we tested the hypothesis that the aldosterone antagonist canrenone can improve left ventricular diastolic function in essential hypertension. Using digitized M-mode echocardiography and 24-hour blood pressure monitoring (ABPM), we realized a prospective, randomized, controlled study on 34 never-treated essential hypertensives with left ventricular diastolic dysfunction.

MC(3) receptors are involved in the protective effect of melanocortins in myocardial ischemia/reperfusion-induced arrhythmias.

Myocardial ischemia/reperfusion induces ventricular tachycardia (VT), ventricular fibrillation (VF) and a high degree of lethality. Since ACTH-(1-24) (adrenocorticotropin) protects against such injuries in rats, we investigated which melanocortin MC receptor is involved. Ischemia was produced in anesthetized rats by ligature of the left anterior descending coronary artery (5 min), and reperfusion-induced VT, VF, lethality and time-course of arterial blood pressure within the 5 min following reperfusion were evaluated.

Relation of extent of nocturnal blood pressure decrease to cardiovascular remodeling in never-treated patients with essential hypertension.

The clinical significance of the extent of a decrease in nocturnal blood pressure (BP) and the resulting classification of hypertensives as "dipper" (decrease in BP >10% day BP) or "nondipper" (decrease in BP <10% day BP) has been questioned recently. The aim of our study was to evaluate if the extent of a nocturnal BP decrease, established on the basis of a single 24-hour BP monitoring, is related to cardiovascular remodeling in essential hypertension. We enrolled 253 never-treated essential hypertensives (24-hour BP > or = 140 and/or 90 mm Hg); for each patient we recorded 24-hour BP, left ventricular (LV) echocardiogram, Doppler transmitral flow velocities, and carotid-femoral pulse-wave velocities.

Cannabinoid CB(1) receptor blockade enhances the protective effect of melanocortins in hemorrhagic shock in the rat.

Activation of peripheral cannabinoid CB(1) receptors contributes to hemorrhagic hypotension, and endocannabinoids produced by macrophages and platelets may be mediators of this effect. A number of studies have provided evidence that functional links exist in the mechanisms of action of cannabinoids and opioid peptides; and opioids too play an important role in the pathophysiology of hemorrhagic hypotension and shock. On the other hand, melanocortin peptides, which are the main endogenous functional antagonists of opioid peptides, have an antishock effect in animals and humans.

Pharmacological manipulation of brain galaninergic system and sexual behavior in male mice.

Rationale: Available data suggest a complex role for the brain galaninergic system in male sexual behavior; however, the results so far obtained in animals with either galanin or galanin antagonists are conflicting.

Objective: To define the better influence of galanin on male sexual behavior by studying, in mice, (i) the effect of galanin and of the chimeric galanin peptide M40 on the copulatory performance, and (ii) galanin mRNA levels in hypothalamic arcuate and dorso-medial nuclei.

Methods: For the behavioral testing, only sexually sluggish male mice were used.

Evidence for a role of nuclear factor-kappaB in acute hypovolemic hemorrhagic shock.

Background: In acute hypovolemic shock, a rapid systemic release of the inflammatory cytokine tumor necrosis factor (TNF-alpha) contributes to vascular failure. Nuclear factor kappaB (NF-kappaB) is an ubiquitous rapid-response transcription factor involved in inflammatory reactions and exerts its effect by expressing cytokines, chemokines, and cell adhesion molecules. The purpose of this study was to evaluate the role of NF-kappaB in acute hypovolemic hemorrhagic shock.

Involvement of the central nervous system in the protective effect of melanocortins in myocardial ischaemia/reperfusion injury.

Melanocortin peptides exert, in rats, a protective effect in myocardial ischaemia followed by reperfusion, or permanent occlusion of a coronary artery. Moreover, melanocortins have an anti-shock effect. Since the mechanism of the life-saving effect of these peptides in haemorrhagic shock includes an essential brain loop, we aimed to determine whether the central nervous system (CNS) is also involved in the protective effect against the outcome of short-term myocardial ischaemia followed by reperfusion.

Left ventricular changes in isolated office hypertension: a blood pressure-matched comparison with normotension and sustained hypertension.

Background: Isolated office (IO) hypertension is a benign condition according to some researchers, whereas others believe it is associated with cardiovascular abnormalities and increased cardiovascular risk. The aim of this study is to compare morphofunctional characteristics of the left ventricle (LV) in IO hypertensive subjects, normotensive subjects (hereafter, hypertensives and normotensives), and never-treated sustained hypertensives. The 3 groups were matched not only by age, sex, and body mass index but also by clinic blood pressure (BP) (IO hypertensives and sustained hypertensives) and daytime BP (IO hypertensives and normotensives).

Influence of SAMe on the modifications of brain polyamine levels in an animal model of depression.

The mechanism(s) of the antidepressant activity of S-adenosyl-L-methionine (SAMe) have not yet been elucidated. SAMe is essential for the synthesis of polyamines, which have a key role in protein synthesis, cell proliferation, and neuronal plasticity. On the other hand, accumulating data indicate that depression is associated with a reduction in regional brain volume and that antidepressants increase neurogenesis in defined brain regions and also influence neuronal plasticity.

Dual acting anti-inflammatory drugs: a reappraisal.

Rheumatic diseases are the most prevalent causes of disability in western countries, and non-steroidal anti-inflammatory drugs (NSAIDs) are still the most commonly used remedies. However, NSAIDs cause several serious adverse effects, the most important being from gastric injury to gastric ulceration and renal damage. Attempts to develop non-steroidal anti-inflammatory remedies devoid of these shortcomings-especially gastrointestinal toxicity-have followed several strategies.

Nuclear factor-kappaB as a target of cyclosporin in acute hypovolemic hemorrhagic shock.

Background: Cyclosporin is an immunosuppressive drug that blocks Nuclear Factor kappaB (NF-kappaB) activation. We investigated the role of NF-kappaB in acute hypovolemic hemorrhagic (Hem) shock and the effects of cyclosporin in this model of experimental shock.

Methods: Hem shock was induced in male anesthetized rats by intermittently withdrawing blood from an iliac catheter over a period of 20 min (bleeding period) until mean arterial blood pressure (MAP) fell and stabilized within the range of 20-30 mmHg.

Survival rate after early treatment for acute type-A aortic dissection with ACTH-(1-24).

Haemorrhagic shock, usually as a consequence of major trauma, is the most frequent cause of death among people younger than 40 years. Reports indicate that melanocortin peptides are effective in reversing haemorrhagic shock. We found that in patients with aortic-dissection-induced haemorrhagic shock, the addition of an early intravenous bolus injection of the melanocortin andrenocorticotrophic hormone (ACTH)-(1-24) to standard treatment significantly improved cardiovascular function and increased survival rate.

Acute cardiotoxicity during capecitabine treatment: a case report.

Capecitabine (Xeloda, Roche, Monza), a fluoropyrimidine carbamate, is an orally administered drug that delivers fluorouracil (5-FU) selectively to the tumor. The drug has demonstrated activity in metastatic breast cancer, pancreatic cancer and colorectal cancer. In this case report the authors describe an unusually and reversible cardiac side effect which occurs to 39-year-old patient treated with capecitabine 2000 mg/m2/day for advanced gastric cancer.