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Biomedical subjects

A Catania

Publications and source records attributed to A Catania.

At least 19 recordsLinked to original sources
PubMed2006

Antimicrobial properties of alpha-MSH and related synthetic melanocortins.

The natural antimicrobial peptides are ancient host defense effector molecules, present in organisms across the evolutionary spectrum. Several properties of alpha-melanocyte stimulating hormone (alpha-MSH) suggested that it could be a natural antimicrobial peptide. Alpha-MSH is a primordial peptide that appeared during the Paleozoic era, long before adaptive immunity developed and, like natural antimicrobial molecules, is produced by barrier epithelia, immunocytes, and within the central nervous system. alpha-MSH was discovered to have antimicrobial activity against two representative pathogens, Staphylococcus aureus and Candida albicans. The candidacidal influences of alpha-MSH appeared to be mediated by increases in cell cyclic adenosine monophosphate (cAMP). The cAMP-inducing capacity of alpha-MSH likely interferes with the yeast's own regulatory mechanisms of this essential signaling pathway. It is remarkable that this mechanism of action in yeast mimics the influences of alpha-MSH in mammalian cells in which the peptide binds to G-protein-linked melanocortin receptors, activates adenylyl cyclase, and increases cAMP. When considering that most of the natural antimicrobial peptides enhance the local inflammatory reaction, the anti-inflammatory and antipyretic effects of alpha-MSH confer unique properties to this molecule relative to other natural antimicrobial molecules. Synthetic derivatives, chemically stable and resistant to enzymatic degradation, could form the basis for novel therapies that combine anti-inflammatory and antimicrobial properties.

Anti-Bacterial Agents↗
PubMed2006

Change in gene expression profile induced by alpha-melanocyte stimulating hormone in a malignant mesothelioma cell line.

We have previously reported that the peptide a-melanocyte stimulating hormone (alpha-MSH) has antiproliferative effects in human malignant mesothelioma cells. To determine the molecular mechanisms underlying such effects, we investigated the changes in gene expression profile induced by the alpha-MSH analog [Nle4 -DPhe7 ]-alpha-MSH (NDP-alpha-MSH) in a human malignant mesothelioma cell line. The cDNA macroarray technique revealed changes in expression of genes involved in cell growth, adhesion, signal transduction, and transcription. In particular, NDP-alpha-MSH down-regulated expression of B-Myb and Myc, two oncogenes considered of paramount importance for cell proliferation and cancer. Further, NDP-alpha-MSH exerted a favorable transcriptional regulation of certain integrins and their signaling pathways. Finally, peptide treatment was associated with a prominent inhibition of IL-13, a cytokine with tumor-promoting effects. The data indicate that the influences of alpha-MSH extend beyond the established anti-inflammatory effects in normal cells to include cell cycle regulatory properties in malignant cells.

Cell Cycle Proteins↗
PubMed2005

Three-dimensional structure of the alpha-MSH-derived candidacidal peptide [Ac-CKPV]2.

Previous research has shown that the immunomodulatory peptide alpha-melanocyte-stimulating hormone (alpha-MSH) and its carboxy-terminal tripeptide KPV (Lys-Pro-Val alpha-MSH11-13) have antimicrobial influences. By inserting a Cys-Cys linker between two units of KPV, we designed the dimer [Ac-CKPV]2 that showed excellent candidacidal effects in pilot tests and was the subject of further investigations. [Ac-CKPV]2 was active against azole-resistant Candida spp. Therefore, the molecule appeared a promising candidate for therapy of fungal infections and was the subject of a structural study. 1H-NMR and restrained mechanic and dynamic calculations suggest that the peptide adopts an extended backbone structure with a beta-turn-like structure. These results open a pathway to development of additional novel compounds that have candidacidal effects potentially useful against clinical infections.

Antifungal Agents↗
PubMed2004

Polymorphonuclear leukocyte membrane fluidity and cytosolic Ca(2+) content in young adults with acute myocardial infarction. Evaluation at the initial stage and after 12 months.

Our aim was to examine two aspects of polymorphonuclear leukocyte (PMN) rheology (membrane fluidity and cytosolic Ca2+ content), at baseline and after in vitro activation, in a group of young adults with acute myocardial infarction (AMI) at the initial stage and after 12 months. We enrolled 21 AMI subjects aged < or = 45 years (mean age 41.1 +/- 3.5 years) and evaluated PMN membrane fluidity, labelling intact PMN cells with the fluorescent probe 1,4-(trimethylamino)-phenyl-4-phenylhexatriene and the PMN cytosolic Ca2+ content marking PMN cells with the fluorescent probe Fura 2-AM, at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). During the initial stage PMN membrane fluidity and cytosolic Ca2+ content did not distinguish AMI patients from control subjects; after 12 months, when compared with the initial stage, PMN cytosolic Ca2+ content was significantly increased. In vitro PMN activation with PMA and fMLP caused no variation of the two PMN parameters in control subjects, while in AMI patients membrane fluidity decreased and cytosolic Ca2+ content increased; the same behaviour pattern was observed after 12 months. The constant functional alteration of PMN cells in young AMI patients highlights the role of activated leukocytes as a component of the inflammatory reaction that follows ischemia.

Adult↗
PubMed2003

Haemorheological pattern in young adults with acute myocardial infarction.

Acute myocardial infarction (AMI) in young people has recently received great attention. Its main characteristics include a typical risk factor profile and a good prognosis. We studied the haemorheological pattern (whole blood viscosity at high and low shear rates, plasma and serum viscosity, whole-blood filtration and erythrocyte aggregation) in 64 subjects, aged <46 years, with recent AMI. We observed marked alterations in blood, plasma and serum viscosity and whole-blood filtration. Subdividing the AMI subjects in accordance with the number of cardiovascular risk factors or the extent of coronary lesions, we did not observe any significative influence of these aspects on the haemorheological determinants, with the exception of low shear rate blood viscosity. The latter was in fact higher than in control subjects only in AMI subgroups with respectively more risk factors and more stenosed coronary vessels. Thirty-three AMI subjects were re-examined after three months and showed, on this occasion, a haemorheological pattern not significantly different from that of the first evaluation. These results demonstrate that in young subjects with AMI there is a hyperviscosity syndrome that persists during subsequent months, despite a good clinical course. Haemorheological impairment may unfavourably influence the long-term prognosis of AMI in young subjects and therefore, in our opinion, management should take into account the monitoring of the haemorheological pattern.

Adult↗
PubMed2002

Polymorphonuclear leukocyte membrane fluidity, at baseline and after in vitro activation, in obesity with or without diabetes mellitus.

We studied a group of 28 obese subjects (mean age 38.2+/-13.5 years, body mass index 35.0+/-5.6 kg/m2) with insulin resistance demonstrated employing an euglycemic hyperinsulinemic clamp, subdivided into a subgroup with normal glucose tolerance (NGT) and a subgroup with type 2 diabetes mellitus (DM). We examined the polymorphonuclear leukocyte (PMN) membrane fluidity at baseline and after activation with 4-phorbol 12-myristate 13-acetate (PMA) or N-formyl-methionyl-leucylphenylalanine (fMLP). At baseline, PMN membrane fluidity was significantly decreased in both subgroups compared to normals. In obese subjects with NGT no correlation was found between this PMN determinant and the parameters reflecting the insulin-resistance degree (glucose disposal [M] and metabolic clearance rate of glucose [MCR]), while in type 2 DM subjects the PMN membrane fluidity was correlated to M and MCR. After activation with PMA and fMLP, no variation in PMN membrane fluidity was observed in normals, while in obese subjects with NGT an early decrease was present only after fMLP activation, and in obese subjects with type 2 DM there was a constant and significant decrease of this PMN parameter after activation with PMA and fMLP. Our interest in the study of the PMN membrane fluidity emerges from its known role in PMN function, especially considering that PMN cells, together with monocytes, may be mediators of vascular damage.

Adult↗
PubMed2002

Increased plasma nitrites in migraine and cluster headache patients in interictal period: basal hyperactivity of L-arginine-NO pathway?

Nitrite concentrations in plasma were investigated in a population of migraine and cluster headache patients and a group of healthy non-headache controls. A hundred migraine patients and 69 cluster headache patients in the interictal period, and 112 controls, were studied. Significantly higher nitrite concentrations were found in migraine patients, with and without aura, and cluster headache patients, in remission and cluster phase, than in controls. These findings suggest that a basal dysfunction in the L-arginine-NO pathway may be involved in the peripheral mechanisms predisposing subjects with neurovascular headaches to individual attacks.

Adult↗
PubMed2002

Scintigraphy with 99mTc-MIBI and echography in the study of primitive hyperparathyroidism.

BACKGROUND: The authors analyse the value of the exams preoperative for the identification of the pathological parathyroid glands. METHODS: The authors examined 58 patients affected by primitive hyperparathyroidism (HPTp) who had undergone surgical treatment for primary hyperparathyroidism at the Third Surgical Department of University "La Sapienza" of Rome, in 175 patients affected by primitive hyperparathyroidism observed between January 1970 and June 2000; all patients had undergone echotomography of the neck and 99mTc-MIBI scintigraphy in the diagnostic phase. The histological valuation confirmed the diagnosis by I.P. RESULTS: 99mTc-MIBI scintigraphy demonstrated the pathological glands in 56 cases (96.6%), the echography in 57 cases (98.2%). The comparison of the two exams demonstrated the pathological glands in 100% of the cases. In 45 cases the scintigraphy localized the side (77.6%), and the echography in 41 cases (70.7%). In one case demonstrated I.P. persistent (1.7%) and never one case demonstrated relapsed. CONCLUSIONS: The authors think that the scintigraphy together with the echography show high sensibility to identification the pathological glands. Neck surgical exploration can still give the side good when the diameter of the parathyroids is inferior to 5 mm.

Female↗
PubMed2002

Retroperitoneal lipoma. Unusual presentation with detrusor instability.

Retroperitoneal lipomas are a heterogeneous group of mesenchymal tumors. They are usually large and occur most frequently in the retroperitoneal, perineal and pelvic regions. Lipomas grow slowly surrounding the retroperitoneal and pelvic organs, with a displacement of bowel and vascular axis. A case of a 61-year-old male patient which referred urinary frequency, urgency and nocturia is presented. Urodynamics evidenced a detrusor instability in a low capacity bladder. CT scan demonstrated a bladder dome compression due to a huge retroperitoneal mass extending from the right hepatic lobe to the hypogastric region and the right thigh. Surgical complete resection was performed: histology demonstrated a lipoma with areas of well differentiated myxoid degeneration. After surgery the irritative urinary symptoms disappeared. This is the first case described in literature of detrusor instability due to bladder compression by retroperitoneal lipoma.

Gait Disorders, Neurologic↗
PubMed2002

Haemorheological profile in metabolic Syndrome.

Metabolic Syndrome (MetS) has been defined as a clinical condition including impaired glucose tolerance or diabetes mellitus and/or insulin-resistance, associated with two or more of the following components: arterial hypertension, central obesity, dyslipidaemia, microalbuminuria. In a group of subjects with MetS we examined the macrohaemorheological profile, demonstrating a significant increase of blood, plasma and serum viscosity and a decrease of whole blood filterability. The results show that in these subjects a secondary hyperviscosity condition is present, but also that several significant correlations are present between the haemorheological variables and some aspects of MetS, especially those reflecting central obesity (waist to hip ratio) and insulin-resistance. The altered haemorheological profile likely contributes to explain the high cardiovascular risk present in MetS, but it may also participate, through its influence on haemodynamic pattern, in the pathogenesis of insulin-resistance.

Adult↗
PubMed2002

Polymorphonuclear leukocyte integrin profile in diabetes mellitus.

We examined the polymorphonuclear leukocyte (PMN) integrin pattern in 45 diabetic subjects without macrovascular complications, including 21 subjects with type 1 and 24 with type 2 diabetes mellitus. The PMN adhesion molecules (CD11a, CD11b, CD11c, CD18) were evaluated using indirect immunofluorescence and a flow cytometer, at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenyl-alanine (fMLP). At baseline, in diabetic subjects the phenotypical expression of CD11a and CD11b was significantly reduced and CD11c was increased, whereas CD18 was unchanged in comparison with normals. Considering type 1 and 2 diabetic subjects separately, CD11a was reduced and CD11c was increased in both subgroups, CD11b was decreased only in type 1 diabetics and CD18, decreased in type 1, was increased in type 2 subjects. After activation with PMA and fMLP, in normal subjects we observed a significant increase of all PMN adhesion molecules whereas in diabetic subjects only CD11c increased significantly with both activating agents, and CD11b increased only after PMA activation. In type 1 diabetic subjects only CD11c expression was increased, and in type 2 diabetic subjects an increase of CD11b (with PMA) and an increase of CD11c (with fMLP) were noted. In conclusion, we found in diabetic subjects of type 1 and 2 an altered behaviour pattern of PMN integrins both at baseline and, in particular, after in vitro activation. These data may help in explaining the role of PMN in the evolution of diabetic vascular complications.

Adult↗
PubMed2001

Granulocyte integrins before and after activation in acute ischaemic stroke.

We examined in 19 subjects with acute ischaemic stroke (AIS) the PMN integrin pattern (CD11a, CD11b, CD11c, CD18), using indirect immunofluorescence and adopting a flow cytometer, at baseline and during activation, prolonged for 5 and 15 min, with 4-phorbol 12-myristate 13-acetate (PMA). At baseline, an increase in the expression of CD11c and CD18 and a decrease in the CD11b were evident in AIS subjects compared to normals. After activation, we found in normals a constant and significant increase of all PMN adhesive molecules, while in AIS subjects, we found an increase in CD11b and CD18, a decrease in CD11a and no variation in CD11c. While the basal upregulation of CD11c and CD18 may depend on the PMN spontaneous activation or on the increase of cytokines, the decrease of CD11b may be due to its self-consumption. After activation, the decrease in CD11a noted in AIS may be related to its cleavage or to an altered integrin phosphorylation/dephosphorylation balance.

Acute Disease↗
PubMed2001

Expression and localization of cyclin-dependent kinase 5 in apoptotic human glioma cells.

Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family, is expressed predominately in mature neurons and is implicated in neurite extension, neuronal migration, and neuronal differentiation. Cdk5 protein expression also has been associated with apoptosis in a number of nonneuronal model systems. In normal brain, substrates for Cdk5 include neurofilament and tau proteins. Because human tumors of glial origin can express neuronal proteins, we examined whether Cdk5 and its activator protein, P35, are present in early passage human glioblastoma multiforme (GBM) cells lines and primary tumor specimens. Here we report the expression of Cdk5 and an "active" proteolytic form of P35 in human GBM cells and demonstrate kinase activity of the holoenzyme. We also show that Cdk5 kinase activity and expression of its activator protein, P35, is increased in the human GBM cell line M059J after exposure to ionizing radiation and that P35 is localized within M059J cells undergoing apoptosis. These results suggest a possible role for Cdk5 in mediating apoptosis in human GBM cells.

Apoptosis↗
PubMed2000

The human astrocytoma cell line U373MG produces monocyte chemotactic protein (MCP)-1 upon stimulation with beta-amyloid protein.

Astrocytes associated with beta-amyloid (Abeta) accumulate in senile plaques of Alzheimer's disease (AD). To investigate the biological effects of Abeta/astrocyte interaction, we examined chemokine production by the human astrocytoma cell line U373MG stimulated with Abeta peptides. Northern blot analysis and specific immunoassays demonstrate that Abeta [1-42] and Abeta [25-35] induce mRNA expression and release of monocyte chemotactic protein (MCP)-1 but not of gamma-interferon inducible protein (IP)-10 by U373MG cells. The observation that Abeta induces astrocyte production of the potent microglia chemoattractant MCP-1 contributes to understanding mechanism of damage exerted by Abeta in AD senile plaques.

Amyloid beta-Peptides↗
PubMed2000

Antimicrobial effects of alpha-MSH peptides.

The presence of the ancient anti-inflammatory peptide alpha-melanocyte-stimulating hormone [alpha-MSH (1-13), SYSMEHFRWGKPV] in barrier organs such as gut and skin suggests a role in the nonspecific (innate) host defense. alpha-MSH and and its carboxy-terminal tripeptide (11-13, KPV) were determined to have antimicrobial influences against two major and representative pathogens: Staphylococcus aureus and Candida albicans. alpha-MSH peptides significantly inhibited S. aureus colony formation and reversed the enhancing effect of urokinase on colony formation. Antimicrobial effects occurred over a broad range of concentrations including the physiological (picomolar) range. Small concentrations of alpha-MSH peptides likewise reduced viability and germ tube formation of the yeast C. albicans. Antimicrobial influences of alpha-MSH peptides could be mediated by their capacity to increase cellular cAMP. Indeed, this messenger was significantly augmented in peptide-treated yeast and the potent adenylyl cyclase inhibitor dideoxyadenosine (ddAdo) partly reversed the killing activity of alpha-MSH peptides. Reduced killing of pathogens is a detrimental consequence of therapy with anti-inflammatory drugs. Because alpha-MSH has potent anti-inflammatory effects we determined influences of alpha-MSH on C. albicans and S. aureus killing by human neutrophils. alpha-MSH peptides did not reduce killing but rather enhanced it, likely as a consequence of the direct antimicrobial activity. alpha-MSH peptides that combine antipyretic, anti-inflammatory, and antimicrobial effects could be useful in treatment of disorders in which infection and inflammation coexist.

Anti-Bacterial Agents↗
PubMed2000

Alpha-melanocyte-stimulating hormone in normal human physiology and disease states.

Over the past two decades, research in animal models has indicated that alpha-melanocyte-stimulating hormone (alpha-MSH) has potent anti-inflammatory properties. Furthermore, recent data show that the peptide has antimicrobial effects and probably contributes to innate immunity. alpha-MSH, which is produced by many extrapituitary human cells, should no longer be considered solely a pituitary hormone; rather, it should be viewed as a ubiquitous modulatory peptide.

Animals↗