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Biomedical subjects

A Lentini

Publications and source records attributed to A Lentini.

At least 19 recordsLinked to original sources
PubMed2006

Enhancement of transglutaminase activity and polyamine depletion in B16-F10 melanoma cells by flavonoids naringenin and hesperitin correlate to reduction of the in vivo metastatic potential.

The in vitro and in vivo effects of two flavonons, naringenin (NG) and hesperitin (HP) on the proliferation rate of highly metastatic murine B16-F10 melanoma cell were investigated. NG or HP treatment of melanoma cells produced a remarkable reduction of cell proliferation, paralleled with both the lowering of the intracellular levels of polyamine, spermidine and spermine and the enhancement of transglutaminase (TGase, EC 2.3.2.13) activity. Orally administered NG or HP in C57BL6/N mice inoculated with B16-F10 cells affected the pulmonary invasion of melanoma cells in an in vivo metastatic assay. The number of lung metastases detected by a computerized image analyzer was reduced, compared to untreated animals, by about 69% in NG-treated mice and by about 36% in HP-treated mice. Survival studies showed that 50% of the NG-treated animals died 38 +/- 3.1 days after tumor cell injection (control group: 18 +/- 1.5 days) and HP-treated mice died 27 +/- 2.3 days after cell inoculation. Taken together, these findings provide further evidences for the potential anticancer properties of dietary flavonoids as chemopreventive agents against malignant melanoma.

Animals↗
PubMed2005

Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice.

The administration of mineral sulphur water is an alternative experimental approach for the treatment of rheumatic diseases, such as osteoarthritis (OA), that cause the degeneration of bone and cartilage and sufferance to the patients. Chondroitin sulfate (CS) is a symptomatic slow acting nutropeucital agent currently used in molecular therapy of OA. Therefore, we have studied the role and efficacy of the selective soil paste from the mineral sulphur enriched spring (mud)-therapy alone or in combination with CS in the treatment of OA. The study was performed on 40 C57 Black 6N mice, an experimental model which spontaneously develop an osteoarthritic process. The animals were divided in 4 groups and were treated with the single agents or with the combination. After 30 days of treatment all the mice were sacrificed and right knees and blood were collected. It was found that CS determined a reduction of radiological and histological features of chondrodegeneration and that mud-therapy increased the effects of CS in the animal group treated with the combination. However, the effects of thermal therapy alone were not statistically significant. Since OA is characterized by an increase of the production of nitric oxide (NO) by chondrocytes in extracellular matrix with its consequent elevation in serum and synovial fluid, we have evaluated the effects of the treatments on serum NO levels. CS alone induced a statistically significant reduction of NO serum levels (90+/-13 micromM vs 219+/-60 microM of control group, P<0.05) while mud-therapy alone induced a not statistically significant reduction of serum NO (170+/-62 microM, P>0.05). However, the latter strongly potentiated the decrease of serum NO induced by CS (31+/-1.5 microM) with a high statistical significance if compared to both the control group (P<0.01) and the CS-treated group (P<0.05). In conclusion, this study demonstrates that mud-therapy with sulphur mineral water could represent an important phase of the therapeutic strategy of OA. This experimental strategy could integrate and potentiate the standard pharmacological tools. Moreover, we have set a valid experimental in vivo model for the study of the thermal effects on the development of OA.

Animals↗
PubMed2005

Apolipoprotein E polymorphism and stroke subtypes in an Italian cohort.

BACKGROUND: Studies have indicated that apolipoprotein E (ApoE)-epsilon4 is a risk factor for ischemic cerebrovascular diseases (ICVD), but the existence of this association is still controversial. The aims of this study were: (1) to compare ApoE genotype and allele frequencies in Italian cases with ICVD and in healthy control subjects and (2) to compare ApoE allele frequencies among ischemic stroke subtypes. METHODS: A hospital-based cohort of 302 Italian subjects with ICVD and 228 healthy subjects have been recruited to investigate the role of ApoE polymorphisms as risk factors for ICVD. TOAST criteria were employed to stratify ICVD cases by subtypes. RESULTS: No significant differences in ApoE genotype and allele frequencies were found between cases and control subjects. The frequency of ApoE-epsilon4 was lower in cases than in control subjects (6% vs. 10.1%), although not significantly. No differences in ApoE genotype and allele frequencies were evident among ICVD subtypes. However, out of 36 ApoE-epsilon4 alleles 23 (3.7%) were found in subjects with ICVD related to primary degenerative arterial disease related to large vessel disease and small vessel disease, and 13 (2.1%) in remaining subjects. Using logistic regression analysis we assessed whether ApoE-epsilon4 allele was independently associated with risk of ICVD related to a primary degenerative arterial disease compared to other ICVD subtypes. While classical risk factors were significantly associated with higher risk for ICVD due to large vessel disease and small vessel disease than other ICVD subtypes, the role of ApoE-epsilon4 allele was not significant (OR 1.25, 95% CI 0.57-2.74). CONCLUSION: Our study shows similar ApoE-epsilon4 genotype and allele frequencies in patients with ICVD and in control subjects. No differences were found among different ICVD subtypes either.

Adult↗
PubMed2005

Restricted pain and thermal sensory loss in a patient with pontine lacunar infarction: a clinical MRI study.

Pure sensory syndrome (PSS) is characterized by hemisensory symptoms without other major neurological signs. It was initially attributed to thalamic lacunar infarction, but several reports have shown the PSS can be due to small infarcts involving the posterior part of the internal capsula, the cerebral cortex and the brainstem. Paramedian and lateral pontine infarctions are associated respectively with lemniscal and spinothalmic (ST) sensory impairment. We describe a patient with an isolated impairment of the ST modalities caused by a segmental paramedian pontine infarction.

Brain Infarction↗
PubMed2004

Interleukin-18 (IL-18) and matrix metalloproteinase-9 (MMP-9) in post-menopausal osteoporosis.

This survey covered 60 post-menopausal women with osteoporosis. The patients were divided into three equal groups, and each group was treated with one of the three so-called anti-resorptive drugs, namely alendronate (10 mg/day) risedronate (5 mg/day) and raloxifene (60 mg/day) for 12 months. The Elisa technique was used to measure circulating IL-18 and MMP-9. Lumbar bone mineral density (BMD) levels were determined by using dexa mineralometry (Lunar DPX) at baseline and after 12 months of treatment. The results showed comparable responses of the patients treated with alendronate or risedronate, being a significant increase in BMD, an increase in circulating IL-18, and only slight modifications in circulating MMP-9 levels. After 12 months of treatment with raloxifene, there were minimal, non-significant increases in BMD, slight modifications in IL-18 levels, and a significant reduction in circulating MMP-9 levels. The conclusions can be drawn that all three drugs, albeit through different mechanisms, can be considered valid treatments for post-menopausal osteoporosis. Although measurements of circulating IL-8 and MMP-9 levels allowed us to differentiate the effects of the three drugs used, as of today, they have no real role in the diagnosis and/or follow-up of osteoporosis.

Alendronate↗
PubMed2004

Stroke in young patients: etiopathogenesis and risk factors in different age classes.

The aim of our study was to evaluate the etiopathogenesis and the vascular risk factors in a consecutive series of patients with juvenile ischemic stroke. We enrolled 273 patients (158 males and 115 females), aged between 16 and 49 years, with ischemic cerebrovascular events (ICVE), including transient ischemic attack (TIA) or stroke, referred to our neurology ward between January 1994 and December 2001. Our protocol included medical history, cardiac and neurological examinations, assessment of risk factors and laboratory tests. The instrumental assessment included transthoracic echocardiography (70%), transesophageal echocardiography (60%), conventional angiography (30%), MR angiography (30%), cranial computed tomography (100%) and brain MRI (48%). The ICVE was a stroke in 60% of the cases, a reversible ischemic neurologic deficit in 14% and a TIA in 26%. Thirty-three patients were aged less than 29, 59 were aged between 30 and 39 and 181 between 40 and 49. The percentage of females was higher in patients aged less than 29 while males were prevalent in the 4th and 5th decade. The patients were subtyped according to etiopathogenesis. A large-vessel disease (LVD) was diagnosed in 43 patients (16% of the cases), mostly in patients aged more than 40 years (36 cases). A small-vessel disease (SVD) was found in 48 patients (17% of cases), mostly in patients aged more than 40 years (41 cases). A cardioembolic stroke (CE) was diagnosed in 66 patients (24% of the cases). In the majority of the cases, the cardiopathies were at low-uncertain embolic risk: patent foramen ovale (PFO, 39 cases, in 8 patients associated with an atrial septal aneurism), atrial septal aneurism (12 cases) and myxomatous mitral valve prolapse (3 cases). Stroke due to other causes was found in 51 patients (19% of the cases). Arterial dissection, more frequently involving the carotid region, was diagnosed in 35 patients. Coagulopathies and vasculitis were found in 5 and 6 patients, respectively. Stroke of unknown etiology was found in 65 patients (24% of the cases) with a homogeneous distribution among decades. Our study highlights the role of minor cardiac sources of embolism and arterial dissection in the etiology of juvenile ischemic stroke, whereas coagulopathies and vasculitis are less relevant. LVD and SVD were relevant only in the 5th decade.

Adult↗
PubMed2004

Protein-polyamine conjugation by transglutaminase in cancer cell differentiation: review article.

Considerable and intense progress has been made in the understanding of the chemistry, molecular biology and cell biology of transglutaminases (TGases: EC 2.3.2.13). The knowledge that very different processes such as cell growth, reproduction and death are dependent on the presence of adequate levels of these enzymes and that the amount of both free and protein-conjugated polyamines, formed by the enzyme, are capable of modulating the differentiation and proliferative capability of several cell types, has prompted a multitude of researchers to study the role of these fascinating molecules in cancer cell differentiation.

Animals↗
PubMed2004

Translational and post-translational modifications of proteins as a new mechanism of action of alpha-interferon: review article.

Interferon-alpha (IFNalpha) is a recombinant protein widely used in the therapy of several neoplasms such as myeloma, renal cell carcinoma, epidermoid cervical and head and neck tumours and melanoma. IFNalpha, the first cytokine to be produced by recombinant DNA technology, has emerged as an important regulator of cancer cell growth and differentiation, affecting cellular communication and signal transduction pathways. However, the way by which tumour cell growth is directly suppressed by IFNalpha is not well known. Wide evidence exists on the possibility that cancer cells undergo apoptosis after the exposure to the cytokine. Here we will discuss data obtained by us and others on the post-translational regulation of the expression of proteins involved in the occurrence of apoptotic process such as tissue transglutaminase (tTG) or in the modulation of cell cycle such as the cyclin-dependent kinase inhibitor p27. This new way of regulation of p27 and tTG occurs through the modulation of their proteasome-dependent degradation induced by the cytokine. We will also review the involvement of protein synthesis machinery in the induction of cell growth inhibition by IFNalpha. In details, we will describe the effects of IFNalpha on the expression and activity of the protein kinase dependent from dsRNA (PKR) and on the eukaryotic initiation factor of protein synthesis 5A (eIF-5A) and their correlations with the regulation of cancer cell growth. These data strongly suggest that the antitumour activity of IFNalpha against human tumours could involve still unexplored mechanisms based on post-translational and translational control of the expression of proteins that regulate cell proliferation and apoptosis.

Animals↗
PubMed2002

The leptin, a new hormone of adipose tissue: clinical findings and perspectives in geriatrics.

Obesity has gained a great importance during the last decades, and this fact stimulated numerous studies regarding the genetic causes of this disease. A recently discovered new molecule, called leptin, raised a wide interest. It is a product of the adipocytes, it exerts inhibitory effects on the center of appetite and increases the energy expenditure of the organism. The present study evaluated blood leptin levels in 57 elderly subjects and searched for eventual correlations between this parameter and the age, the body mass index (BMI), the fat body mass (fat%), the waist (W) and hip (H) circumference, as well as the ratio (R) of these latter two values (WHR). Blood leptin levels do not correlate with age, body height and the WHR, but display significant positive correlations with the body weight, the BMI, the fat%, the W, H and WHR. A deeper knowledge on leptin and the correlations of this hormone with other body parameters might be helpful in a better understanding of several pathogenetic mechanisms related to aging and involved in a deterioration of the quality of life in elderly, like multiple atherosclerotic and metabolic diseases (diabetes, dyslipidemias).

Journal Article↗
PubMed2001

Transglutaminase activity is involved in polyamine-induced programmed cell death.

Natural polyamines, i.e., putrescine, spermidine, and spermine, are ubiquitous molecules essential for cell proliferation and differentiation. In the present study, the effect of polyamines on primary cultures of bovine aortic endothelial cells (BAECs), rat aortic smooth muscle cells (RASMCs), and a human melanoma cell line was examined. While in the absence of fetal calf serum (FCS) polyamines had no effect on viability, in the presence of FCS spermidine and spermine, at concentrations close to physiologic levels, induced a dose-dependent cell death, whereas putrescine was ineffective. RASMCs were significantly more sensitive than other cells. FACS analysis, oligo-nucleosome ELISA, Hoechst nuclear staining, and Annexin V-FITC quantification showed that cell death was likely due to apoptosis. Cells exposed to spermidine showed a marked increase of intracellular transglutaminase (TGase) activity ( approximately 30-fold over control). Inhibitors of polyamine oxidation or inhibitors of TGase activity prevented polyamine-induced apoptosis. Moreover, tissue TGase overexpression significantly increased cell sensitivity to polyamine, suggesting that this effect is likely related to enhanced intracellular TGase activity. These data indicate that polyamines may modulate cell viability through a novel TGase-dependent process.

Animals↗
PubMed2001

The role of eukaryotic initiation factor 5A in the control of cell proliferation and apoptosis.

In the past years, the attention of scientists has mainly focused on the study of the genetic information and alterations that regulate eukaryotic cell proliferation and that lead to neoplastic transformation. An increasing series of data are emerging about the involvement of the initiation phase of translational processes in the control of cell proliferation. In this paper we review the novel insights on the biochemical and molecular events leading to the initiation and its involvement in cell proliferation and tumourigenesis. We describe the structure, regulation and proposed functions of the eukaryotic initiation factor 5A (eIF-5A) focusing the attention on its involvement in the regulation of apoptosis and cell proliferation. Moreover, we describe the modulation of its activity (through the reduction of hypusine synthesis) in apoptosis induced either by tissue transglutaminase or interferon a. Finally, we propose eIF-5A as an additional target of anti-cancer strategies.

Active Transport, Cell Nucleus↗
PubMed2001

Polymeric protein-polyamine conjugates: a new class of uremic toxins affecting erythropoiesis.

BACKGROUND: Preliminary evidence on the accumulation of polyamine-protein conjugates (PPCs) was obtained in uremic patients. The presence of these substances in the plasma of hemodialysis (HD) patients was evaluated, and their possible contribution to uremic anemia was investigated by testing the effect of PPC synthesized in vitro on erythroid cell proliferation. METHODS: Plasma PPC was measured by high-performance liquid chromatography. The in vitro synthesis of PPC from human plasma was carried out by means of the enzyme transglutaminase in the presence of either [3H]-labeled or unlabeled spermidine (SPD). After gel filtration chromatography and detection of the fractions containing [3H]SPD, the latter were tested for their effect on mononuclear bone marrow cell proliferation. RESULTS: In three out of four patients examined, mainly SPD-protein conjugates (SPD-PC) were observed to accumulate during HD. The levels ranged from 0.17 to 4.93 pmol/mg proteins before dialysis, and these values increased at 30 minutes and at the end of the dialysis up to levels 11.90 pmol/mg. SPD-PC levels in healthy controls were 1.46 +/- 0.82. SPD-PCs synthesized in vitro were recovered in two main fractions showing a molecular weight of> 100 kD (peak 1) and of approximately 30 to 50 kD (peak 3), respectively. The SPD-PC contained in peak 1 showed the greatest inhibitory effect on colony-forming units-erythroid (CFU-E) proliferation without any appreciable effect on burst-forming units-erythroid (BFU-E). CONCLUSION: We demonstrate that SPD-PC can accumulate in HD patients. These substances, which affect CFU-E proliferation, can be considered as an at yet unrevealed class of uremic toxins contributing to the onset of the uremic anemia.

Aged↗