Biomedical subjects

R Caruso

Publications and source records attributed to R Caruso.

At least 19 recordsLinked to original sources

PubMed2006

Intramedullary teratomas: Two case reports and a review of the literature.

OBJECTIVE: Intramedullary teratomas are extremely rare tumours. A review of the literature found only reports of 59 cases, three of which were treated by us. The most common localisation for these tumours is in the medullary conus. According to our experience as well as more recent reports, MRI images allow a preoperative diagnosis to be made. CLINICAL PRESENTATION: We treated two cases of intramedullary teratoma of the conus: that of a 41-year-old woman and that of a 40-year-old man. Both suffered from motor and sensory disorders, and the woman also suffered from urinary disorders. CT and MRI enabled us to diagnose an intramedullary tumour and to suspect a dysembryogenic origin. INTERVENTION: Both patients were treated surgically; the surgical removal of the tumour was extensive but not total because of the tenacious adhesions of the tumour to the adjacent parenchyma. CONCLUSION: Surgery is the therapy of choice in cases of intramedullary teratomas; the removal, though incomplete, leads to a definite improvement of symptoms. In our two cases the follow-up has been 7 years and 6 years, respectively. No tumour regrowth occurred during this period.

Adult↗

PubMed2006

Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21.

BACKGROUND: T cell-mediated immunity plays a central part in the pathogenesis of tissue damage in inflammatory bowel disease (IBD). The mechanism by which T cells mediate tissue damage during IBD remains unclear, but evidence indicates that T cell-derived cytokines stimulate fibroblasts to synthesise matrix metalloproteinases (MMPs), which then mediate mucosal degradation. We have previously shown that, in IBD, there is high production of interleukin (IL) 21, a T cell-derived cytokine, which enhances Th1 activity. AIM: To investigate whether IL21 controls MMP production by intestinal fibroblasts. METHODS: IL21 receptor (IL21R) was evaluated in intestinal fibroblasts by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. Fibroblasts were stimulated with IL21 and MMPs were evaluated by RT-PCR and western blotting. The effect of a neutralising IL21R fusion protein (IL21R/Fc) on the induction of MMPs in fibroblasts stimulated with IBD lamina propria mononuclear cell (LPMC) supernatants was also evaluated. RESULTS: Intestinal fibroblasts constitutively express both IL21R and the common gamma chain receptor, which are necessary for IL21-driven signalling. IL21 enhances fibroblast production of MMP-1, MMP-2, MMP-3 and MMP-9, but not tissue inhibitors of MMP-1 and MMP-2. Moreover, IL21 synergises with tumour necrosis factor alpha to increase synthesis of MMP synthesis. IL21 enhances MMP secretion without affecting gene transcription and protein synthesis. IBD LPMC supernatants stimulate MMP secretion by intestinal fibroblasts, and this effect is partly inhibited by IL21R/Fc. CONCLUSIONS: These results suggest that fibroblasts are a potential target of IL21 in the gut and that IL21 controls MMP secretion by fibroblasts.

Cells, Cultured↗

PubMed2006

Somatomotor functional MRI in a hypertensive arachnoid cyst.

In this article the authors report the study by functional MRI, before and after surgery, of the motor cerebral cortex surrounding a large hypertensive arachnoid cyst. They stress that the functional modifications due to surgery are more relevant than suggested by the simple morphological data.

Arachnoid Cysts↗

PubMed2006

Silencing of SH-PTP2 defines a crucial role in the inactivation of epidermal growth factor receptor by 5-aminosalicylic acid in colon cancer cells.

Recent studies have suggested that 5-aminosalicylic acid (5-ASA) inhibits colorectal cancer (CRC) development. However, the mechanism underlying the antineoplastic effect of 5-ASA remains unknown. We here examined the effect of 5-ASA on epidermal growth factor receptor (EGFR) activation, a pathway that triggers mitogenic signals in CRC cells. We show that 5-ASA inhibits EGFR activation, through a mechanism that does not rely on CRC cell death induction. 5-ASA enhances the activity, but not expression, of phosphorylated (p)-EGFR-targeting phosphatases (PTPs), and treatment of cells with PTP inhibitors abrogates the 5-ASA-mediated EGFR dephosphorylation. Both SH-PTP1 and SH-PTP2 interact with EGFR upon 5-ASA treatment. However, knockdown of SH-PTP2 but not SH-PTP1 by small interference RNAs prevents the 5-ASA-induced EGFR dephosphorylation. Finally, we show that 5-ASA attenuates p-EGFR in ex vivo organ cultures of CRC explants. Data indicate that 5-ASA disrupts EGFR signalling by enhancing SH-PTP2 activity, and suggest a mechanism by which 5-ASA interferes with CRC growth.

Adenocarcinoma↗

PubMed2006

Gastric adenomas: relationship between clinicopathological findings, Helicobacter pylori infection, APC mutations and COX-2 expression.

Gastric adenomas are rare neoplastic growths characterized by localized polypoid proliferations of dysplastic epithelium that tend to progress to infiltrating adenocarcinoma. Therefore, the identification of molecular markers that could reliably recognize adenomas at risk of progression is advocated in the clinical management. In this study we investigated, in a series of gastric adenoma specimens from an area at high risk of gastric cancer, the relationship between clinicopathological characteristics of adenoma and Helicobacter pylori infection, APC mutational status, and COX-2 and the down-stream enzyme mPGES1 expression. Helicobacter pylori infection, detected in 24%, and 33% by histology and PCR analyses, respectively, did not show any relationship with growth pattern, localization, size, dysplasia grade and presence of synchronous cancer. Pathogenetic mutations of MCR region (codons 1269-1589) of the APC gene were detected only in one case corresponding to a single, small size, low grade, H. pylori-negative adenoma. The expression of COX-2 largely matched that of mPGES(1). Both were overexpressed in 79% of cases showing a relationship with high-grade dysplasia, size >10 mm and presence of a synchronous carcinoma. In conclusion, COX-2 may play a key role in the development and progression of gastric adenoma and could be an attractive target in the management of gastric adenoma at major risk of cancer development.

Adenocarcinoma↗

PubMed2006

Paragangliomas of the cauda equina. Report of one case and review of the literature.

The authors report one case of cauda equina paraganglioma and review the neurosurgical, radiological and pathological literatureon this rare tumour. Although it is difficult to distinguish preoperatively the paraganglioma from other tumours of the cauda equina, like neurinoma or ependymoma, this neuroendocrine tumour should be included in differential diagnosis.

Cauda Equina↗

PubMed2005

Effects of combined dietary supplementation on oxidative and inflammatory status in dyslipidemic subjects.

BACKGROUND AND AIM: Dyslipidemia is one of the main risk factors for atherosclerosis, usually the underlying cause of cardiovascular diseases which are the major cause of morbidity and mortality in developed countries. The aim of this study was to assess the effects and the advantages of a combined dietary supplementation with PUFA n-3, vitamin E, niacin and gamma-oryzanol on lipid profile, inflammatory status and oxidative balance. METHODS AND RESULTS: Fifty-seven dyslipidemic volunteers were randomly assigned to receive: placebo (group A, 19 subjects); PUFA n-3 and vitamin E (group B, 18 subjects); the same as B plus gamma-oryzanol and niacin (group C, 20 subjects). Lipid profile, reactive oxygen species (ROS), total antioxidant capacity (TAC), vitamin E, interleukin 1-beta (IL1-beta), tumor necrosis factor (TNF-alpha) and thromboxane B2 (TXB2) were determined at baseline (T0) and after four months (T1). All dyslipidemic subjects showed, at baseline, oxidative stress and, after four months, all biochemical markers improved significantly in groups treated with dietary supplementation. Particularly in group C all lipid patterns improved significantly. CONCLUSIONS: Our findings demonstrate that the strategy of combining different compounds, which protect each other and act together at different levels of the lipid chain production, improves lipid profile, inflammatory and oxidative status, allowing us to reduce the dose of each compound under the threshold of its side effects.

Adult↗

PubMed2005

SPE-HPLC determination of new tetrahydroisoquinoline derivatives in rat plasma.

Recently a novel class of non-competitive AMPA receptor (AMPAR) antagonists, such as, N-acetyl-1-(p-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (PS3Ac) have been developed using molecular modeling studies. In this study we present a validated method for detecting PS3Ac in biological matrices by high performance liquid chromatography with ultraviolet detection. In this study PS3Ac was administered to Wistar rats. After intraperitoneal administration, the plasma concentrations of PS3Ac and its potential metabolic products, i.e., PS3OH, PS3 and PS3OHAc were determined. Serum samples (0.5 ml) were purified by solid-phase extraction of analytes using Oasis cartridges. The chromatographic separation was performed on a LiChrosorb RP-1 at 30 degrees C. The eluent was made of potassium dihydrogen phosphate/acetonitrile in ratio of 50:50 (v/v); the flow rate was 1 ml/min. The detection was performed at 220 nm. The method exhibited a large linear range from 0.05 to 5 microg/ml for all studied compounds. The intra-assay accuracy ranged from 92% determined at 0.1 microg/ml of PS3OH, to 108% determined at 0.05 microg/ml of PS3OHAc. The average coefficient of variation of inter-assay was 6.27%. The average recovery from plasma was 78.5%. The limits of quantification for all the tetrahydroisoquinoline derivatives was 20 ng. The method proved to be highly sensitive and specific for the determination of the studied compounds in rat plasma and has been successfully applied to the evaluation of the pharmacokinetic profile of the inoculated compound.

Animals↗

PubMed2004

Interleukin-15, as interferon-gamma, induces the killing of Leishmania infantum in phorbol-myristate-acetate-activated macrophages increasing interleukin-12.

The potential leishmanicidal activity of interleukin-15 (IL-15) was examined while priming with the cytokine phorbol-myristate-acetate (PMA)-activated macrophages and infecting them with Leishmania infantum parasites. The activation of macrophage cultures with IL-15 determined a significant anti-leishmanial activity, comparable with that induced by interferon-gamma (IFN-gamma). The killing of Leishmania in macrophages primed with IL-15, as well as with IFN-gamma, was followed by an increase in the IL-12 synthesis. The neutralization of IL-15 or IFN-gamma, by specific monoclonal antibodies (MoAb) caused a significant reduction in leishmanicidal activity. Furthermore, in PMA-activated macrophages, the neutralization of IL-12 production by a specific anti-IL-12 MoAb reduced leishmanicidal activity induced by IL-15 and IFN-gamma. Data indicate that IL-15 could have a role as an activator of leishmanicidal activity, directly or indirectly, by inducing IL-12 production.

Animals↗

PubMed2004

Evaluation of an IgM-ELISA test for the diagnosis of human leptospirosis.

Leptospirosis is a zoonosis with a worldwide distribution very common in most countries. In Italy this acute febrile illness is more frequent in the Northern than in the Southern regions. In the period 1994-1996, the number of cases of Leptospirosis in Sicily was lower with respect to the northern-central regions (7.2% and 73.4% respectively). Between January 1990 and December 1999, a total of 9 leptospirosis cases were observed in the Regional Centre for Leptospirosis of Palermo. The patients were all males (age between 22 and 59 years) and their occupations varied. Laboratory diagnosis is performed by the classical microagglutination microscopical (MAT) but this test is very complex and time-consuming. This study compared the classical MAT with ELISA IgM by using 19 serum samples from 9 patients with confirmed leptospirosis. We also tested 23 serum samples from blood-donors and 29 serum samples from patients with other infectious diseases. By the MAT and the PanBio IgM ELISA all sera from patients were found to be positive. Our results indicate that MAT represents the test with the highest degree of specificity (100%), but ELISA is simpler to perform, considering the favourable degree of sensitivity (100%) and specificity (95.9%).

Adult↗

PubMed2003

Matrix metalloproteinases production in malignant pleural effusions after talc pleurodesis.

In this study we have evaluated the modifications of matrix metalloproteinases (MMPs) in malignant pleural fluids taken from patients suffering from lung cancer and treated with intrapleural talc instillation to induce pleurodesis. Furthermore, we have analysed the variations of some inflammatory mediators (C-reactive protein, alpha-1 antitrypsin) and of a protein (plasminogen) involved in MMP activation. In all patients the clinical improvement after talc pleurodesis was followed by a reduction in MMP-1, TIMP-1, C-reactive protein, alpha-1 antitrypsin and plasminogen activity. Furthermore, MMP-9 levels were variable; in fact, in some patients they were high at the beginning of treatment, in others they increased a few days after pleurodesis induction. These inhibitory effects of talc on MMP-1 and inflammatory mediators associated with the reduction of pleural effusion could constitute an effective means to evaluate the evolution of the treatment.

Aged↗

PubMed2002

Diagnosis of juvenile hemochromatosis in an 11-year-old child combining genetic analysis and non-invasive liver iron quantitation.

UNLABELLED: Juvenile or type2 hemochromatosis is a rare autosomal recessive disorder which leads to severe iron overload early in life. As in the classic adult form of the disease iron toxicity causes liver cirrhosis, cardiomyopathy, and endocrine complications, but the onset of the disease is anticipated in the second to third decades of life. Experience of this disease in children is limited. Molecular diagnosis is unfeasible because the type2 hemochromatosis gene is still unknown, although it is known that the disease locus maps to chromosome 1q. Combining linkage analysis with markers encompassing chromosome 1 locus and a non-invasive method for liver iron quantitation we diagnosed juvenile hemochromatosis in a presymptomatic stage in an 11-year-old Italian child. A regular phlebotomy protocol reduced iron overload preventing all the disease complications. CONCLUSION: Juvenile hemochromatosis patients have severe iron overload within the first years of life, strengthening the greater iron absorption that occurs in this as compared to other types of hemochromatosis. Early detection is essential, because treatment in presymptomatic stages prevents organ damage.

Child↗

PubMed2002

IL-15 in human visceral leishmaniasis caused by Leishmania infantum.

Interleukin (IL)-15 is a recently discovered cytokine with the ability to stimulate the proliferation activity of Th1 and/or Th2 lymphocytes. Here, we investigated the involvement of IL-15 in the immune response to Leishmania infantum infection by studying patients with visceral leishmaniasis (VL). We found that IL-15 is produced by leishmanial antigen (LAg)-stimulated peripheral blood mononuclear cells (PBMC) from active VL patients at a significantly higher level than those produced by cells from healed VL subjects or healthy controls. A significant increase in IL-15 serum blood levels was also observed in acute VL patients compared with healed ones. Furthermore, recombinant IL-15 had an appreciable effect in vitro in reducing IL-4 and increasing the production of IL-12 in response to LAg, but it was ineffective in altering the production of interferon-gamma (IFN-gamma). The production of endogenous IL-15 in acute VL patients appeared to be insufficient to activate both IFN-gamma and IL-12, as attested by the absence of modification of these two cytokines by neutralization experiments in the presence of anti-IL-15 monoclonal antibodies (MoAB). On the contrary, the neutralization of IL-15 increased IL-4 production. Together, these results indicate that endogenous IL-15 plays a role in the suppression of Th2-type cytokines, even though it does not enhance the production of Th1 cytokines in acute VL patients. Since IL-15, in the presence of anti-IL-4 MoAb, caused a further increase in IL-12 production and led to a significant production of IFN-gamma, one of its indirect effects on Th1 cell activation could be due to the latter's effect on Th2 cytokines such as IL-4. Therefore, our observations indicate that there is a potential for IL-15 to augment the T-cell response to human intracellular pathogens.

Adult↗

PubMed2002

Hep Par 1 in gastric and bowel carcinomas: an immunohistochemical study.

AIMS: Hep Par 1 has been described as a specific marker of hepatocellular differentiation and its immunohistochemical use has been suggested as a helpful tool for hepatocellular carcinoma (HCC) diagnosis. Most metastatic liver tumours come from the gastrointestinal tract and usually can be distinguished from HCC only through histology. We evaluated by immunohistochemistry the specificity of Hep Par 1, studying the presence of the epitope that reacts with Hep Par 1 in primary gastric and colorectal cancers. METHODS: A series of 39 cases of primary gastric and 18 cases of colorectal carcinoma were selected. Twenty-six of the 39 gastric carcinomas were of the intestinal type, six of the diffuse type, three of the mixed type and five had hepatoid differentiation. Two of the 18 colorectal adenocarcinomas were well differentiated, 14 moderately differentiated, one poorly differentiated and one was of the mucinous type. Five-microm sections were stained by immunohistochemistry using Hep Par 1 as primary antibody. RESULTS: Immunohistochemical staining was observed in 26 gastric carcinomas (69%) and nine large bowel carcinomas (50%). Fifteen of the 26 positive-stained gastric cancers were of intestinal type, four of diffuse type and two of mixed type cases. All of the five hepatoid type cases stained positively. Two of the nine positively stained colorectal cancers were well differentiated, six were moderately differentiated and one was a mucinous type adenocarcinoma. The staining pattern was cytoplasmic and granular as described in benign and malignant hepatocytes. The percentage of immunostained cells was graded as follows: 0 (no staining); 1 (>0-5%); 2 (> 5-50%); 3 (> 50%). Of the 26 positive gastric tumours, 13 showed a staining score of 1, eight scored 2, and five scored 3. Four of the nine positive intestinal carcinomas showed a staining score of 1, and five scored 2. CONCLUSIONS: Our results show that Hep Par 1 is a highly sensitive marker of hepatocellular differentiation as demonstrated by the expression in gastric tumours with hepatoid histotype. However, the frequent reaction with neoplastic cells of gastric and bowel carcinomas shows a low grade of specificity of this antibody.

Adenocarcinoma↗

PubMed2002

Use of spiral computerized tomography angiography in patients with cerebral aneurysm. Our experience.

BACKGROUND: The purpose is to highlight the usefulness of CT angiography (CTA) in the diagnosis and surgical treatment of cerebral aneurysms. METHODS: Thirty-one patients with subarachnoid haemorrhages were subjected to CT angiography and in those cases where this test did not reveal the aneurysm or did not supply sufficient information relating to it, subsequently a digital subtraction angiography was also performed. Each aneurysm-positive CTA was re-processed using the 3-D techniques, with the neuro-radiologist and the neuro-surgeon working in close co-operation. RESULTS: In 27 cases the CTA diagnosed an aneurysm, and in the 4 cases where no vascular malformations were revealed, also the traditional angiography did not show any pathology. In 17 out of 18 cases operated on in order to clip the aneurysm, the CTA supplied all the information needed for the surgery and it was possibile to reconstruct images similar to those of the surgical field. This led to improvement in the programming of the surgical intervention; in 1 case only was it also necessary to perform the DSA before the operation. CONCLUSIONS: CT angiography, because it is non-invasive, easy to perform, diagnostically reliable, and because the 3-D re-constructions offer the chance to create images of the possible operating field, is the first-choice test to be adopted in the treatment of subarachnoid haemorrhages, even though in some cases the use of the traditional angiography is still necessary and should be carried out whenever the CTA does not reveal vascular malformations.

Adult↗

PubMed2001

Phase I clinical trial of alitretinoin and tamoxifen in breast cancer patients: toxicity, pharmacokinetic, and biomarker evaluations.

PURPOSE: To determine the overall and dose-limiting toxicities (DLTs) of alitretinoin (9-cis-retinoic acid) in combination with tamoxifen and the pharmacokinetics of alitretinoin alone and when combined with tamoxifen in patients with metastatic breast cancer. The effect of tamoxifen and alitretinoin on MIB-1, a marker of proliferation, in unaffected breast tissue was explored. PATIENTS AND METHODS: Eligible patients had metastatic breast cancer. Previous tamoxifen therapy was allowed. Planned dose levels for alitretinoin ranged from 50 to 140 mg/m2/d with 20 mg/d tamoxifen in all patients after 4 weeks of alitretinoin as a single agent. Plasma concentrations of alitretinoin and retinol were measured at baseline and after 1, 2, and 3 months. Breast core biopsies were obtained at baseline and after 2 months of therapy. RESULTS: Twelve patients with metastatic breast cancer received a total of 86 cycles of therapy. At 90 mg/m2/d, three of five patients experienced a DLT: grade 3 headache, grade 3 hypercalcemia, and grade 3 noncardiogenic pulmonary edema. At 70 mg/m2/d, one of six patients experienced a DLT (headache), and this level was considered the maximal tolerated dose in this study. Three toxicities occurred that had not been reported previously with alitretinoin: an asymptomatic delay in dark adaptation, a marked decrease in high-density lipoprotein cholesterol, and the occurrence of enthesopathy. Two of the nine assessable patients had a durable clinical response: one partial response and stable disease for 18 months and one complete response in continuous remission for 48+ months. Both responding patients were estrogen receptor-positive and had had previous tamoxifen therapy. There was a high degree of interpatient variability of plasma alitretinoin concentrations, although a significant decline in alitretinoin plasma levels over time was observed. MIB-1 scores declined in four of the eight paired breast specimens obtained. CONCLUSION: The combination of tamoxifen and alitretinoin is well tolerated and has antitumor activity in metastatic breast cancer. The recommended phase II dose is 70 mg/m2/d with 20 mg/d tamoxifen.

Adult↗

PubMed2001

Anti-inflammatory effects of chemically modified tetracyclines by the inhibition of nitric oxide and interleukin-12 synthesis in J774 cell line.

We investigated the effects of chemically modified tetracyclines (CMTs) on the production of nitric oxide (NO) and on the synthesis of some cytokines: tumour necrosis factor alpha (TNF-alpha), interleukin(IL)-10 and IL-12 in lipopolysaccharide (LPS)-treated J774 cell line. Furthermore, we studied the ability of these drugs to modify the viability in LPS-stimulated J774 macrophages. CMTs decreased, in a dose-dependent manner, inducible NO synthase (iNOS) activity and, consequently, nitrite formation in J774 cultures. The CMT-induced decrease in NO production is due to the inhibition of enzyme activity rather than to a direct effect on enzyme expression. The absence of the inhibition in mRNA accumulation indicates that the inhibiting activity is mainly post-transcriptional. CMTs were unable to modulate TNF-alpha and IL-10 synthesis and they were not effective in modifying the transcription of relative mRNA in J774 macrophages. On the contrary, IL-12 mRNA expression was significantly increased by CMT-1 and CMT-8 with LPS activation. Since IL-12 protein secretion was inhibited by CMTs, these compounds interfere in the blocking of post-transcriptional events. The studies on cell viability showed that various CMTs induced a dose-dependent decrease in J774 macrophage viability. The cytotoxic activity was present even though NO production was inhibited by CMTs. These compounds appear to be able to activate apoptosis in aNO-independent way. Altogether, these results indicate that CMTs can exert anti-inflammatory effects by inhibiting NO synthesis, and they are able to modify cell viability by exerting a strong apoptotic activity.

Acridine Orange↗

PubMed2001

Adhesion molecule expression, clinical features and therapy outcome in childhood acute lymphoblastic leukemia.

In view of the relevance of adhesion molecule expression for the mechanisms of homing, trafficking and spreading of malignant cells, we have investigated the expression of surface adhesion molecules in lymphoblasts from 57 acute lymphoblastic leukemia (ALL) cases and tried to correlate the adhesive phenotype with immunological typing, prognostic factors at diagnosis and clinical follow-up. Blasts from all cases expressed adhesion molecules at high rates. Beta1 integrin chain (CD18) was consistently found on blasts from most ALL cases: among integrins of the beta2 family. LFA-1 was detected in 58% of cases, in the virtual absence of other alpha chains. CD54 and CD58 were expressed in variable proportions by ALL blasts and CD44 was detected in the majority of the malignant cells, whereas the CD62L selectin was only present in 24% of cases. B-lineage ALL's displayed similar adhesion molecule phenotypes irrespective of maturational stages of the leukemic cells. We found a significantly reduced expression of beta2 alphaL integrins in the hybrid ALL cases (CD13 and/or CD33 positive). However, these cases did not show differences in clinical presentation and behaviour in comparison with patients of other groups. We did not find a significant correlation between adhesion molecule expression and well established risk factors (age, white blood cell count, central nervous system involvement, chromosomal abnormalities), with the exception of splenomegaly, that was significantly associated with CD18 expression. In the follow-up, no evidence of significant correlation between adhesive phenotype and adverse events such as leukemic relapse and death was found. In conclusion, although expression of adhesion molecules on lymphoblasts confirms the phenotypic heterogeneity of ALL, it appears that this is not relevant for the clinical aspects of the disease and for prognosis.

Adolescent↗