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Biomedical subjects

L Bello

Publications and source records attributed to L Bello.

At least 19 recordsLinked to original sources
PubMed2007

Skin-derived stem cells transplanted into resorbable guides provide functional nerve regeneration after sciatic nerve resection.

The regeneration in the peripheral nervous system is often incomplete and the treatment of severe lesions with nerve tissue loss is primarily aimed at recreating nerve continuity. Guide tubes of various types, filled with Schwann cells, stem cells, or nerve growth factors are attractive as an alternative therapy to nerve grafts. In this study, we evaluated whether skin-derived stem cells (SDSCs) can improve peripheral nerve regeneration after transplantation into nerve guides. We compared peripheral nerve regeneration in adult rats with sciatic nerve gaps of 16 mm after autologous transplantation of GFP-labeled SDSCs into two different types of guides: a synthetic guide, obtained by dip coating with a L-lactide and trimethylene carbonate (PLA-TMC) copolymer and a collagen-based guide. The sciatic function index and the recovery rates of the compound muscle action potential were significantly higher in the animals that received SDSCs transplantation, in particular, into the collagen guide, compared to the control guides filled only with PBS. For these guides the morphological and immunohistochemical analysis demonstrated an increased number of myelinated axons expressing S100 and Neurofilament 70, suggesting the presence of regenerating nerve fibers along the gap. GFP positive cells were found around regenerating nerve fibers and few of them were positive for the expression of glial markers as S-100 and glial fibrillary acidic protein. RT-PCR analysis confirmed the expression of S100 and myelin basic protein in the animals treated with the collagen guide filled with SDSCs. These data support the hypothesis that SDSCs could represent a tool for future cell therapy applications in peripheral nerve regeneration.

Action Potentials↗
PubMed2004

Sexually transmitted diseases and pelvic inflammatory disease.

AIM: The aim of this study was to determine the prevalence in the Turin area of the pathogens most implicated in pelvic inflammatory disease (PID), with particular regard to which risk factors the population taken into consideration is exposed to. METHODS: From January 1st 1997 to December 31(st) 2001, 13809 women, aged between 14-54, all subjects being fertile and sexually active, were examined for the first time at St. Anna Hospital in Turin for the diagnosis of sexually transmitted diseases (STDs). A total of 5559 unselected patients were divided into 2 groups according to the presence (1721) or absence (3838) of subjective symptoms related to PID. Both groups underwent a cervico-vaginal bacteriological test for common pathogens, Candida spp., T. vaginalis, bacterial vaginosis, C. trachomatis, Mycoplasma spp., N. gonorrhoeae. The prevalence of each micro-organism was coupled with the anamnestic data collected from a pre-determined questionnaire submitted to all patients. The questionnaire collected personal data: age at the time of first sexual intercourse; the number of partners in the last 6 months; the type of contraceptives used. Statistical analysis was performed using a chi squared test. RESULTS: In our analysis 2 factors proved to be decisive for a correct PID diagnosis: a subjective symptomatology and an anamnesis mainly focused on risk factor evaluation. This result is in accordance with what has been emphasized many times in the literature, i.e. many of these infections have only a few or no symptoms at all. CONCLUSION: Greater attention to the anamnestic data collection would therefore be the key to focusing the clinical investigations on those who are at a major risk to contracting STDs.

Adolescent↗
PubMed2004

Chlamydia trachomatis prevalence in North-West Italy.

AIM: Chlamydia (C.) trachomatis infection is the most common sexually transmitted disease (STD) among sexually active adolescents and young adults in Europe. The aim of this study was to determine the prevalence of C. trachomatis among sexually active women in Piedmont, Italy and the correlation between some risk factors and C. trachomatis infection. METHODS: In our study 31,419 sexually active women aged 12-55 were screened for C. trachomatis by Abbott's ligase chain reaction (LCR) using cervical swabs during the period 1997-2001 at St. Anna Obstetric-Gynecological Hospital, Turin. All the patients answered a specific questionnaire. RESULTS: In our analysis the prevalence of C. trachomatis infection was found to be 1.23%, and the average age among the infected patients was 36.98 years. Statistical analysis was performed using the chi squared test; a p<0.05 was considered significant. A correlation was found between a positive test result and the age at the first intercourse (p<0.001), the number of sexual partners in the preceding 6 months (p<0.001), the presence of symptoms (p<0.001), a low level of education (p<0.001) and an East-European and Central-Northern African citizenship (p<0.001). No statistically significant differences were found among the contraceptive methods used, whether an hormonal or a barrier type; a marked increment of the risk was observed when no contraception was used. CONCLUSION: Frequent microbiological examinations are desirable for patients whose anamnesis shows an augmented risk of contracting sexually transmitted infections in order to avoid long term complications from misdiagnosed or asymptomatic pathologies, as often happens with C. trachomatis.

Adolescent↗
PubMed2003

Long-term inhibition of glioma growth by systemic administration of human PEX.

AIM: The growth of gliomas depends on the balance of factors stimulating or inhibiting angiogenesis, tumor cell invasion and proliferation. The administration of endogenous inhibitors to experimental human gliomas in animal models resulted in a significant inhibition of tumor growth. It is becoming apparent that resistance can develop over time to many types of endogenous inhibitors and seems to be influenced by the tumor type and system of delivery. METHODS: We recently isolated a potent endogenous inhibitor, called human PEX, from human glioma cells in culture. Human PEX is a potent inhibitor of angiogenesis, tumor and endothelial cell proliferation and migration. In this paper, we investigated the ability of human PEX to sustain inhibition of glioma growth for a prolonged period of time. We initially developed a recombinant form of the inhibitor and showed that this form had similar in vitro and in vivo activities to the natural one. Human PEX was then administered to nude mice intracranial human glioma model, in combination with metronomic chemotherapy, for a period of 185 days, starting 15 days after tumor cells implantation. RESULTS: Our data showed that the systemic administration of human PEX mantained a very prolonged inhibition of glioma growth (50% survival of animals treated with 2 mg/kg/days was 160 days vs 24 days of the control) and had a synergistic effect with low dose chemotherapy. Histological analysis of tumors, showed that treatment with PEX was associated with a decrease of vascularity, cell proliferation, and increase in apoptosis. CONCLUSION: These data indicate that human PEX controls tumor growth by separate mechanisms. In addition, treatment with PEX produced well delineated tumors, indicating the persistence of a direct anti-invasive effect of the molecule even after a prolonged period of treatment.

Angiogenesis Inhibitors↗
PubMed2002

[A new method of neovagina in Rokitansky's syndrome. A review of the literature and description of a series].

BACKGROUND: The absence or hypoplasia of the vagina is a frequent finding in Rokitansky-Mayer-Küster-Hauser syndrome. METHODS: A group of 13 patients with Rokitansky-Mayer-Küster-Hauser syndrome were treated between 1982 and December 2001 at the Plastic Surgery Department of C.T.O. (Turin) and the 2nd Obstetrics-Gynecology Clinic of Turin University. Surgery was the proposed therapy in all patients, using a modified version of the McIndoe technique. RESULTS: In this series, the cytological tests of neovaginal tissue carried out one year after surgery showed a syndrome of slight atrophy in 8 cases, but this was not sufficient to impede the sexual activity of these patients. Two patients were lost in the follow-up; 3 patients declared that they were reasonably satisfied with their sex life, whereas the remaining 8 reported a normal sex life. CONCLUSIONS: The treatment of choice for complete vaginal agenesia is a neovagina using the skin graft method. This technique produces excellent anatomical results, especially in young patients, even without regular dilatation or frequent sexual relationships. The only drawback of this method is that the vagina tends to retract in some patients, a problem that has been largely solved by the most recently proposed surgical variants.

Abnormalities, Multiple↗
PubMed2002

[Cervico-vaginal infections. Study of a population in the Turin area].

BACKGROUND: Aim of this study is to determine the prevalence, in the Turin area, of the pathogens chiefly involved in the genesis of the most common infections of the female genitalia. METHODS: This is a retrospective study. During the period of time beginning from January 1, 1997 and ending December 31, 1999, we examined 10,249 women from 14 years to 54 years of age, who were seen at the out-patient diagnosis service of the Sant'Anna Hospital. The patients' cervical specimens were screened for common germs, Candida spp., Trichomonas vaginalis, Bact. Vaginosis, Chlamydia trachomatis, Microplasms, and Neisseria gonorrhea. The prevalence of each micro-organism was found. The obtained data were cross-referenced with the risk factors in the clinical history of each patient. The chi(2) test with a C.I. of 95% was used for the statistical evaluations. RESULTS: It is shown by a detailed analysis of the data in our possession that an anamnesis oriented mainly for the evaluation of the various risk factors would be more effective than one oriented for the presence of a subjective symptomatology, since many of these infections are either weakly symptomatic or totally asymptomatic (especially in the case of C. trachomatis), as has been many times underlined in the international literature. CONCLUSIONS: Greater attention should be given to the collection of anamnestic information in order to more precisely target for examination those subjects at greater risk of contracting a sexually transmitted infection.

Adolescent↗
PubMed2001

Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2.

Angiogenesis, tumor cell proliferation, and migration are the hallmarks of solid tumors, such as gliomas. This study demonstrates that a fragment derived from the autocatalytic digestion of matrix metalloproteinase (MMP)-2, called PEX, acts simultaneously as an inhibitor of glioma angiogenesis, cell proliferation, and migration. PEX is detected in the cultured medium of various human glioma, endothelial, breast, and prostate carcinoma cell lines. PEX is purified from the medium of glioma cell lines by chromatography, where PEX is constitutively expressed as a free and a TIMP-2-bound form. In human glioma tissue, PEX expression correlates with histological subtype and grade and with alpha v beta 3 integrin expression to which it is bound. Systemic administration of PEX to s.c. and intracranial human glioma xenografts results in a 99% suppression of tumor growth with no signs of toxicity. Thus, PEX is a very promising candidate for the treatment of human malignant gliomas.

Adult↗
PubMed2001

Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo.

This study evaluates the efficacy of the combination of an antiangiogenic drug and conventional chemotherapeutics for the treatment of experimental human gliomas. As an antiangiogenic, we used recombinant human PEX, a fragment of matrix metalloproteinase-2 that we have previously shown to have a significant antimitotic, anti-invasive, and antiangiogenic properties against human glioblastoma in vitro and in vivo. We used carboplatin and etoposide as the two chemotherapeutic drugs routinely used in our institution (Ospedale Maggiore de Milano) for the treatment of malignant gliomas. Conventional chemotherapeutic drugs were administered at high dose or at a low and semicontinuous regimen. Combined treatment of high-dose chemotherapy and PEX did not produce an improvement of survival in comparison with chemotherapy alone, but it was associated with a decrease in tumor volume, vascularity, and proliferative index and an increased apoptosis. All of these animals experienced severe side effects. The longest survival was documented in animals submitted to low and semicontinuous chemotherapy and antiangiogenic treatment. This regimen was associated with no side effects, marked decrease in tumor volume, vascularity, and proliferative index, and an increased apoptosis. Our data suggest that low-dose chemotherapy in combination with PEX can be successfully used against human malignant glioma in vivo.

Angiogenesis Inhibitors↗
PubMed2001

Alpha(v)beta3 and alpha(v)beta5 integrin expression in glioma periphery.

OBJECTIVE: This study analyzed the expression of integrins alpha(v)beta3 and alpha(v)beta5 in glioma tissue and focused on the periphery of high-grade gliomas. METHODS: The analysis was performed with Western blot, immunohistochemistry, and immunofluorescence, by use of two monoclonal antibodies able to recognize the functional integrin heterodimer. The expression of integrin-related ligands and growth factors also was studied. Sections from the tumor periphery were classified as either tumor periphery (light tumor infiltrate or scant visible cells) or peritumor (heavy tumor infiltration). RESULTS: Our data on glioma tissues demonstrated that both integrins were expressed in glioma cells and vasculature and their expression correlated with the histological grade. Alpha(v)beta3 expression was prominent in astrocytic tumors. Both integrins were markers of tumor vasculature, particularly of endothelial proliferation. A high-grade glioma periphery demonstrated a prominent expression of integrin alpha(v)beta3. Cells demonstrating alpha(v)beta3 positivity were identified as tumor astrocytes and endothelial cells by double imaging. The same cells were surrounded by some alpha(v)beta3 ligands and co-localized fibroblast growth factor 2. Matrix metalloproteinase 2 also was found to be co-localized with alpha(v)beta3 in the same cells. Alpha(v)beta3 expression was more relevant in tumor astrocytes. Alpha(v)beta3 integrin and vascular endothelial growth factor expression increased from the periphery to the tumor center. CONCLUSION: Our data support the role of integrins alpha(v)beta3 and alpha(v)beta5 in glioma-associated angiogenesis. In addition, they suggest a role for integrin alpha(v)beta3 in neoangiogenesis and cell migration in high-grade glioma periphery.

Adult↗
PubMed2000

Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398.

The up-regulation of cyclooxygenase 2 (COX-2) expression is a frequent occurrence in a variety of different tumors. In this study, COX-2 protein expression was investigated in 50 glioma and 3 normal brain specimens by immunohistochemistry. Expression of COX-2 protein was observed in all normal brain and glioma specimens by immunohistochemistry, regardless of histological grade. The immunoreactive score was significantly higher in high-grade glioma than low-grade glioma and normal brain specimens. For a subset of these tumors (nine gliomas and three normal brain), Western blot analysis was also performed. COX-2 protein was detected in all specimens by Western blot analysis. The effect of the specific COX-2 inhibitor NS-398 on monolayer cell cultures and three-dimensional glioma spheroids was investigated using U-87MG and U-251MG human glioblastoma cell lines. The proliferation rate was assessed in monolayer cultures. In addition, a growth assay, a migration assay, an apoptosis assay, and a tumor invasion assay were performed in a three-dimensional spheroid culture system. NS-398 was able to reduce the proliferation of monolayer cell cultures, as well as the growth of spheroids and tumor cell migration, in a dose-dependent manner. There was also a moderate increase in the number of apoptotic cells in the treated spheroids. NS-398 did not have an inhibitory effect on tumor invasion in the coculture spheroid system. Our study provides evidence that COX-2 is up-regulated in the majority of high-grade gliomas and that a potential role of COX-2 inhibitors as an adjuvant therapy for brain tumors may exist.

Adult↗
PubMed2000

Parathyroid hormone-related protein and its receptor in human glial tumors.

OBJECTIVE: Parathyroid hormone-related protein (PTHrP) and its mRNA have been found to be expressed in a variety of human tumors including breast, prostate, colon, lung, renal and ovarian cancers. The purpose of this study is to evaluate the expression of PTH/PTHrP receptor and ligand in human glial tumors. METHODS: We examined the coexpression of PTH/PTHrP receptor and ligand in 73 glial tumors of different histological grades and 4 nonneoplastic human brain specimens and three glioblastoma cell lines, by using Western Blot analysis and immunohistochemical analysis. RESULTS: PTHrP and PTH/PTHrP receptors were shown in the neurons, reactive astrocytes and the endothelial cells of normal brain tissue as well as tumor cells, reactive astrocytes and vasculature of nonneoplastic tissue. They were expressed at higher levels in pure astrocytic tumors as compared to tumors with oligodendroglial components. CONCLUSION: PTH/PTHrP receptor and PTHrP ligand are co-expressed in human glial tumors. There increased expression suggests an autocrine and/or paracrine loop may exist.

Adult↗
PubMed2000

Combined treatment of fourth ventricle ependymomas: report of 26 cases.

BACKGROUND: This study investigated the relevance of prognostic factors and the impact of histological features in posterior fossa ependymoma. METHODS: The charts of 26 patients (aged 1-59 years, mean 20.6 years; 11 adults) with posterior fossa ependymoma operated on between January 1983 and December 1994 were reviewed and patients followed up (mean: 93 months). RESULTS: Gross total resection was performed in 18 patients (69%), subtotal in seven patients (27%), biopsy in one patient (4%). One patient (3.8%) developed respiratory complications and died. All patients underwent posterior fossa radiotherapy (5000 cGy) after surgery. Four children first received chemotherapy and then radiotherapy only when at least 3 years old. Eleven patients (42%) received radiotherapy and subsequently chemotherapy. The 5-year survival rate was 90% for adults and 40% for children (</= 6 years). CONCLUSIONS: This review suggests that a) younger patients (</= 6 years), despite multimodality treatment, have a poor prognosis; b) the microanatomical location of the tumor (lateral recess, roof, and floor) influences the extent of tumor removal (p < 0.05); c) longer survivals are associated with complete removal (p < 0.05); d) the histological feature most often related to a poor prognosis is a high mitotic index (p < 0.05), whereas vascular proliferation (p = 0.149), necrosis (p = 0.215), nuclear atypia (p = 0.384) and high cellularity (p = 0.786) do not affect survival; e) histological classification (WHO) does not reflect different survival rates between ependymomas and anaplastic ependymomas (p = 0.082).

Adolescent↗
PubMed2000

Alpha(v)beta3 and alpha(v)beta5 integrin expression in meningiomas.

OBJECTIVE: Integrins are emerging as alternative receptors capable of mediating several biological functions, such as cell-matrix and cell-cell adhesion, cell migration, signal transduction, and angiogenesis. Two alpha(v) integrins, i.e., alpha(v)beta3 and alpha(v)beta5, play critical roles in mediating these activities, particularly in tumors. No data are available on the expression of these integrins in meningiomas. METHODS: Using Western blot and immunohistochemical analyses with LM609 and PG32, two monoclonal antibodies capable of recognizing the functional integrin heterodimer, we evaluated the expression of alpha(v)beta3 and alpha(v)beta5 integrins in a series of 34 meningiomas of different histological subtypes and grades. We studied their expression in tumor cells and vasculature, as well as the expression of their related angiogenic factors (fibroblast growth factor 2 and vascular endothelial growth factor) and the alpha(v)beta3 ligand vitronectin. RESULTS: Alpha(v)beta3 and alpha(v)beta5 integrins were expressed by neoplastic vasculature and cells. Alpha(v)beta3 and alpha(v)beta5 expression was associated and correlated with that of their respective growth factors (fibroblast growth factor 2 and vascular endothelial growth factor) and microvessel counts and densities. Alpha(v)beta3 was more strongly expressed than alpha(v)beta5 in two cases of histologically benign meningiomas with aggressive clinical behavior. Alpha(v)beta3 expression was associated with that of its related ligand vitronectin and was also evident in small vessels of brain tissue closely surrounding meningiomas. CONCLUSION: Our data demonstrate the expression of alpha(v)beta3 and alpha(v)beta5 integrins in meningioma cells and vasculature. Our findings suggest a role for both of these integrins, and particularly alpha(v)beta3, in meningioma angiogenesis.

Adult↗
PubMed2000

Shoulder-hand syndrome in neurosurgical patients treated with barbiturates. A long term evaluation.

OBJECTIVES: To assess the incidence of shoulder-hand syndrome (SHS) in neurosurgical patients (head injuries, intracranial ruptured aneurysms and intracranial meningiomas), treated with barbiturates. SHS is a chronic condition characterized by intense tenderness and functional impairment affecting one hand, the shoulder or both. Barbiturates have been identified as cause of SHS, although there is controversial evidence on the incidence of this disorder in patients started on long-term Phenobarbital (PB) therapy. METHODS: One hundred and twenty-six neurosurgical patients, treated with barbiturates, and a control group of 108 patients, treated with carbamazepine or phenytoin, were enrolled. Both groups were followed up for at least 24 to 36 months. RESULTS: Thirty-five PB-treated patients (27.6%) experienced SHS. In these patients SHS developed during the first 7 months of therapy and regressed after PB discontinuation or, in 2 cases, after dosage reduction. None of the patients in the control group developed SHS. CONCLUSIONS: The occurrence of SHS in the study group was much more common than that reported previously. This higher incidence should depend upon the coexistence of separate risk factors such as age over 50 years, surgery and intracranial pathology. Early diagnosis and rapid withdrawl of treatment are important for symptomatic relief and full functional recovery.

Adult↗
PubMed1999

KDR activation in astrocytic neoplasms.

BACKGROUND: The development of new capillary networks appears to be necessary for the growth of solid tumors. Tumor angiogenesis is believed to be mediated by soluble factors released from tumor cells that then act on endothelial cells in a paracrine manner. Vascular endothelial growth factor (VEGF) is a prime regulator of normal and tumor angiogenesis as well as vasculogenesis. VEGF is expressed in glioma cells and its receptors (Flt-1 and KDR) are expressed in the same gliomas. The two receptors are tyrosine kinases and have an extracellular domain containing seven immunoglobulin-like loops and a split tyrosine-kinase domain. KDR is a receptor for the various VEGF isoforms and for VEGF-C; Flt-1 is a receptor for the various isoforms. Studies suggest that the VEGF receptors are induced in endothelial cells during tumor angiogenesis. Stimulation of aortic endothelial cells results in receptor tyrosine phosphorylation (receptor activation). In this study the activation state of the KDR receptors was determined in low grade, anaplastic, and high grade gliomas. METHODS: A synthetic tyrosine phosphopeptide was used to raise an antibody that recognizes the phosphorylation state of tyrosine 1054/1059 in the KDR receptor. Western blot analysis was performed on 37 astrocytic neoplasms (7 low grade astrocytomas, 13 anaplastic astrocytomas, and 17 cases of glioblastoma multiforme). RESULTS: Immunoblotting with this antibody found that tyrosines 1054/1059 were phosphorylated constitutively within multiple fresh surgical specimens of glioblastomas (71%) and anaplastic gliomas (15%), but not in low grade gliomas. CONCLUSIONS: The findings of the current study strongly support the hypothesis that the onset of angiogenesis is an important event during the disease progression of gliomas.

Antibodies↗
PubMed1999

Parasagittal solitary fibrous tumor of the meninges. Case report and review of the literature.

The clinical, radiologic and pathologic features of a case of parasagittal solitary fibrous tumor of the meninges are reported. The patient was a 44 year-old male who presented with a complex partial seizure and a history of headaches and confusion. Radiological studies showed a large extra-axial dural-based mass in the right parietal region, predominantly isointense with gray matter and hypointense with respect to white matter on T1-weighted images, and hypointense with respect to gray matter on T2-weighted images. At surgery, the mass was very vascular, quite firm and very adherent to the convexity. Histologically the tumor was composed of spindle-shaped cells growing in fascicles within a collagenous matrix. Solitary fibrous tumor of the meninges is a newly described entity, which should be kept in mind in the clinical and radiological differential diagnosis of extra-axial brain tumors.

Adult↗
PubMed1999

Idiopathic pinealitis. Case report.

This 63-year-old man presented with complaints of "having a feeling of falling backward" over a 3-month period. Results of his general physical examination, laboratory studies, and neurological examination were unremarkable. A magnetic resonance image revealed a 1.8 x 1.4 x 1.2-cm enhancing mass in the posterior third ventricle just above the corpora quadrigemina. The pineal gland was found to be diffusely enlarged at operation and separable from the posterior thalamus and was totally resected. The patient had an uneventful postoperative course but continues to be somewhat confused. The lesion consisted of a remarkable chronic inflammatory cell infiltrate permeating the pineal lobules and was composed of T and B lymphocytes, macrophages, eosinophils, and mast cells. Immunoperoxidase studies did not demonstrate Langerhans cells, and a search for microorganisms was unrevealing. There was no evidence of neoplasia; results of immunostaining for germ cell markers and other tumor-associated antigens were negative.

B-Lymphocytes↗