199 results on '"Fiorini, S."'
Search Results
152. Polymer-coated superparamagnetic iron oxide nanoparticles as T 2 contrast agent for MRI and their uptake in liver.
- Author
-
Ali LM, Marzola P, Nicolato E, Fiorini S, Heras Guillamón ML, Piñol R, Gabilondo L, Millán A, and Palacio F
- Abstract
Aim: To study the efficiency of multifunctional polymer-based superparamagnetic iron oxide nanoparticles (bioferrofluids) as a T
2 magnetic resonance contrast agent and their uptake and toxicity in liver., Materials & Methods: Mice were intravenously injected with bioferrofluids and Endorem® . The magnetic resonance efficiency, uptake and in vivo toxicity were investigated by means of magnetic resonance imaging (MRI) and histological techniques., Results: Bioferrofluids are a good T2 contrast agent with a higher r2 /r1 ratio than Endorem. Bioferrofluids have a shorter blood circulation time and persist in liver for longer time period compared with Endorem. Both bioferrofluids and Endorem do not generate any noticeable histological lesions in liver over a period of 60 days post-injection., Conclusion: Our bioferrofluids are powerful diagnostic tool without any observed toxicity over a period of 60 days post-injection., Competing Interests: Financial & competing interests disclosure Financial support from the Spanish Ministry of Science and Innovation research grant MAT2014-54975-R, and from the Programa Operativo FEDER Aragón 2014-2020 ‘Construyendo Europa desde Aragón’, is gratefully acknowledged. Additional support from the Diputación General de Aragón (DGA-M4) is also acknowledged. LMA Ali acknowledges financial support from the Spanish Ministry of Science and Innovation FPI research grants. The Servicio de Experimentación Animal (SAI), and servicio de Microscopia Electrónica de Materiales of Zaragoza University. P Marzola acknowledges financial support from Fondazione Cariverona (Verona, Italy) through the project ‘Verona Nanomedicine Initiative’ and from MIUR through FIRB project RBAP114AMK – RI.NA.ME. ‘Rete Integrata per la Nanomedicina’. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.- Published
- 2017
- Full Text
- View/download PDF
153. Data-driven strategies for robust forecast of continuous glucose monitoring time-series.
- Author
-
Fiorini S, Martini C, Malpassi D, Cordera R, Maggi D, Verri A, and Barla A
- Subjects
- Blood Glucose Self-Monitoring, Humans, Insulin Infusion Systems, Machine Learning, Retrospective Studies, Blood Glucose analysis
- Abstract
Over the past decade, continuous glucose monitoring (CGM) has proven to be a very resourceful tool for diabetes management. To date, CGM devices are employed for both retrospective and online applications. Their use allows to better describe the patients' pathology as well as to achieve a better control of patients' level of glycemia. The analysis of CGM sensor data makes possible to observe a wide range of metrics, such as the glycemic variability during the day or the amount of time spent below or above certain glycemic thresholds. However, due to the high variability of the glycemic signals among sensors and individuals, CGM data analysis is a non-trivial task. Standard signal filtering solutions fall short when an appropriate model personalization is not applied. State-of-the-art data-driven strategies for online CGM forecasting rely upon the use of recursive filters. Each time a new sample is collected, such models need to adjust their parameters in order to predict the next glycemic level. In this paper we aim at demonstrating that the problem of online CGM forecasting can be successfully tackled by personalized machine learning models, that do not need to recursively update their parameters.
- Published
- 2017
- Full Text
- View/download PDF
154. Medication errors in intensive care units: nurses' training needs.
- Author
-
Di Simone E, Tartaglini D, Fiorini S, Petriglieri S, Plocco C, and Di Muzio M
- Subjects
- Clinical Competence, Female, Humans, Intensive Care Units, Italy, Male, Surveys and Questionnaires, Critical Care Nursing, Education, Nursing, Graduate, Medication Errors prevention & control, Nursing Staff, Hospital education
- Abstract
Aim: To describe which elements of nurses' knowledge, training, behaviour and attitude can prevent errors in intensive care units during all steps of the administration of intravenous medication., Method: An anonymous questionnaire made up of 43 items was drafted and delivered to a sample of 123 nurses at 2 university hospitals in Rome., Results: The majority of the sample (96.7%) stated that topics related to the preparation and administration of intravenous medications were covered during the basic nursing course. Just over 95% of the sample considered it important to improve their knowledge about preparation and administration of intravenous medications; 94.3% said that teaching about the use of intravenous medications should be enhanced during the degree course they attended and 91.1% agreed that specific postgraduate courses should be set up on the use of intravenous drugs., Conclusion: Pharmacological knowledge is a prerequisite for the proper administration of drugs and for the clinical evaluation of the effects on the patient. This knowledge implies the understanding of the theoretical and clinical principles of pharmacology, the ability to contextualise medication management according to the complex and changing needs of patients, and it also includes the appropriate skills of drug administration.
- Published
- 2016
- Full Text
- View/download PDF
155. A machine learning pipeline for multiple sclerosis course detection from clinical scales and patient reported outcomes.
- Author
-
Fiorini S, Verri A, Tacchino A, Ponzio M, Brichetto G, and Barla A
- Subjects
- Humans, Machine Learning, Patient Reported Outcome Measures, Quality of Life, Multiple Sclerosis
- Abstract
In this work we present a machine learning pipeline for the detection of multiple sclerosis course from a collection of inexpensive and non-invasive measures such as clinical scales and patient-reported outcomes. The proposed analysis is conducted on a dataset coming from a clinical study comprising 457 patients affected by multiple sclerosis. The 91 collected variables describe patients mobility, fatigue, cognitive performance, emotional status, bladder continence and quality of life. A preliminary data exploration phase suggests that the group of patients diagnosed as Relapsing-Remitting can be isolated from other clinical courses. Supervised learning algorithms are then applied to perform feature selection and course classification. Our results confirm that clinical scales and patient-reported outcomes can be used to classify Relapsing-Remitting patients.
- Published
- 2015
- Full Text
- View/download PDF
156. Pancreatic cancer growth using magnetic resonance and bioluminescence imaging.
- Author
-
Ritelli R, Ngalani Ngaleu R, Bontempi P, Dandrea M, Nicolato E, Boschi F, Fiorini S, Calderan L, Scarpa A, and Marzola P
- Subjects
- Animals, Cell Line, Tumor, Disease Models, Animal, Female, Humans, Mice, Mice, Nude, Neoplasms, Experimental, Luminescent Measurements, Magnetic Resonance Imaging, Pancreatic Neoplasms diagnosis
- Abstract
Object: Pancreatic cancer is one of the most lethal human cancer and appropriate experimental tumor models are needed for the development of innovative therapeutic approaches. This paper describes an experimental model of human pancreatic cancer and a related non invasive imaging technique suitable for monitoring tumor growth and metastatization. The aim of the work was the implementation of an experimental platform suitable for assessing the efficacy of new therapeutic agents., Materials and Methods: Human pancreatic cancer cells (PANC-1-Luc+) were injected into the pancreas of female athymic CD1 mice. Magnetic Resonance Imaging (MRI) at 4.7T and Bioluminescence Imaging (BLI) were performed in each mouse at three time points after cell inoculation (1, 2 and 3months). Two groups of mice were studied: the first group of n=13 mice in which 5*10(6) cells were injected and the second group of n=10 mice in which 2*10(6) cells were injected. MRI examination included T2w acquisitions and (at the last time point) Dynamic-contrast-enhanced-MRI (DCE-MRI)., Results: Each mouse underwent three longitudinal MRI and BLI examinations. BLI was more sensitive than MRI producing higher detection rate at early time points. Moreover in one case of abdominal dissemination of pancreatic tumor cells, small tumoral masses were detected by BLI and not detected by MRI. However BLI appears more prone to experimental error most likely due to photon attenuation. In 4 mice BLI produced false negative results. DCE-MRI experiments providing information on tumor perfusion were conducted successfully in this anatomical district and demonstrated that the tumor tissues from the second experimental group are more vascularized compared to the first group., Conclusion: The present study performed on the experimental model of pancreatic cancer here described shows that MRI and BLI are complementary techniques and that synergistic application of both can overcome the intrinsic limitations of each., (Copyright © 2015. Published by Elsevier Inc.)
- Published
- 2015
- Full Text
- View/download PDF
157. [Mycobacterium infection in prehistoric humans: co-evolution in remote ages].
- Author
-
Sabbatani S and Fiorini S
- Subjects
- Africa, Ancient Lands, Animal Husbandry history, Animals, Cattle, Cattle Diseases microbiology, Cultural Evolution history, History, 17th Century, History, 18th Century, History, 19th Century, History, 20th Century, History, 21st Century, History, Ancient, History, Medieval, Humans, North America, Paleopathology history, Paleopathology methods, Phylogeny, Phylogeography, Cattle Diseases history, DNA, Bacterial history, Emigration and Immigration history, Genome, Bacterial, Medical Illustration history, Mycobacterium tuberculosis genetics, Tuberculosis history
- Abstract
The introduction of agriculture and animal husbandry at the end of the Mesolithic era, despite enabling a significant demographic growth through an increase in food storage and availability, caused new infectious noxae to enter the pathocoenosis. However in the Palaeolithic era, hunter-gatherers were already in contact with infectious diseases of animal origin, albeit episodically. Modern biomedical technologies allow us to estimate, with better approximation, how long mankind has been in contact with Mycobacterium tuberculosis. Archaeological finds, including human and animal remains (especially the aurochs), are particularly studied by palaeopathologists, as mycobacteria frequently cause bone involvement and this characteristic is of particular interest for palaeopathological (even macroscopic) studies; the interest is to detect the ancient DNA of MT, which is the cause of bone tuberculosis in skeletal remains as well as in mummies. According to our present knowledge, palaeopathological findings, confirmed by molecular techniques, suggest that tuberculosis in human skeletons goes back at most to 9000 years ago, while, in a veterinary environment, the most ancient DNA of MTBC to be detected in an American bison dates back about 17,000 years. The possibility of discovering archaeological finds making even more ancient human remains available leaves opens up the possibility of dating back to previous eras the transmission of MTBC infection to mankind. Phylogenetic works examining the available materials (DNAa) suggest that Mycobacterium tuberculosis, the cause of tuberculosis infection in humans and cattle (Aurochs), would have had a co-evolutionary process. On the basis of recent phylogenetic studies, the MTBC genome would have had a wide span of time to reach a suitable adjustment, co-evolving in geographical environments both at high and low host density. It is likely that the strains that did not show this strong "flexibility" underwent extinction, in favour of more versatile, adaptable strains, that are able to infect susceptible hosts "always" and in any environmental condition.
- Published
- 2015
158. Pediatric trauma. Epidemiological study among patients admitted to Hospital de Niños "Ricardo Gutiérrez".
- Author
-
Fiorentino JA, Molise C, Stach P, Cinder P, Solla MM, Hoffman E, Tomezzoli S, Fiorini S, Djourian C, Caorsi N, Fosco M, Dartiguelongue JB, Barbaro C, and Rossi S
- Subjects
- Adult, Argentina epidemiology, Child, Child, Preschool, Epidemiologic Studies, Female, Hospitals, Pediatric, Humans, Infant, Injury Severity Score, Male, Patient Admission, Prospective Studies, Young Adult, Wounds and Injuries epidemiology
- Abstract
Introduction: In Argentina, trauma is the most common cause of death among children older than 1 year old, has a high morbidity rate, and results in large costs for the health system., Objective: To identify causes of injuries in patients admitted to the hospital due to a trauma, and to analyze the relationship between epidemiological factors and severe trauma., Population and Methods: Prospective study. Children and adolescents aged 0 to 18 years old admitted to the hospital due to unintentional trauma between April 2012 and March 2013 were included. They were divided into two groups based on severity according to the pediatric trauma score (8 or lower) to identify risk factors by means of a logistic regression model. PREDICTIVE OUTCOME MEASURES: patients' and parents' demographic characteristics, socioeconomic factors, event data, initial care, course, and risk factors. Patients were stratified into three age groups for the analysis of the type of injury and the anatomic location., Results: Two hundred and thirty-seven patients were included. Traumatic brain injuries were predominant among children younger than 3 years old, while limb fractures were most common among children older than 3 years old. In the bivariate analysis, foreign parents, a state of poverty or destitution, an immediate preventable cause, dangerous heights, and an unsafe heating system were statistically significant outcome measures. Based on multiple regression, outcome measures included were foreign parents, living in a slum area, an immediate preventable cause, and an unsafe heating system., Conclusions: The main cause of trauma was related to falls from heights, and some of the studied socioeconomic factors were associated with a higher risk of trauma. This information may be useful to develop prevention measures.
- Published
- 2015
- Full Text
- View/download PDF
159. In vivo long-term magnetic resonance imaging activity of ferritin-based magnetic nanoparticles versus a standard contrast agent.
- Author
-
Valero E, Fiorini S, Tambalo S, Busquier H, Callejas-Fernández J, Marzola P, Gálvez N, and Domínguez-Vera JM
- Subjects
- Animals, Liver metabolism, Mice, Mice, Inbred BALB C, Tissue Distribution, Apoferritins, Contrast Media, Magnetic Resonance Imaging methods, Magnetite Nanoparticles, Nanoparticles
- Abstract
New long-circulating maghemite nanoparticles of 4 and 6 nm, coated with an apoferritin protein capsid, exhibit useful properties to act as magnetic resonance imaging (MRI) contrast agents. A full in vivo study of the so-called apomaghemites reveals that their long-term MRI properties are better than those of a standard superparamagnetic iron oxide (SPIO) widely used in biomedical applications. The biodistribution of apomaghemites and standard SPIO was investigated by MRI in mice at two different concentrations, 6 and 2.5 mg of Fe·kg(-1), over 60 days. Significant differences are found at low dose (2.5 mg of Fe·kg(-1)). Thus, whereas apomaghemites are active for MR bioimaging of liver for 45 days, standard SPIO is not effective beyond 7 days. On the basis of our data, we may concluded that apomaghemites can act as new long-term MRI liver contrast agents, allowing first the diagnosis of a liver pathology and then monitoring after treatment without the need for a second injection.
- Published
- 2014
- Full Text
- View/download PDF
160. Manganese-enhanced magnetic resonance imaging investigation of the interferon-α model of depression in rats.
- Author
-
Daducci A, Tambalo S, Fiorini S, Osculati F, Teti M, Fabene PF, Corsi M, Bifone A, Sbarbati A, and Marzola P
- Subjects
- Animals, Contrast Media, Depression chemically induced, Depression pathology, Humans, Interferon-alpha, Male, Mental Disorders chemically induced, Rats, Sprague-Dawley, Reproducibility of Results, Sensitivity and Specificity, Chlorides, Depression physiopathology, Disease Models, Animal, Manganese Compounds, Mental Disorders pathology, Mental Disorders physiopathology, Pituitary Gland pathology, Pituitary Gland physiopathology
- Abstract
Therapeutic effects of interferon-α (IFN-α) are known to be associated with CNS toxicity in humans, and in particular with depression symptoms. Animal models of IFN-α-induced depression (sickness behaviour) have been developed in rodents using various preparations, dosing schedules or routes of administrations. In this work, Manganese Enhanced MRI (MEMRI) has been applied to investigate an experimental model of sickness behaviour induced by administration of IFN-α in rats. IFN-α (3.10(5) U/kg), or vehicle, was daily administered i.p., for 7days in rats (n=20 IFN-α treated and n=20 controls). After treatment, animals were assigned to behavioural (n=10 treated, n=10 control) or MRI (n=10 treated and n=10 control) studies. Animals assigned to the MRI study received two repeated i.p. injections of MnCl2, before image acquisition. Images were acquired at 4.7T using T1 mapping for determination of Mn concentration in brain. After co-registration of T1 maps to a digital brain atlas, differences between brains of treated and untreated animals were assessed pixel-to-pixel by statistical analysis. Behavioural tests showed alterations in freezing and struggling parameters, as expected in an experimental model of sickness behaviour. MRI showed a well defined brain region, mainly contained in the visual cortex, in which Mn uptake was significantly lower in treated than in control animals, indicating probably altered functionality. No significant difference was detected in other brain regions. In addition, a statistically significant decrease in the volume of the pituitary gland, paralleled by a slight increase in its Mn content, was detected in treated animals. MEMRI provides both morphological and functional information in the brain of small laboratory animals and can constitute a valuable tool in the investigation of experimental models of psychiatric diseases., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
161. Representing part-whole relations in conceptual spaces.
- Author
-
Rama Fiorini S, Gärdenfors P, and Abel M
- Subjects
- Humans, Cognition physiology, Concept Formation physiology, Models, Psychological, Space Perception physiology
- Abstract
In this paper, we propose a cognitive semantic approach to represent part-whole relations. We base our proposal on the theory of conceptual spaces, focusing on prototypical structures in part-whole relations. Prototypical structures are not accounted for in traditional mereological formalisms. In our account, parts and wholes are represented in distinct conceptual spaces; parts are joined to form wholes in a structure space. The structure space allows systematic similarity judgments between wholes, taking into consideration shared parts and their configurations. A point in the structure space denotes a particular part structure; regions in the space represent different general types of part structures. We argue that the structural space can represent prototype effects: structural types are formed around typical arrangements of parts. We also show how structure space captures the variations in part structure of a given concept across different domains. In addition, we discuss how some taxonomies of part-whole relations can be understood within our framework.
- Published
- 2014
- Full Text
- View/download PDF
162. Cellular localization of BARF1 oncoprotein and its cell stimulating activity in human epithelial cell.
- Author
-
Sakka E, Zur Hausen A, Houali K, Liu H, Fiorini S, and Ooka T
- Subjects
- Cell Cycle drug effects, Cell Line, Cell Nucleus chemistry, Cytoplasm chemistry, Humans, Microscopy, Confocal, Cell Proliferation, Epithelial Cells virology, Herpesvirus 4, Human pathogenicity, Viral Proteins metabolism
- Abstract
BARF1 gene encoded by Epstein-Barr virus is capable of immortalizing the primary monkey epithelial cells and of inducing malignant transformation in human EBV-negative B cell lines as well as rodent fibroblast. This oncoprotein is a secreted protein capable of acting as a powerful mitogen. We have studied the effect of BARF1 protein in transfected or BARF1 protein treated human HaCaT epithelial cells. In BARF1-transfected cells, cell growth was activated and its protein was found both in culture medium and cellular compartment (membrane, cytoplasm and nuclei). When purified BARF1 protein was exogenously added in the cell culture medium of HaCaT cells in absence of fetal calf serum led to its entrance into cells and its intracellular localization in cytoplasm, nuclear periphery and nuclei at 14h treatment, determined by confocal and immunoelectron microscopy. Cell fractionation confirmed its nuclear localization. Nuclear localization was observed in both systems. More interestingly, purified BARF1 protein p29 exogenously added in the cell culture medium activated cell passage of G1 to S phase. S phase activation by its autocrine activity and its tumorigenic activity would be associated with the development of EBV-associated carcinomas., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
163. Modulation of fronto-cortical activity by modafinil: a functional imaging and fos study in the rat.
- Author
-
Gozzi A, Colavito V, Seke Etet PF, Montanari D, Fiorini S, Tambalo S, Bifone A, Zucconi GG, and Bentivoglio M
- Subjects
- Animals, Brain Mapping, Frontal Lobe metabolism, Magnetic Resonance Imaging, Male, Modafinil, Nerve Net metabolism, Proto-Oncogene Proteins c-fos metabolism, Rats, Rats, Sprague-Dawley, Somatosensory Cortex metabolism, Benzhydryl Compounds pharmacology, Central Nervous System Stimulants pharmacology, Frontal Lobe drug effects, Nerve Net drug effects, Somatosensory Cortex drug effects
- Abstract
Modafinil (MOD) is a wake-promoting drug with pro-cognitive properties. Despite its increasing use, the neuronal substrates of MOD action remain elusive. In particular, animal studies have highlighted a putative role of diencephalic areas as primary neuronal substrate of MOD action, with inconsistent evidence of recruitment of fronto-cortical areas despite the established pro-cognitive effects of the drug. Moreover, most animal studies have employed doses of MOD of limited clinical relevance. We used pharmacological magnetic resonance imaging (phMRI) in the anesthetized rat to map the circuitry activated by a MOD dose producing clinically relevant plasma exposure, as here ascertained by pharmacokinetic measurements. We observed prominent and sustained activation of the prefrontal and cingulate cortex, together with weaker but significant activation of the somatosensory cortex, medial thalamic domains, hippocampus, ventral striatum and dorsal raphe. Correlation analysis of phMRI data highlighted enhanced connectivity within a neural network including dopamine projections from the ventral tegmental area to the nucleus accumbens. The pro-arousing effect of MOD was assessed using electroencephalographic recording under anesthetic conditions comparable to those used for phMRI, together with the corresponding Fos immunoreactivity distribution. MOD produced electroencephalogram desynchronization, resulting in reduced delta and increased theta frequency bands, and a pattern of Fos induction largely consistent with the phMRI study. Altogether, these findings show that clinically relevant MOD doses can robustly activate fronto-cortical areas involved in higher cognitive functions and a network of pro-arousing areas, which provide a plausible substrate for the wake-promoting and pro-cognitive effects of the drug.
- Published
- 2012
- Full Text
- View/download PDF
164. TESTING THE EFFECTS OF ELEVATED PCO2 ON COCCOLITHOPHORES (PRYMNESIOPHYCEAE): COMPARISON BETWEEN HAPLOID AND DIPLOID LIFE STAGES(1).
- Author
-
Fiorini S, Middelburg JJ, and Gattuso JP
- Abstract
The response of Emiliania huxleyi (Lohmann) W. W. Hay et H. Mohler, Calcidiscus leptoporus (G. Murray et V. H. Blackman) J. Schiller, and Syracosphaera pulchra Lohmann to elevated partial pressure of carbon dioxide (pCO2 ) was investigated in batch cultures. We reported on the response of both haploid and diploid life stages of these three species. Growth rate, cell size, particulate inorganic carbon (PIC), and particulate organic carbon (POC) of both life stages were measured at two different pCO2 (400 and 760 parts per million [ppm]), and their organic and inorganic carbon production were calculated. The two life stages within the same species generally exhibited a similar response to elevated pCO2 , the response of the haploid stage being often more pronounced than that of the diploid stage. The growth rate was consistently higher at elevated pCO2 , but the response of other processes varied among species. Calcification rate of C. leptoporus and of S. pulchra did not change at elevated pCO2 , whereas it increased in E. huxleyi. POC production and cell size of both life stages of S. pulchra and of the haploid stage of E. huxleyi markedly decreased at elevated pCO2 . It remained unaltered in the diploid stage of E. huxleyi and C. leptoporus and increased in the haploid stage of the latter. The PIC:POC ratio increased in E. huxleyi and was constant in C. leptoporus and S. pulchra. Elevated pCO2 has a significant effect on these three coccolithophore species, the haploid stage being more sensitive. This effect must be taken into account when predicting the fate of coccolithophores in the future ocean., (© 2011 Phycological Society of America.)
- Published
- 2011
- Full Text
- View/download PDF
165. DCE-MRI using small-molecular and albumin-binding contrast agents in experimental carcinomas with different stromal content.
- Author
-
Farace P, Merigo F, Fiorini S, Nicolato E, Tambalo S, Daducci A, Degrassi A, Sbarbati A, Rubello D, and Marzola P
- Subjects
- Animals, Cell Line, Tumor, Image Enhancement methods, Image Interpretation, Computer-Assisted, Immunoenzyme Techniques, Male, Mice, Mice, Nude, Pancreatic Neoplasms diagnosis, Prostatic Neoplasms diagnosis, Contrast Media, Gadolinium, Gadolinium DTPA, Magnetic Resonance Imaging methods, Neoplasms, Experimental diagnosis, Organometallic Compounds
- Abstract
Objectives: To compare DCE-MRI experiments performed using a standard small-molecular (Gd-DTPA) and an albumin-binding (MS-325) contrast agent in two carcinoma models with different stromal content., Materials and Methods: DU-145 or BXPC-3 cancer cells were subcutaneously injected into nude mice. DCE-MRI was performed by a bolus injection of Gd-DTPA or MS-325 about 2 weeks after inoculation. For quantitative analysis a volume of interest was manually drawn over each tumor. To address the heterogeneous enhancement, each tumor volume was then divided into the 20% most-enhancing and the remaining 80% least-enhancing fractions. Mean tumor enhancement was calculated over these selected tumor volumes and compared between tumor groups and contrast agents. Maps of differential enhancement, peak enhancement and time-to-peak were used for visual evaluation. CD31 and VEGF immunohistochemistry were performed in excised tumors., Results: In the 80% least-enhancing volume, at late time points of the dynamic scan, the mean enhancement elicited by MS-325 was higher in BXPC-3 than in DU-145 tumors. In the 20% most-enhancing volume, using either contrast agents, significant difference between the two tumors types were observed only early, while at later time points of the dynamic scan the difference were obscured by the faster washout observed in the BXPC-3 tumors. Enhancement maps confirmed that BXPC-3 tumors were characterized by marked washout rate using either contrast agent, particularly in the higher enhancing peripheral rim. With MS-325 this washout pattern appeared to be specific to the BXPC-3 carcinomas, since it was not observed in the DU-145 tumors. Finally, in both tumor types, MS-325 produced significantly higher enhancement than Gd-DTPA in the late phase of the dynamic scan. Ex vivo analysis confirmed the marked presence of aberrant infiltrative stroma in BXPC-3 tumors, in which tumor vessels were embedded. In all tumors the central portion was less viable and less infiltrated by stromal tissue then the peripheral areas., Conclusions: Contrast distribution proved to be related to stromal content, which presumably produced the higher enhancement and faster washout observed in the BXPC-3 tumors. In particular, 'early' contrast-enhanced MRI, appeared as the most sensitive technique to detect the tumor portions characterized by a high stromal content, i.e. the peripheral rim of the BXPC-3 tumors. Since the same tumor models were recently investigated using FDG-PET imaging, showing inverse relationship between FDG uptake and stromal content, contrast-enhanced MRI and FDG-PET could provide complementary and comprehensive sensitivity in the assessment of carcinomas., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
166. Early versus late GD-DTPA MRI enhancement in experimental glioblastomas.
- Author
-
Farace P, Tambalo S, Fiorini S, Merigo F, Daducci A, Nicolato E, Conti G, Degrassi A, Sbarbati A, and Marzola P
- Subjects
- Animals, Brain Neoplasms diagnosis, Cell Line, Tumor, Edema, Glioblastoma diagnosis, Humans, Image Processing, Computer-Assisted, Male, Mice, Mice, Inbred BALB C, Neoplasm Transplantation, Neoplasms, Experimental pathology, Brain Neoplasms pathology, Contrast Media pharmacology, Gadolinium DTPA pharmacology, Glioblastoma pathology, Magnetic Resonance Imaging methods
- Abstract
Purpose: To compare early versus late enhancement in two glioblastoma models characterized by different infiltrative/edematous patterns., Materials and Methods: Three weeks after inoculation into nude mice of U87MG and U251 cells, T1-weighted images were acquired early (10.5 min), intermediate (21 min) and late (30.5 min) after a bolus injection of Gd-DTPA at 300 μ mol/kg dosage. EARLY(TH) and LATE(TH) were the corresponding volumes with an enhancement higher than a threshold TH, defined by the mean (μ) and standard deviation (σ) on a contralateral healthy area. ADD(TH) was the enhancing volume found in LATE(TH) but not in EARLY(TH). T2 imaging of both tumors was performed, and T2 mapping of U251., Results: In all tumors, LATE(TH) was significantly higher than EARLY(TH) for TH ranging from μ+σ to μ+5σ. The ADD(TH) /EARLY(TH) ratio was not significantly different when U251 and U87MG tumors were compared. In the U87MG tumors, some enhancement was observed outside the regularly demarcated T2-hyperintense area. In the U251 tumors, irregularly T2 demarcated, a large portion of ADD(μ+3σ) had normal T2 values. At histology, U251 showed a higher infiltrative pattern than U87MG., Conclusion: In these models, the increase over time in the enhancing volume did not depend on the different infiltrative/edematous patterns and was not closely related with edema., (Copyright © 2011 Wiley-Liss, Inc.)
- Published
- 2011
- Full Text
- View/download PDF
167. Investigation of adipose tissues in Zucker rats using in vivo and ex vivo magnetic resonance spectroscopy.
- Author
-
Mosconi E, Fontanella M, Sima DM, Van Huffel S, Fiorini S, Sbarbati A, and Marzola P
- Subjects
- Animals, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy methods, Male, Rats, Rats, Zucker, Triglycerides analysis, Adipose Tissue chemistry, Adipose Tissue, Brown chemistry, Adipose Tissue, White chemistry, Fatty Acids analysis, Fatty Acids, Unsaturated analysis, Lipids analysis
- Abstract
In vivo single-voxel magnetic resonance spectroscopy (MRS) at 4.7T and ex vivo high-resolution proton magnetic resonance spectroscopy (HR-NMR) at 500 MHz were used to study the composition of adipose tissues in Zucker obese and Zucker lean rats. Lipid composition was characterized by unsaturation and polyunsaturation indexes and mean chain lengths. In vitro experiments were conducted in known mixtures of triglycerides and oils in order to validate the method. To avoid inaccuracies due to partial peak overlapping in MRS, peak quantification was performed after fitting of spectral peaks by using the QUEST algorithm. The intensity of different spectral lines was also corrected for T2 relaxation. Albeit with different sensitivity and accuracy, both techniques revealed that white adipose tissue is characterized by lower unsaturation and polyunsaturation indexes in obese rats compared with controls. HR-NMR revealed similar differences in brown adipose tissue. The present findings confirm the hypothesis that obese and lean Zucker rats have different adipose tissue composition.
- Published
- 2011
- Full Text
- View/download PDF
168. Response of the calcifying coccolithophore Emiliania huxleyi to low pH/high pCO 2 : from physiology to molecular level.
- Author
-
Richier S, Fiorini S, Kerros ME, von Dassow P, and Gattuso JP
- Abstract
The emergence of ocean acidification as a significant threat to calcifying organisms in marine ecosystems creates a pressing need to understand the physiological and molecular mechanisms by which calcification is affected by environmental parameters. We report here, for the first time, changes in gene expression induced by variations in pH/pCO
2 in the widespread and abundant coccolithophore Emiliania huxleyi . Batch cultures were subjected to increased partial pressure of CO2 (pCO2 ; i.e. decreased pH), and the changes in expression of four functional gene classes directly or indirectly related to calcification were investigated. Increased pCO2 did not affect the calcification rate and only carbonic anhydrase transcripts exhibited a significant down-regulation. Our observation that elevated pCO2 induces only limited changes in the transcription of several transporters of calcium and bicarbonate gives new significant elements to understand cellular mechanisms underlying the early response of E. huxleyi to CO2 -driven ocean acidification.- Published
- 2011
- Full Text
- View/download PDF
169. Washout of small molecular contrast agent in carcinoma-derived experimental tumors.
- Author
-
Galiè M, Farace P, Merigo F, Fiorini S, Tambalo S, Nicolato E, Sbarbati A, and Marzola P
- Subjects
- Animals, Female, Lymphatic Vessels pathology, Mammary Neoplasms, Experimental blood supply, Mammary Neoplasms, Experimental immunology, Mice, Mice, Inbred Strains, Microvessels pathology, Neoplasm Transplantation, Neovascularization, Pathologic pathology, Contrast Media pharmacokinetics, Gadolinium DTPA pharmacokinetics, Mammary Neoplasms, Experimental diagnosis
- Abstract
The use of contrast-enhanced magnetic resonance imaging (MRI) for the assessment of breast carcinomas reveals satisfactory sensitivity, but due to low specificity, it does not obviate the need for subsequent tissue sampling. Its capability to differentiate benign from malignant lesion is under continuous investigation. Dynamic contrast-enhanced MRI (DCE-MRI) could improve specificity of MRI through the analysis of the kinetic of contrast enhancement. In particular, the study of the washout pattern is considered a promising tool to improve in vivo diagnosis and even to evaluate the response under chemotherapy. To provide a comprehensive characterization of this parameter in malignant tumor models, in vivo mapping of the washout of small molecular contrast agent (Gd-DTPA, molecular weight 0.57 kDa) was carried out in three transplanted/spontaneous mammary tumors, which differed in their histopathological and microvascular features. It resulted that in all models around 40% of tumor volume lacks efficient washout; washout areas are frequently, but not always, restricted to the tumor periphery and that non-washout areas are not restricted to necrotic regions. Difference in the distribution of lymphatic vessels characterized spontaneous vs. transplanted tumors but did not produce a corresponding different washout pattern, confirming that Gd-DTPA drainage does not mainly depend on lymphatic architecture. Finally, the efficiency of washout is correlated with parameters obtainable during the earlier phases of the enhancement curve and in malignant tumors it could be indirectly estimated from them.
- Published
- 2009
- Full Text
- View/download PDF
170. Further studies at neuropeptide s position 5: discovery of novel neuropeptide S receptor antagonists.
- Author
-
Guerrini R, Camarda V, Trapella C, Caló G, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, and Salvadori S
- Subjects
- Calcium analysis, Cell Line, Drug Discovery, Humans, Structure-Activity Relationship, Neuropeptides chemistry, Receptors, G-Protein-Coupled antagonists & inhibitors
- Abstract
Neuropeptide S (NPS) regulates various biological functions by activating the NPS receptor (NPSR). Previous studies demonstrated that the substitution of Gly(5) with d-amino acids generates NPSR antagonists. Eleven [d-Xaa(5)]NPS derivatives were synthesized and pharmacologically tested measuring [Ca(2+)](i) in HEK293(mNPSR) cells. The results confirmed that the [d-Xaa(5)] substitution promotes antagonist activity with potency inversely related to the side chain size and allowed identification of the novel potent NPSR peptide antagonist [(t)Bu-d-Gly(5)]NPS.
- Published
- 2009
- Full Text
- View/download PDF
171. In vivo visualization of transplanted pancreatic islets by MRI: comparison between in vivo, histological and electron microscopy findings.
- Author
-
Marzola P, Longoni B, Szilagyi E, Merigo F, Nicolato E, Fiorini S, Paoli GT, Benati D, Mosca F, and Sbarbati A
- Subjects
- Animals, Immunohistochemistry, Rats, Rats, Sprague-Dawley, Rats, Wistar, Tissue Survival, Islets of Langerhans cytology, Islets of Langerhans ultrastructure, Islets of Langerhans Transplantation, Magnetic Resonance Imaging, Microscopy, Electron
- Abstract
The aim of the work was to compare in vivo MRI visualization of pancreatic islets labeled with clinical-grade superparamagnetic iron oxide (SPIOs) contrast agents with ex vivo examination of liver tissue in an experimental model of marginal mass transplantation in rats. Seven hundred IEq (Islet Equivalent) from Wistar rats, labeled by incubation with Endorem or Resovist, were transplanted into Sprague-Dawley rats through the portal vein. Liver MR images of recipient rats were acquired at different time points (3-42 days) after transplantation. Animals were sacrificed during this period and their livers were excised and prepared for histology and electron microscopy. Hypointense spots originating from iron particles were observed in MR images. The number of separate spots was counted. Three days after transplantation one spot for every three or four transplanted islets was observed. Seven days after transplantation, histological sections showed the presence of iron within pancreatic islets. The time course of MR images showed a decrease in the number of spots, at 42 days, amounting to 65 and 22% of the initial value, for Resovist and Endorem respectively, while no immunopositive endocrine cells were detected in histological slices. The present work shows that pancreatic islets can be labeled using clinically approved SPIO contrast agents and visualized using in vivo MRI with high sensitivity, consistently with findings in the literature. Differently from reports in the literature, our findings indicate that iron particles could last in the liver for long periods, independently of the presence of intact pancreatic islets., (Copyright (c) 2009 John Wiley & Sons, Ltd.)
- Published
- 2009
- Full Text
- View/download PDF
172. Evaluation of cryopreserved donor skin viability: the experience of the regional tissue bank of Verona.
- Author
-
Franchini M, Zanini D, Bosinelli A, Fiorini S, Rizzi S, D'Aloja C, Vassanelli A, Gandini G, and Aprili G
- Subjects
- Algorithms, Cadaver, Humans, Indicators and Reagents pharmacokinetics, Italy, Retrospective Studies, Tetrazolium Salts, Tissue Preservation methods, Transplantation, Homologous, Burns surgery, Cell Survival, Cryopreservation methods, Skin, Skin Transplantation, Tissue Banks
- Abstract
Background: Allogeneic human skin removed from cadaveric donors is the covering of choice for deep burns, since it accelerates the re-epithelialisation of autologous skin. In this study we evaluated the cellular viability of cryopreserved skin at the regional tissue bank of Verona (Italy)., Methods: From 1st June 2007 to 30th September 2007, tests of cutaneous cell viability were carried out on 21 consecutive skin donors using the MTT (tetrazolium salt) method on samples prior to freezing and on thawed samples after a period of cryopreservation., Results: The mean percentage viability was 45.1% (+/-20.1%), which is similar to results obtained in other tissue banks. It was noted that viability decreased with increasing age of the donor., Conclusions: The results of the evaluation of cutaneous cell viability document the validity of the skin cryopreservation procedure in use at the tissue bank in Verona.
- Published
- 2009
- Full Text
- View/download PDF
173. Synthesis and biological activity of human neuropeptide S analogues modified in position 5: identification of potent and pure neuropeptide S receptor antagonists.
- Author
-
Guerrini R, Camarda V, Trapella C, Calò G, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, and Salvadori S
- Subjects
- Amino Acid Sequence, Animals, Cell Line, Dose-Response Relationship, Drug, Humans, Locomotion drug effects, Male, Mice, Molecular Sequence Data, Neuropeptides chemical synthesis, Structure-Activity Relationship, Neuropeptides chemistry, Neuropeptides pharmacology, Receptors, G-Protein-Coupled antagonists & inhibitors
- Abstract
Neuropeptide S (NPS), the endogenous ligand of a previously orphan receptor now named NPSR, regulates various biological functions in the brain, including arousal, locomotion, anxiety, and food intake. Here we report on a focused structure-activity study of Gly5, which has been replaced with L and D amino acids. Fifteen NPS related peptides were synthesized and pharmacologically tested for intracellular calcium mobilization using HEK293 cells stably expressing the mouse NPSR. The results of this study demonstrated that peptide potency is inversely related to the side chain size, while peptide efficacy strongly depends on the relative L and D configuration, with the L amino acids favoring agonist while D amino acids display antagonist pharmacological activity. [D-Val5]NPS behaved as NPSR pure antagonist in HEK293(mNPSR) cells showing the highest potency (pK(B) 7.56) among this series of peptides. The antagonist action of [D-Val5]NPS was confirmed in vivo in mice, where the peptide at a dose of 10 nmol completely blocked the stimulatory effect of 0.1 nmol NPS on locomotor activity.
- Published
- 2009
- Full Text
- View/download PDF
174. [Nasal septal abscess].
- Author
-
Barril MF, Ferolla FM, José P, Echave C, Tomezzoli S, Fiorini S, and López EL
- Subjects
- Child, Community-Acquired Infections diagnosis, Community-Acquired Infections therapy, Humans, Male, Abscess diagnosis, Abscess therapy, Methicillin-Resistant Staphylococcus aureus, Nasal Septum, Staphylococcal Infections diagnosis, Staphylococcal Infections therapy
- Abstract
A nasal septal abscess (NA) is defined as a collection of pus between the cartilage or bony septum and its normally applied mucoperichondrium or mucoperiostium. It is an uncommon disease which should be suspected in a patient with acute onset of nasal obstruction and recent history of nasal trauma, periodontal infection or an inflammatory process of the rhinosinusal region. We report a case of an 8-year-old boy with bilateral NA caused by community-acquired methicillin-resistant Staphylococcus aureus(MR-CO) in order to emphasize the importance of prompt diagnosis and adequate treatment to prevent the potentially dangerous spread of infection and the development of severe functional and cosmetic sequelae.
- Published
- 2008
- Full Text
- View/download PDF
175. New implications in the use of imposex as a suitable tool for tributyltin contamination: experimental induction in Hexaplex trunculus (Gastropoda, Muricidae) with different stressors.
- Author
-
Garaventa F, Centanni E, Fiorini S, Noventa S, Terlizzi A, Faimali M, and Pavoni B
- Subjects
- Animals, Disorders of Sex Development, Female, Male, Organotin Compounds analysis, Polychlorinated Biphenyls analysis, Polychlorinated Biphenyls toxicity, Trialkyltin Compounds toxicity, Vas Deferens drug effects, Environmental Monitoring methods, Gastropoda drug effects, Gastropoda growth & development, Trialkyltin Compounds analysis, Water Pollutants, Chemical toxicity
- Abstract
Imposex, i.e. the development of additional male sex organs (penis and/or vas deferens), in females of gonochorist marine and freshwater gastropods, is known to be caused by tributyltin (TBT), and it has been widely used as a biomonitoring tool in environmental surveys for TBT pollution assessment. In this study, we experimentally tested the potential to induce imposex by another endocrine disruptor (polychlorinated biphenyls [PCBs] mixture--Aroclor 1260). Adults of Hexaplex trunculus with low imposex level, coming from an Italian Marine Protected Area, were injected separately with different doses of tributyltin chloride (TBTCl) and Aroclor 1260. The compounds were dissolved in ethanol and the organisms were narcotised by immersion in MgCl(2) solution before injection. Before and after the experiment, butyltin compounds (BuTs) and PCB tissue concentrations were determined. A significant increase in imposex with respect to non-treated organisms was observed in all treatments, including artefact controls. No clear correlation was observed between BuTs and PCB tissue concentrations and indices of imposex incidence. Based on these results, no assumption can be formulated about PCB effect on imposex development. Nevertheless, they suggest that the imposex level increase, at least in H. trunculus, in laboratory conditions might not be caused by TBT only, but it would rather be a non-specific response to different stress stimuli.
- Published
- 2008
- Full Text
- View/download PDF
176. [Superior mesenteric artery syndrome (Wilkie syndrome): case report].
- Author
-
Fiorini S, Sáenz Tejeira MM, Tennina C, Tomezzoli S, and Requejo N
- Subjects
- Adolescent, Humans, Male, Scoliosis surgery, Postoperative Complications diagnosis, Postoperative Complications therapy, Superior Mesenteric Artery Syndrome diagnosis, Superior Mesenteric Artery Syndrome therapy
- Abstract
Superior mesenteric artery syndrome is an uncommon cause of upper gastrointestinal tract obstruction. The syndrome results from compression of the third portion of duodenum as it crosses underneath the superior mesenteric artery, related to conditions that reduce the aortomesenteric angle (acute weight loss) or after scoliosis surgery. Patients may present symptoms of gastrointestinal obstruction, such as upper abdominal distension and epigastric tenderness, usually relieved by posture changing. Diagnose must be complemented with an upper gastrointestinal barium-contrast radiography. Conservative treatment is usually effective with early diagnosis. Surgery is needed when conservative measures are ineffective. We present the case of a 18 year-old patient with Wilkie's syndrome secondary to scoliosis surgery. The patient presented symptoms of gastrointestinal obstruction, and diagnosis was confirmed with upper gastrointestinal barium-contrast radiography. The patient started conservative treatment with proper positioning after eating and nutritional support to provide optimal calories supply.
- Published
- 2008
- Full Text
- View/download PDF
177. Structure-activity study at positions 3 and 4 of human neuropeptide S.
- Author
-
Camarda V, Trapella C, Calo' G, Guerrini R, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, and Salvadori S
- Subjects
- Amino Acid Sequence, Arginine chemistry, Arginine metabolism, Asparagine chemistry, Asparagine metabolism, Binding Sites, Calcium metabolism, Cell Line, Humans, Kidney embryology, Kidney metabolism, Kidney pathology, Ligands, Molecular Sequence Data, Neuropeptides chemical synthesis, Phenylalanine chemistry, Phenylalanine metabolism, Structure-Activity Relationship, Amino Acid Substitution, Neuropeptides pharmacology
- Abstract
Neuropeptide S (NPS) has been identified as the endogenous ligand of a previously orphan receptor now named NPSR. Previous studies demonstrated that the N-terminal sequence Phe(2)-Arg(3)-Asn(4) of the peptide is crucial for biological activity. Here, we report on a focused structure-activity study of Arg(3) and Asn(4) that have been replaced with a series of coded and non-coded amino acids. Thirty-eight human NPS analogues were synthesized and pharmacologically tested for intracellular calcium mobilization using HEK293 cells stably expressing the mouse NPSR. The results of this study demonstrated the following NPS position 3 structure-activity features: (i) the guanidine moiety and its basic character are not crucial requirements, (ii) an aliphatic amino acid with a linear three carbon atom long side chain is sufficient to bind and fully activate NPSR, (iii) the receptor pocket allocating the position 3 side chain can accommodate slightly larger side chains at least to a certain degree [hArg, Arg(NO2) or Arg(Me)2 but not Arg(Tos)]. Position 4 seems to be more sensitive to amino acids replacement compared to position 3; in fact, all the amino acid replacements investigated produced either an important decrease of biological activity or generated inactive derivatives suggesting a pivotal role of the Asn(4) side chain for NPS bioactivity.
- Published
- 2008
- Full Text
- View/download PDF
178. Further studies on lead compounds containing the opioid pharmacophore Dmt-Tic.
- Author
-
Balboni G, Fiorini S, Baldisserotto A, Trapella C, Sasaki Y, Ambo A, Marczak ED, Lazarus LH, and Salvadori S
- Subjects
- Analgesics pharmacology, Animals, Mice, Receptors, Opioid, delta antagonists & inhibitors, Receptors, Opioid, delta metabolism, Receptors, Opioid, mu metabolism, Structure-Activity Relationship, Tail drug effects, Dipeptides chemistry, Dipeptides metabolism, Receptors, Opioid, delta agonists, Tetrahydroisoquinolines chemistry, Tetrahydroisoquinolines metabolism
- Abstract
Some reference opioids containing the Dmt-Tic pharmacophore, especially the delta agonists H-Dmt-Tic-Gly-NH-Ph (1) and H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid (4) (UFP-512) were evaluated for the influence of the substitution of Gly with aspartic acid, its chirality, and the importance of the -NH-Ph and N(1)H-Bid hydrogens in the inductions of delta agonism. The results provide the following conclusions: (i) Asp increases delta selectivity by lowering the mu affinity; (ii) -NH-Ph and N(1)H-Bid nitrogens methylation transforms the delta agonists into delta antagonists; (iii) the substitution of Gly with L-Asp/D-Asp in the delta agonist H-Dmt-Tic-Gly-NH-Ph gave delta antagonists; the same substitution in the delta agonist H-Dmt-Tic-NH-CH2-Bid yielded more selective agonists, H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid and H-Dmt-Tic-NH-(R)CH(CH2-COOH)-Bid; (iv) L-Asp seems important only in functional bioactivity, not in receptor affinity; (v) H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid(N(1)-Me) (10) evidenced analgesia similar to 4, which was reversed by naltrindole only in the tail flick. 4 and 10 had opposite behaviours in mice; 4 caused agitation, 10 gave sedation and convulsions.
- Published
- 2008
- Full Text
- View/download PDF
179. Secretion of Epstein-Barr virus-encoded BARF1 oncoprotein from latently infected B cells.
- Author
-
Fiorini S and Ooka T
- Subjects
- Blotting, Western, Cell Line, Chromatography, Affinity, Culture Media chemistry, Gene Expression Profiling, Humans, Malawi, RNA, Messenger biosynthesis, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction, Viral Proteins genetics, Viral Proteins isolation & purification, B-Lymphocytes virology, Herpesvirus 4, Human physiology, Viral Proteins biosynthesis
- Abstract
Epstein-Barr virus (EBV) encodes two oncogenes, LMP1(Latent Membrane Protein-1) and BARF1 (BamH1-A Reading Frame-1). LMP1 belongs to latent gene family and BARF1 is considered so far as one of early gene family. However BARF1 oncogene was expressed highly in Nasopharyngeal (NPC) and gastric (GC) carcinoma as a type II latency, and in EBV-positive Akata cell and primary epithelial cell infected in vitro by EBV as type I latency. Its expression was also reported in Burkitt's lymphoma's biopsy frequent in Malawi in Africa as well as in nasal NK/T-cell lymphoma. We recently observed a massive secretion of BARF1 protein in serum and saliva of NPC patients. NPC-derived c666-1 epithelial cells also expressed and secreted BARF1 protein without other lytic genes expression. We asked whether this oncogene belongs to latent gene family. To investigate, we examined its transcriptional and translational expression in IB4 and Akata B cells where both cell lines belong to latent cell family. Transcriptional expression was analyzed by RT-PCR. As BARF1 protein is one of secreted proteins, its translational expression was analyzed by immunoblot after concentration of culture medium. Secreted BARF1 protein was futher purified by concanavalin A affinity column. BARF1 was transcribed in both EBV-positive AKATA and IB4 cells, and BARF1 protein was secreted from these latently infected human B cells. Its secretion does not depend EBV genome form in infected cells. Both episomal and integrated form of EBV genome were capable of expressing BARF1 gene. These results suggests that BARF1 is expressed in latent stage and increases its expression during lytic stage.
- Published
- 2008
- Full Text
- View/download PDF
180. [Acute abdomen as initial manifestation of meningococcemia].
- Author
-
Tomezzoli S, Juárez Mdel V, Rossi SI, Lema DA, Barbaro CR, and Fiorini S
- Subjects
- Child, Preschool, Humans, Male, Abdomen, Acute microbiology, Bacteremia complications, Bacteremia diagnosis, Meningococcal Infections complications, Meningococcal Infections diagnosis, Neisseria meningitidis
- Abstract
Abdominal pain as an initial symptom of meningococcemia is an infrequent entity, rarely described in literature. We present a case of a 4 year-old, male, previously healthy child with a 24 hour history of fever and abdominal pain. He is admitted in a surgical unit with a diagnosis of acute abdomen for surgical resolution. The clinical course turns unfavorably, and patient presents signs of severe sepsis. Urgent laparotomy is performed, observing little brownish fluid and mesenteric adenitis. He then exhibits palpable purpuric rapidly progressive lesions in lower extremities, progressing to septic shock. Later, Neisseria meningitidis serogroup B is isolated from blood cultures. The aim of this article is drawing attention to a nontypical form of manifestation of meningococcemia, as a delayed diagnosis and treatment has an impact on morbidity and mortality among the pediatric population.
- Published
- 2008
- Full Text
- View/download PDF
181. Tumor microvasculature observed using different contrast agents: a comparison between Gd-DTPA-Albumin and B-22956/1 in an experimental model of mammary carcinoma.
- Author
-
Boschi F, Marzola P, Sandri M, Nicolato E, Galiè M, Fiorini S, Merigo F, Lorusso V, Chaabane L, and Sbarbati A
- Subjects
- Animals, Contrast Media therapeutic use, Female, Image Enhancement, Magnetic Resonance Imaging methods, Mammary Neoplasms, Experimental blood supply, Mice, Albumins, Gadolinium DTPA, Mammary Neoplasms, Experimental pathology, Neovascularization, Pathologic, Organometallic Compounds
- Abstract
Objective: The aim of this study was to compare a pure macromolecular contrast agent (Gd-DTPA-albumin) with a new protein-binding blood pool contrast agent (B22956/1) in terms of their capacity to investigate the microvasculature in an experimental model of mammary carcinoma., Materials and Methods: Tumors were induced by subcutaneous injection of 5 x 10(5) BB1 cells into the backs of 5-7 week-old female FVB/neuNT233 mice. The animals were observed using DCE-MRI when the longest diameter of the tumor was 10.2+/-2.0 mm. DCE-MRI experiments were carried out using B22956/1 and (24 h later) Gd-DTPA-albumin., Results: DCE-MRI data showed that vasculature in the tumor rim was characterized by greater fractional plasma volume and transendothelial permeability than vasculature in the tumor core as measured by both contrast agents. Permeability to Gd-DTPA-albumin in the tumor core was hardly measurable while permeability to B22956/1 was substantial. Histologically the tumor core showed areas of well vascularized, viable tissue surrounded by necrotic regions., Conclusions: DCE-MRI experiments performed with B22956/1 are useful in the investigation of vasculature in those tumor regions that are characterized by low permeability to macromolecules.
- Published
- 2008
- Full Text
- View/download PDF
182. Role of benzimidazole (Bid) in the delta-opioid agonist pseudopeptide H-Dmt-Tic-NH-CH(2)-Bid (UFP-502).
- Author
-
Salvadori S, Fiorini S, Trapella C, Porreca F, Davis P, Sasaki Y, Ambo A, Marczak ED, Lazarus LH, and Balboni G
- Subjects
- Animals, Brain-Derived Neurotrophic Factor genetics, Humans, RNA, Messenger drug effects, Structure-Activity Relationship, Up-Regulation drug effects, Up-Regulation genetics, Benzimidazoles, Molecular Mimicry, Opioid Peptides chemistry, Receptors, Opioid, delta agonists
- Abstract
H-Dmt-Tic-NH-CH(2)-Bid (UFP-502) was the first delta-opioid agonist prepared from the Dmt-Tic pharmacophore. It showed interesting pharmacological properties, such as stimulation of mRNA BDNF expression and antidepression. To evaluate the importance of 1H-benzimidazol-2-yl (Bid) in the induction of delta-agonism, it was substituted by similar heterocycles: The substitution of NH(1) by O or S transforms the reference delta-agonist into delta-antagonists. Phenyl ring of benzimidazole is not important for delta-agonism; in fact 1H-imidazole-2-yl retains delta-agonist activity.
- Published
- 2008
- Full Text
- View/download PDF
183. Vinyl ester-based cyclic peptide proteasome inhibitors.
- Author
-
Baldisserotto A, Marastoni M, Fiorini S, Pretto L, Ferretti V, Gavioli R, and Tomatis R
- Subjects
- Chromatography, High Pressure Liquid, Chymotrypsin metabolism, Cyclization, Endopeptidases metabolism, Humans, Magnetic Resonance Spectroscopy, Models, Chemical, Molecular Structure, Peptides, Cyclic chemistry, Peptides, Cyclic pharmacology, Protease Inhibitors chemical synthesis, Protease Inhibitors chemistry, Protein Conformation, Spectrometry, Mass, Electrospray Ionization, Trypsin metabolism, Vinyl Compounds chemistry, Vinyl Compounds pharmacology, Esters chemistry, Peptides, Cyclic chemical synthesis, Protease Inhibitors pharmacology, Proteasome Inhibitors, Vinyl Compounds chemical synthesis
- Abstract
The 20S proteasome is a multicatalytic protease complex responsible for the degradation of many proteins in mammalian cells. Specific inhibition of proteasome enzymatic subunits represents a topic of great interest for the development of new drug therapies. Following our previous development of a new class of peptide-based inhibitors bearing a C-terminal vinyl ester residue as a pharmacophoric unit that are able to interact with the catalytic threonine, we report here the synthesis and biological properties of a new series of vinyl ester cyclopeptide analogues. Some of these derivatives were shown to inhibit the chymotrypsin-like activity of the proteasome at nanomolar concentration and their potency was found to depend on the size of the tetrapeptidic cyclic portion.
- Published
- 2008
- Full Text
- View/download PDF
184. Synthesis and biological activity of human neuropeptide S analogues modified in position 2.
- Author
-
Camarda V, Trapella C, Calo G, Guerrini R, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, and Salvadori S
- Subjects
- Amino Acid Substitution, Animals, Calcium metabolism, Cell Line, Humans, Mice, Neuropeptides chemistry, Neuropeptides pharmacology, Phenylalanine chemistry, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled metabolism, Structure-Activity Relationship, Neuropeptides chemical synthesis
- Abstract
Neuropeptide S (NPS) has been identified as the endogenous ligand of a previously orphan receptor now named NPSR. Previous studies demonstrated that the N-terminal sequence Phe (2)-Arg(3)-Asn(4) of the peptide is crucial for biological activity. Here we report on a focused structure-activity study of Phe(2) which has been replaced with a series of coded and noncoded amino acids. Thirty-one human NPS analogues were synthesized and pharmacologically tested for intracellular calcium mobilization by using HEK293 cells stably expressing the mouse NPSR. The results of this study demonstrated the following NPS position 2 structure-activity features: (i) lipophilicity but not aromaticity is crucial, (ii) both the size of the chemical moiety and its distance from the peptide backbone are important for biological activity, and (iii) this position plays a role in both receptor binding and activation, since [4,4'-biphenyl-Ala(2)]hNPS behaved as a partial agonist.
- Published
- 2008
- Full Text
- View/download PDF
185. A new opioid designed multiple ligand derived from the micro opioid agonist endomorphin-2 and the delta opioid antagonist pharmacophore Dmt-Tic.
- Author
-
Salvadori S, Trapella C, Fiorini S, Negri L, Lattanzi R, Bryant SD, Jinsmaa Y, Lazarus LH, and Balboni G
- Subjects
- Dipeptides chemistry, Drug Design, Ligands, Molecular Structure, Oligopeptides chemistry, Structure-Activity Relationship, Tetrahydroisoquinolines chemistry, Dipeptides chemical synthesis, Dipeptides pharmacology, Oligopeptides chemical synthesis, Oligopeptides pharmacology, Receptors, Opioid, delta antagonists & inhibitors, Receptors, Opioid, mu agonists, Tetrahydroisoquinolines chemical synthesis, Tetrahydroisoquinolines pharmacology
- Abstract
Opioid compounds with mixed micro agonist/delta antagonist properties could be used as analgesics with low propensity to induce tolerance and dependence. Here we report the synthesis of a new designed multiple ligand deriving from the micro selective agonist endomorphin-2 and the delta selective antagonist pharmacophore Dmt-Tic. As predicted, the resulting bivalent ligand showed a micro agonist/delta antagonist profile deriving from the corresponding activities of each pharmacophore.
- Published
- 2007
- Full Text
- View/download PDF
186. A new diagnostic marker for secreted Epstein-Barr virus encoded LMP1 and BARF1 oncoproteins in the serum and saliva of patients with nasopharyngeal carcinoma.
- Author
-
Houali K, Wang X, Shimizu Y, Djennaoui D, Nicholls J, Fiorini S, Bouguermouh A, and Ooka T
- Subjects
- Adult, Animals, Antigens, CD analysis, Cell Line, Tumor, Enzyme-Linked Immunosorbent Assay, Humans, Lymphocyte Activation, Mice, Mitogens pharmacology, Nasopharyngeal Neoplasms virology, Platelet Membrane Glycoproteins analysis, Tetraspanin 30, Viral Matrix Proteins blood, Viral Matrix Proteins pharmacology, Viral Proteins blood, Viral Proteins pharmacology, Nasopharyngeal Neoplasms diagnosis, Saliva chemistry, Viral Matrix Proteins analysis, Viral Proteins analysis
- Abstract
Purpose: EBV has been associated with nasopharyngeal carcinomas (NPC). In North Africa, the incidence is bimodal-the first peak occurring at approximately 20 years of age and the second peak occurring at approximately 50 years. Standard diagnostic tests based on immunofluorescence using anti-IgA EBV have shown that young North African patients have a negative serology compared with older patients. We are interested in two EBV-encoded oncoproteins, LMP1 and BARF1, which have thus far not been studied in terms of their potential as diagnostic markers for NPC. These two viral oncoproteins have been detected in cell culture media, so we tested whether they could be detected in the serum and saliva of patients with NPC., Experimental Design: LMP1 and BARF1 proteins were analyzed in the sera and saliva of young patients and adult patients with NPC from North Africa and China. We then examined whether the secreted proteins had biological activity by analyzing their mitogenic activity., Results: Both LMP1 and BARF1 were present in the serum and saliva from North African and Chinese patients with NPC. All young North African patients secreted both proteins, whereas 62% and 100% of adult patients secreted LMP1 and BARF1, respectively. From animal studies, the secreted LMP1 was associated with exosome-like vesicles. These secreted EBV oncoproteins showed a powerful mitogenic activity in B cells., Conclusion: Both proteins will be a good diagnostic marker for NPC whereas BARF1 is a particularly promising marker for all ages of patients with NPC. Their mitogenic activity suggests their implication in the oncogenic development of NPC.
- Published
- 2007
- Full Text
- View/download PDF
187. Ethnicity and biodemographic structure in the Arbëreshe of the province of Cosenza, southern Italy, in the XIX century.
- Author
-
Tagarelli G, Fiorini S, Piro A, Luiselli D, Tagarelli A, and Pettener D
- Subjects
- Culture, Environment, Genetics, Population, History, 19th Century, Humans, Italy ethnology, Registries, Marriage, Minority Groups, Names
- Abstract
Cultural and environmental factors interact in determining the genetic structure of human populations. Bio-demographic investigations of ethnic minorities are able to disentangle the influences that these two components have on the evolution of the genetic structure of a population. The ethnic minority of the Arbëreshe of the province of Cosenza (Calabria, southern Italy) is analyzed in this paper and its bio-demographic structure in the early 1800s is compared with that of neighboring Italian populations. The data derive from surnames recorded in the birth registers of the 19 Arbdreshe municipalities of the province of Cosenza and in 5 non-Arbëreshe municipalities of the same province. Isonymy and repeated pairs of surnames are used to analyze the bio-demographic structure of these populations, while analysis of isonymic relationships is used to investigate the variability between populations. Higher values of marital isonymy and subdivision into subpopulations characterize the Arbëreshe populations with respect to their non-Arbëreshe neighbors. However, the high range of variability of these parameters suggests a strong influence of geographic location on the marriage pattern of each community. At the same time, cultural differences linked to group identity had a strong impact in limiting marriage exchanges between the different ethnic groups living in the province of Cosenza in the early 1800s. In fact, the analysis of isonymic relationships demonstrates that geographic location shaped kinship patterns among the Arbereshe communities, but it also shows that the non-Arbëreshe neighbors formed a clearly separate reproductive cluster.
- Published
- 2007
188. The role and modulation of the oxidative balance in pregnancy.
- Author
-
Biondi C, Pavan B, Lunghi L, Fiorini S, and Vesce F
- Subjects
- Antioxidants chemistry, Antioxidants pharmacology, Female, Homeostasis drug effects, Humans, Oxidative Stress drug effects, Pregnancy, Antioxidants metabolism, Oxidative Stress physiology, Reactive Oxygen Species metabolism
- Abstract
Oxidative processes exert a fundamental regulatory function during pregnancy. It depends on the influence of oxygen, nitric oxide, reactive oxygen species and reactive nitrogen species metabolic pathways upon the vascular changes in the maternal organism, as well as on the regulation of uterine and cervical tone throughout gestation and delivery. These functions are strictly linked with the mediators of the inflammatory pathway. At the beginning of pregnancy, when a certain grade of inflammatory change is necessary to the trophoblast invasion of maternal tissue, the activation of the process by nitric oxide and reactive nitrogen species is welcome. Indeed, these products modulate the metalloproteinases, which are responsible for the remodelling of uterine extracellular matrix. At this stage estrogens are involved as well in the regulation of the delicate balance of pro-oxidant and anti-oxidant effects. Furthermore, reactive oxygen and nitrogen species appear to play an important role both in normal and pathologic embryogenesis. During advanced pregnancy, a derangement of the oxidative balance can lead to the improper activation of inflammatory changes, thus triggering premature labour as well as other complications, such as foetal growth restriction and preeclampsia. Although a number of pro- and anti-oxidant agents are available to influence the above-mentioned processes, there is no way to adequately measure the oxidative needs in single cases, in order to modulate the oxidative balance in clinical practice. Pharmacological research should be addressed to the development of new drugs, as well as to selective methods of delivery to the gestational tissues.
- Published
- 2005
- Full Text
- View/download PDF
189. Somatostatin coupling to adenylyl cyclase activity in the mouse retina.
- Author
-
Pavan B, Fiorini S, Dal Monte M, Lunghi L, Biondi C, Bagnoli P, and Cervia D
- Subjects
- Animals, Blotting, Western, Female, GTP-Binding Protein alpha Subunits, Gi-Go metabolism, Male, Mice, Mice, Knockout, Octreotide pharmacology, Pertussis Toxin pharmacology, Receptors, Somatostatin genetics, Signal Transduction, Adenylyl Cyclases metabolism, Receptors, Somatostatin agonists, Receptors, Somatostatin antagonists & inhibitors, Retina metabolism, Somatostatin metabolism
- Abstract
The peptide somatostatin-14 (SRIF) acts in the mammalian retina through its distinct receptors (sst(1-5)). Scarce information is available on SRIF function in the retina, including the elucidation of transduction pathways mediating SRIF action. We have investigated SRIF and SRIF receptor modulation of adenylyl cyclase (AC) activity in both wild-type (WT) retinas and sst1 or sst2 knock-out (KO) retinas, which are known to over-express sst2 or sst1 receptors respectively. In WT retinas, application of SRIF compounds does not affect forskolin-stimulated AC activity. In contrast, activation of sst1 or sst2 receptors inhibits AC in the presence of sst2 or sst1 receptor antagonists respectively. Results from sst1 KO retinas demonstrate that either SRIF or the sst2 receptor preferring agonist octreotide, pertussis toxin-dependently inhibit AC activity. In contrast, in sst2 KO retinas, neither SRIF nor CH-275, an sst1 receptor agonist, are found to influence AC activity. As revealed by immunoblotting experiments, in sst1 KO retinas, levels of G(o)alpha proteins are 60% higher than in WT retinas and this increase in G(o)alpha protein levels is concomitant with an increase in sst2A receptor expression. We conclude that interactions between sst1 and sst2 receptors may prevent SRIF effects on AC activity. In addition, we suggest that the density of sst2 receptors and/or G(o)alpha proteins may represent the rate-limiting factor for the sst2 receptor-mediated inhibition of AC.
- Published
- 2004
- Full Text
- View/download PDF
190. Interactions between the nitric oxide and prostaglandin E2 biosynthetic pathways in human amnion-like WISH cells.
- Author
-
Biondi C, Fiorini S, Pavan B, Ferretti ME, Barion P, and Vesce F
- Subjects
- Arginine chemistry, Cells, Cultured, Cyclic AMP metabolism, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors pharmacology, Humans, Indomethacin pharmacology, Isoenzymes metabolism, Membrane Proteins, Nitric Oxide Synthase metabolism, Nitric Oxide Synthase Type II, Nitroprusside chemistry, Prostaglandin-Endoperoxide Synthases metabolism, RNA, Messenger metabolism, Signal Transduction, Amnion metabolism, Interleukin-1 pharmacology, Nitric Oxide biosynthesis, Prostaglandins E biosynthesis
- Abstract
The aim of this study was to investigate the possible relationship between prostaglandin (PG) and nitric oxide (NO) biosynthetic pathways in human amnion-like WISH cells. Our results indicate that: (1) sodium nitroprusside (SNP), a NO donor, dose-dependently increases spontaneous prostaglandin E2 (PGE2) release while it inhibits the prostanoid output induced by the inflammatory cytokine, interleukin-1beta (IL-1beta); (2) L-arginine, the substrate of nitric oxide synthase (NOS), is ineffective in both conditions; (3) IL-1beta, which greatly enhances mRNA expression for cyclooxygenase (COX)-inducible isoform (COX-2), does not modify the mRNA expression for the NOS-inducible (iNOS) isoform; (4) indomethacin, which as expected inhibits both basal and IL-1beta-induced PGE2 release, permits the expression of iNOS mRNA in the presence of the cytokine; (5) a similar permissive action on IL-1beta action is exerted by the synthetic steroid betamethasone, which is able to inhibit both mRNA COX-2 expression and IL-1beta-induced PGE2 output in WISH cells; (6) exogenous PGE2 inhibits iNOS mRNA expression induced by indomethacin plus IL-1beta treatment; and (7) PGE2 significantly increases intracellular adenosine 3',5'-cyclic monophosphate (cAMP). The results reported here suggest the existence of a relationship between the prostaglandinergic and nitridergic pathways in WISH cells. In particular, we demonstrate that exogenous NO inhibits PGE2 release evoked by IL-1beta whereas high levels of the prostanoid, in the presence of proinflammatory agents, exert a negative feed-back control on iNOS mRNA expression, possibly through a cAMP-dependent mechanism.
- Published
- 2003
- Full Text
- View/download PDF
191. 17Beta-eEstradiol stimulates arachidonate release from human amnion-like WISH cells through a rapid mechanism involving a membrane receptor.
- Author
-
Fiorini S, Ferretti ME, Biondi C, Pavan B, Lunghi L, Paganetto G, and Abelli L
- Subjects
- Arachidonic Acids pharmacology, Cell Line, Cell Membrane Permeability, Dinoprostone metabolism, Enzyme Inhibitors pharmacology, Estrogen Receptor alpha, Estrogen Receptor beta, Female, Fluorescein-5-isothiocyanate, Fluorescent Dyes, Fulvestrant, Humans, Phospholipases A antagonists & inhibitors, Pregnancy, RNA, Messenger analysis, Receptors, Estrogen antagonists & inhibitors, Receptors, Estrogen genetics, Reverse Transcriptase Polymerase Chain Reaction, Serum Albumin, Bovine pharmacology, Tritium, Amnion drug effects, Amnion metabolism, Arachidonic Acid metabolism, Cell Membrane chemistry, Estradiol analogs & derivatives, Estradiol pharmacology, Receptors, Estrogen physiology
- Abstract
17beta-Estradiol (17beta-E(2)) greatly and dose-dependently stimulates [(3)H]arachidonic acid (AA) release from the human amnion-like Wistar Institute Susan Hayflick (WISH) cells. This action is abolished by the phospholipase A(2) inhibitor AACOCF(3), significantly reduced by the estrogen receptor (ER) antagonist ICI 182,780, and uninfluenced by cycloheximide. The estradiol-BSA conjugate E(2)coBSA, which binds putative membrane ERs and is unable to enter the cell, also highly stimulates [(3)H]AA release from WISH cells, although to a lesser extent compared with 17beta-E(2). The fluorescent conjugate E(2)coBSA-FITC specifically binds to the surface of a subset of intact WISH cells, and labeling intensity appears dose and time dependent. Cell permeabilization results in a dense intracellular staining, mainly in the peripheral cytoplasm. H-150, an antibody against the N terminus of human ERbeta, also labels the plasma membrane of intact WISH cells and the cytoplasm of permeabilized cells. Almost no labeling is observed using ER-21, an antibody against the N terminus of human ERalpha. RT-PCR evidences the presence of mRNA for ERbeta, not for ERalpha. Our data suggest that 17beta-E(2) stimulates [(3)H]AA release from WISH cells through an apparently nongenomic pathway and interaction with membrane binding sites. These last are, at least in part, similar if not identical to ERbeta.
- Published
- 2003
- Full Text
- View/download PDF
192. WISH cells as a model for the "in vitro" study of amnion pathophysiology.
- Author
-
Pavan B, Fiorini S, Ferretti ME, Vesce F, and Biondi C
- Subjects
- Amnion metabolism, Cytokines biosynthesis, Humans, Prostaglandins biosynthesis, Amnion cytology, Amnion physiopathology, Cell Line
- Abstract
In the course of pregnancy amnion cells produce a number of factors which include cytokines and prostaglandins (PGs) produced in response to autocrine, paracrine and endocrine signals. Recent studies performed by several researchers contributed to elucidate the mechanism through which amnion tissue is involved in the triggering of physiological labor. However, there are other possible functions to be ascribed to amniotic cells, depending on the high number of factors that they produce as well as on the receptors that enable them to act in turn as target. For instance, it has been demonstrated that amnion cells are able to produce lecithin upon the regulation of several factors, such as glucocorticoids and epidermal growth factor, a finding that suggests a protective role of the tissue on fetal pulmonary function. As regards to triggering the uterine contractions, it is accepted that prostaglandin release by amnion cells represents a key event. It is under the control of hormones, growth factors, cytokines and probably PGs themselves. A striking analogy has been found between the mechanism of inflammation and the onset of myometrial activity in labor. In this context, it has been shown that for-Met-Leu-Phe (fMLP), the prototype of a series of formylated peptides traditionally considered chemotactic agents, is also involved in the regulation of amniotic PG release. The similitude between labor and inflammatory response is enforced by the antiprostaglandin action of some classes of antibiotics observed in amnion tissue, that enable them as effective tools against preterm labor, both in the absence and in the presence of infection. As for the mechanisms responsible for the regulation of PG synthesis, some agents act by influencing protein synthesis, while others exert their effects through the production of intracellular second messengers, mainly represented by phosphatidyl-inositol-4-5 bisphosphate and cyclic AMP. The mechanism whereby second messengers induce PG release is not clear, and a crosstalk between the two transduction pathways could be hypothesized. This interaction has extensively been analysed in "WISH" cells, a human amnion-derived cell line, which represent a model for the in vitro study of amnion functions. In the present review, we intend to report the results of the studies regarding the mechanisms through which the control of the above mentioned functions is executed.
- Published
- 2003
193. Nitric oxide-mediated arachidonic acid release from perifused Venus verrucosa oocytes.
- Author
-
Barbin L, Boarini I, Borasio PG, Barion P, Fiorini S, Rossi R, and Biondi C
- Subjects
- Animals, Dose-Response Relationship, Drug, Female, In Vitro Techniques, Membrane Lipids metabolism, Nitric Oxide Donors metabolism, Nitric Oxide Synthase metabolism, Phospholipases A metabolism, Reproduction physiology, Arachidonic Acid metabolism, Bivalvia metabolism, Calcium metabolism, Nitric Oxide metabolism, Oocytes metabolism
- Abstract
This study was undertaken in order to investigate the possible interactions between nitric oxide and arachidonic acid (AA) in Venus verrucosa oocytes. We perifused isolated oocytes to determine the effect of the following substances on [3H]arachidonic acid release ([3H]AA): (1) A 23187, a calcium ionophore; (2) nitric oxide (NO) donors; (3) 1,1,1-trifluoromethyl-6,9,12,15 heicosatetraen-2-one (AACOCF(3)), a specific phospholipase A(2) (PLA(2)) inhibitor; (4) [5'-hydroxymethyl-2'-furyl]-1-benzyl indazole (YC-1) and 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), specific soluble guanylyl cyclase activator and inhibitor, respectively; (5) L-arginine, the substrate of nitric oxide synthase; (6) L-nitroarginine methyl esther (L-NAME), an inhibitor of nitric oxide synthase. Our results demonstrated that: (a) the calcium ionophore dose-dependently increased [3H]arachidonic acid release; (b) the NO donors sodium nitroprusside (SNP) and linsidomine (SIN-1) highly increased [3H]arachidonic acid output, while S-nitroso-N-acetylpenicillamine (SNAP) was without effect; (c) AACOCF(3) completely blocked the [3H]arachidonic acid release induced by SNP and SIN-1; (d) YC-1 increased [3H]arachidonic acid release, while ODQ completely counteracted SNP response; (e) [3H]arachidonic acid output was also increased by L-arginine; (f) a similar effect was, paradoxically, obtained in the presence of L-NAME. Furthermore, using RT-PCR we demonstrated in the same cells the presence of a nitric oxide synthase (NOS) mRNA, whose expression was not modulated by interleukin 1beta (IL-1beta). These results demonstrate the presence of a both calcium-dependent and NO-sensitive PLA(2) and of nitric oxide synthase in V. verrucosa oocytes. Our data also suggest a co-action of the two pathways in the control of reproduction in this bivalve., (Copyright 2003 Elsevier Science (USA))
- Published
- 2003
- Full Text
- View/download PDF
194. Somatostatin (SRIF) modulates distinct signaling pathways in rat pituitary tumor cells; negative coupling of SRIF receptor subtypes 1 and 2 to arachidonic acid release.
- Author
-
Cervia D, Fiorini S, Pavan B, Biondi C, and Bagnoli P
- Subjects
- Animals, Cyclic AMP metabolism, Dose-Response Relationship, Drug, Octreotide pharmacology, Oligopeptides pharmacology, Phospholipases A metabolism, Phospholipases A2, Pituitary Neoplasms pathology, Rats, Receptors, Somatostatin agonists, Receptors, Somatostatin antagonists & inhibitors, Somatostatin pharmacology, Tumor Cells, Cultured, Arachidonic Acid metabolism, Calcium metabolism, Pituitary Neoplasms metabolism, Receptors, Somatostatin metabolism, Signal Transduction, Somatostatin analogs & derivatives, Somatostatin metabolism
- Abstract
The somatotropin release-inhibiting factor somatostatin-14 (SRIF) is known to activate distinct receptor subtypes (sst1-5). In rat pituitary tumor cells (GC cells), sst2 but not sst1 receptors mediate the SRIF-induced inhibition of intracellular concentration of Ca2+ ([Ca2+]i) and are negatively coupled to cAMP-dependent pathways. In the present study, transduction mechanisms coupling distinct SRIF receptors to their specific functional role were investigated with the use of both SRIF agonists with well-known affinity at individual SRIF receptors and the sst2 receptor antagonist L-Tyr(8) isomer of Cyanamid 154806 (CYN-154806). Our results demonstrate that sst1 and sst2 receptors are coupled to distinct signaling pathways in GC cells. In particular, sst2 receptors are negatively coupled to the cAMP-dependent pathway and this pathway is partially responsible for the sst2 receptor-mediated inhibition of [Ca2+]i. In addition, sst1 and sst2 receptors are both coupled to a decrease of arachidonic acid (AA) release with an efficacy similar to that of SRIF, suggesting that SRIF reduces AA release through either a partial activation of both receptors or the activation of one at a time. This finding is important given the well-accepted role for phospholipase A2 (PLA2) as a positive signaling component in transduction pathways of SRIF receptors. sst1 and sst2 receptor negative coupling to PLA2/AA pathways does not seem to be implicated in the SRIF-induced inhibition of [Ca2+]i. The possible role for the SRIF-mediated inhibition of AA release in GC cell function remains to be elucidated.
- Published
- 2002
- Full Text
- View/download PDF
195. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome.
- Author
-
Pasquali R, Gambineri A, Biscotti D, Vicennati V, Gagliardi L, Colitta D, Fiorini S, Cognigni GE, Filicori M, and Morselli-Labate AM
- Subjects
- Abdomen, Adult, Combined Modality Therapy, Double-Blind Method, Estradiol blood, Female, Follicle Stimulating Hormone blood, Humans, Leptin blood, Luteinizing Hormone blood, Obesity complications, Obesity physiopathology, Placebos, Polycystic Ovary Syndrome physiopathology, Progesterone blood, Sex Hormone-Binding Globulin analysis, Viscera, Adipose Tissue anatomy & histology, Androgens blood, Body Composition, Diet, Reducing, Hypoglycemic Agents therapeutic use, Insulin blood, Metformin therapeutic use, Obesity therapy, Polycystic Ovary Syndrome complications
- Abstract
Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities. This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight, fat distribution, the glucose-insulin system, and hormones in a group of 20 obese PCOS women [body mass index (BMI) > 28 kg/m2] with the abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS. At baseline, we measured sex hormone, sex hormone-binding globulin (SHBG), and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women were then given a low-calorie diet (1,200-1,400 kcal/day) alone for one month, after which anthropometric parameters and CT scan were newly measured. While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8, respectively) or placebo (8 and 12, respectively), according to a double-blind design, for the following 6 months. Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment. During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance; and 2 PCOS women, both treated with metformin, were also excluded because they became pregnant. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo). The treatment was well tolerated. In the PCOS group, metformin therapy improved hirsutism and menstrual cycles significantly more than placebo. Baseline anthropometric and CT parameters were similar in all groups. Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups, without any significant effect on CT scan parameters. In both PCOS and control women, however, metformin treatment reduced body weight and BMI significantly more than placebo. Changes in the waist-to-hip ratio values were similar in PCOS women and controls, regardless of pharmacological treatment. Metformin treatment significantly decreased SAT values in both PCOS and control groups, although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment. On the contrary, visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups, but only in the former was the effect of metformin treatment significantly higher than that of placebo. Fasting insulin significantly decreased in both PCOS women and controls, regardless of treatment, whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin. Neither metformin or placebo significantly modified the levels of LH, FSH, dehydroepiandrosterone sulphate, and progesterone in any group, whereas testosterone concentrations decreased only in PCOS women treated with metformin. SHBG concentrations remained unchanged in all PCOS women; whereas in the control group, they significantly increased after both metformin and placebo. Leptin levels decreased only during metformin treatment in both PCOS and control groups. (ABSTRACT TRUNCATED)
- Published
- 2000
- Full Text
- View/download PDF
196. C677T substitution in the methylenetetrahydrofolate reductase gene as a risk factor for venous thrombosis and arterial disease in selected patients.
- Author
-
Gemmati D, Serino ML, Trivellato C, Fiorini S, and Scapoli GL
- Subjects
- Adult, Aged, Alleles, Amino Acid Substitution, Arterial Occlusive Diseases epidemiology, Case-Control Studies, Female, Gene Frequency, Genetic Predisposition to Disease, Genetic Testing, Genotype, Humans, Hyperhomocysteinemia epidemiology, Male, Methylenetetrahydrofolate Reductase (NADPH2), Middle Aged, Myocardial Infarction epidemiology, Myocardial Infarction genetics, Odds Ratio, Risk Factors, Thrombophilia epidemiology, Arterial Occlusive Diseases genetics, Hyperhomocysteinemia genetics, Oxidoreductases Acting on CH-NH Group Donors genetics, Point Mutation, Thrombophilia genetics
- Abstract
Background and Objective: Hyperhomocysteinemia, due to a combination of genetic and environmental factors, is considered to be a risk factor for vascular disease. Individuals with the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR), due to homozygous C677T MTHFR gene mutation, have significantly raised plasma levels of homocysteine and may be at increased risk of vascular disease. However, it is still controversial a direct association between C677T homozygosity and the occurrence of vascular disease is still controversial., Design and Methods: To clarify the contribution of C677T MTHFR mutation in arterial occlusive disease (AOD) or venous thromboembolism (VTE), we performed a case-controlled study including 160 cases with AOD and 180 cases with VTE attending our referral center and compared them with 200 matched healthy controls. MTHFR gene mutation was evaluated by PCR and odds ratios (OR) and the 95% confidence intervals (CI) were used to estimate the risk for venous or arterial thrombosis., Results: There was a high prevalence of homozygotes for the mutated MTHFR allele among the whole group of cases with arterial disease (OR = 2.35, p = 0.001). Considering the AOD cases with and those without associated risk factors for arterial disease separately the difference remained significant only in the latter group (p = 0.168 and P<0.001 respectively). In contrast, the prevalence of mutated homozygotes among the whole group of cases with VTE was not significantly different from that in the control group (OR = 1.67; p = 0.070). Excluding VTE cases with inherited thrombophilia or with circumstantial risk situations the value increased in both subgroups (OR = 2.26; p = 0.006 and OR = 2.03; p = 0.033 respectively). Considering only VTE cases with neither inherited thrombophilia nor circumstantial risk situations the risk increased further (OR = 2.57; p = 0.017)., Interpretation and Conclusions: These data suggest that in selected patients homozygosity for the MTHFR mutation increases the risk of both arterial and venous thromboses and that differences in selection criteria for the patient group may be responsible in part for the controversial association of the MTHFR mutation and vascular disease.
- Published
- 1999
197. Tubercular involvement of the thyroid gland: a report of two cases.
- Author
-
Orlandi F, Fiorini S, Gonzatto I, Saggiorato E, Pivano G, Angeli A, and Pasquali R
- Subjects
- Abscess microbiology, Aged, Aged, 80 and over, Antitubercular Agents therapeutic use, Biopsy, Needle, Ethambutol therapeutic use, Female, Humans, Isoniazid therapeutic use, Lymph Nodes pathology, Mycobacterium tuberculosis isolation & purification, Rifampin therapeutic use, Thyroid Diseases pathology, Tuberculosis, Endocrine drug therapy, Thyroid Diseases microbiology, Tuberculosis, Endocrine diagnosis
- Abstract
Thyroid tuberculosis is rare. In the last decade, however, the incidence of extrapulmonary forms of tuberculosis has increased. We report on 2 cases of thyroid tuberculosis. In case 1, a tubercular abscess mimicking acute thyroiditis was found which was correctly diagnosed by fine-needle aspiration biopsy (FNAb). No evidence of active disease was noticed. Pleural thickening on chest X-ray was the only sign compatible with a previous infection. In case 2, tubercular thyroiditis with lymph node enlargement was also diagnosed by FNAb in a reevaluation setting. In both cases treatment with antitubercular drugs resulted in complete recovery. Thyroid tuberculosis should be kept in mind in the differential diagnosis of thyroid nodules, notably in patients with a history of tuberculous disease. FNAb represents the main approach to making the diagnosis., (Copyright 2000 S. Karger AG, Basel)
- Published
- 1999
- Full Text
- View/download PDF
198. Computed tomography in hepatolenticular degeneration.
- Author
-
Rachele MG, Spallone A, Giagheddu M, Fiorini S, and Silipo P
- Subjects
- Adolescent, Adult, Child, Female, Humans, Male, Tomography, X-Ray Computed, Hepatolenticular Degeneration diagnostic imaging
- Published
- 1983
199. [Methodology: preparation in optic microscopy for an electron microscopic study of problems of nervous physiopathology].
- Author
-
Fiorini S, Fulga S, and Testa C
- Subjects
- Brain Diseases diagnosis, Humans, Methods, Microscopy, Microscopy, Electron, Nervous System Diseases diagnosis, Brain Diseases pathology, Nervous System Diseases pathology
- Published
- 1973
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.