85 results on '"Saporito, M"'
Search Results
2. Il trattamento artroscopico
- Author
-
Porcellini, G., Campi, F., Paladini, P., and Saporito, M.
- Published
- 2008
- Full Text
- View/download PDF
3. Defining suitable Safe System Projects in Africa
- Author
-
Usami, D. S., Gonzalez, Brayan, Persia, L., Kunsoa, N. B., Meta, E., Saporito, M. R., Schermers, G., Carnis, L., Yerpez, J., Bouhamed, N., Cardoso, J., Kluppels, L., and Vandemeulebroek, F.
- Subjects
safety system ,Africa ,vision zero ,road safety ,road safety management - Published
- 2020
4. Il trattamento artroscopico delle fratture glenoidee
- Author
-
Saporito, M., Paladini, P., Campi, F., and Porcellini, G.
- Published
- 2011
- Full Text
- View/download PDF
5. Surgical time for graft preparation using different suture techniques
- Author
-
Camarda, L., primary, Giambartino, S., additional, Lauria, M., additional, Saporito, M., additional, Triolo, V., additional, and D’Arienzo, M., additional
- Published
- 2019
- Full Text
- View/download PDF
6. Predicting the failure in distal femur fractures
- Author
-
Peschiera, V., primary, Staletti, L., additional, Cavanna, M., additional, Saporito, M., additional, and Berlusconi, M., additional
- Published
- 2018
- Full Text
- View/download PDF
7. Snapping Triceps
- Author
-
Ciaramella, G., Saporito, M., Fauci, F., and Porcellini, G.
- Published
- 2017
8. Biomolecular Investigations in Osteoarthritis
- Author
-
Boniforti, F, Saporito, M, Minafra, L., BRAVATA', Valentina, Boniforti, F, Saporito, M, BRAVATA', V, and Minafra, L
- Subjects
osteoarthritis, single nucleotide polymorphism - Published
- 2012
9. Biomolecular investigation in osteoarthritis
- Author
-
Saporito, M, Minafra, L, Cammarata, F, Caldarella, S, Boniforti, F., BRAVATA', Valentina, Saporito, M, Bravatà, V, Minafra, L, Cammarata, F, Caldarella, S, and Boniforti, F
- Subjects
single nucleotide polymorphism, osteoarthritis - Published
- 2012
10. Integrazione dei saperi per la salute
- Author
-
GIANI, UMBERTO, TRIASSI, MARIA, SANTOIANNI, FLAVIA, GARZILLO, CARMINE, Pacifico A., Citro V., Ventre V., Cillo B., Sandri S., Montella E., Giani E., Noschese S., Sibilia L., RANISIO, GIANFRANCA ANGELA RITA, Pavic B., Griffo G., Sorrentino M., Lamberti E., Citarella A., Cirillo G., Saporito M., Arsieri R., Trevisan M., Cito F., Giordano V., Giani, Umberto, Triassi, Maria, Santoianni, Flavia, Pacifico, A., Citro, V., Ventre, V., Cillo, B., Sandri, S., Montella, E., Giani, E., Noschese, S., Sibilia, L., Ranisio, GIANFRANCA ANGELA RITA, Pavic, B., Griffo, G., Sorrentino, M., Lamberti, E., Citarella, A., Cirillo, G., Saporito, M., Arsieri, R., Trevisan, M., Cito, F., Garzillo, Carmine, and Giordano, V.
- Subjects
multiprofessionalità e multidisciplinarità ,medicina e complessità ,integrazione dei saperi - Abstract
Il volume nasce dall’iniziativa di un gruppo di persone confluite in un’associazione culturale Knowledge Integration for Health il cui obiettivo è superare la parcellizzazione del sapere medico in una pluralità di iperspecializzazioni formate da professionisti che spesso non comunicano tra loro. Tutto ciò si riflette non solo sulla cura dei pazienti, costretti a peregrinare tra diversi specialisti, non di rado in disaccordo tra loro, ma anche sulla ricerca scientifica, sulla formazione, sull'organizzazione dei servizi sanitari e sulla spesa pubblica. Sebbene tale esigenza sia avvertita dai cittadini, dai profes-sionisti della salute e dai ricercatori, tuttora non è emerso un modello e/o una teoria coerente dell'integrazione dei saperi per la salute a causa di barriere culturali, economiche ed organizzative. Il volume, espressione del progetto ambizioso di abbattere tali barriere, raccoglie le riflessioni scaturite da una serie di inziative (convegni, workshop, corsi di perfezionamento, sperimentazioni didattiche, ricerche sul campo, conversazioni telematiche e in-formali, e così via) realizzatesi a partire dall'anno 2010. Esso è concepito come uno strumento di lavoro e aperto alla discussione volto a creare una rete comunicativa ed informativa tra esperti di "discipline" diverse, e tra questi e gli stessi pazienti che sono portatori di conoscenze e saperi poco rappresentati nell’attuale scenario scientifico e organizzativo. Su questa falsariga è stata data voce anche a saperi "minoritari" che si configurano a volte come ipotesi di lavoro, più o meno eterodosse, ancora da provare scientificamente ma che sono un sintomo dell’esigenza sempre più sentita di una visione unitaria della salute, della malattia e della terapia. I contributi sono stati scritti da professionisti diversi appartenenti non solo al mondo accademico, ma anche istanze extrauniver-sitarie, istituzionali e non: medici di medicina generale,, ostetriche, fisioterapisti riabilitatori, pediatri, infermieri, logopedisti, tecnici di radiolo-gia, tecnici di laboratorio, epidemiologi, pedagogisti, antropo-logi, psichiatri, chimici, veterinari, statistici, urbanisti, igienisti, informatici. E'stato altresì dato spazio anche ai lavori condotti da studenti e discussi sotto forma di tesi di laurea. La struttura del volume si articola su tre livelli interconnessi: clinico, sociale ed ecologico. Il livello clinico, centrato sull'individuo e la sua malattia, ha co-me paradigma di riferimento il cosiddetto modello bio-medico, noto anche come modello dell'acuzie, fondato sul processo diagnostico-terapeutico e sulla diade terapeuta-paziente. Al secondo livello, quello sociale, il malessere del paziente è iscritto in una serie di dinamiche interpersonali, espressione di comportamenti individuali e collettivi, fattori economici, cultu-rali, e così via. Mentre il modello dell'acuzie concettualizza la malattia come un evento che ha un inizio ed una fine (almeno momentanea), il modello sociale si incentra su cronicità e disabilità che richiedono la partecipazione di familiari, badanti, servizi di riabilitazione e di supporto sociale per un tempo indefinito. I due modelli non sono mutuamente incompatibili perché spesso le condizioni di cronicità e disabilità sono costel-late da esacerbazioni o nuovi eventi che richiedono il ricorso ad interventi clinici. Il livello ecologico riguarda il modo in cui le popolazioni umane si modificano a seguito dell'interazione con altre popolazioni umane, con il mondo animale e vegetale e con l'ambiente chimi-co-fisico, formando ecosistemi la cui dinamica si dipana su scale temporali e geografiche differenti e si riflette sui profili delle malattie di ciascuna popolazione. Così, ad esempio, le grandi trasformazioni demografiche dovute ai processi migratori e alla creazione di barriere efficienti contro alcuni micro-organismi (attraverso il miglioramento delle condizioni igieniche e della conservazione degli alimenti) determinano modificazioni della composizione per età delle popolazioni che a loro volta com-portano transizioni epidemiologiche caratterizzate da cambia-menti più o meno profondi della prevalenza e l'incidenza dei diversi tipi di patologia.
- Published
- 2012
11. Evaluation of Clutch Plate Integrity with Non-Destructive Methods
- Author
-
CERNIGLIA, Donatella, LOMBARDO, Elio, NIGRELLI, Vincenzo, Saporito, M., Cerniglia, D, Lombardo, E, Nigrelli, V, and Saporito, M
- Subjects
product life cycle, product control, laser ultrasound, guided waves ,Settore ING-IND/15 - Disegno E Metodi Dell'Ingegneria Industriale - Abstract
Nondestructive evaluation (NDE) represents an important phase in the life cycle of a product to detect defects both in service and in production. NDE techniques most commonly used to detect surface defects are visual inspection and methods based on eddy current and ultrasound. Laser and non-contact sensors have been recently used to inspect ultrasonically without contact. Components with complex geometry are usually inspected combining several NDE techniques, or simply visually where analysis and evaluation of results are performed by an operator based on specific parameters of acceptance. This last method is currently used to inspect the clutch plates since their complex geometry, for the presence of grooves, limits the use of other methods. This work shows the possibility of using a non-contact ultrasonic technique and guided waves (Lamb) to detect surface defects in clutch plates. An appropriate source/receiver configuration allows to overcome the limitations due to the complexity of the geometry. This technique allows, compared to the visual inspection, to detect smaller and internal defects, and to obtain objective results, not depending on the evaluation of the operator. The inspection method can be very fast and applicable in the production line by using a fully automated control system.
- Published
- 2009
12. An Update of the Evolving Epidemic of blaKPC Carrying Klebsiella pneumoniae in Sicily, Italy, 2014: Emergence of Multiple Non-ST258 Clones
- Author
-
BONURA, Celestino, GIUFFRE, Mario, ALEO, Aurora, Fasciana, Teresa Maria Assunta, Di Bernardo, F., Stampone, T., GIAMMANCO, Anna, Palma, D., MAMMINA, Caterina, GERACI, Daniela Maria, GRAZIANO, Giorgio, SAPORITO, Laura, Saporito, M., Sodano, C., Verde, M., Baldi, M., Donato, E., Amato, T., Immordino, R., Distefano, S., Bonura, C., Giuffrè, M., Aleo, A., Fasciana, T., Di Bernardo, F., Stampone, T., Giammanco, A., Palma, D., Mammina, C., Geraci, D., Graziano, G., Saporito, L., Saporito, M., Sodano, C., Verde, M., Baldi, M., Donato, E., Amato, T., Immordino, R., and Distefano, S.
- Subjects
Carbapenem ,Klebsiella pneumoniae ,lcsh:Medicine ,Gene Expression ,Drug resistance ,Plasmid ,beta-Lactamase ,Disease Outbreaks ,Molecular typing ,Fluoroquinolone ,Drug Resistance, Multiple, Bacterial ,polycyclic compounds ,lcsh:Science ,Membrane Protein ,Disease Outbreak ,Multidisciplinary ,biology ,Medicine (all) ,Incidence ,Hospitals ,Anti-Bacterial Agents ,Electrophoresis, Gel, Pulsed-Field ,Italy ,Epidemiological Monitoring ,Human ,Fluoroquinolones ,Plasmids ,Research Article ,medicine.drug ,Bacterial Protein ,Aminoglycosides ,Bacterial Proteins ,Carbapenems ,Clone Cells ,Colistin ,Humans ,Klebsiella Infections ,Membrane Proteins ,Multilocus Sequence Typing ,Mutation ,beta-Lactamases ,Agricultural and Biological Sciences (all) ,Biochemistry, Genetics and Molecular Biology (all) ,Microbiology ,Clone Cell ,Hospital ,Antibiotic resistance ,Anti-Bacterial Agent ,medicine ,Aminoglycoside ,lcsh:R ,Carbapenemase producing ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,biology.organism_classification ,Virology ,Multilocus sequence typing ,lcsh:Q ,Klebsiella Infection - Abstract
Background: In Italy, Klebsiella pneumoniae carbapenemase producing K. pneumoniae (KPC-Kp) strains are highly endemic and KPC producing CC258 is reported as the widely predominating clone. In Palermo, Italy, previous reports have confirmed this pattern. However, recent preliminary findings suggest that an epidemiological change is likely ongoing towards a polyclonal KPC-Kp spread. Here we present the results of molecular typing of 94 carbapenem non susceptible K. pneumoniae isolates detected during 2014 in the three different hospitals in Palermo, Italy. Methods and Results: Ninety-four consecutive, non replicate carbapenem non susceptible isolates were identified in the three largest acute general hospitals in Palermo, Italy, in the six-month period March-August 2014. They were characterized by PCR for β-lactam, aminoglycoside and plasmid mediated fluoroquinolone resistance genetic determinants. The mgrB gene of the colistin resistant isolates was amplified and sequenced. Clonality was assessed by pulsed field gel electrophoresis and multilocus sequence typing. Eight non-CC258 sequence types (STs) were identified accounting for 60% of isolates. In particular, ST307 and ST273 accounted for 29% and 18% of isolates. CC258 isolates were more frequently susceptible to gentamicin and non-CC258 isolates to amikacin. Colistin non susceptibility was found in 42% of isolates. Modifications of mgrB were found in 32 isolates. Conclusions: Concurrent clonal expansion of some STs and lateral transmission of genetic resistance determinants are likely producing a thorough change of the KPC-Kp epidemiology in Palermo, Italy. In our setting mgrB inactivation proved to substantially contribute to colistin resistance. Our findings suggest the need to continuously monitor the KPC-Kp epidemiology and to assess by a nationwide survey the possible shifting towards a polyclonal epidemic.
- Published
- 2015
13. DVWA gene polymorphisms and osteoarthritis
- Author
-
Bravatà, V, Minafra, L, Forte, G, Cammarata, F, Saporito, M, Boniforti, F, Lio, D, Gilardi, M, Messa, M, GILARDI, MARIA CARLA, MESSA, MARIA CRISTINA, Bravatà, V, Minafra, L, Forte, G, Cammarata, F, Saporito, M, Boniforti, F, Lio, D, Gilardi, M, Messa, M, GILARDI, MARIA CARLA, and MESSA, MARIA CRISTINA
- Abstract
Background: Osteoarthritis (OA) is a degenerative joints disorder influenced by genetic predisposition. We reported that rs11718863 DVWA SNP was represented in Sicilian with a more severe Kellgren and Lawrence (KL) radiographic grade, displaying its predictive role as OA marker progression. Here, we describe the DVWA SNPs: rs11718863, rs7639618, rs7651842, rs7639807 and rs17040821 probably able to induce protein functional changes. Findings: Sixty-one Sicilian patients with knee OA and 100 healthy subjects were enrolled. Clinical and radiographic evaluation was performed using AKSS scores and KL. Linkage Disequilibrium (LD) analyses were performed in order to verify whether the SNPs segregate as haplotype. All DVWA SNPs'MinorAllele Frequencies (MAF) were greater than in the European. The rs7639618 SNP showed a statistical association with KL. Our analyses show that a LD exists among rs11718863 and rs7639618, as well as between rs7651842, rs7639807 and rs17040821 SNPs. We also observed that three out of the 161 individuals investigated were simultaneously homozygous carriers of the rs7651842, rs7639807 and rs17040821 MAF alleles. Conclusions: In summary, the purpose of this preliminary research was to highlight possible associations between DVWA SNPs and OA clinical and radiographic data. This work represents a multidisciplinary medicine approach to study OA where clinical, radiological and genetic evaluation could contribute to better define OA grading.
- Published
- 2015
14. L’incremento delle nascite da parto cesareo in Campania nel 2000
- Author
-
TRIASSI, MARIA, SAPORITO M, ARSIERI R, PUGLIESE A, FORMISANO V., Triassi, Maria, Saporito, M, Arsieri, R, Pugliese, A, and Formisano, V.
- Subjects
Parto cesareo ,Nascite - Abstract
Cesarean deliveries (CS) are increasing in Italy, especially in the Campania region, where they reached a peak incidence of 52% in the year 2000. This study analyses CS rate variability by hospital type, foetal risk factors (low birth-weight, prematurity, plurality, anomalous presentations), maternal characteristics (age and parity) and delivery time. Data are drawn from birth certificates of 31,182 babies, that is 64.2% of all delivered in 65 out of 98 Campania birth-places. 16,251 (52%) babies are born by CS; 559 (1.8%) by operative vaginal delivery. The Attributable Risk for foetal risk factors is 6.9%. In absence of these the CS rate would be 48.5% instead of 52%. CS rate of primigravid women was 53.2%. 63% of CS take place during morning hours and 93% on working days. CS rate is higher in private than in public hospitals (58 vs 46%), though foetal risk factors are lower. Rate of older women was higher in public hospitals, rate of primigravid women was higher in private ones. Campania data confirm the marginal role of foetal risk factors in the increase of CS rate. In order to reduce CS rates it seems reasonable to offer special support to primigravid low risk mothers and to provide behavioural obstetrical guidelines for the peculiar Italian reality.
- Published
- 2003
15. Enteral feeding policies for extremely low birth weight infants. A survey in 74 Italian neonatal intensive cAre units
- Author
-
Mario De Curtis, Saporito, M., Giuffré, M., Corsello, G., De Curtis M., Saporito M., Giuffre M., and Corsello G.
- Subjects
Extremely low birthweight infants ,Enteral feeding ,Human milk ,Neonatal intensive care units - Abstract
Background: Enterai feeding for infants with birth weight1000 g (ELBWI) is still a controversial issue. The aim of the present survey was to ascertain the attitudes of Italian neonatal intensive care units (NICUs) regarding this point. Method: A questionnaire, with multiple choice answers, regarding the timing of enteral feeding, its progression, the different techniques utilised, the eventual use of fortifiers and the interrupting criteria, was mailed to 92 Italian NICUs. Results: 74 NICUs all over the country participated in the study.1153 ELBWI were hospitalised in 1996 in these Units. Enterai feeding for babies between 501 g and 750 g is started on the 1st day of life in 23.3% of the NICUs and for babies between 751 g and 1000 g in 36.5%. NICUs that start enteral feeding not later than the 3rd day of life are 75.3% and 86.5% respectively. The most frequent investigation prior to starting enterai feeding was the evaluation of gastric aspirate. Mechanical ventilation is considered a contraindication for starting enterai feeding only in 1/4 of NICUs. Enterai feeding is started most often with glucose water solution and raw human milk. The most frequent administration techniques are interminent oro- and nasogastric gavage. Pasteurization facilities are available in 31 % of NICUs, but are located mostly in the Centre and North of Italy. Conclusion: This survey shows that enterai feeding policy for ELBWI varies among different Italian NICUs. In Italy there is a common tendency to start feeding early, even in ventilated infants.
- Published
- 1999
16. Auditoria como Ferramenta no Controle da Qualidade
- Author
-
Saporito, M. F. M. W., primary and Villela, R. D., additional
- Published
- 2015
- Full Text
- View/download PDF
17. Ruolo del trapianto allogenico di cellule staminali ematopoietiche nel trattamento delle malattie emato-oncologiche pediatriche: dieci anni di esperienza del Centro di Catania
- Author
-
Saporito, M, Tumino, M, Samperi, P, DI CATALDO, Andrea, Marino, S, and LO NIGRO, L.
- Published
- 2010
18. Genetic, clinical and radiographic signs in knee osteoarthritis susceptibility
- Author
-
Minafra, L, Bravatà, V, Saporito, M, Cammarata, F, Forte, G, Caldarella, S, D. Arienzo, M, Gilardi, M, Messa, M, Boniforti, F, Boniforti, F., GILARDI, MARIA CARLA, MESSA, MARIA CRISTINA, Minafra, L, Bravatà, V, Saporito, M, Cammarata, F, Forte, G, Caldarella, S, D. Arienzo, M, Gilardi, M, Messa, M, Boniforti, F, Boniforti, F., GILARDI, MARIA CARLA, and MESSA, MARIA CRISTINA
- Abstract
Osteoarthritis (OA) is considered to be a multifactorial and polygenic disease and diagnosis is mainly clinical and radiological. Correlation between radiographic data and clinical status has been reported. However, very few studies, especially in Caucasian people, describe the association between the Kellgren and Lawrence OA grading scale (KL) and genetic alterations to better understand OA etiopathogenesis and susceptibility. In order to update the knee OA grading, in this study we assessed the associations between KL grade, clinical features such as American Knee Society Score (AKSS), age, and polymorphisms in the principal osteoarthritis susceptibility (OS) genes in Sicilian individuals.
- Published
- 2014
19. ADX71441, a novel, potent and selective positive allosteric modulator of the GABABreceptor, shows efficacy in rodent models of overactive bladder
- Author
-
Kalinichev, M, primary, Palea, S, additional, Haddouk, H, additional, Royer-Urios, I, additional, Guilloteau, V, additional, Lluel, P, additional, Schneider, M, additional, Saporito, M, additional, and Poli, S, additional
- Published
- 2014
- Full Text
- View/download PDF
20. Correlation between clinical and radiographic classification of osteoarthritis and SNPs linked to osteoarthritis susceptibility
- Author
-
Saporito, M., primary, Minafra, L., additional, Bravatà, V., additional, Cammarata, F.P., additional, and Boniforti, F., additional
- Published
- 2013
- Full Text
- View/download PDF
21. Contact between the components of a knee prosthesis: numerical and experimental study
- Author
-
Cerniglia, D., primary, Ingrassia, T., additional, D’Acquisto, L., additional, Saporito, M., additional, and Tumino, D., additional
- Published
- 2012
- Full Text
- View/download PDF
22. Ongoing spread of colistin-resistant Klebsiella pneumoniae in different wards of an acute general hospital, Italy, June to December 2011
- Author
-
Mammina, C, primary, Bonura, C, additional, Di Bernardo, F, additional, Aleo, A, additional, Fasciana, T, additional, Sodano, C, additional, Saporito, M A, additional, Verde, M S, additional, Tetamo, R, additional, and Palma, D M, additional
- Published
- 2012
- Full Text
- View/download PDF
23. ADX71441, a novel, potent and selective positive allosteric modulator of the GABAB receptor, shows efficacy in rodent models of overactive bladder.
- Author
-
Kalinichev, M, Palea, S, Haddouk, H, Royer ‐ Urios, I, Guilloteau, V, Lluel, P, Schneider, M, Saporito, M, and Poli, S
- Subjects
GABA receptors ,ALLOSTERIC regulation ,OVERACTIVE bladder ,LABORATORY rats ,BACLOFEN ,URINARY catheterization ,SPASTICITY ,HYPERKINESIA - Abstract
Background and Purpose The GABA
B receptor agonist baclofen reduces urethral resistance and detrusor overactivity in patients with spasticity. However, baclofen's side effects limit its use for the treatment of overactive bladder ( OAB). Here, we tested a novel GABAB positive allosteric modulator ( PAM) ADX71441 in models of OAB in mice and guinea pigs. Experimental Approach Mice were left untreated or given (p.o.) vehicle (1% CMC), ADX71441 (1, 3, 10 mg kg−1 ) or oxybutynin (100 mg kg−1 ; Experiment 1) or vehicle (1% CMC), baclofen (1, 3, 6 mg kg−1 ) or oxybutynin (Experiment 2). Treated mice were then overhydrated with water, challenged with furosemide, before being placed into micturition chambers and monitored for urinary parameters. In anaesthetized guinea pigs, intravesical infusion of acetic acid was used to induce OAB and the effects of ADX71441 (1, 3 mg kg−1 ) or baclofen (1 mg kg−1 ), administered i.v., on cystometric parameters were monitored. Key Results In mice, 10 mg kg−1 ADX71441 increased urinary latencies, reduced the number of urinary events and the total and average urinary volumes. In guinea pigs, ADX71441 (1 and 3 mg kg−1 ) increased the intercontraction interval ( ICI) and bladder capacity ( BC), and reduced micturition frequency ( MF) compared to vehicle. At 3 mg kg−1 ADX71441 completely inhibited the micturition reflex and induced overflow incontinence in five out of 10 animals. Baclofen slightly increased ICI and BC and reduced MF. Conclusion and Implications Our findings demonstrate, for the first time, that a GABAB PAM has potential as a novel approach for the treatment of OAB. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
24. Examination of Ginna pressure vessel nozzle welds using focussed probes
- Author
-
Saporito, M., primary, Lewis, P., additional, Ammirator, F., additional, Kietzman, K., additional, Willetts, T., additional, and Clayton, W., additional
- Published
- 1992
- Full Text
- View/download PDF
25. Ultrasonic examination of Ginna reactor pressure vessel nozzle welds using focussed probes
- Author
-
Saporito, M., primary, Lewis, P., additional, Ammirato, F., additional, Kietzman, E.K., additional, and Clayton, W., additional
- Published
- 1992
- Full Text
- View/download PDF
26. Mixed lineage kinase activity of indolocarbazole analogues
- Author
-
Murakata, C., Kaneko, M., Gessner, G., Angeles, T. S., Ator, M. A., O'Kane, T. M., McKenna, B. A., Thomas, B. A., Mathiasen, J. R., and Saporito, M. S.
- Published
- 2002
- Full Text
- View/download PDF
27. CEP-1347/KT-7515, an inhibitor of c-jun N-terminal kinase activation, attenuates the 1-methyl-4-phenyl tetrahydropyridine-mediated loss of nigrostriatal dopaminergic neurons In vivo.
- Author
-
S, Saporito M, M, Brown E, S, Miller M, and S, Carswell
- Abstract
We have identified a bis-ethylthiomethyl analog of K-252a, CEP-1347/KT-7515, that promotes neuronal survival in culture and in vivo. The neuronal survival properties of CEP-1347/KT-7515 may be related to its ability to inhibit the activation of c-jun N-terminal kinase, a key kinase in some forms of stress-induced neuronal death and perhaps apoptosis. There is evidence that the selective nigrostriatal dopaminergic neurotoxin, MPTP, produces neuronal apoptosis in culture and in adult mice. Thus, our studies were designed to determine if CEP-1347/KT-7515 could protect dopaminergic neurons from MPTP-mediated neurotoxicity. CEP-1347/KT-7515 was assessed for neuroprotective activity in a low dose MPTP model (20 mg/kg) where there was a 50% loss of striatal dopaminergic terminals in the absence of substantia nigra neuronal loss, and a high dose (40 mg/kg) MPTP model where there was a complete loss of dopaminergic terminals and 80% loss of dopaminergic cell bodies. In the low dose MPTP model, CEP-1347/KT-7515 (0.3 mg/kg/day) attenuated the MPTP-mediated loss of striatal dopaminergic terminals by 50%. In the high dose model, CEP-1347/KT-7515 ameliorated the loss of dopaminergic cell bodies by 50% and partially preserved striatal dopaminergic terminals. CEP-1347/KT-7515 did not inhibit monoamine oxidase B or the dopamine transporter, suggesting that the neuroprotective effects of CEP-1347/KT-7515 occur downstream of the metabolic conversion of MPTP to MPP+ and accumulation of MPP+ into dopaminergic neurons. These data implicate a c-jun N-terminal kinase signaling system in MPTP-mediated dopaminergic degeneration and suggest that CEP-1347/KT-7515 may have potential as a treatment for Parkinson's disease.
- Published
- 1999
28. Dopaminergic neurotoxicity of 1-methyl-4-phenylpyridinium analogs in cultured neurons: relationship to the dopamine uptake system and inhibition of mitochondrial respiration.
- Author
-
Saporito, M S, Heikkila, R E, Youngster, S K, Nicklas, W J, and Geller, H M
- Abstract
Several analogs of 1-methyl-4-phenylpyridinium (MPP+) were evaluated for their affinity for the dopamine uptake system and their ability to inhibit NADH dehydrogenase (complex I) of the mitochondrial electron-transport chain. Moreover, these compounds were tested for their ability to cause selective dopaminergic neurotoxicity in cultured mesencephalic neurons. Simultaneous [3H]dopamine and gamma-amino-[14C]butyric acid uptake and immunocytochemical techniques were used as indices of neuronal damage in cultured cells. The compounds that were potent and selective dopaminergic neurotoxins had high affinity for the dopamine transport system, as measured by their ability to cause dopamine release, and were similar to MPP+ in inhibiting mitochondrial respiration. One compound (1-methyl-4-phenylpyrimidinium) had high affinity for the dopamine uptake system but was a weak inhibitor of mitochondrial respiration and, accordingly, was not neurotoxic. The 4'-alkylated analogs of MPP+, which were poor substrates for the dopamine uptake system and extremely potent inhibitors of mitochondrial respiration, caused a nonselective damage of neurons in culture. Analogs that were not substrates for the dopamine carrier and not inhibitors of mitochondrial respiration were not neurotoxic. This study describes the neurotoxicity of a number of analogs of MPP+ and highlights the importance of the dopamine uptake system and the ability to inhibit mitochondrial respiration as critical processes in conferring selectivity and neurotoxicity, respectively, to MPP+ and analogs, for dopaminergic neurons in culture.
- Published
- 1992
29. Systemic dexamethasone administration increases septal Trk autophosphorylation in adult rats via an induction of nerve growth factor.
- Author
-
Saporito, M S, Brown, E R, Hartpence, K C, Wilcox, H M, Robbins, E, Vaught, J L, and Carswell, S
- Abstract
Nerve growth factor (NGF) maintains cholinergic neurons in various animals models of neurodegeneration and is thus a potential treatment for certain neurodegenerative disorders such as Alzheimer's disease. Because NGF does not cross the blood-brain barrier, we have proposed elevating endogenous levels of NGF in the central nervous system with small molecules that induce NGF expression, as an alternative strategy. The present studies were conducted to determine whether pharmacologically elevated levels of NGF are sufficient to cause subsequent stimulation of its high affinity receptor, as measured by increased levels of Trk phosphorylation. Dexamethasone (0.5-20 mg/kg, intraperitoneally) caused a time- and dose-dependent increase in NGF mRNA and NGF protein in the hippocampus and septum of adult male Sprague-Dawley rats. Exogenously administered NGF (1 microgram, intracerebroventricularly) led to a rapid (30 min) and transient increase in Trk phosphorylation in the septum, which has high levels of NGF-specific TrkA. Similarly, dexamethasone led to an increase in Trk phosphorylation only within the septum. Dexamethasone-mediated Trk phosphorylation was dose and time dependent, with peak increases being observed 12 hr after injection, concurrently with peak increases in NGF protein. These data demonstrate an increase in activation of the high affinity NGF receptor with a compound that elevates levels of NGF in the central nervous system, and they support the strategy of discovering a pharmacological agent that induces NGF as a method for treating neurodegenerative disorders.
- Published
- 1994
30. Preservation of cholinergic activity and prevention of neuron death by CEP-1347/KT-7515 following excitotoxic injury of the nucleus basalis magnocellularis
- Author
-
Saporito, M. S., Brown, E. R., Carswell, S., Dicamilio, A. M., Miller, M. S., Murakata, C., Neff, N. T., Vaught, J. I., and Haun, F. A.
- Published
- 1998
- Full Text
- View/download PDF
31. Subacute sclerosing panencephalitis: A case report
- Author
-
Praticò, A. D., Saporito, M., Iacono, O., Castellano-Chiodo, D., and Piero Pavone
- Subjects
Myoclonus ,Dysarthria ,Measles Vaccine ,Interferon-alpha ,Electroencephalography ,Interferon-beta ,Perinatology and Child Health ,Prognosis ,Antiviral Agents ,Severity of Illness Index ,Pediatrics ,Inosine pranobex ,Measles virus ,Neurological disorders ,Pediatrics, Perinatology and Child Health ,Disease Progression ,Humans ,Drug Therapy, Combination ,Female ,Subacute Sclerosing Panencephalitis ,Child ,Measles - Abstract
Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of childhood and early adolescence caused by persistent defective measles virus. Clinical manifestations appear many years after the acute measles infection. The incidence of SSPE has substantially declined after the introduction of an effective vaccine. We report a case of a child with SSPE that began with atonia, dysarthria, and intellectual deterioration without the presence of any particular EEG anomalies. We have reported this girl who was affected by this severe affliction in the hope that, because of the rarity of SSPE, it would not go undiagnosed.
32. Conservative management of rotator cuff tears: Literature review and proposal for a prognostic. Prediction Score
- Author
-
Merolla, G., Paolo Paladini, Saporito, M., and Porcellini, G.
- Subjects
shoulder ,conservative treatment ,prediction score ,rotator cuff ,Original Article - Abstract
Rotator cuff tears are a common cause of pain and shoulder dysfunction. The prevalence of the rotator cuff tears increases with the age reaching the 80% in patients aged more than 80 year. Symptomatic shoulders usually are initially treated conservatively and then, in case of poor outcomes, with surgery. Different parameters are still used to decide between the conservative or surgical treatment in patients with rotator cuff tears. Aim of the current study is to characterize the various features used in decision making and to validate a “Prediction Score” that let us know which patients could have a good and stable outcome with non operative treatment. We enrolled 60 patients (mean age 52 years) with symptomatic rotator cuff tears who were assigned to conservative treatment and were evaluated at 6,9 and 12 months follow-up. We developed a score based on 18 clinical and radiographic parameters. 27 patients (“non conservative”) (45%) with a mean prediction score of 16.1 ± 1.7 interrupted the conservative treatment, while 33 patients (“conservative”) (55%) with an average prediction score of 11.3 ± 1.8 remained conservatively treated at last follow-up. The conservative patients were 14 years older than non conservative patients. According to the results of this study we identified a value of 13 points as a “cut-off” score to predict good results by conservative management of rotator cuff tear. These outcomes support the assumption that a predictive prognostic score may guarantee a rational approach in the management of subjects with RC tears, especially in elderly who continue to have the higher rate of recurrence and therefore could be well treated with standard conservative therapies.
33. Collaboration in action. Camp Golden Treasures: a multidisciplinary weight-loss and a healthy lifestyle camp for adolescent girls.
- Author
-
Pratt KJ, Lamson AL, Collier DN, Crawford YS, Harris N, Gross K, Ballard S, Sarvey S, and Saporito M
- Abstract
Camp Golden Treasures, (CGT) the first non-profit weight loss camp for overweight adolescent girls in the nation, was held for six weeks from June 24 to August 3, 2007 at the East Carolina University campus in Greenville, NC. The primary goal was to support campers to lose weight, raise self esteem, and to learn the tools necessary to lead a healthy lifestyle while reducing risks for developing chronic disease or mitigating the effects of existing obesity-related conditions (sleep apnea, insulin resistance, hypertension, lower extremity dysfunction, etc.). While at CGT, campers learned about the importance of physical activity and proper nutrition through workshops, discussion groups and hands-on activities. Additionally campers were taught the necessary tools and strategies needed to make concrete, positive lifestyle changes so they can achieve a healthy weight. Due to the nature of a chronic disease such as obesity, multidisciplinary collaborators including physical therapy, nutrition, health education, management, family therapy, risk management, fundraising, public relations, medical, nursing, and physician coverage were involved in designing, planning, and implementing CGT. (PsycINFO Database Record (c) 2009 APA, all rights reserved) [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
34. Surgical time for graft preparation using different suture techniques
- Author
-
Michele Saporito, Sebastian Giambartino, Lawrence Camarda, Michele Lauria, Vito Triolo, Michele D'Arienzo, Camarda, L., Giambartino, S., Lauria, M., Saporito, M., Triolo, V., and D'Arienzo, M
- Subjects
Orthodontics ,Suturing techniques ,030222 orthopedics ,medicine.medical_specialty ,business.industry ,modified finger-trap, suture, time consuming, krakow stitch, whipstitch ,Interobserver reproducibility ,Surgery ,Tendon ,03 medical and health sciences ,Surgical time ,0302 clinical medicine ,medicine.anatomical_structure ,Suture (anatomy) ,Settore MED/33 - Malattie Apparato Locomotore ,Medicine ,Operative time ,Original Article ,Orthopedics and Sports Medicine ,030212 general & internal medicine ,business - Abstract
Background: The purpose of the present study was to compare the operative time for graft prepa- ration using different techniques for graft sutur- ing. Material and methods: Flexor profundus tendons were harvested from fresh pig hind-leg trotters. Three different suture techniques were investigat- ed: the Krackow stitch (K), the Whipstitch (W), and the Modified Finger-Trap suture (MFT). Ten- dons were sutured starting at 10 mm from the dis- tal free end of the tendon. The suture configura- tions of the Krackow stitch and Whipstitch were completed with five suture throws. According to the MFT technique, the suture was wrapped five times around the tendon over a distance of 30 mm. The time required to perform a complete su- ture on each tendon was measured. Five indepen- dent examiners of different levels of training mea- sured the time required for graft preparation dur- ing 3 separate occasions to determine intraob- server repeatability and interobserver reproduci- bility. Results: The mean time required for graft prepa- ration following the Krackow technique was 69.1 seconds ± 18.3 SD (range 31.8-120). The Whip- stitch technique took an average of 59.9 seconds ± 21.2 SD (range 27-93). The MFT suture required a mean of 29.3 seconds ± 11.4 SD for completing the suture (range 21.6-33). In all examiners the time required to complete the MFT suture was significantly less than the other suture tech- niques (p < 0.05). Intraobserver intraclass correla- tion coefficients for each examiner ranged from 0.72 to 0.83. Conclusion: Low graft preparation time is re- quired to complete a MFT suture in a porcine ten- don model. Further, time required for graft prepa- ration using the MFT was shorter than other su- turing techniques such as the Krackow and Whip- stitch techniques. Clinical relevance: The MFT suture could be used for graft set-up with the main advantage of reduc- ing the time required in comparison with other su- ture techniques.
- Published
- 2019
35. DVWA gene polymorphisms and osteoarthritis
- Author
-
Valentina Bravatà 1, Luigi Minafra 1, Giusi I Forte 1, Francesco P Cammarata 1, Michele Saporito 2, Filippo Boniforti 3, Domenico Lio 4, Maria C Gilardi 1, 5, 6, Cristina Messa 1, 7, BRAVATA', V, Minafra, L, Forte, GI, Cammarata, FP, Saporito, M, Boniforti, F, Lio, D, Gilardi, MC, Messa, C, Bravatà, V, Forte, G, Cammarata, F, Gilardi, M, and Messa, M
- Subjects
Male ,Linkage disequilibrium ,Short Report ,Single-nucleotide polymorphism ,Osteoarthritis ,Collagen Type VI ,Bioinformatics ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Linkage Disequilibrium ,White People ,Gene Frequency ,Haplotype ,Genetic predisposition ,DVWA ,Medicine ,SNP ,Humans ,Genetic Predisposition to Disease ,Allele ,Osteoarthritis, DVWA, Single nucleotide polymorphisms, Haplotypes, KL ,Allele frequency ,Sicily ,Alleles ,Aged ,Medicine(all) ,Aged, 80 and over ,Biochemistry, Genetics and Molecular Biology(all) ,business.industry ,Homozygote ,General Medicine ,Single nucleotide polymorphisms ,Middle Aged ,Osteoarthritis, Knee ,medicine.disease ,Single nucleotide polymorphism ,KL ,Haplotypes ,Osteoarthriti ,Female ,business ,Pseudogenes - Abstract
Background: Osteoarthritis (OA) is a degenerative joints disorder influenced by genetic predisposition. We reported that rs11718863 DVWA SNP was represented in Sicilian with a more severe Kellgren and Lawrence (KL) radiographic grade, displaying its predictive role as OA marker progression. Here, we describe the DVWA SNPs: rs11718863, rs7639618, rs7651842, rs7639807 and rs17040821 probably able to induce protein functional changes. Findings: Sixty-one Sicilian patients with knee OA and 100 healthy subjects were enrolled. Clinical and radiographic evaluation was performed using AKSS scores and KL. Linkage Disequilibrium (LD) analyses were performed in order to verify whether the SNPs segregate as haplotype. All DVWA SNPs'MinorAllele Frequencies (MAF) were greater than in the European. The rs7639618 SNP showed a statistical association with KL. Our analyses show that a LD exists among rs11718863 and rs7639618, as well as between rs7651842, rs7639807 and rs17040821 SNPs. We also observed that three out of the 161 individuals investigated were simultaneously homozygous carriers of the rs7651842, rs7639807 and rs17040821 MAF alleles. Conclusions: In summary, the purpose of this preliminary research was to highlight possible associations between DVWA SNPs and OA clinical and radiographic data. This work represents a multidisciplinary medicine approach to study OA where clinical, radiological and genetic evaluation could contribute to better define OA grading.
- Published
- 2015
36. Contact between the components of a knee prosthesis: numerical and experimental study
- Author
-
Tommaso Ingrassia, Donatella Cerniglia, M. Saporito, L. D’Acquisto, Davide Tumino, Cerniglia, D, Ingrassia, T, D'Acquisto, L, Saporito, M, and Tumino, D
- Subjects
Reverse engineering ,Materials science ,business.industry ,Mechanical Engineering ,lcsh:Mechanical engineering and machinery ,Work (physics) ,lcsh:TA630-695 ,Analisi FEM ,Surface finish ,Structural engineering ,lcsh:Structural engineering (General) ,computer.software_genre ,Finite element method ,Mechanics of Materials ,Service life ,Ultrasuoni ,Ultrasonic sensor ,lcsh:TJ1-1570 ,business ,Contact area ,computer ,Protesi di ginocchio ,Reliability (statistics) ,Biomedical engineering - Abstract
The aim of this work is the analysis of the contact area in a knee prosthesis using two different approaches. In particular, the interface between the femoral component and the polyethylene insert has been studied both numerically and experimentally. The interest in studying the contact area is related to the fact that the wear of the polyethylene insert, due to the high contact pressures, represents one of the major causes of failure of the total knee prosthesis. The possibility to evaluate the contact area at different loads and mutual position between femur and tibia is, therefore, of fundamental importance to study the service life of a prosthesis and to improve its performance. The finite element numerical approach has required the acquisition, through reverse engineering, and CAD modelling of the prosthetic components. Then the FEM simulations have been developed considering two different load conditions. In order to compare the calculated data, the same load configurations have been used for experimental tests based on ultrasonic method. In this case, some preliminary tests were required to calibrate the system depending on the particular characteristics of materials, geometries and surface finish of the prosthesis. The results show a good correlation between the data obtained with the two different approaches and, consequently, a good level of reliability of the procedures developed for the numerical and experimental evaluation of the contact area. The numerical procedure can be used to determine the area for different angles and loads, but especially in the design phase. The ultrasonic technique can be used to validate the numerical data.
- Published
- 2012
37. Ongoing spread of colistin-resistant Klebsiella pneumoniae in different wards of an acute general hospital, Italy, June to December 2011
- Author
-
Daniela Maria Palma, Caterina Mammina, Maria Antonietta Saporito, Aurora Aleo, Concetta Sodano, F. Di Bernardo, Teresa Fasciana, Romano Tetamo, Celestino Bonura, Maria Stella Verde, Mammina, C., Bonura, C., Di Bernardo, F., Aleo, A., Fasciana, T., Sodano, C., Saporito, M., Verde, M., Tetamo, R., and Palma, D.
- Subjects
DNA, Bacterial ,Settore MED/07 - Microbiologia E Microbiologia Clinica ,Epidemiology ,Klebsiella pneumoniae ,Microbial Sensitivity Tests ,Settore MED/42 - Igiene Generale E Applicata ,Hospitals, General ,Polymerase Chain Reaction ,Klebsiella pneumoniae, carbapenems, colistin resistance, ICU, epidemiology ,beta-Lactamases ,Microbiology ,Disease Outbreaks ,Antibiotic resistance ,Virology ,Intensive care ,Drug Resistance, Multiple, Bacterial ,Patients' Rooms ,Medicine ,Humans ,colistin-resistance ,MLST ,General hospital ,Cross Infection ,biology ,business.industry ,Colistin ,Public Health, Environmental and Occupational Health ,Outbreak ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Anti-Bacterial Agents ,Bacterial Typing Techniques ,Klebsiella Infections ,Intensive Care Units ,Carbapenems ,Italy ,Multilocus sequence typing ,business ,Horizontal transmission ,medicine.drug ,Multilocus Sequence Typing - Abstract
We describe polyclonal spread of colistin-resistant Klebsiella pneumoniae in an acute general hospital in Italy. Between June and December 2011, 58 colistin-resistant K. pneumoniae isolates were recovered from 28 patients admitted to different wards, but mainly in the intensive care units. All isolates were tested for drug susceptibility and the presence of beta-lactamase (bla) genes. Clonality was investigated by repetitive extragenic palindromic (rep)-PCR and multilocus sequence typing (MLST). Fifty-two isolates had minimum inhibitory concentrations (MICs) for colistin of 6-128 mg/L, carried blaKPC3 and were attributed to sequence type ST258. The remaining six isolates were susceptible to carbapenems, exhibited MICs for colistin of 3-32 mg/L, and belonged to two different types, ST15 and ST273. Rep-PCR included all isolates in three clusters, one containing all ST258 KPC-3-producing isolates and two containing ST15 and ST273 isolates. Cross-transmission containment measures and intensification of staff and environmental hygiene could not stop the outbreak. Selective pressure and horizontal transmission probably contributed to emergence and spread of three different strains of colistin-resistant K. pneumoniae in the hospital. Strict implementation of the above measures and a wider awareness of the antimicrobial resistance threat are crucial to preserve the last therapeutic options of the multidrug-resistant Gram-negative infections. .
- Published
- 2012
38. Genetic, clinical and radiographic signs in knee osteoarthritis susceptibility
- Author
-
Valentina Bravatà, Michele Saporito, Luigi Minafra, Cristina Messa, Giusi Irma Forte, Francesco Paolo Cammarata, Salvatore Caldarella, Filippo Boniforti, Michele D'Arienzo, Maria Carla Gilardi, Minafra, L, Bravatà, V, Saporito, M, Cammarata, FP, Forte, GI, Caldarella, S, D'Arienzo, M, Gilardi, MC, Messa, C, Boniforti, F, Cammarata, F, Forte, G, D. Arienzo, M, Gilardi, M, and Messa, M
- Subjects
Male ,medicine.medical_specialty ,Pathology ,dbSNP ,Genotype ,Single Nucleotide Polymorphisms ,Immunology ,Single-nucleotide polymorphism ,Osteoarthritis ,Polymorphism, Single Nucleotide ,Radiographic ,Rheumatology ,Internal medicine ,Settore MED/33 - Malattie Apparato Locomotore ,OMIM : Online Mendelian Inheritance in Man ,Humans ,Immunology and Allergy ,Medicine ,Genetic Predisposition to Disease ,Grading (tumors) ,Aged ,Aged, 80 and over ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Middle Aged ,Osteoarthritis, Knee ,medicine.disease ,Radiography ,Orthopedic surgery ,Cohort ,Female ,Osteoarthriti ,business ,Research Article - Abstract
INTRODUCTION: Osteoarthritis (OA) is considered to be a multifactorial and polygenic disease and diagnosis is mainly clinical and radiological. Correlation between radiographic data and clinical status has been reported. However, very few studies, especially in Caucasian people, describe the association between the Kellgren and Lawrence OA grading scale (KL) and genetic alterations to better understand OA etiopathogenesis and susceptibility. In order to update the knee OA grading, in this study we assessed the associations between KL grade, clinical features such as American Knee Society Score (AKSS), age, and polymorphisms in the principal osteoarthritis susceptibility (OS) genes in Sicilian individuals. METHODS: In 66 Sicilian individuals affected by primary knee OA, the clinical and radiographic evaluation was performed using 2 sub-scores of AKSS (knee score (KS) and function score (FS)) and KL. The patients were also classified according to age. Online Mendelian Inheritance in Man (OMIM) and Database of Single Nucleotide Polymorphisms (dbSNP) Short Genetic Variations databases were used to select gene regions containing the following polymorphisms to analyze: FRZB rs288326 and rs7775, MATN3 rs77245812, ASPN D14 repeats, PTHR2 rs76758470, GDF5 rs143383 and DVWA rs11718863. Patient genotypes were obtained using Sanger DNA sequencing analysis. RESULTS: In our cohort of patients a statistical association between the variables analyzed was reported in all associations tested (KL versus KS, FS and age). We observed that a mild to severe OA radiographic grade is related to severe clinical conditions and loss of articular function and that the severity of symptoms increases with age. Concerning the genotyping analysis, our results revealed a significant statistical association between KL grading and GDF5 rs143383 and DVWA rs11718863 genetic alterations. The latter was also associated with a more severe radiographic grade, displaying its predictive role as OA marker progression. Statistically significant association between clinical, radiographic and genetic signs observed, suggests extending the actual grading of knee OA based mainly on X-ray features. CONCLUSIONS: This work represents a multidisciplinary and translational medicine approach to study OA where clinical, radiological, and OS5 and OS6 SNPs evaluation could contribute to better define grading and progression of OA and to the development of new therapies.
- Published
- 2014
39. Correlation between clinical and radiographic classification of osteoarthritis and SNPs linked to osteoarthritis susceptibility
- Author
-
Michele Saporito, Luigi Minafra, Francesco Paolo Cammarata, Filippo Boniforti, Valentina Bravatà, Saporito, M, Minafra, L, Bravatà, V, Cammarata, FP, and Boniforti, F
- Subjects
medicine.medical_specialty ,business.industry ,Radiography ,Biomedical Engineering ,Single-nucleotide polymorphism ,Osteoarthritis ,medicine.disease ,Correlation ,SNP, Osteoarthritis ,Rheumatology ,Internal medicine ,Medicine ,Orthopedics and Sports Medicine ,business - Full Text
- View/download PDF
40. Complex Metabolism of the Novel Neurosteroid, Ganaxolone, in Humans: A Unique Challenge for Metabolites in Safety Testing Assessment.
- Author
-
Fitch WL, Smith S, Saporito M, Busse G, Zhang M, Ren J, Fitzsimmons ME, Yi P, English S, Carter A, and Baillie TA
- Subjects
- Animals, Humans, Male, Pregnanolone analysis, Mass Spectrometry, Chromatography, Liquid, Chromatography, High Pressure Liquid, Feces chemistry, Neurosteroids analysis
- Abstract
The human pharmacokinetics, metabolism, and excretion of [
14 C]-ganaxolone (GNX) were characterized in healthy male subjects ( n = 8) following a single 300-mg (150 μ Ci) oral dose. GNX exhibited a short half-life of 4 hours in plasma, whereas total radioactivity had a half-life of 413 hours indicating extensive metabolism to long-lived metabolites. Identification of the major GNX circulating metabolites required extensive isolation and purification for liquid chromatography-tandem mass spectrometry analysis, together with in vitro studies, NMR spectroscopy, and synthetic chemistry support. This revealed that the major routes of GNX metabolism involved hydroxylation at the 16 α -hydroxy position, stereoselective reduction of the 20-ketone to afford the corresponding 20 α -hydroxysterol, and sulfation of the 3 α -hydroxy group. This latter reaction yielded an unstable tertiary sulfate, which eliminated the elements of H2 SO4 to introduce a double bond in the A ring. A combination of these pathways, together with oxidation of the 3 β -methyl substituent to a carboxylic acid and sulfation at the 20 α position, led to the major circulating metabolites in plasma, termed M2 and M17. These studies, which led to the complete or partial identification of no less than 59 metabolites of GNX, demonstrated the high complexity of the metabolic fate of this drug in humans and demonstrated that the major circulating products in plasma can result from multiple sequential processes that may not be easily replicated in animals or with animal or human in vitro systems. SIGNIFICANCE STATEMENT: Studies on the metabolism of [14 C]-ganaxolone in humans revealed a complex array of products that circulated in plasma, the two major components of which were formed via an unexpected multi-step pathway. Complete structural characterization of these (disproportionate) human metabolites required extensive in vitro studies, along with contemporary mass spectrometry, NMR spectroscopy, and synthetic chemistry efforts, which served to underscore the limitations of traditional animal studies in predicting major circulating metabolites in man., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)- Published
- 2023
- Full Text
- View/download PDF
41. Functional characterization of a novel p.Ser76Thr variant in IGFBP4 that associates with body mass index in American Indians.
- Author
-
Muller YL, Saporito M, Day S, Bandesh K, Koroglu C, Kobes S, Knowler WC, Hanson RL, Van Hout CV, Shuldiner AR, Bogardus C, and Baier LJ
- Subjects
- Animals, Body Mass Index, Humans, Mice, Obesity genetics, PPAR gamma genetics, Phosphatidylinositol 3-Kinases genetics, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-akt genetics, American Indian or Alaska Native, Indians, North American genetics, Insulin-Like Growth Factor Binding Protein 4 genetics
- Abstract
Insulin-like growth factor binding protein 4 (IGFBP4) is involved in adipogenesis, and IGFBP4 null mice have decreased body fat through decreased PPAR-γ expression. In the current study, we assessed whether variation in the IGFBP4 coding region influences body mass index (BMI) in American Indians who are disproportionately affected by obesity. Whole exome sequence data from a population-based sample of 6779 American Indians with longitudinal measures of BMI were used to identify variation in IGFBP4 that associated with BMI. A novel variant that predicts a p.Ser76Thr in IGFBP4 (Thr-allele frequency = 0.02) was identified which associated with the maximum BMI measured during adulthood (BMI 39.8 kg/m
2 for Thr-allele homozygotes combined with heterozygotes vs. 36.2 kg/m2 for Ser-allele homozygotes, β = 6.7% per Thr-allele, p = 8.0 × 10-5 , adjusted for age, sex, birth-year and the first five genetic principal components) and the maximum age- and sex-adjusted BMI z-score measured during childhood/adolescence (z-score 0.70 SD for Thr-allele heterozygotes vs. 0.32 SD for Ser-allele homozygotes, β = 0.37 SD per Thr-allele, p = 8.8 × 10-6 ). In vitro functional studies showed that IGFBP4 with the Thr-allele (BMI-increasing) had a 55% decrease (p = 0.0007) in FOXO-induced transcriptional activity, reflecting increased activation of the PI3K/AKT pathway mediated through increased IGF signaling. Over-expression and knock-down of IGFBP4 in OP9 cells during differentiation showed that IGFBP4 upregulates adipogenesis through PPARγ, CEBPα, AGPAT2 and SREBP1 expression. We propose that this American Indian specific variant in IGFBP4 affects obesity via an increase of IGF signaling., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)- Published
- 2022
- Full Text
- View/download PDF
42. Surgical time for graft preparation using different suture techniques.
- Author
-
Camarda L, Giambartino S, Lauria M, Saporito M, Triolo V, and D'Arienzo M
- Abstract
Background: The purpose of the present study was to compare the operative time for graft preparation using different techniques for graft suturing., Material and Methods: Flexor profundus tendons were harvested from fresh pig hind-leg trotters. Three different suture techniques were investigated: the Krackow stitch (K), the Whipstitch (W), and the Modified Finger-Trap suture (MFT). Tendons were sutured starting at 10 mm from the distal free end of the tendon. The suture configurations of the Krackow stitch and Whipstitch were completed with five suture throws. According to the MFT technique, the suture was wrapped five times around the tendon over a distance of 30 mm. The time required to perform a complete suture on each tendon was measured. Five independent examiners of different levels of training measured the time required for graft preparation during 3 separate occasions to determine intraobserver repeatability and interobserver reproducibility., Results: The mean time required for graft preparation following the Krackow technique was 69.1 seconds ± 18.3 SD (range 31.8-120). The Whipstitch technique took an average of 59.9 seconds ± 21.2 SD (range 27-93). The MFT suture required a mean of 29.3 seconds ± 11.4 SD for completing the suture (range 21.6-33). In all examiners the time required to complete the MFT suture was significantly less than the other suture techniques (p < 0.05). Intraobserver intraclass correlation coefficients for each examiner ranged from 0.72 to 0.83., Conclusion: Low graft preparation time is required to complete a MFT suture in a porcine tendon model. Further, time required for graft preparation using the MFT was shorter than other suturing techniques such as the Krackow and Whipstitch techniques., Clinical Relevance: The MFT suture could be used for graft set-up with the main advantage of reducing the time required in comparison with other suture techniques.
- Published
- 2016
- Full Text
- View/download PDF
43. Erythema Nodosum and Mycoplasma pneumoniae Infections in Childhood: Further Observations in Two Patients and a Literature Review.
- Author
-
Greco F, Catania R, Pira AL, Saporito M, Scalora L, Aguglia MG, Smilari P, and Sorge G
- Abstract
Erythema nodosum (EN) is the most frequent panniculitis in childhood and has been associated with various conditions, such as infectious and autoimmune disorders, medications, and malignancies. The author reports on two children affected with EN associated with Mycoplasma pneumoniae infection, which occurred in one patient without pulmonary detection. The available literature on EN and M. pneumoniae infection in childhood is also reviewed.
- Published
- 2015
- Full Text
- View/download PDF
44. DVWA gene polymorphisms and osteoarthritis.
- Author
-
Bravatà V, Minafra L, Forte GI, Cammarata FP, Saporito M, Boniforti F, Lio D, Gilardi MC, and Messa C
- Subjects
- Aged, Aged, 80 and over, Alleles, Female, Gene Frequency, Haplotypes, Homozygote, Humans, Linkage Disequilibrium, Male, Middle Aged, Osteoarthritis, Knee ethnology, Osteoarthritis, Knee pathology, Sicily, White People, Collagen Type VI genetics, Genetic Predisposition to Disease, Osteoarthritis, Knee genetics, Polymorphism, Single Nucleotide, Pseudogenes genetics
- Abstract
Background: Osteoarthritis (OA) is a degenerative joints disorder influenced by genetic predisposition. We reported that rs11718863 DVWA SNP was represented in Sicilian with a more severe Kellgren and Lawrence (KL) radiographic grade, displaying its predictive role as OA marker progression. Here, we describe the DVWA SNPs: rs11718863, rs7639618, rs7651842, rs7639807 and rs17040821 probably able to induce protein functional changes., Findings: Sixty-one Sicilian patients with knee OA and 100 healthy subjects were enrolled. Clinical and radiographic evaluation was performed using AKSS scores and KL. Linkage Disequilibrium (LD) analyses were performed in order to verify whether the SNPs segregate as haplotype. All DVWA SNPs'MinorAllele Frequencies (MAF) were greater than in the European. The rs7639618 SNP showed a statistical association with KL. Our analyses show that a LD exists among rs11718863 and rs7639618, as well as between rs7651842, rs7639807 and rs17040821 SNPs. We also observed that three out of the 161 individuals investigated were simultaneously homozygous carriers of the rs7651842, rs7639807 and rs17040821 MAF alleles., Conclusions: In summary, the purpose of this preliminary research was to highlight possible associations between DVWA SNPs and OA clinical and radiographic data. This work represents a multidisciplinary medicine approach to study OA where clinical, radiological and genetic evaluation could contribute to better define OA grading.
- Published
- 2015
- Full Text
- View/download PDF
45. Genetic, clinical and radiographic signs in knee osteoarthritis susceptibility.
- Author
-
Minafra L, Bravatà V, Saporito M, Cammarata FP, Forte GI, Caldarella S, D'Arienzo M, Gilardi MC, Messa C, and Boniforti F
- Subjects
- Aged, Aged, 80 and over, Female, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Radiography, Reverse Transcriptase Polymerase Chain Reaction, Genetic Predisposition to Disease genetics, Osteoarthritis, Knee diagnostic imaging, Osteoarthritis, Knee genetics
- Abstract
Introduction: Osteoarthritis (OA) is considered to be a multifactorial and polygenic disease and diagnosis is mainly clinical and radiological. Correlation between radiographic data and clinical status has been reported. However, very few studies, especially in Caucasian people, describe the association between the Kellgren and Lawrence OA grading scale (KL) and genetic alterations to better understand OA etiopathogenesis and susceptibility. In order to update the knee OA grading, in this study we assessed the associations between KL grade, clinical features such as American Knee Society Score (AKSS), age, and polymorphisms in the principal osteoarthritis susceptibility (OS) genes in Sicilian individuals., Methods: In 66 Sicilian individuals affected by primary knee OA, the clinical and radiographic evaluation was performed using 2 sub-scores of AKSS (knee score (KS) and function score (FS)) and KL. The patients were also classified according to age. Online Mendelian Inheritance in Man (OMIM) and Database of Single Nucleotide Polymorphisms (dbSNP) Short Genetic Variations databases were used to select gene regions containing the following polymorphisms to analyze: FRZB rs288326 and rs7775, MATN3 rs77245812, ASPN D14 repeats, PTHR2 rs76758470, GDF5 rs143383 and DVWA rs11718863. Patient genotypes were obtained using Sanger DNA sequencing analysis., Results: In our cohort of patients a statistical association between the variables analyzed was reported in all associations tested (KL versus KS, FS and age). We observed that a mild to severe OA radiographic grade is related to severe clinical conditions and loss of articular function and that the severity of symptoms increases with age. Concerning the genotyping analysis, our results revealed a significant statistical association between KL grading and GDF5 rs143383 and DVWA rs11718863 genetic alterations. The latter was also associated with a more severe radiographic grade, displaying its predictive role as OA marker progression. Statistically significant association between clinical, radiographic and genetic signs observed, suggests extending the actual grading of knee OA based mainly on X-ray features., Conclusions: This work represents a multidisciplinary and translational medicine approach to study OA where clinical, radiological, and OS5 and OS6 SNPs evaluation could contribute to better define grading and progression of OA and to the development of new therapies.
- Published
- 2014
- Full Text
- View/download PDF
46. Conservative management of rotator cuff tears: literature review and proposal for a prognostic. Prediction Score.
- Author
-
Merolla G, Paladini P, Saporito M, and Porcellini G
- Abstract
Rotator cuff tears are a common cause of pain and shoulder dysfunction. The prevalence of the rotator cuff tears increases with the age reaching the 80% in patients aged more than 80 year. Symptomatic shoulders usually are initially treated conservatively and then, in case of poor outcomes, with surgery. Different parameters are still used to decide between the conservative or surgical treatment in patients with rotator cuff tears. Aim of the current study is to characterize the various features used in decision making and to validate a "Prediction Score" that let us know which patients could have a good and stable outcome with non operative treatment. We enrolled 60 patients (mean age 52 years) with symptomatic rotator cuff tears who were assigned to conservative treatment and were evaluated at 6,9 and 12 months follow-up. We developed a score based on 18 clinical and radiographic parameters. 27 patients ("non conservative") (45%) with a mean prediction score of 16.1 ± 1.7 interrupted the conservative treatment, while 33 patients ("conservative") (55%) with an average prediction score of 11.3 ± 1.8 remained conservatively treated at last follow-up. The conservative patients were 14 years older than non conservative patients. According to the results of this study we identified a value of 13 points as a "cut-off" score to predict good results by conservative management of rotator cuff tear. These outcomes support the assumption that a predictive prognostic score may guarantee a rational approach in the management of subjects with RC tears, especially in elderly who continue to have the higher rate of recurrence and therefore could be well treated with standard conservative therapies.
- Published
- 2011
47. [Risk factors analysis for elective caesarean section in Campania region (Italy)].
- Author
-
Giani U, Bruzzese D, Pugliese A, Saporito M, and Triassi M
- Subjects
- Abortion, Induced statistics & numerical data, Adult, Educational Status, Emigrants and Immigrants statistics & numerical data, Female, Hospitals, Private statistics & numerical data, Hospitals, Public statistics & numerical data, Humans, Italy, Maternal Age, Middle Aged, Parity, Pregnancy, Reproductive Techniques, Assisted, Risk Factors, Unnecessary Procedures, Young Adult, Cesarean Section statistics & numerical data, Elective Surgical Procedures statistics & numerical data
- Abstract
Objective: to assess both clinical and non clinical factors associated with elective caesarean section practice and to highlight those typologies of expectant mothers who underwent elective caesarean delivery even in the absence of clinical risk factors., Setting and Participants: Birth Certificates archive has been used as data source: 62888 available records of all the births that occurred in the Campania region in 2005 both in public and private hospitals. Only those births pertained to women without previous caesarean sections were analyzed., Main Outcome Measures: type of delivery, dichotomized as elective caesarean section and vaginal delivery., Results: after adjusting the data for known risk factors, elective caesarean section practice emerged as much more prevalent in private hospitals than in public ones (53.1% vs 24.3%, p<0.001). A multivariate logistic regression model showed a significant association between primiparity and elective caesarean section. This association was stronger in private hospitals (OR for interaction between parity and hospital typology 1.81, CI 95% 1.62-2.04). Being older than 34 years, having recoursed to medically assisted procreation and a previous voluntary termination of pregnancy cause an increase in the odd of resorting to elective caesarean section (p<0.01). Being foreigner, high educational qualification and young age were protective factors for elective caesarean section (respectively, OR 0.36 CI 95% 0.31-0.42, OR 0.81 CI 95% 0.77-0.86 e OR 0.84 CI 95% 0.78 -0.90). Five different typologies of primiparous women were found by means of a hierarchical classification procedure. A high percentage of elective caesarean section was found in women assisted in private structure with no clinical risk., Conclusions: in Campania there is an excess of elective caesarean sections among primiparous women without manifest clinical risk factors; this excess is higher when the delivery occurs in Private Hospitals. Public health policy and actions aimed at reducing caesarean section rates should be addressed mainly to this typology of women.
- Published
- 2011
48. Subacute sclerosing panencephalitis: a case report.
- Author
-
Praticò AD, Saporito M, Iacono O, Castellano-Chiodo D, and Pavone P
- Subjects
- Antiviral Agents therapeutic use, Child, Disease Progression, Drug Therapy, Combination, Dysarthria, Electroencephalography, Female, Humans, Inosine Pranobex therapeutic use, Interferon-beta therapeutic use, Measles Vaccine adverse effects, Prognosis, Severity of Illness Index, Subacute Sclerosing Panencephalitis immunology, Subacute Sclerosing Panencephalitis therapy, Measles complications, Subacute Sclerosing Panencephalitis diagnosis
- Abstract
Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of childhood and early adolescence caused by persistent defective measles virus. Clinical manifestations appear many years after the acute measles infection. The incidence of SSPE has substantially declined after the introduction of an effective vaccine. We report a case of a child with SSPE that began with atonia, dysarthria, and intellectual deterioration without the presence of any particular EEG anomalies. We have reported this girl who was affected by this severe affliction in the hope that, because of the rarity of SSPE, it would not go undiagnosed.
- Published
- 2011
49. Lung abscess in a child with Mycoplasma pneumoniae infection.
- Author
-
Leonardi S, del Giudice MM, Spicuzza L, Saporito M, Nipitella G, and La Rosa M
- Subjects
- Child, Diagnosis, Differential, Follow-Up Studies, Humans, Lung Abscess diagnostic imaging, Male, Pneumonia, Mycoplasma diagnostic imaging, Pneumonia, Mycoplasma microbiology, Radiography, Thoracic, Tomography, X-Ray Computed, Lung Abscess microbiology, Mycoplasma pneumoniae isolation & purification, Pneumonia, Mycoplasma complications
- Abstract
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in children, while lung abscess is a severe complication of bacterial pneumonias caused mainly by pyogenes. Here we report a previously healthy 10-year-old boy admitted to our unit for a right upper lobe pneumonia, with a 15-day history of fever and cough insensitive to oral amoxicillin and intramuscular ceftriaxone. Chest computed tomography scan revealed that the right upper lobe consolidation was an abscess and that a similar formation was present in the right mid region. Serology allowed the diagnosis of M. pneumoniae infection. The clinical picture rapidly improved after initiation of oral clarithromycin, and radiographic resolution, without sequelae, was observed after 1-month treatment. Lung abscess in children is a rare complication of M. pneumoniae infection and only three previous cases have been described in the literature, all associated with a delayed diagnosis and late initiation of macrolide therapy. A long-term treatment with oral macrolide allows a prompt recovery and restitution ad integrum of the lung.
- Published
- 2010
- Full Text
- View/download PDF
50. CEP-11004, an inhibitor of the SAPK/JNK pathway, reduces TNF-alpha release from lipopolysaccharide-treated cells and mice.
- Author
-
Ciallella JR, Saporito M, Lund S, Leist M, Hasseldam H, McGann N, Smith CS, Bozyczko-Coyne D, and Flood DG
- Subjects
- Animals, Cell Line, Cell Survival drug effects, Dinoprostone biosynthesis, Dose-Response Relationship, Drug, Enzyme Activation drug effects, Enzyme-Linked Immunosorbent Assay, Humans, Interleukin-6 metabolism, MAP Kinase Kinase 4 metabolism, Mice, Mice, Inbred C57BL, Mitogen-Activated Protein Kinase 8 antagonists & inhibitors, Mitogen-Activated Protein Kinase 8 genetics, Monocytes cytology, Monocytes metabolism, Nitric Oxide biosynthesis, Phagocytosis drug effects, Phosphorylation drug effects, RNA, Messenger genetics, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction drug effects, Tumor Necrosis Factor-alpha genetics, p38 Mitogen-Activated Protein Kinases metabolism, Carbazoles pharmacology, Indoles pharmacology, Lipopolysaccharides pharmacology, Mitogen-Activated Protein Kinase 8 metabolism, Monocytes drug effects, Tumor Necrosis Factor-alpha metabolism
- Abstract
CEP-11004, a mixed lineage kinase (MLK) inhibitor, was examined for its effects on tumor necrosis factor-alpha (TNF-alpha) production in human THP-1 monocytes, mouse BV-2 microglia, and C57Bl/6 mice. CEP-11004 inhibited TNF-alpha secretion up to 90% in THP-1 cells incubated with 3 mug/ml lipopolysaccharide, with an IC50 of 137+/-14 nM. CEP-11004 also inhibited TNF-alpha production in lipopolysaccharide-stimulated microglial cells, but did not inhibit the initial increase in TNF-alpha mRNA expression as measured by real-time polymerase chain reaction (PCR). The mitogen-activated protein kinases (MAPKs) phospho-c-jun N-terminal kinase (JNK), phospho-p38, and phospho-MAPK kinase 4 (MKK4) levels were increased in THP-1 cells following lipopolysaccharide treatment, and were reduced by CEP-11004 treatment. For in vivo studies, CEP-11004 was injected 2 h prior to lipopolysaccharide (20 mg/kg) administration. CEP-11004 significantly inhibited TNF-alpha production at doses of 1-10 mg/kg as measured by enzyme-linked immunosorbent assay (ELISA). These results suggest that MLK blockade may be useful in inhibiting pro-inflammatory cytokine production in a wide range of diseases.
- Published
- 2005
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.