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Drug delivery has been greatly improved over the years by means of chemical and physical agents that increase bioavailability, improve pharmacokinetic and reduce toxicities. At the same time, cell based delivery systems have also been developed. These possesses a number of advantages including prolonged delivery times, targeting of drugs to specialized cell compartments and biocompatibility. Here we’ll focus on erythrocyte-based drug delivery. These systems are especially efficient in releasing drugs in circulations for weeks, have a large capacity, can be easily processed and could accommodate traditional and biologic drugs. These carriers have also been used for delivering antigens and/or contrasting agents. Carrier erythrocytes have been evaluated in thousands of drug administration in humans proving safety and efficacy of the treatments. Erythrocyte-based delivery of new and conventional drugs is thus experiencing increasing interests in drug delivery and in managing complex pathologies especially when side effects could become serious issues.
F. Pierigèa S. Serafinia L. Rossia M. MagnaniaEmail:mauro.magnani@uniurb.it
[a]Institute of Biological Chemistry “Giorgio Fornaini”, University of Urbino “Carlo Bo”, Urbino, Italy
Objective-To evaluate pulsed-wave Doppler spectral parameters as a method for distinguishing between neoplastic and inflammatory peripheral lymphadenopathy in dogs. Sample Population-40 superficial lymph nodes from 33 dogs with peripheral lymphadenopathy. Procedures-3 Doppler spectral tracings were recorded from each node. Spectral Doppler analysis including assessment of the resistive index, peak systolic velocity-to-end diastolic velocity (S:D) ratio, diastolic notch velocity-to-peak systolic velocity (N:S) ratio, and end diastolic velocity-to-diastolic notch velocity ratio was performed for each tracing. Several calculation methods were used to determine the Doppler indices for each lymph node. After the ultrasonographic examination, fine needle aspirates or excisional biopsy specimens of the examined lymph nodes were obtained, and lymphadenopathy was classified as either inflammatory or neoplastic (lymphomatous or metastatic) via cytologic or histologic examination. Results of Doppler analysis were compared with cytologic or histopathologic findings. Results-The Doppler index with the highest diagnostic accuracy was the S:D ratio calculated from the first recorded tracing; a cutoff value of 3.22 yielded sensitivity of 91%, specificity of 100%, and negative predictive value of 89% for detection of neoplasia. Overall diagnostic accuracy was 95%. At a sensitivity of 100%, the most accurate index was the N:S ratio calculated from the first recorded tracing; a cutoff value of 0.45 yielded specificity of 67%, positive predictive value of 81%, and overall diagnostic accuracy of 86.5%. Conclusions and Clinical Relevance-Results suggested that noninvasive Doppler spectral analysis may be useful in the diagnosis of neoplastic versus inflammatory peripheral lymphadenopathy in dogs.
Santa DD Gaschen L Doherr MG Citi S Marchetti V Lang J
Dipartimento di Clinica Veterinaria, Facolta di Medicina Veterinaria, Universita di Pisa, Via Livornese, San Piero a Grado (PI), Italy.
The concept of tissue and cell guidance is rapidly evolving as more information regarding the effect of the microenvironment on cellular function and tissue morphogenesis become available. These disclosures have lead to a tremendous advancement in the design of a new generation of multifunctional biomaterials able to mimic the molecular regulatory characteristics and the three-dimensional architecture of the native extracellular matrix. Micro- and nano-structured scaffolds able to sequester and deliver in a highly specific manner biomolecular moieties have already been proved to be effective in bone repairing, in guiding functional angiogenesis and in controlling stem cell differentiation. Although these platforms represent a first attempt to mimic the complex temporal and spatial microenvironment presented in vivo, an increased symbiosis of material engineering, drug delivery technology and cell and molecular biology may ultimately lead to biomaterials that encode the necessary signals to guide and control developmental process in tissue- and organ-specific differentiation and morphogenesis. Abbreviation list: bFGF; basic fibroblast growth factor; BMP; bone morphogenetic protein; BSA; bovine serum albumin; CASD; computer-aided scaffold design; DS; delivery systems; ECM; extracellular matrix; EGF; epidermal growth factor; EVAc; ethylene-vinyl acetate copolymers; GF; growth factor; HBDS; heparin-based delivery systems; NT-3; neurotrophin-3; PA; peptide amphiphile; PCL; poly(-caprolactone); PDGF; platelet derived growth factor; PEG; poly(ethylene glycol); PEO; poly(ethylene oxide); PLA; poly(lactide); PLGA; poly(lactide-co-glycolide); POE; poly(ortho esters); PTH; parathyroid hormone; SFF; solid free-form fabrication; TE; tissue engineering; TGF-β1; transforming growth factor-beta1; VEGF; vascular endothelial growth factor
Marco Biondia Francesca Ungaroa Fabiana Quagliaa Paolo Antonio NettiaEmail:nettipa@unina.it
[a]Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, Italy
PURPOSE: To assess the usefulness of CT virtual endoscopy (VE) as an integration of CT-urography, for the detection of upper urinary tract tumor in patients with hematuria. MATERIALS AND METHODS: Fourteen patients with hematuria and high risk of transitional cell carcinoma of the upper urinary tract underwent urinary cytology, ultrasonography, excretory urography, cystoscopy, CT-urography with VE, and optical ureteroscopy. The CT urograms and VE were correlated with the pathological findings of surgical specimen (6/14) and cytological examination of ureteroscopy biopsy (8/14). RESULTS: VE revealed three renal pelvic and one ureteral tumors, not producing further information did not detected at CT-urography. In two patients VE showed findings strongly indicative of malignancies, not noticed at CT-urography: ureteroscopic biopsy revealed an advanced dysplastic lesion and a malignancy, confirmed at surgery. In one patient VE was questionable (narrowing of the distal ureter) and ureteroscopic biopsy revealed an inflammation. Finally, VE diagnosed a fibrosis of the lumbar ureteral tract, confirmed at ureteroscopic biopsy. In other six patients, VE and ureteroscopy did not find abnormalities. CONCLUSION: VE should be useful as an integration of CT-urography for a complete evaluation of the upper urinary tract in patients with suspected tumor, limiting the need for fiberoptic ureteroscopic examination.
Battista G Sassi C Schiavina R Franceschelli A Baglivo E Martorana G Canini R
Clinical Department of Radiological and Histopatological Sciences, Divison of Diagnostic Imaging, S. Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, 40138, Bologna, Italy, giuseppe.battista@aosp.bo.it.
Contrast-enhanced ultrasound (CEUS) represents a significant breakthrough in sonography and it is being increasingly used for the evaluation of focal liver lesions (FLLs). The unique feature of CEUS of non-invasively assessing in real-time liver perfusion throughout the vascular phase has led to a dramatic improvement in diagnostic accuracy of US in either detection or characterization of FLLs, as well as in the guidance and evaluation of response of therapeutic procedures. Currently, CEUS is included as a part of the suggested diagnostic work-up of FLLs, resulting in a better patient management and cost-effective therapy delivering. After a brief description of the basis of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs, among hepatic pseudolesions, will be described and discussed on the basis of our experience and literature data. At the same time, the most recent concepts and the use of CEUS in different clinical settings will be presented.
Bartolotta TV Taibbi A Midiri M Lagalla R
Department of Radiology, University of Palermo, Via Del Vespro 127, Palermo, 90129, Italy, tv.bartolotta@unipa.it.
The purpose of this research was to study the compression force influence on polymers, tablet behavior; drug release rate. Several tablet batches were produced by varying the compression force; by using hydroxyethyl cellulose (HEC); Carbopol 940 in the 1:1 ratio as matrix forming polymers. All batches were characterized by DSC; X-ray analyses; in terms of swelling, ex vivo; in vivo mucoadhesive time, ex vivo mucoadhesion force,; in vitro; in vivo release. No significant excipient–excipient or excipient–drug interactions were observed in any of the batches. All the tablets hydrated quickly; their high hydration percentage showed that the compression forces used did not remarkably affect the water penetration; the polymeric chain stretching. Mucoadhesion performances; drug release were mainly influenced by compression force; its increase produced higher ex vivo; in vivo mucoadhesion; the in vitro; in vivo drug releases were seen to decrease with the increase of the compression force. However tablets fabricated by using the lowest compression force showed the best in vivo mucoadhesive time; hydrated faster when compared to the others. Tablets 4; 5, prepared with the highest forces, caused pain during in vivo application; gave rise to irritation needing to be detached by the volunteers while tablet 1, prepared with the lowest force, gave the best results because it was able to produce the highest drug salivary concentration; no pain. All tablets exhibited an anomalous release mechanism.
Luana Perioli1 Email:luanaper@unipg.it Valeria Ambrogi1 Stefano Giovagnoli1 Paolo Blasi1 Aless ra Mancini1 Maurizio Ricci1 Carlo Rossi1
[1] Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia, Via del Liceo, 1, Perugia, 06123, Italy
Many physiological processes of domestic animals exhibit daily rhythmicity. The goal of the present study was to investigate the daily rhythms of calcium, inorganic phosphorus and 24,25-(OH)2-D3, 25-(OH)-D3 and 1,25-(OH)2-D3 in the blood serum of horses. Five Thoroughbred mares from the same farm, clinically healthy and placed in individual stalls, at the same environmental temperature and photoperiod were used. For 30 days prior to the study, the animals underwent the same pattern of daily activity. Blood samples were collected at 4 h-intervals for 48 consecutive h, starting at 08:00 h of the first day and finishing at 04:00 h of the second day, via intravenous cannula inserted into the jugular vein. Each individual sample was assessed for serum concentration of calcium and inorganic phosphorus by means of a UV spectrophotometric test, and serum concentration of 24, 25-(OH)-D3, 25-(OH)-D3, and 1,25-(OH)2-D3 were assessed by means of HPLC method. Data analysis was conducted by one-way repeated measures analysis of variance (ANOVA) and by the single cosinor method. ANOVA showed a significant effect of time on all the variables studied (p<0.0001) and post-hoc test (SNK) showed significant differences (p<0.001) comparing all the time intervals of 4 h, on either day. The application of the periodic model and the statistical analysis of the cosinor procedure allowed defining the periodic variables and their acrophases (expressed in hours) during the 2 days of monitoring. Calcium showed diurnal acrophases at 15:00 h for the 1st day and at 15:48 for the 2nd day; inorganic phosphorus showed diurnal coincident acrophases at 14:32 h both for the 1st and 2nd day and 25-(OH)-D3 showed diurnal acrophases at 14:08 h for the 1st day and at 15:04 h for the 2nd day. The results obtained could be useful for standardizing blood sampling according to the time of day and for optimizing the administration of these substances according to their circadian or other rhythms.
Piccione, G. Assenza, A. Fazio, F. Bergero, D. Caola, G.
Department of Experimental Science and Applied Biotechnology, Laboratory of Veterinary Chronophysioloey, Faculty of Veterinary Medicine University of Messina, Polo Universitario dell’Annunziata, 98168 Messina, Italy.