Plasma pharmacokinetics, faecal excretion and efficacy of pyrantel pamoate paste and granule formulations following per os administration in donkeys naturally infected with intestinal strongylidae

The plasma disposition, faecal excretion and efficacy of two formulations of pyrantel pamoate in donkeys were examined in a controlled trial. Three groups of seven donkeys received either no medication (control) or pyrantel paste or granule formulations at horse dosage of 20mg/kg B.W. (equals 6.94 mg/kg PYR base) of body weight. Heparinized blood and faecal samples were collected at various times between 1 and 144 h after treatment. The samples were analysed by high-performance liquid chromatography. The last detectable plasma concentration (tmax) of paste formulation was significantly earlier (36.00 h) compared with granule formulation (46.29 h). Although, there was no significant difference on terminal half lives (t1/2: 12.39 h vs. 14.86 h), tmax (14.86 h vs. 14.00) and MRT (24.80 h vs. 25.44 h) values; the Cmax (0.09 ??g/ml) AUC (2.65 ??gh/ml) values of paste formulation were significantly lower and smaller compared with those of granule formulation (0.21 ??g/ml and 5.60 ??gh/ml), respectively. The highest dry faecal concentrations were 710.46 ??g/g and 537.21 ??g/g and were determined at 48 h for both paste and granule formulation of PYR in donkeys, respectively. Pre-treatment EPG of 1104, 1061 and 1139 were observed for the control, PYR paste and PYR granule groups, respectively. Pre-treatment EPG were not significantly different (P>0.1) between groups. Post-treatment EPG for both PYR treatment groups were significantly different (P95% efficacy) until day 28. In all studied donkeys, coprocultures performed at day-3 revealed the presence of Cyathostomes, S. vulgaris. Faecal cultures performed on different days from C-group confirmed the presence of the same genera. Coprocultures from treated animals revealed the presence of few larvae of Cyathostomes

Peptide-based hydrogels and nanogels for delivery of doxorubicin

Introduction: The clinical use of the antitumoral drug doxorubicin (Dox) is reduced by its dose-limiting toxicity, related to cardiotoxic side effects and myelosuppression. In order to overcome these drawbacks, here we describe the synthesis, the structural characterization and the in vitro cytotoxicity assays of hydrogels (HGs) and nanogels (NGs) based on short peptide sequences loaded with Dox or with its liposomal formulation, Doxil. Methods: Fmoc-FF alone or in combination with (FY)3 or PEG8-(FY)3 peptides, at two different ratios (1/1 and 2/1 v/v), were used for HGs and NGs formulations. HGs were prepared according to the “solvent-switch” method, whereas NGs were obtained through HG submicroni-tion by the top-down methodology in presence of TWEEN®60 and SPAN®60 as stabilizing agents. HGs gelation kinetics were assessed by Circular Dichroism (CD). Stability and size of NGs were studied using Dynamic Light Scattering (DLS) measurements. Cell viability of empty and filled Dox HGs and NGs was evaluated on MDA-MB-231 breast cancer cells. Moreover, cell internalization of the drug was evaluated using immunofluorescence assays. Results: Dox filled hydrogels exhibit a high drug loading content (DLC=0.440), without syneresis after 10 days. Gelation kinetics (20–40 min) and the drug release (16–28%) over time of HGs were found dependent on relative peptide composition. Dox filled NGs exhibit a DLC of 0.137 and a low drug release (20–40%) after 72 h. Empty HGs and NGs show a high cell viability (>95%), whereas Dox loaded ones significantly reduce cell viability after 24 h (49–57%) and 72 h (7–25%) of incubation, respectively. Immunofluorescence assays evidenced a different cell localization for Dox delivered through HGs and NGs with respect to the free drug. Discussion: A modulation of the Dox release can be obtained by changing the ratios of the peptide components. The different cellular localization of the drug loaded into HGs and NGs suggests an alternative internalization mechanism. The high DLC, the low drug release and preliminary in vitro results suggest a potential employment of peptide-based HGs and NGs as drug delivery tools

Self-supporting hydrogels based on fmoc-derivatized cationic hexapeptides for potential biomedical applications

Peptide-based hydrogels (PHGs) are biocompatible materials suitable for biological, biomedical, and biotechnological applications, such as drug delivery and diagnostic tools for imaging. Recently, a novel class of synthetic hydrogel-forming amphiphilic cationic peptides (referred to as series K), containing an aliphatic region and a Lys residue, was proposed as a scaffold for bioprinting applications. Here, we report the synthesis of six analogues of the series K, in which the acetyl group at the N-terminus is replaced by aromatic portions, such as the Fmoc protecting group or the Fmoc-FF hydrogelator. The tendency of all peptides to self-assemble and to gel in aqueous solution was investigated using a set of biophysical techniques. The structural characterization pointed out that only the Fmoc-derivatives of series K keep their capability to gel. Among them, Fmoc-K3 hydrogel, which is the more rigid one (G’ = 2526 Pa), acts as potential material for tissue engineering, fully supporting cell adhesion, survival, and duplication. These results describe a gelification process, allowed only by the correct balancing among aggregation forces within the peptide sequences (e.g., van der Waals, hydrogen bonding, and π–π stacking)

Adolescent and parent use of new technologies for health communication: a study in an urban Latino community

Background. Mobile communication technologies provide novel opportunities to support clinic-based health initiatives. Adoption of technologies for daily use and for health communication can differ between communities, depending upon demographic and cultural characteristics. Design and methods. A survey was administered in adolescent primary care and subspecialty clinics to assess parent-adolescent preferences in use of mobile technologies and social media to support provider-patient communication in an urban Latino community. Results. Of 130 respondents (65 parent-adolescent pairs), approximately half frequently sent and received text messages but lacked agreement regarding the other’s text messaging use. In contrast, adolescents only rarely used email compared to parents (15.4% versus 37.5%, P=0.006). Of social media, FacebookTM/MySpaceTM was most frequently used by parents and youth (60% and 55.4%, P=0.59); however, most lacked interest in using social media for health communication. Parents reported more interest than adolescents in receiving email (73.4% versus 35.9%, P<0.001) and text messages (58.5% versus 33.9%, P=0.005) for health, but had more concerns about privacy issues (26.2% versus 9.2%, P=0.01). Respondents who were American born (aOR 5.7, 95%CI 1.2-28.5) or regularly used Instant Messaging or FacebookTM/MySpaceTM (aOR 4.6, 95%CI 1.4-14.7) were more likely to be interested in using social media for health communication. Conclusions. These findings underscore the importance of targeted assessment for planning the utilization of communication technologies and social media in clinical care or research for underserved youth

Management of Bladder Cancer following Solid Organ Transplantation

Objective. Present our experience managing bladder cancer following liver and renal transplantation. Methods. Single institution retrospective review of patients diagnosed with bladder urothelial carcinoma (BUC) following solid organ transplantation between January 1992 and December 2007. Results. Of the 2,925 renal and 2,761 liver transplant recipients reviewed, we identified eleven patients (0.2%) following transplant diagnosed with BUC. Two patients with low grade T1 TCC were managed by TURBT. Three patients with CIS and one patient with T1 low grade BUC were treated by TURBT and adjuvant BCG. All four are alive and free of recurrence at a mean follow-up of 51 ± 22 months. One patient with T1 high grade BUC underwent radical cystectomy and remains disease free with a follow-up of 98 months. Muscle invasive TCC was diagnosed in four patients at a median of 3.6 years following transplantation. Two patients are recurrence free at 24 and 36 months following radical cystectomy. Urinary diversion and palliative XRT were performed in one patient with un-resectable disease. Conclusions. Bladder cancer is uncommon following renal and liver transplantation, but it can be managed successfully with local and/or extirpative therapy. The use of intravesical BCG is possible in select immunosuppressed patients

Microbiological, rheological and physical-chemical characteristics of bovine meat subjected to a prolonged ageing period

he aim of this study was to evaluate the effects of a long ageing period on the microbiological, rheological and physical-chemical characteristics of bovine beef. For the trial n. 3 Marchigiana bovine breed (live weight of 760 kg approximately), slaughtered at 34 months were chosen and the loin muscles were undergone to a prolonged ageing process. The analytical determinations performed were: pH and aw values, texture profile analysis, Warner-Bratzler shear force, colour (CIE L*a*b*), centesimal analysis, total bacterial count, Enterobacteriaceae, Listeria monocytogenes, yeasts and moulds. The results indicate that extended ageing has a negative effect on weight loss but, by the means of the standardization of dry aging parameters, reduce lipid oxidation and improve tendernes

Implantation of Autologous Bone-Marrow-Derived Cells Reconstructs Functional Urethral Sphincters in Rabbits

The purpose of this study was to determine if implantation of autologous bone-marrow-derived cells has the potential to treat stress urinary incontinence caused by intrinsic sphincter deficiency. Bone marrow cells harvested from femurs of New Zealand White rabbits were cultured for 10 days. Seven days before implantation, the urethral sphincters located at the internal urethral orifice were cryo-injured by spraying liquid nitrogen for 15 s. The cultured autologous bone-marrow-derived cells were implanted 7 days after cryo-injury. For controls, cell-free solutions were injected. At 7 and 14 days after implantation, leak point pressures were determined and the urethral sphincters were examined by immunohistochemistry. At 7 and 14 days, the cell-implanted regions contained numerous striated and smooth muscle-like cells expressing myoglobin and smooth muscle actin, respectively. The proportions of myoglobin- and smooth muscle actin-expressing areas in both the 7- and 14-day cell-implanted regions were significantly higher than in controls. By 14 days, these differentiated cells formed contacts with similar cells, creating layered muscle structures. At that time, the leak point pressure of the cell-implanted rabbits was significantly higher than that of the controls. In conclusion, autologous bone-marrow-derived cells can reconstruct functional urethral sphincters.ArticleTISSUE ENGINEERING PART A. 17(41098):1069-1081 (2011)journal articl