A method to Quantify the Affinity of Cabazitaxel for PLA-PEG Nanoparticles and Investigate the Influence of the Nano-Assembly Structure on the Drug/Particle Association.

PURPOSE: To study the impact of the size and the structure of the nano-assembly on the drug/particle association, determining the intrinsic partition coefficient, in order to better master the encapsulation and release properties of the carrier. METHODS: An experimental methodology is proposed to characterize the drug/nanoparticle association by mean of a partition coefficient between the PLA-PEG nanoparticles and the suspending aqueous medium, referred to as Kp. The determination was made from apparent values (referred to as Kp (ap)) measured in the presence of solubilizing agents (albumin and hydroxypropyl-ßcyclodextrin) and extrapolation to zero concentration. The structure of nanoparticles was investigated by Transmission Electron Microscopy and static light scattering. RESULTS: Depending on the manufacturing process and the PEG length of the copolymer, the nanoparticles structured either as aggregates of copolymer chains or micelles exhibiting significantly different Kp values. CONCLUSION: The methodological tool described here showed that the difference in cabazitaxel/nanoparticle association between aggregates and micelles could be attributed to the difference in PLA-PEG chains packing.

Effects of etanercept, a tumour necrosis factor-alpha antagonist, in an experimental model of periodontitis in rats.

BACKGROUND AND PURPOSE: Etanercept is a tumour necrosis factor antagonist with anti-inflammatory effects. The aim of our study was to evaluate, for the first time, the therapeutic efficacy of in vivo inhibition of TNF-alpha in an experimental model of periodontitis. EXPERIMENTAL APPROACH: Periodontitis was induced in adult male Sprague-Dawley rats by placing a nylon thread ligature around the lower 1st molars. Etanercept was administered at a dose of 5 mg kg-1, s.c., after placement of the ligature. KEY RESULTS: Periodontitis in rats resulted in an inflammatory process characterized by oedema, neutrophil infiltration and cytokine production that was followed by the recruitment of other inflammatory cells, production of a range of inflammatory mediators, tissue damage, apoptosis and disease. Treatment of the rats with etanercept (5 mg kg-1, s.c., after placement of the ligature) significantly reduced the degree of (1) periodontitis inflammation and tissue injury (histological score), (2) infiltration of neutrophils (MPO evaluation), (3) iNOS (the expression of nitrotyrosine and cytokines (eg TNF-alpha)) and (4) apoptosis (Bax and Bcl-2 expression). CONCLUSIONS AND IMPLICATIONS: Taken together, our results clearly demonstrate that treatment with etanercept reduces the development of inflammation and tissue injury, events associated with periodontitis.

Intensity-modulated radiotherapy: first results with this new technology on neoplasms of the head and neck.

Intensity-modulated beam radiotherapy (IMRT) delivers a highly conformal, three-dimensional (3-D) distribution of radiation doses that is not possible with conventional methods. When administered to patients with head and neck tumors, IMRT allows for the treatment of multiple targets with different doses, while simultaneously minimizing radiation to uninvolved critical structures such as the parotid glands, optic chiasm, and mandible. With 3-D computerized dose optimization, IMRT is a vast improvement over the customary trial-and-error method of treatment planning. We retrospectively reviewed the charts of the first 28 head and neck patients at our institution who were treated with IMRT. All had head and neck neoplasms, including squamous cell carcinoma, adenoid cystic carcinoma, paraganglioma, and angiofibroma. Total radiation doses ranged from 1,400 to 7,100 cGy, and daily doses ranged from 150 to 400 cGy/day. A quality assurance system ensured that computer-generated dosimetry matched film dosimetry in all cases. For midline tumors, this system allowed us to decrease the dose to the parotid glands to less than 3,000 cGy. The incidence of acute toxicity was drastically lower than that seen with conventional radiotherapy delivery to similar sites. This is the first report of the application of IMRT strictly to head and neck neoplasms. We discuss the indications, technique, and initial results of this promising new technology. We also introduce the concept of the Simultaneous Modulated Accelerated Radiation Therapy boost technique, which has several advantages over other altered fractionation schemes.

[Fibrin glue in free gingival grafts]. / La colla di fibrina negli innesti gengivali liberi.

The clinical use of tissucol in the surgery of free gingival grafts has been considered. The positive results obtained encourage continuation of its use and the extension of its fields of application.

[Roxithromycin in dental infections]. / La roxitromicina nelle infezioni odontostomatologiche.

Roxithromicin is a semisynthetic macrolide antibiotic, with similar antibacterial activity to erythromycin. It is characterized by an excellent pharmacokinetic profile and a good tissue penetration. Particularly at the dose of 300 mg per day the dental tissue diffusion is extremely good, and this is important to oppose the oral cavity infections. Oral cavity infections can be either odontogenic or non odontogenic. Odontogenic infections are typically primary and are caused by commensal bacteria (oral Streptococci, Bacteroides sp., Veillonella sp. and Fusobacterium sp.). The antibacterial spectrum of roxithromycin is very large and includes many of the most frequent strains responsible for oral cavity infections. A very interesting characteristic of roxithromycin is its penetration in macrophages (uptake) that allow a more rapid inhibition of bacterial activity. To evaluate the clinical efficacy and tolerance of roxithromycin in the treatment of odontogenic infections, an open study was performed. This study evaluated both the microbiological and clinical aspects. Thirty patients (21 females and 9 males) who had not been previously treated with antibiotic or antibacterial drugs, affected by infective dysodontiasis, gingivitis and periodontal diseases, received 300 mg per day (once a day) of roxithromycin for an average period of 6 days. The symptomatology considered was: intumescence, redness, pain, lymphangitis and presence of trismus. Clinical symptomatology was assessed at the start and at the end of the treatment. The symptomatological improvement due to roxithromycin was rapid and very effective. After 6 days of therapy, the improvement was statistically significant (p < 0.01) compared to basal conditions. No adverse reactions or side-effects were complained during the study. No changement were detected in laboratory parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Histologic evaluation of absorbable and non-absorbable barrier coated mesh secured to the peritoneum with fibrin sealant in a New Zealand white rabbit model.

PURPOSE: The purpose of this study is to evaluate the histologic response to fibrin sealant (FS) as an alternative fixation method for laparoscopic ventral hernia repair. METHODS: One non-absorbable barrier mesh (Composix™) and three absorbable barrier meshes (Sepramesh™, Proceed™, and Parietex™ Composite) were used for the study, with uncoated macroporous polypropylene mesh (ProLite Ultra™) as the control. Three methods of fixation were used: #0-polypropylene suture + FS (ARTISS™, Baxter Healthcare Corp.), FS alone (ARTISS™), or tacks alone (n = 10 for each group). Two pieces of mesh (of dimensions 4 × 4-cm) were secured intraperitoneally in 75 New Zealand white rabbits. After 8 weeks, hematoxylin and eosin (H&E)-stained specimens were evaluated for host tissue response. Statistical significance (P < 0.05) was determined using a one-way analysis of variance (ANOVA) with Fisher's least significant difference (LSD) post hoc test. RESULTS: Composix™ with FS only showed significantly greater cellular infiltration than with suture + FS (P = 0.0007), Proceed™ with FS only had significantly greater neovascularization than with suture + FS (P = 0.0172), and ProLite Ultra™ with suture + FS had significantly greater neovascularization than with tacks only (P = 0.046). Differences due to mesh type showed that Composix™ exhibited less extensive cellular infiltration (P ≤ 0.0032), extracellular matrix (ECM) deposition, and neovascularization, and demonstrated less inflammatory cells and more fibroblasts compared to the other meshes (P < 0.05). CONCLUSIONS: FS did not have a significant histologic effect compared to tacks when utilized for the fixation of mesh to the peritoneum of New Zealand White rabbits. However, the mesh type did have a significant histologic effect. The permanent barrier mesh (Composix™) was associated with less histologic incorporation than absorbable barrier and macroporous meshes, as evidenced by lower levels of cellular infiltration, ECM deposition, and neovascularization, independent of the fixation method used.

Histologic and biomechanical evaluation of a novel macroporous polytetrafluoroethylene knit mesh compared to lightweight and heavyweight polypropylene mesh in a porcine model of ventral incisional hernia repair.

PURPOSE: To evaluate the biocompatibility of heavyweight polypropylene (HWPP), lightweight polypropylene (LWPP), and monofilament knit polytetrafluoroethylene (mkPTFE) mesh by comparing biomechanics and histologic response at 1, 3, and 5 months in a porcine model of incisional hernia repair. METHODS: Bilateral full-thickness abdominal wall defects measuring 4 cm in length were created in 27 Yucatan minipigs. Twenty-one days after hernia creation, animals underwent bilateral preperitoneal ventral hernia repair with 8 × 10 cm pieces of mesh. Repairs were randomized to Bard(®)Mesh (HWPP, Bard/Davol, http://www.davol.com), ULTRAPRO(®) (LWPP, Ethicon, http://www.ethicon.com), and GORE(®)INFINIT Mesh (mkPTFE, Gore & Associates, http://www.gore.com). Nine animals were sacrificed at each timepoint (1, 3, and 5 months). At harvest, a 3 × 4 cm sample of mesh and incorporated tissue was taken from the center of the implant site and subjected to uniaxial tensile testing at a rate of 0.42 mm/s. The maximum force (N) and tensile strength (N/cm) were measured with a tensiometer, and stiffness (N/mm) was calculated from the slope of the force-versus-displacement curve. Adjacent sections of tissue were stained with hematoxylin and eosin (H&E) and analyzed for inflammation, fibrosis, and tissue ingrowth. Data are reported as mean ± SEM. Statistical significance (P < 0.05) was determined using a two-way ANOVA and Bonferroni post-test. RESULTS: No significant difference in maximum force was detected between meshes at any of the time points (P > 0.05 for all comparisons). However, for each mesh type, the maximum strength at 5 months was significantly lower than that at 1 month (P < 0.05). No significant difference in stiffness was detected between the mesh types or between timepoints (P > 0.05 for all comparisons). No significant differences with regard to inflammation, fibrosis, or tissue ingrowth were detected between mesh types at any time point (P > 0.09 for all comparisons). However, over time, inflammation decreased significantly for all mesh types (P < 0.001) and tissue ingrowth reached a slight peak between 1 and 3 months (P = 0.001) but did not significantly change thereafter (P > 0.09). CONCLUSIONS: The maximum tensile strength of mesh in the abdominal wall decreased over time for HWPP, LWPP, and mkPTFE mesh materials alike. This trend may actually reflect inability to adequately grip specimens at later time points rather than any mesh-specific trend. Histologically, inflammation decreased with time (P = 0.000), and tissue ingrowth increased (P = 0.019) for all meshes. No specific trends were observed between the polypropylene meshes and the monofilament knit PTFE, suggesting that this novel construction may be a suitable alternative to existing polypropylene meshes.

Early biocompatibility of crosslinked and non-crosslinked biologic meshes in a porcine model of ventral hernia repair.

PURPOSE: Biologic meshes have unique physical properties as a result of manufacturing techniques such as decellularization, crosslinking, and sterilization. The purpose of this study is to directly compare the biocompatibility profiles of five different biologic meshes, AlloDerm(®) (non-crosslinked human dermal matrix), PeriGuard(®) (crosslinked bovine pericardium), Permacol(®) (crosslinked porcine dermal matrix), Strattice(®) (non-crosslinked porcine dermal matrix), and Veritas(®) (non-crosslinked bovine pericardium), using a porcine model of ventral hernia repair. METHODS: Full-thickness fascial defects were created in 20 Yucatan minipigs and repaired with the retromuscular placement of biologic mesh 3 weeks later. Animals were euthanized at 1 month and the repair sites were subjected to tensile testing and histologic analysis. Samples of unimplanted (de novo) meshes and native porcine abdominal wall were also analyzed for their mechanical properties. RESULTS: There were no significant differences in the biomechanical characteristics between any of the mesh-repaired sites at 1 month postimplantation or between the native porcine abdominal wall without implanted mesh and the mesh-repaired sites (P > 0.05 for all comparisons). Histologically, non-crosslinked materials exhibited greater cellular infiltration, extracellular matrix (ECM) deposition, and neovascularization compared to crosslinked meshes. CONCLUSIONS: While crosslinking differentiates biologic meshes with regard to cellular infiltration, ECM deposition, scaffold degradation, and neovascularization, the integrity and strength of the repair site at 1 month is not significantly impacted by crosslinking or by the de novo strength/stiffness of the mesh.

[Use of the Maryland bridge in periodontology]. / Applicazione del Maryland bridge in parodontologia.

The authors have reported the investigations about the Maryland Bridge and its importance in periodontology. The Authors have suggested the clinical application of this kind of prosthesis and the Authors have reported about two clinical cases that have had first a periodontal treatment then a Maryland Bridge prosthesis.

[Periodontal disease during pregnancy]. / Considerazioni cliniche sulle paradenziopatie nel corso della gravidanza.

The authors have reported three clinical cases of gingivitis during the pregnancy in the women. These gingivitis were noticed more frequently during the end of the second and the third quarter. The patients were educated to maintain a better oral hygiene and they were treated with scaling and root-planing to obtain the periodontal healing.

[Effect of spiramycin on the interbacterial aggregation process in dental plaque formation]. / Interferenza della spiramicina sui processi di aggregazione interbatterica nella formazione della placca dentale.

The Authors valued on 18 periodontal patients the bleeding, probing depth, plaque indexes before and after antibiotic therapy with spiramycin. After bacteriological test and coaggregation test the Authors concluded spiramycin all day long is endowed with a good activity in periodontal diseases.

Oral contrast enhanced bowel ultrasonography in the assessment of small intestine Crohn's disease. A prospective comparison with conventional ultrasound, x ray studies, and ileocolonoscopy.

UNLABELLED: BACKGROUND/ AIM: Although ultrasound (US) has proved to be useful in intestinal diseases, barium enteroclysis (BE) remains the gold standard technique for assessing patients with small bowel Crohn's disease (CD). The ingestion of anechoic non-absorbable solutions has been recently proposed in order to distend intestinal loops and improve small bowel visualisation. The authors' aim was to evaluate the accuracy of oral contrast US in finding CD lesions, assessing their extent within the bowel, and detecting luminal complications, compared with BE and ileocolonoscopy. METHODS: 102 consecutive patients with proven CD, having undergone complete x ray and endoscopic evaluation, were enrolled in the study. Each US examination, before and after the ingestion of a polyethylene glycol (PEG) solution (500-800 ml), was performed independently by two sonographers unaware of the results of other diagnostic procedures. The accuracy of conventional and contrast enhanced US in detecting CD lesions and luminal complications, as well as the extent of bowel involvement, were determined. Interobserver agreement between sonographers with both US techniques was also estimated. RESULTS: After oral contrast, satisfactory distension of the intestinal lumen was obtained in all patients, with a mean time to reach the terminal ileum of 31.4 (SD 10.9) minutes. Overall sensitivity of conventional and oral contrast US in detecting CD lesions were 91.4% and 96.1%, respectively. The correlation coefficient between US and x ray extent of ileal disease was r1 = 0.83 (p<0.001) before and r2 = 0.94 (p<0.001) after PEG ingestion; r1 versus r2 p<0.01. Sensitivity in detecting strictures was 74% for conventional US and 89% for contrast US. Overall interobserver agreement for bowel wall thickness and disease location within the small bowel was already good before but significantly improved after PEG ingestion. CONCLUSIONS: Oral contrast bowel US is comparable with BE in defining anatomic location and extension of CD and superior to conventional US in detecting luminal complications, as well as reducing interobserver variability between sonographers. It may be therefore regarded as the first imaging procedure in the diagnostic work up and follow up of small intestine CD.