Mechanistic analysis of PLGA/HPMC-based in-situ forming implants for periodontitis treatment.

In-situ forming implant formulations based on poly(lactic-co-glycolic acid) (PLGA), acetyltributyl citrate (ATBC), minocycline HCl, N-methyl pyrrolidone (NMP) and optionally hydroxypropyl methylcellulose (HPMC) were prepared and thoroughly characterized in vitro. This includes electron paramagnetic resonance (EPR), nuclear magnetic resonance ((1)H NMR), mass change and drug release measurements under different conditions, optical microscopy, size exclusion chromatography (SEC) as well as antibacterial activity tests using gingival crevicular fluid samples from periodontal pockets of periodontitis patients. Based on these results, deeper insight into the physico-chemical phenomena involved in implant formation and the control of drug release could be gained. For instance, the effects of adding HPMC to the formulations, resulting in improved implant adherence and reduced swelling, could be explained. Importantly, the in-situ formed implants effectively hindered the growth of bacteria present in the patients' periodontal pockets. Interestingly, the systems were more effectively hindering the growth of pathogenic bacterial strains (e.g., Fusobacterium nucleatum) than that of strains with a lower pathogenic potential (e.g., Streptococcus salivarius). In vivo, such a preferential action against the pathogenic bacteria can be expected to give a chance to the healthy flora to re-colonize the periodontal pockets.

In-vivo monitoring of acute DSS-Colitis using Colonoscopy, high resolution Ultrasound and bench-top Magnetic Resonance Imaging in Mice.

OBJECTIVE: The aim of this study was to establish and evaluate (colour Doppler-) high-resolution-ultrasound (hrUS) and bench-top magnetic resonance imaging (btMRI) as new methods to monitor experimental colitis. MATERIALS AND METHODS: hrUS, btMRI and endoscopy were performed in mice without colitis (n = 15), in mice with acute colitis (n = 14) and in mice with acute colitis and simultaneous treatment with infliximab (n = 19). RESULTS: Determination of colon wall thickness using hrUS (32 MHz) and measurement of the cross-sectional colonic areas by btMRI allowed discrimination between the treatment groups (mean a vs. b vs. c - btMRI: 922 vs. 2051 vs. 1472 pixel, hrUS: 0.26 vs. 0.45 vs. 0.31 mm). btMRI, endoscopy, hrUS and colour Doppler-hrUS correlated to histological scoring (p < 0.05), while endoscopy and btMRI correlated to post-mortem colon length (p < 0.05). CONCLUSIONS: The innovative in vivo techniques btMRI and hrUS are safe and technically feasible. They differentiate between distinct grades of colitis in an experimental setting, and correlate with established post-mortem parameters. In addition to endoscopic procedures, these techniques provide information regarding colon wall thickness and perfusion. Depending on the availability of these techniques, their application increases the value of in vivo monitoring in experimental acute colitis in small rodents. KEY POINTS: • Improved in vivo monitoring might balance interindividual differences in murine colitis. • In monitoring murine colitis, btMRI and hrUS are safe and technically feasible. • Very short examination times underline the usefulness especially of hrUS. • Results of btMRI and hrUS correlate with endoscopic and post-mortem findings.

In-situ forming composite implants for periodontitis treatment: How the formulation determines system performance.

Periodontitis is the primary cause of tooth loss in adults and a very wide-spread disease. Recently, composite implants, based on a drug release rate controlling polymer and an adhesive polymer, have been proposed for an efficient local drug treatment. However, the processes involved in implant formation and the control of drug release in these composite systems are complex and the relationships between the systems' composition and the implants' performance are yet unclear. In this study, advanced characterization techniques (e.g., electron paramagnetic resonance, EPR) were applied to better understand the in-situ forming implants based on: (i) different types of poly(lactic-co-glycolic acid) (PLGA) as drug release rate controlling polymers; (ii) hydroxypropyl methylcellulose (HPMC) as adhesive polymer; and (iii) doxycycline or metronidazole as drugs. Interestingly, HPMC addition to shorter chain PLGA slightly slows down drug release, whereas in the case of longer chain PLGA the release rate substantially increases. This opposite impact on drug release was rather surprising, since the only difference in the formulations was the polymer molecular weight of the PLGA. Based on the physico-chemical analyses, the underlying mechanisms could be explained as follows: since longer chain PLGA is more hydrophobic than shorter chain PLGA, the addition of HPMC leads to a much more pronounced facilitation of water penetration into the system (as evidenced by EPR). This and the higher polymer lipophilicity result in more rapid PLGA precipitation and a more porous inner implant structure. Consequently, drug release is accelerated. In contrast, water penetration into formulations based on shorter chain PLGA is rather similar in the presence and absence of HPMC and the resulting implants are much less porous than those based on longer chain PLGA.

Fabrication and characterization of a biomimetic composite scaffold for bone defect repair.

For successful bone tissue engineering, scaffolds with tailored properties are a basic requirement. The combination of different available materials not only appears to be desirable but also very challenging. In this study, a composite material consisting of hydroxyapatite and collagen was produced by a biomimetic precipitation method and characterized by X-ray diffraction (XRD) and thermogravimetry (TGA). Subsequently, a suspension-quick-freezing and lyophilization method was used to incorporate the hydroxyapatite into a polymeric matrix consisting of collagen and chitosan. Before physicochemical characterization, the highly porous scaffolds were consolidated by a dehydrothermal treatment (DHT). The main attention was focused on the particle size of hydroxyapatite, which should be in the nanometer range. This is relevant to achieve a homogeneous resorption of the material by osteoclasts. Small-angle X-ray scattering (SAXS), atomic force microscopy (AFM), and environmental scanning electron microscopy (ESEM) were used to evaluate the outcome. The results suggest a successful polymeric embedding of nanoscaled hydroxyapatite particles into the matrix of the spongy construct. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

[CT-computer-template-assisted planning of implant and magnet position in epi-prosthetic management of facial defects]. / CT-Computer-Schablonengestützte Planung der Implantat- und Magnetposition bei der epithetischen Versorgung von Gesichtsdefekten.

BACKGROUND: The aesthetic result of a prosthetic reconstruction in the facial area depends on precise, long-term stable positioning of the facial prosthesis. For fixation of the facial prosthesis and contouring of the soft tissue, good long-term success can be achieved by implant-magnet systems. The precise positioning of the implants and magnets when only little bone is available is difficult and without any planning is often not possible. COMPUTER EVALUATION: Computer-supported evaluation of CT data with the aid of CT and drill templates can optimise the planning and carrying out of surgery. This procedure is illustrated with reference to the treatment of a patient following obital exenteration due to an embryonic rhabdomyosarcoma. The programs SIM/Plant and coDiagnostiX were compared with one another when carrying out the CT evaluation and planning the orbital prosthesis. In so doing, the great advantage of the definition of the CT window (grey levels), the freely definable panorama sections and cross-sections, as well as the three-dimensional, spatial representation using the programme coDiagnostiX on a conventional PC are made clear. The results of planning can be applied and implemented during surgery, with the aid of the CT and drill templates. DISCUSSION: The CT computer template-supported procedure is suitable for routine clinical use and can be recommended for planning of implant-fixed facial prosthesis in the orbital area when little bone is available or in the case of difficult anatomical relationships.

Giant orbital cyst after strabismus surgery.

We describe the clinical, histopathologic, and radiologic findings and management of a patient who had a giant orbital cyst after reoperative strabismus surgery. In the case report, we describe, in detail, a giant orbital cyst developing on the medial side of the globe after the third operation for repair of strabismus. Imaging studies, including computed tomographic (CT) scan and orbital ultrasound, demonstrate the findings. The observations at surgery and the surgical pathologic condition of the cyst are described. The orbital cyst was successfully removed, advancing the remaining medial rectus muscle and recessing the lateral rectus muscle, which resulted in reduction of a large-angle exotropia to a small exodeviation. Adduction was improved but not normalized. The pathologic examination indicated a benign inclusion cyst of the conjunctiva with fibrosis and chronic inflammation. A possible cause of this type of cyst is an epithelial remnant inadvertently placed with the muscle substance during previous surgery.

[Late form with psychiatric presentation of Wilson's disease, with pseudo-compulsive stereotyped movements. Neuro-radiological correlations]. / Forme tardive à présentation psychiatrique de la maladie de Wilson, avec mouvements stéréotypés pseudo-compulsifs. Corrélations neuro-radiologiques.

Wilson's disease rarely starts after the third decade and may present with misleading psychiatric signs. We observed a 39-year-old white male who developed hysterical behaviour followed by frank delusional psychosis. Secondary neurological symptoms like astasia and dyarthria were misinterpreted as drug-induced. Despite a treatment with D-penicillamine and zinc sulfate there was further deterioration with anarthria and pseudo-compulsive stereotypies. These latter signs cleared after five months, whereas astasia and abasia remained the same and MRI imaging showed further deterioration characterized by marked bilateral putaminal cavitation. SPECT imaging could not predict the clinical evolution. Our case emphasizes that Wilson's disease can have variable initial presentations, and confirms the relationship between pseudo-compulsive stereotypies and bilateral lenticular lesions, as already described in other diseases of the basal ganglia.

Sex and size in cosexual plants.

There are conceptual and practical difficulties in measuring the exact shape of fitness-gain curves and sex allocation, and these hamper empirical testing of some of the basic predictions of sex allocation theory for plants. Nevertheless, our knowledge of the processes that shape fitness-gain curves allows us to formulate hypotheses to test predictions of sex allocation theory. One such hypothesis is that plants adjust their gender according to size. The connection between plant size and gender was generally thought to be weak. Recent data, however, suggest that size-dependent sex allocation (SDS) is a common phenomenon in hermaphrodites and other cosexual plants.

Redox potential measurements of plasma in patients undergoing coronary artery bypass graft and its clinical significance.

The apparent redox potentials (Em) of plasma as a marker of oxidant injury during coronary artery bypass graft (CABG) is determined, and their clinical significance is discussed. We measured plasma Em of normal volunteers (n = 20) and samples drawn at different time points from patients undergoing elective CABG (n = 60) directly and by adding 5 microl (20 mM) oxidants or reductants with known redox potential to plasma (95 microl), using a micro Pt/AgCl combination redox electrode. The Em value stays elevated up to 30 min during the surgery, after the administration of protamine it came down toward a more reduced state. Similar changes are seen with the lactate pyruvate ratio. Smaller changes of Em than normal are observed in plasma samples from patients treated with Aprotinin (antiprotease), Carmeda (heparin-coated) circuit and aspirin reflecting their protective effect. Redox potential (Em) measurements appear to be effective and useful in monitoring redox shifts wherever oxidative stress needs to be monitored.

Genetic variability of the CYP 2D6 gene is not a risk factor for sporadic Parkinson's disease.

Genetic studies of the frequencies of mutant alleles for coding cytochrome P-450 monooxygenase (CYP 2D6) in Parkinson's disease (PD) patients have been inconsistent. We studied the mutants A and B in 80 strictly defined sporadic PD patients divided into young age onset of the disease (< 40 years, N = 20), mid age onset (40-50 years, N = 12), and older age onset (> 50 years, N = 48). They were compared with 108 controls from the same geographic area. There were no significant differences in allele or genotype frequencies between PD patients and controls. Future genetic studies in PD should focus on other alleles or other areas of the genome.

Change in the cycle of circadian strabismus.

PURPOSE/METHODS: We observed a change in the typical circadian, 24-hour pattern of strabismus (esotropia) in a 2-year-old patient. Methods used include study of the history of the deviation pattern, observation, and measurement of the deviation on the day after travel and six weeks later. RESULTS/CONCLUSIONS: The patient responded to standard recession-resection surgery with a straight eye position daily, through three months of follow-up. Rapid travel over six time zones probably caused the change in the circadian pattern of strabismus.

Modified periodontal probe for simplified forced duction measurements.

A periodontal probe has been modified for use at surgery as a quantitative length-tension measuring device. It is simple and rapid to use, as well as inexpensive. In addition to zero length and tension, readings can be made at 25 g and 30 g of tension. Results of the test are described in four patients with restrictive or paralytic strabismus.