pH-Responsive Metal-Organic Framework Thin Film for Drug Delivery.

In this work, surface-supportive MIL-88B(Fe) was explored as a pH-stimuli thin film to release ibuprofen as a model drug. We used surface plasmon resonance microscopy to study the pH-responsive behaviors of MIL-88B(Fe) film in real time. A dissociation constant of (6.10 ± 0.86) × 10-3 s-1 was measured for the MIL-88B(Fe) film in an acidic condition (pH 6.3), which is about 10 times higher than the dissociation of the same film in a neutral pH condition. MIL-88B(Fe) films are also capable of loading around 6.0 µg/cm2 of ibuprofen, which was measured using a quartz crystal microbalance (QCM). Drug release profiles were compared in both acidic and neutral pH conditions (pH 6.3 and 7.4) using a QCM cell to model the drug release in healthy body systems and those containing inflammatory tissues or cancerous tumors. It was found that the amount of drug released in acidic environments had been significantly higher compared to that in a neutral system within 55 h of testing time. The pH-sensitive chemical bond breaking between Fe3+ and the carboxylate ligands is the leading cause of drug release in acidic conditions. This work exhibits the potential of using MOF thin films as pH-triggered drug delivery systems.

In vivo measurements and numerical analysis of the biomechanical characteristics of the human periodontal ligament.

The periodontal ligament is a complex tissue with respect to its biomechanical behaviour. It is important to understand the mechanical behaviour of the periodontal ligament during physiological loading in healthy patients as well as during the movement of the tooth in orthodontic treatment or in patients with periodontal disease, as these might affect the mechanical properties of the periodontal ligament (PDL). Up to now, only a limited amount of in vivo data is available concerning this issue. The aim of this study has been to determine the time dependent material properties of the PDL in an experimental in vivo study, using a novel device that is able to measure tooth displacement intraorally. Using the intraoral loading device, tooth deflections at various velocities were realised in vivo on human teeth. The in vivo investigations were performed on the upper left central incisors of five volunteers aged 21-33 years with healthy periodontal tissue. A deflection, applied at the centre of the crown, was linearly increased from 0 to 0.15mm in a loading period of between 0.1 and 5.0s. Individual numerical models were developed based on the experimental results to simulate the relationship between the applied force and tooth displacement. The numerical force/displacement curves were fitted to the experimental ones to obtain the material properties of the human PDL. For the shortest loading time of 0.1s, the experimentally determined forces were between 7.0 and 16.2N. The numerically calculated Young's modulus varied between 0.9MPa (5.0s) and 1.2MPa (0.1s). By considering the experimentally and numerically obtained force curves, forces decreased with increasing loading time. The experimental data gained in this study can be used for the further development and verification of a multiphasic constitutive law of the PDL.

Medical management of endometriosis: emerging evidence linking inflammation to disease pathophysiology.

Progesterone action normally mediates the balance between anti-inflammatory and proinflammatory processes throughout the female reproductive tract. However, in women with endometriosis, endometrial progesterone resistance, characterized by alterations in progesterone responsive gene and protein expression, is now considered a central element in disease pathophysiology. Recent studies additionally suggest that the peritoneal microenvironment of endometriosis patients exhibits altered physiological characteristics that may further promote inflammation-driven disease development and progression. Within this review, we summarize our current understanding of the pathogenesis of endometriosis with an emphasis on the role that inflammation plays in generating not only the progesterone-resistant eutopic endometrium but also a peritoneal microenvironment that may contribute significantly to disease establishment. Viewing endometriosis from the emerging perspective that a progesterone resistant endometrium and an immunologically compromised peritoneal microenvironment are biologically linked risk factors for disease development provides a novel mechanistic framework to identify new therapeutic targets for appropriate medical management.

The suction pseudopolyp technique: a novel method for the removal of small flat nonpolypoid lesions of the colon and rectum.

BACKGROUND AND STUDY AIMS: Small flat nonpolypoid lesions of the colorectum can be technically difficult to target and completely remove; techniques such as hot biopsy forceps electrocauterization are associated with serositis, delayed bleeding, and perforation. This study aimed to describe a novel technique for the removal of such lesions and demonstrate its safety and efficacy. PATIENTS AND METHODS: Patients aged 18 - 80 years with flat nonpolypoid lesions (Paris-Japanese classification 0-IIa and 0-IIb, measuring less than 10 mm) identified at colonoscopy were included in this prospective study. The lesions were removed by the suction pseudopolyp technique (SPT): the lesion is aspirated into the suction channel of the colonoscope and continuous suction applied for 5 seconds whilst the colonoscope is gently retracted. On release of the suction, the resulting pseudopolyp containing the lesion and a margin of normal tissue is easily ensnared and resected. The primary outcomes were endoscopic completeness of polyp resection and complication rate. RESULTS: Over a 12-month period, 1231 polyps were removed during 2656 colonoscopies; 126 polyps (in 101 patients) met inclusion criteria. Complete endoscopic resection was achieved in 100 % of the polyps, without immediate or delayed complication. Of the resected lesions, 57 % had malignant potential (adenomas 47 % and sessile serrated lesions 10 %); a higher proportion of lesions removed from the right colon had malignant potential compared with those from the left colon (75 % vs. 41 %, P = 0.0066). CONCLUSIONS: Diminutive flat lesions of the colorectum are predominantly adenomas and sessile serrated lesions. SPT is a safe, effective, and reproducible therapy for removal of these lesions.

The potential role of environmental toxins in the pathophysiology of endometriosis.

Environmental contaminants that are known to disrupt steroid action can influence the development of reproductive diseases. Our group has focused on whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) can disrupt steroid regulation of endometrial matrix metalloproteinase (MMP) expression. The MMPs regulate extracellular matrix turnover in normal tissues, but the inappropriate expression of these enzymes is associated with numerous disease states that involve invasive processes. We have previously shown that secretion of MMPs by human endometrium is critical for establishment of ectopic lesions in a nude mouse model of experimental endometriosis. In this report, we show that TCDD exposure promotes establishment of experimental endometriosis by interfering with the ability of progesterone to suppress endometrial MMP expression. Copyrightz1999S. KargerAG,Basel