Erosion of biodegradable block copolymers made of poly(d,l-lactic acid) and poly(ethylene glycol)

Biodegradable block copolymers made of poly(ethylene glycol) monomethylether (Me.PEG) and poly(d,l-lactic acid) (PLA) were investigated for their erosion properties. Wide angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC) investigations prior to erosion revealed that despite the low content of crystallizable Me.PEG of 10%, Me.PEG5-PLA45 is a partially crystalline polymer. The erosion of the polymer was investigated using cylindrical polymer matrix discs with a diameter of 8mm and a height of 1.5mm. WAXD and DSC spectra obtained from eroded polymer matrix discs suggest that both polymer blocks separate completely during erosion. The crystallinity of Me.PEG5-PLA45 was found to increase during erosion, which is probably due to the improved mobility of Me.PEG inside the polymer with a progressive degree of degradation. The erosion kinetics were found to be similar to that of PLA or poly(lactic-co-glycolic acid). During erosion the polymer matrix weight of dried samples remains constant for 11 weeks after which erosion sets in rapidly. From this observation one can conclude that the impact of the relatively small Me.PEG chains on Me.PEGS-PLA45 erosion is not pronounced. This is beneficial for all those applications that require the stability of the polymer matrix and in which the Me.PEG chain is intended to bring about other effects such as the modification of the surface properties of PLA polymers.     

Laparoscopic antirefiux surgery provides excellent results and quality of life in gastroesophageal refiux disease patients with respiratory symptoms

Medical and surgical treatment are able to improve symptoms in patients with gastroesophageal refiux disease(GERD).Theaim of this study was to evaluate the outcomefollowing laparoscopic antirefiux surgery in GERD patients with primary respiratory-related symptoms and to investigate the quality of life index before and after therapy. Three hundred thirty-eight consecutive patients underwent surgical treatment for GERD-induced symptoms. Of this group 126 patients had primary respiratory symptoms related to GERD. All patients were studied by means of a symptom questionnaire, endoscopy, esophageal manometry, 24-hour esophageal pH monitoring, and a barium esophagogram. In addition, the quality of life was measured by the means of the Gastrointestinal Quality of Life Index (GIQLI). All patients had medical therapy with proton pump inhibitors preoperatively. A laparoscopic fundoplication was performed in all patients. The outcome was assessed 3 and 12 months postoperatively. Following surgery, all respiratory symptoms were significantly improved. While GIQLI was highly impaired before surgical therapy, a significant improvement of quality of life was obtained. Because medical treatment is likely to fail in GERD patients with respiratory symptoms, the need for surgery arises and may be the only successful treatment in the long term. Quality of life was significantly improved by surgical treatment. Presented at the Forty-Fifth Annual Meeting of The Society for Surgery of the Alimentary Tract, May 15–19, 2004, New Orleans, Louisiana (poster presentation).     

Binocular vision in strabismic humans with alternating fixation

Grating acuity, interocular suppression and binocular interaction were evaluated at different positions in the visual field of strabismic humans with alternating fixation. In all cases, the suppression of the deviated eye was most intense in a region corresponding to the fovea of the fixating eye, but reduced or absent in the periphery. In addition, suppression was found in part of the peripheral visual field of the fixating eye. For most subjects, the monocular properties of both eyes were normal. However, for one subject with a strong preference for one of the eyes, visual acuity and luminance detection were selectively impaired in the chronically suppressed regions of the non-preferred eye. Regardless of which eye was currently used for fixation, the visual information available to the subject came from both eyes. In parts of the visual field, the two eyes tended to replace each other. In the far periphery, and especially in the upper and lower hemifield, signals from the two eyes were often combined in a binocular perception of depth.     

Biodistribution of Long-Circulating PEG-Grafted Nanocapsules in Mice: Effects of PEG Chain Length and Density

Purpose: To study the pharmacokinetics and biodistribution of novel polyethyleneglycol (PEG) surface-modified poly(rac-lactide) (PLA) nanocapsules (NCs) and to investigate the influence of PEG chain length and content. Methods: The biodistribution and plasma clearance in mice of different NC formulations were studied with [³H]-PLA. PLA-PEG copolymers were used in NC preparations at different chain lengths (5 kDa and 20 kDa) and PEG contents (10% and 30% w/w of total polymer). In vitro and in vivo stability were also checked. Results: Limited [³H]-PLA degradation was observed after incubation in mouse plasma for 1 h, probably because of to the large surface area and thin polymer wall. After injection into mice, NCs prepared with PLA-PEG copolymers showed an altered distribution compared to poloxamer-coated PLA NCs. An increased concentration in plasma was also observed for PLA-PEG NCs, even after 24 h. A dramatic difference in the pharmacokinetic parameters of PLA-PEG 45-20 30% NCs compared to poloxamer-coated NCs indicates that covalent attachment, longer PEG chain lengths, and higher densities are necessary to produce an increased half-life of NCs in vivo. Conclusions: Covalently attached PEG on the surface of NCs substantially can reduce their clearance from the blood compartment and alter their biodistribution.     

Protein threading by learning

By using techniques borrowed from statistical physics and neural networks, we determine the parameters, associated with a scoring function, that are chosen optimally to ensure complete success in threading tests in a training set of proteins. These parameters provide a quantitative measure of the propensities of amino acids to be buried or exposed and to be in a given secondary structure and are a good starting point for solving both the threading and design problems.     

Stilbene analogues affect cell cycle progression and apoptosis independently of each other in an MCF-7 array of clones with distinct genetic and chemoresistant backgrounds

The development of chemoresistant breast cancer is poorly understood and second treatment options are barely investigated. The term 'chemoresistance' is ill-defined and thus, our experimental analyses aimed to disentangle the resistance to cell cycle arrest from the resistance to trigger apoptosis, both of which are important mechanisms to be targeted by anticancer therapy. Therefore, an MCF-7 array, which encompassed clones harboring distinct genetically- and pharmacologically-induced stages of resistance, was established. For this, MCF-7 cells were stably transfected with erbB2 cDNA and a dominant negative p53 mutation and the two clones were subjected to long-term treatment with the clinical agents 2'-deoxy-5-fluorouridine (5-FdUrd) or arabinosylcytosine (AraC) to develop specific chemoresistance. This array was tested with 3,4',5-trihydroxy-trans-stilbene (resveratrol) and the methoxylated paired stilbene analogue 3,4',5-trimethoxy-trans-stilbene (M5) to investigate whether these agents can overcome genetically- and pharmacologically-induced chemoresistance and to correlate the structure-activity relationship of resveratrol and M5. In all conditions tested, M5 exhibited stronger anticancer activity than resveratrol, but the cell cycle inhibitory properties of the tested drugs were dependent on the genetic background and the chemoresistant phenotype. In contrast, the proapoptotic properties were rather similar in the distinct genetic backgrounds of the clone array and therefore, apoptotic triggers and cell cycle checkpoints were distinctly affected and are thus independent of each other. The study demonstrates the merits or virtues of the genotypically- and phenotypically-defined clones of the MCF-7 array as a testing tool for novel drugs, which discriminates the two types of chemoresistance mechanisms.     

Natural orifice translumenal endoscopic surgery (NOTES) second-look peritoneoscopy for staging of limited peritoneal carcinomatosis

Background

Over the past decades, staging laparoscopy evolved as a useful tool in multimodality treatment of patients with abdominal malignancies, especially for detection of incurable peritoneal and liver metastasis. Natural orifice translumenal endoscopic surgery (NOTES) is a new, evolving technique which represents the next logical progression in minimally invasive surgery and has theoretical advantages in comparison with standard laparoscopic surgery. A review of the current literature revealed a continuous increasing number of fundamental and clinical studies addressing NOTES approach in multimodal management of oncologic patients. Technical possibility to use this new minimally invasive approach for oncological resection of abdominal malignancies was proved by some investigators.

Hypothesis

NOTES can be used as an alternative method for staging patients with limited peritoneal carcinomatosis and may have better results compared to current imaging techniques for small diameter metastatic disease.

Conclusions

With the continuous development of the NOTES techniques and technology, the second-look peritoneoscopy by NOTES may become an alternative method for staging in patients with peritoneal carcinomatosis. Nevertheless, NOTES is at a very early stage of its development, and its implementation in oncologic surgery should be made very caution, and only after careful evaluation.     

Oral health–related quality of life in different clinical forms of oral lichen planus

Clinical Oral Investigations - The aim of the study was to determine the prevalence of clinical forms in a group of oral lichen planus (OLP) patients and to investigate whether the oral...