Comparison of intracellular accumulation and cytotoxicity of free mTHPC and mTHPC-loaded PLGA nanoparticles in human colon carcinoma cells

The second generation photosensitizer mTHPC was approved by the European Medicines Agency (EMA) for the palliative treatment of advanced head and neck cancer in October 2001. It is known that mTHPC possesses a significant phototoxicity against a variety of human cancer cells in vitro but also exhibits dark toxicity and can cause adverse effects (especially skin photosensitization). Due to its poor water solubility, the administration of hydrophobic photosensitizer still presents several difficulties. To overcome the administration problems, the use of nanoparticles as drug carrier systems is much investigated. Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) have been extensively studied as delivery systems into tumours due to their biocompatibility and biodegradability. The goal of this study was the comparison of free mTHPC and mTHPC-loaded PLGA nanoparticles concerning cytotoxicity and intracellular accumulation in human colon carcinoma cells (HT29). The nanoparticles delivered the photosensitizer to the colon carcinoma cells and enabled drug release without losing its activity. The cytotoxicity assays showed a time- and concentration-dependent decrease in cell proliferation and viability after illumination. However, first and foremost mTHPC lost its dark toxic effects using the PLGA nanoparticles as a drug carrier system. Therefore, PLGA nanoparticles are a promising drug carrier system for the hydrophobic photosensitizer mTHPC.     

Compound prism design principles, I

Prisms have been needlessly neglected as components used in modern optical design. In optical throughput, stray light, flexibility, and in their ability to be used in direct-view geometry, they excel over gratings. Here we show that even their well-known weak dispersion relative to gratings has been overrated by designing doublet and double Amici direct-vision compound prisms that have 14° and 23° of dispersion across the visible spectrum, equivalent to 800 and 1300 lines/mm gratings. By taking advantage of the multiple degrees of freedom available in a compound prism design, we also show prisms whose angular dispersion shows improved linearity in wavelength. In order to achieve these designs, we exploit the well-behaved nature of prism design space to write customized algorithms that optimize directly in the nonlinear design space. Using these algorithms, we showcase a number of prism designs that illustrate a performance and flexibility that goes beyond what has often been considered possible with prisms.     

Compound prism design principles, III: linear-in-wavenumber and optical coherence tomography prisms

We extend the work of the first two papers in this series [Appl. Opt. 50, 4998-5011 (2011), Appl. Opt. 50, 5012-5022 (2011)] to design compound prisms for linear-in-wavenumber dispersion, especially for application in spectral domain optical coherence tomography (OCT). These dispersive prism designs are believed to be the first to meet the requirements of high resolution OCT systems in direct-view geometry, where they can be used to shrink system size, to improve light throughput, to reduce stray light, and to reduce errors resulting from interpolating between wavelength- and wavenumber-sampled domains. We show prism designs that can be used for thermal sources or for wideband superluminescent diodes centered around wavelengths 850, 900, 1300, and 1375 nm.     

Is apoptosis involved in mechanisms to eliminate Onchocerca ochengi during Simulium damnosum s.l. immune response?

Co-injection of the parasite Onchocerca ochengi and the caspase inhibitors z-VAD.fmk and boc-D.fmk into the natural vector Simulium damnosum s.l. led to significantly increased survival of the parasites. Subsequent in situ apoptosis detection assays demonstrated that in the case of boc-D.fmk the enhanced survival was due to a diminished apoptosis level of the microfilariae in vivo. Additional assays using O. ochengi microfilariae which were coinjected with serine protease inhibitors into S. damnosum s.l. revealed that certain serine protease inhibitors can reduce the level of apoptosis.     

Applying burnable poison particles to reduce the reactivity swing in high temperature reactors with batch-wise fuel loading

Burnup calculations have been performed on a standard HTR fuel pebble with a radius of 3 cm containing 9 g of 8% enriched uranium and burnable poison particles (BPP) made of B₄C highly enriched in ¹⁰B. The radius of the BPP and the number of particles per fuel pebble have been varied to find the flattest reactivity-to-time curve. It was found that for a k∞ of 1.1, a reactivity swing as low as 2% can be obtained when each fuel pebble contains about 1070 BPP with a radius of 75 μm. For coated BPP that consist of a graphite kernel with a radius of 300 μm covered with a B₄C burnable poison layer, a similar value for the reactivity swing can be obtained. Cylindrical particles seem to perform worse. In general, the modification of the geometry of BPP is an effective means to tailor the reactivity curve of HTRs.     

Visual simulation of shallow-water waves

A commodity-type graphics card (GPU) is used to simulate nonlinear water waves described by a system of balance laws called the shallow-water system. To solve this hyperbolic system we use explicit high-resolution central-upwind schemes, which are particularly well suited for exploiting the parallel processing power of the GPU. In fact, simulations on the GPU are found to run 15–30 times faster than on a CPU. The simulated cases involve dry-bed zones and nontrivial bottom topographies, which are real challenges to the robustness and accuracy of the discretization.     

Development of an existing method for fabrication of polyesters by modeling of the process

Conclusion The model presented above covers the basic physical and chemical processes in synthesis of polyesters. It describes the method with DMT and TPA in a wide range of parameters and compositions and simultaneously considers the processes in the final reactor. The model is a tool for optimizing the parameters of the process and designing reactors and thus deepens knowledge concerning synthesis of polyesters. It points out the path to new technical solutions, improving the conditions of the process, increasing the economy and output, and improving product quality.It was possible to decrease the number of reactors for Karl Fisher's continuous method of production of PET to four based on the parameters of the process conducted in existing installations and model calculations. For the method calculated for three reactors [5, 6], the model has serious drawbacks with respect to product quality, economy, and flexibility of the installations, which probably restrict the use of such a system to lower-quality products.In addition, the model provides for increasing the individual line output from 180–200 tons/day to 300 or even 400 tons/day.Translated from Khimicheskie Volokna, No. 4, pp. 9–14, July–August, 1994.     

Obstetric analgesia in Norwegian hospitals]

We report the results of a questionnaire sent to anaesthetists and midwives on the use of obstetric analgesia and anaesthesia in Norwegian hospitals in 1996. 95% of the 49 hospitals involved responded to the questionnaire, representing a total of 56,884 births. The use of epidural analgesia in labour varied from 0 to 25% in the different hospitals with a mean value of 15%. Epidural analgesia was much more widely used in university and regional hospitals than in local hospitals (p < 0.001). Five of the local hospitals did not offer epidural analgesia during labour at all. The combination of low-dose local anaesthetic and an opioid (either sufentanil or fentanyl) had not been introduced in nine of the hospitals (20%). The optimal use of epidural analgesia to relieve labour pain was judged to be more frequent by the anaesthetists than by the midwives (19% versus 11%, p < 0.01). In response to what factors limited the frequency of epidural analgesia, the anaesthetists specified factors related to the attitude of the midwife, and the midwives specified factors related to the anaesthetist. Only five of the hospitals provided written information on the various analgesic methods that could be employed during labour. The majority of midwives considered the analgesic methods employed on their maternity ward to be good or excellent. The frequency of Caesarean section was 12%; spinal anaesthesia was used in 55%, epidural anaesthesia in 17%, and general anaesthesia in 28% of the cases.     

Treatment of advanced gastroesophageal reflux disease with Collis gastroplasty and Belsey partial fundoplication

OBJECTIVE: To examine the factors affecting outcome in patients with advanced gastroesophageal reflux disease. DESIGN: Retrospective analysis. SETTING: University tertiary referral center. PATIENTS: Thirty-seven patients with advanced gastroesophageal reflux disease and no previous antireflux surgery. INTERVENTIONS: Thirty patients underwent Collis gastroplasty for esophageal lengthening and Belsey partial fundoplication. Seven patients with esophageal stricture and global loss of esophageal body motility who underwent primary esophagectomy and reconstruction were used as a comparison group. OUTCOME MEASURES: Symptomatic outcome in all 37 patients was assessed by questionnaire at a median of 25 months (range, 5-156 months) after surgery. In a subset of 11 patients undergoing the Collis-Belsey procedure, outcome was measured using 24-hour pH and results of motility studies. RESULTS: The Collis-Belsey procedure was successful in relieving symptoms of gastroesophageal reflux in 21 (70%) of the 30 patients. The outcome was excellent or good in 16 (89%) of 18 patients who presented with symptoms other than dysphagia, but only in 5 (42%) of 12 patients with dysphagia (P = .01). The outcome was particularly poor if dysphagia was associated with a previously dilated esophageal stricture. Persistent or induced dysphagia was the reason for failure in all but 1 patient. Results of 24-hour esophageal pH studies were returned to normal in 8 (73%) of 11 patients undergoing postoperative evaluation. Contraction amplitudes in the distal esophagus and the prevalence of simultaneous contractions in these segments did not change after the operation. All 7 patients who underwent primary esophagectomy were classified as having an excellent or good outcome and were relieved of their reflux symptoms, including dysphagia. Six of these could eat 3 meals per day and enjoyed an unrestricted diet. CONCLUSIONS: The outcome of the Collis-Belsey procedure in patients with advanced gastroesophageal reflux disease without dysphagia is excellent. It is less so in patients with dysphagia as a preoperative symptom. Esophagectomy can provide a good outcome in patients who have a combination of dysphagia stricture and a profound loss of esophageal motility.