Enhanced Proapoptotic Effects of Water Dispersed Complexes of 4-Thiazolidinone-Based Chemotherapeutics with a PEG-Containing Polymeric Nanocarrier.

AIM: To study whether water formulation of the complex of 4-thiazolidinone derivatives with a PEG-containing polymeric nanocarrier enhances their pro-apoptotic action towards rat glioma C6 cells. METHODS: Mechanisms of antineoplastic effects of 4-thiazolidinone derivatives were investigated in vitro with rat glioma C6 cells. Cell nativity, cell cycling pattern, and Annexin V expression were evaluated and DNA damage was estimated by DNA comet analysis. A novel water-based formulation of 4-thiazolidinone derivatives complexed with a polymeric nanocarrier was utilized for enhancing pro-apoptotic action towards C6 cells. RESULTS: The studied 4-thiazolidinone derivatives use apoptosis mechanisms for killing rat glioma C6 cells, as confirmed by FACS analysis of these cells in pre-G1 stage, the appearance of Annexin V positive C6 cells, and an increased number of DNA comets of higher classes. Complexation of the studied compounds with a PEG-containing polymeric nanocarrier significantly increased pro-apoptotic effects in rat glioma C6 cells measured by all methods mentioned above. CONCLUSION: Complexation of 4-thiazolidinone derivatives with a PEG-containing polymeric nanocarrier provided them with water solubility and enhanced pro-apoptotic effects in rat glioma C6 cells.

Glycosylation of random IgG distinguishes seropositive and seronegative rheumatoid arthritis.

The N-glycosylation of human immunoglobulins, especially IgGs, plays a critical role in determining affinity of IgGs towards their effector (pro- and anti-inflammatory) receptors. However, it is still not clear whether altered glycosylation is involved in only antibody-dependent disorders like seropositive rheumatoid arthritis (RA) or also in pathologies with similar clinical manifestations, but no specific autoantibodies like seronegative RA. The clarification of that uncertainty was the aim of the current study. Another study aim was the detection of specific glycan forms responsible for altered exposure of native glycoepitopes. We studied sera from seropositive RA (n = 15) and seronegative RA (n = 12) patients for exposure of glycans in native IgG molecules, followed by determination of specific glycans by capillary electrophoresis with laser-induced fluorescent detection (CE-LIF). Aged-matched groups of normal healthy donors (NHD) and samples of intravenous immunoglobulin IgG preparations (IVIG) served as controls. There was significantly stronger binding of Lens culinaris agglutinin (LCA) and Aleuria aurantia lectin (AAL) lectins towards IgG from seropositive RA compared to seronegative RA or NHD. CE-LIF analysis revealed statistically significant increases in bisecting glycans FA2BG2 (p = .006) and FABG2S1 (p = .005) seropositive RA, accompanied by decrease of bisecting monogalactosylated glycan FA2(6)G1 (p = .074) and non-bisecting monosialylated glycan FA2(3)G1S1 (p = .055). The results suggest that seropositive RA is distinct from seronegative RA in terms of IgG glycan moieties, attributable to specific immunoglobulin molecules present in seropositive disease. These glycans were determined to be bisecting GlcNAc-bearing forms FA2BG2 and FABG2S1, and their appearance increased the availability of LCA and AAL lectin-binding sites in native IgG glycoepitopes.

Activity and safety of bevacizumab plus fotemustine for recurrent malignant gliomas.

BACKGROUND: No established chemotherapeutic regimen exists for the treatment of recurrent malignant gliomas (rMGs). Herein, we report the activity and safety results of the bevacizumab (B) plus fotemustine (FTM) combination for the treatment of rMGs. PATIENTS AND METHODS: An induction phase consisted of B 10 mg/kg days 1, 15 plus FTM 65 mg/m(2) days 1, 8, and 15. Nonprogressive patients entered the maintenance phase with B 10 mg/kg plus FTM 75 mg/m(2) every 3 weeks. The primary endpoint was response rate; secondary endpoints included safety, progression free survival (PFS), and overall survival (OS). RESULTS: Twenty-six patients affected by recurrent MGs (50% glioblastoma) were enrolled. Eight partial responses (31%) were observed. Median PFS and OS were 4 (95% C.I.: 2.8-5.1) and 6 months (95% C.I.: 4.2-7.8), respectively. Responses were significantly associated with both improved PFS and OS (P = 0.002 and P = 0.001, resp.). Treatment adverse events were mostly mild to moderate in intensity. Bevacizumab-related adverse events included grade 3 venous thromboembolic event (8%), grade 2 epistaxis (4%), hypertension (8%), and gastrointestinal perforation (4%). CONCLUSIONS: Bevacizumab plus FTM showed activity and good tolerability in pretreated MGs. Further investigations are needed in order to verify the benefits deriving from the addition of B to a cytotoxic in this clinical setting of patients.

Hungarian web-based nationwide anaesthesia and intensive care data collection and reporting system: its development and experience from the first 5 yr.

BACKGROUND: Annual data collection is obligatory in Hungary for every department in the fields of anaesthesia and intensive care. A new, web-based data-reporting system was introduced in Hungary in 2003. The present paper summarizes experience from the first 5 yr of its operation. METHODS: The Information Technology Working Group of Hungarian Society of Anaesthesia and Intensive Care developed a data collection system, which was Internet-based, provided web surface for every accredited department, and used the integration of international code systems. The analysis mode summarized the data automatically at loco-regional, national, or both levels. In 2008, a questionnaire was sent to the users in order to evaluate the usefulness of, and user satisfaction with, the web-based system. RESULTS: The examples of anaesthetic and intensive therapy workload activities reflect the status of the discipline in Hungary. There have been no significant changes in the total number of anaesthesias per year in the past 5 yr, except that the number of combined general and regional anaesthesias has been elevated by more than 30%. The physicians' workload has increased by 13.2% in relation to the total number of anaesthetic procedures per physician per year. In this field, our data have verified that the number of physicians has decreased in Hungary. On the basis of the opinion of the users, the web-based data collection system has increased the effectiveness and accuracy of annual data collection. CONCLUSIONS: The developed web-based system is an effective tool for data collection. Its usefulness was also borne out by its users on the basis of experience from the first 5 yr.

Excimer laser (308 nm) recanalisation of in-stent restenosis: thermal considerations.

Excimer laser recanalisation of in-stent restenosis may be a viable modality for improving coronary patency. However, the presence of arterial stents modifies the thermal properties of the irradiated area and may alter temperature patterns generated during ablation. The goal of this study was to evaluate, in vitro, temperature changes during excimer laser ablation of stented vessels and compare them with those obtained from unstented (control) vessels. Six different stent types (AVE Microstent-II, AVE-GFX, ACS Multi-link, JJ Palmaz-Schatz, JJ Crown, and NIR) were deployed in freshly excised porcine coronary vessels. Three control unstented samples were also measured. Blood or saline was infused through the vessels, while the tissue environment was kept at approximately 37 degrees C. A 308 nm excimer laser (Spectranetics, CVX300) with an eccentric 2.0 mm laser catheter (Spectranetics, EII) delivered two trains of 200 pulses each, 10 s apart, at 60 mJ/mm2, and 40 Hz, simulating maximum clinical exposure. The catheter was positioned midway in the stent, first coaxially parallel to the vessel wall, and then at an angle against the stent and vessel wall. Temperature measurements (n= 168 for blood, n=96 for saline) were performed with a approximately 210 microm diameter, fast-response thermocouple with 0.1 degrees C resolution. The probe was positioned to within approximately 250 microm from the inner surface of the vessels. Tissue temperature was measured at the catheter tip and at the distal and proximal edges of the stents. Maximum recorded temperatures for coaxial and angular alignment, did not exceed 42.2 degrees C (approximately 6 degrees C above baseline) and 54.2 degrees C (approximately 18.1 degrees C above baseline) respectively, for all stents types tested, controls, and all probe locations. Both stented and unstented vessels exhibited comparable temperature gradients. The observed maximum temperatures, obtained under extreme lasing conditions, indicated that 308 nm ablation, in the presence of stents under blood or saline infusion, produces clinically acceptable temperatures.

Regional and international integrated telemedicine network for organ transplant (HC 4028 & IN 4028 European Commission DGXIII).

A substantial portion of future medical practice will depend greatly on improved collaboration between the providers throughout the healthcare sector, and effective sharing of data and expertise by different healthcare professionals. In organ transplant it is a rule, donor organs are matched to recipients via national or multinational organ-sharing organizations. Only through close co-operation between transplant surgeons, immunologists, nephrologists, pathologists, radiologists and other physicians could one increase the efficiency of organ transplantation. Information technology (IT) has become an inevitable and inherent part of transplantation medicine. The RETRANSPLANT project interfaces and integrates IT from the European Union Fourth Framework projects to support the development of regional organ transplant information networks in Central Europe.

Telepathology and imaging spectroscopy as a new modality in histopathology.

Telemedicine started in the late 1950's by transmitting data on patients' pulse and heart rates. In the 1980's it expanded to radiology and orthopedics. The technology is now expanding to other specialties that can digitally gather patient data. Telepathology comprises the transmission of microscopic images via telecommunication network. Image compression and multiplexing technologies enabled high-resolution telepathology as well as real-time video consultations over international telephone lines. Organ transplantation has become a viable treatment and offers new life to an increasing number of patients suffering from chronic end stage diseases and from irreversible organ failure. Rejection is still a major problem in kidney, liver, and heart transplantation. To gain further insight into the complex interactions within the components of the immune system, it has become increasingly necessary to develop rapid and simple methods to monitor the status of the immune system in patients. Clinical signs suggest organ rejection and abnormal laboratory test results, but only histological signs on biopsy specimens are adequately specific. The financial cost of organ transplant makes it imperative to develop tools for the early identification and treatment of organ rejection. An increasingly sensitive and accurate way of localizing key structures and abnormalities is through spectroscopy of either H&E stained samples or with a fluorescent tag (fluorophore) or by relying on natural fluorescence. The system is based on a unique Prism and Mirror Imaging Spectroscopy System ("PARISS), spectrometer originally designed and implemented for remote Earth monitoring from space and aircraft and astronomical imaging spectroscopy. Compact and lightweight both the mirror and prism are presently constructed in inexpensive glass but can also be injection molded in plastic. Any number of vendors anywhere in the world can produce all parts of the assembly. This greatly enhances the chances of future commercial viability. The Interactive Histopathology Consultation Network INTERPATH (PL961121) project integrated of remote control imaging microscopy system, imaging spectroscopy, and communication networks called SPECTROMIC. This telepethology unit will be a useful tool in the Regional and International Integrated Telemedicine Network for Medical Assistance in End Stage Diseases and Organ Transplant, RETRANSPLANT HC 4028 (HC) & IN 4028 (HC).

Regional health care networks.

Communication cross primary and secondary care, between organisations or between different types of professionals causes special problems. The communication often implies exchange of data between different computer systems. The INCO-COPERNICUS project PRIMACOM (PRIMAry Care Physician's COMmunication Network) demonstrates how such communication can be established in regions in Hungary and Slovenia. PRIMACOM is building on European messaging standards for EDI (Electronic Data Interchange) with practical experience from the Danish MedCom project. The paper points out the need for standardising health care messages and via the Danish MedCom project documents the return of investment.

Photodynamic therapy for the treatment of squamous cell carcinoma using benzoporphyrin derivative.

BACKGROUND: Photodynamic therapy (PDT) involves laser light excitation of a tumor-localizing photosensitizer to destroy neoplasms. Benzoporphyrin derivative (BPD) is a new photosensitizer with several favorable characteristics. OBJECTIVE: Studies were designed to: 1) assess the efficacy of BPD-mediated PDT in treating in vivo squamous cell carcinomas (SCC); 2) obtain dosimetry data for BPD and laser parameters; and 3) establish clinical and histologic correlates of BPD-induced tumor regression. METHODS: Human SCC was implanted into nude mice. One group received BPD followed by laser light of 150 J/cm2 from an argon-pumped dye laser at 690 nm. Three control groups included laser energy alone, BPD alone, and no treatment. RESULTS: At day 21 posttreatment only PDT-treated tumors showed a statistically significant decrease in tumor volume and complete cure rate. Clinical resolution (scar) correlated perfectly with histologic resolution (scar). CONCLUSION: Human SCC in a nude mouse model responds to BPD-mediated PDT.

Effect of varying laser parameters on pulsed Ho:YAG ablation of bovine knee joint tissues.

We investigated the effect of varying laser parameters on ablation of fresh bovine knee joint tissues (fibrocartilage, hyaline cartilage, and bone) with a free-running Ho:YAG laser. Ablation rate was measured in saline for each tissue type as a function of laser fluence (160-950 J/cm2), pulse width (150-450 microseconds, full width at half maximum), and fiber core diameter (400 and 600 microns). A weight that was attached to the fiber end was used to exert a constant pressure of 40 g/mm2 to the tissue underneath to ensure a constant contact between the fiber tip and the tissue throughout the ablation process. All tissues could be efficiently ablated, and the ablation rate increased linearly with the fluence. Change in laser pulse width and fiber core diameter resulted in minor variations in the ablation rate for fibro- and hyaline cartilage. On the other hand, use of longer pulses and/or the larger fiber significantly accelerated bone ablation. Histology analysis revealed that zones of thermal damage in Ho:YAG irradiated bovine knee joint tissues differed by tissue types and ranged between 100 and 400 microns, but were independent of fluence, pulse width, and fiber size within the range tested.

Biliary calculi fragmentation by a 308 nm excimer laser: a preliminary study.

The use of a 308-nm XeCl excimer laser for biliary stone fragmentation is reported. The 130-nsec laser pulses are delivered via UV grade fused silica fibers to the target stones immersed in normal saline solution and placed in direct contact with the fiber. Sixty biliary calculi, 20 cholesterol and 40 pigment, were fragmented in vitro. The energy delivered per unit mass of the stone is kept constant at 50 mJ/mg. The effect of laser repetition rate, energy fluence, and fiber core size on stone fragmentation was studied. Fragmentation thresholds for a variety of biliary calculi of known composition were measured. It was found that higher fragmentation efficiency was obtained with larger fluence, lower repetition rate, and fiber of larger core. Our study indicates that the 308-nm excimer laser may be effective as a laser lithotriptor with low threshold and good efficiency for biliary stone fragmentation.

Fragmentation of biliary stones with a 308 nm excimer laser.

The use of a XeCl excimer laser (308 nm) for biliary stone fragmentation is reported. Laser energy is delivered via UV grade fused silica fibers to the target stones immersed in normal saline solution. Sixty biliary calculi--pigment (n = 40), and cholesterol (n = 20)--were fragmented in vitro. The total energy delivered per unit mass of the stone is kept constant. Two energy fluences (80 and 110 mJ/mm2) at two repetition rates (5 and 20 Hz) delivered through fibers of two core sizes (300 and 600 microns) are utilized to study the effect of different laser parameters on the fragmentation process. Although both pigment and cholesterol stones are susceptible to excimer laser fragmentation, higher fragmentation efficiency is obtained for the pigment stones than for the cholesterol stones. Our study suggests that higher energy fluence and larger fiber core size result in higher fragmentation efficiency for pigment stones. Fragmentation thresholds at stone surface for a variety of biliary calculi of known composition were measured. The threshold energy fluence is approximately 3 mJ/mm2 and 17 mJ/mm2 for pigment and cholesterol stones, respectively. Our study indicates that the 308 nm excimer laser may be effective as a laser lithotriptor with low threshold and good efficiency for biliary stone fragmentation.