An immunologically relevant rodent model demonstrates safety of therapy using a tumour-specific IgE.

BACKGROUND: Designing biologically informative models for assessing the safety of novel agents, especially for cancer immunotherapy, carries substantial challenges. The choice of an in vivo system for studies on IgE antibodies represents a major impediment to their clinical translation, especially with respect to class-specific immunological functions and safety. Fcε receptor expression and structure are different in humans and mice, so that the murine system is not informative when studying human IgE biology. By contrast, FcεRI expression and cellular distribution in rats mirror that of humans. METHODS: We are developing MOv18 IgE, a human chimeric antibody recognizing the tumour-associated antigen folate receptor alpha. We created an immunologically congruent surrogate rat model likely to recapitulate human IgE-FcεR interactions and engineered a surrogate rat IgE equivalent to MOv18. Employing this model, we examined in vivo safety and efficacy of antitumour IgE antibodies. RESULTS: In immunocompetent rats, rodent IgE restricted growth of syngeneic tumours in the absence of clinical, histopathological or metabolic signs associated with obvious toxicity. No physiological or immunological evidence of a "cytokine storm" or allergic response was seen, even at 50 mg/kg weekly doses. IgE treatment was associated with elevated serum concentrations of TNFα, a mediator previously linked with IgE-mediated antitumour and antiparasitic functions, alongside evidence of substantially elevated tumoural immune cell infiltration and immunological pathway activation in tumour-bearing lungs. CONCLUSION: Our findings indicate safety of MOv18 IgE, in conjunction with efficacy and immune activation, supporting the translation of this therapeutic approach to the clinical arena.

Investigation on F/M material aspects of IRT-Sofia NCT channel.

The filter/moderator area of IRT-Sofia BNCT channel was investigated in this study in order to find a higher radiation resistant material as a suitable substitution for the Teflon(®). Two options - Al2O3 and graphite - were investigated. The results show, that both graphite and the Al2O3 can be successfully used as a filter/moderator material at IRT-Sofia. Initial evaluation of the in-phantom performance of the IRT-Sofia BNCT channel was made and merits similar to the best existing ones were found.

IRT-Sofia BNCT beam tube optimization study.

An optimization study of IRT-Sofia BNCT beam tube is presented. In the study we used the MIT/FCB experience. The enlarging of filter/moderator cross section dimensions and the decreasing of collimator length within the limits of the IRT-Sofia reactor design were analyzed. The influence of beam and reactor core axes non-coincidence on the beam properties was also evaluated. The irradiation resistance of polytetrafluoroethylene (Teflon(®)) was also evaluated. The results provide information for making decisions on the IRT-Sofia BNCT beam construction.

Building of scientific information system for sustainable development of BNCT in Bulgaria.

Building a boron neutron capture therapy (BNCT) facility is foreseen within the reconstruction of the Research Reactor IRT (IRT) of the Institute for Nuclear Research and Nuclear Energy of the Bulgaria Academy of Sciences (INRNE). The development of BNCT at IRT plays a very significant role in the plan for sustainable application of the reactor. A centralized scientific information system on BNCT is being built at the INRNE with the purpose to collect and sort new information as knowledge accumulated during more than thirty years history of BNCT. This BNCT information system will help the creation and consolidation of a well informed and interconnected interdisciplinary team of physicists, chemists, biologists, and radio-oncologists for establishing BNCT cancer treatment in Bulgaria. It will strengthen more intensive development of the national network as well as its enlargement to the Balkan region countries. Furthermore, to acquaint the public at large with the opportunity for BNCT cancer treatment will be addressed. Human, social, and economics results due to BNCT for many patients from Balkan region are expected.

Preliminary modeling of BNCT beam tube on IRT in Sofia.

The technical design of the research reactor IRT in Sofia is in progress. It includes an arrangement for a BNCT facility for tumor treatment. Modeling of geometry and material composition of filter/collimator for the BNCT beam tube on IRT has been carried out following the beam tube configuration of the Massachusetts Institute of Technology Reactor [Harling et al., 2002. The fission converter-based epithermal neutron irradiation facility at the Massachusetts Institute of Technology Reactor. Nucl. Sci. Eng. 140, 223-240.] and taking into account an ability to include the tube into the IRT reactor geometry. The results of neutron and gamma transport calculations performed for the model have shown that the facility will be able to supply an epithermal neutron flux of about 5 x 10(9) n cm(-2)s(-1), with low contamination from fast neutrons and gamma rays that would be among the best facilities currently available. An optimiziation study has been performed for the beam collimator, following similar studies for the TAPIRO research reactor in Italy. [Nava et al., 2005. Monte Carlo optimization of a BNCT facility for treating brain gliomas at the TAPIRO reactor. Radiat. Prot. Dosim. 116 (1-4), 475-481.].

Ophthalmic complications after functional endoscopic sinus surgery (FESS).

The purpose of this paper is to inform the ophthalmologist about the occurrence of ophthalmological complications after functional endoscopic sinus surgery (FESS). Due to the close anatomical relationship between the paranasal sinuses and the orbit, involvement and/or injury of the orbit from processes primarily located in the paranasal sinuses, may occur. The orbit, the extra-ocular muscles, the optic nerve and the lacrimal drainage system can be damaged during FESS. The risk of injury is correlated to the anatomical variations, the history of previous surgery, the extent and the gravity of the disease and the skill of the surgeon. We hereby present three cases, each showing a different ophthalmologic complication after FESS.

[Hypokalemic periodic paralysis in thyrotoxicosis]. / Khipokaliemichna periodichna paraliza pri tireotoksikoza.

For the first time in Bulgaria a case of hypokalemic periodic paralysis in thyrotoxicosis is described. Three periods of paralysis were observed and documented in a hospital. The thyrotoxicosis was well manifested with disturbed carbohydrate tolerance and responded favourably to methizole treatment. It is suggested that the mechanism for the development of the hypokalemic periodic paralysis is the intracellular blockade of potassium by the surplus of thyroid hormones.

Ultracytochemical localization of ATP-hydrolysing activity in vegetative cells, spores and isolated cytoplasmic membranes of Bacillus subtilis 168.

The localization of ATP-hydrolysing activity in vegetative cells, spores and isolated membranes of Bacillus subtilis 168 was studied by a cytochemical method combined with electron microscopy. The activity was located mainly in the cytoplasmic membrane and the mesosomes, and was also found in the inner layer of the cell wall facing the cytoplasmic membrane. Activity was also detected in the cross-membranes of dividing cells and in spore coats. The product of the reaction was observed either as fine electron-dense granules incorporated into the membranes, or as high-contrast lead precipitates on the surfaces of the membranes.

[Ultrasonic diagnosis of retained tissues after artificial abortion on demand]. / Ultrazvukova diagnoza na zadurzhani tukanni chasti sled izkustven abort po zhelanie.

PIP: The authors examined the possibility of using ultrasound for discovery of retained products of the fertilized ovum. The study included 272 women admitted to the clinic for induced abortion. Women with full bladders were examined by means of ultrasound up to 24 hours after abortion. There were 3 characteristic echographic pictures: 1) an empty uterus in 108 women, 2) a uterus containing blood in 130 women, and 3) a uterus with tissue parts in 34 women. The transverse, longitudinal, and anterior-posterior diameter of the uterus was measured as well. It was inferred that the ultrasound examination is a promising method for establishing the retention of fetal parts following induced abortion and that ultrasound examination of the diameter of the uterus could help in diagnosing the retention of these parts when no other pathology of the uterus is found. (author's modified)^ieng