[Current status and potential perspectives in classical radiotherapy technology]. / Tehnologija u klasicnoj radioterapiji: stanje i potencijalni pravci razvoja.

INTRODUCTION AND POTENTIALS OF CLASSICAL RADIOTHERAPY: After purchase of radiotherapy equipment in 2003, classic radiation therapy in Serbia will reach the highest world level. In order to define the highest standards in radiation technology, we analyzed the current status and potential perspectives of radiation therapy. TECHNOLOGICAL LEVELS OF RADIOTHERAPY IN DEVELOPED COUNTRIES: An analysis of present situation in the USA, assumed as the most developed in the world, was done. Available data, collected in the last 3 years (equipment assortment, therapy modalities, workload and manpower) for 284 radiotherapy centers, out of potential 2050, were analyzed. Results were presented as crude percentage and matched to point current status. RESULTS OF ANALYSIS AND DISCUSSION: The analysis showed that CLINAC accelerators are the most popular (82.7%), as well as, ADAC (43.7%) and Focus (CMS) (27.4%) systems for therapy planning. Movement towards virtual simulation is evident (59.3%), although classic "simulation" is not fully eliminated from the radiotherapy chain. The most popular brachytherapy afterloader is Microselectron HDR (71%). About 64.4% centers use IMPAC communication/verification/record system that seems more open than Varis. All centers practice modern radiotherapy modalities and techniques (CPRT, IMRT, SRS/SRT, TBI, IORT, IVBHRT, HDR BHRT, etc.). CT and MRI availability is out of question, but PET is available in 3% of centers, however this percentage is rapidly growing. Up to 350 new patients per year are treated by one accelerator (about 35 pts. a day). Centers are relatively small and utilize 2-3 accelerators on average. Average FTE staffing norm is 4 radiation oncologists, 2-3 medical radiotherapy physicists, about 3 certified medical dosimetrists and about 6 radiotherapy technologists. TECHNOLOGICAL ASPECTS AND CONCLUSION: In the past 5 years relative stagnation in classic radiotherapy has been observed. In spite of substantial investments in technology and consequent improvements, as well as wide introduction of computers in radiotherapy, radiotherapy results have not changed significantly. Vendor developement strategies do not point that this trend will change in the next 5 years. On the other hand, wide introduction of the PET in each radiotherapy chain ring (diagnostics, planning, follow-up), could improve results (local and regional control, as well as quality of patients' life).

[In vitro study of emulsions containing methoxsalen]. / Methoxszalen in vitro diffúziójának tanulmányozása emulziókból.

Vitiligo is an acute disease of skin with inflammation which means damage of melanocites, their defined partial paint lack. It is a frequent sickness which is very conspicuous and disturbing illness. For its treatment, systematically and topically psoralen-derivatives, UV-A radiation and other possibilities are used. Metoxsalen is one of them which is practically insoluble in water. Authors planned to increase the solubility of the pharmacon, and they studied with in vitro diffusion method, how the type of the emulsions influence the liberation and diffusion of metoxsalen.

The effect of repeated treatment with pramipexole on the central dopamine D3 system.

The study examined the effect of pramipexole (2-amino-4,5,6,7-tetrahydro-6-propyl-aminobenzthiazole dihydrochloride; PRA), a new potent dopamine receptor agonist with the high preference for D3 receptors, as compared to D2 or D4, on the central dopamine D3 system. Experiments were conducted on male Wistar rats. PRA was injected subcutaneously. PRA given repeatedly (14 days, twice a day, in doses of 0.3 and 1 mg/kg), but not acutely, potentiated the locomotor hyperactivity induced by (+/-)-7-OH-DPAT (3mg/kg s.c.), when given 24h after the single or the last dose of PRA. Administration of PRA, 1 mg/kg, for 3 or 7 days produced an effect similar to that described above, whereas a dose of 0.3 mg/kg produced such an effect only after 7, but not 3, days. Repeated treatment with PRA (0.3 and 1 mg/kg, 14 days, twice daily) also enhanced the D3 receptor binding in the islands of Calleja and nucleus accumbens (shell)--the brain region known to be rich in D3 receptors--when [3H]7-OH-DPAT was used as a ligand. Repeated PRA administration did not change the concentration of mRNA coding for D3 receptors in the islands of Calleja. The obtained results indicate that-- like the previously studied typical antidepressants given repeatedly--PRA increases the functional responsiveness and the binding to the brain dopamine D3 receptors. Hence PRA may be considered as a potential antidepressant drug.

The activity of rat brain nitric oxide synthase following chronic antidepressant treatment.

Nitric oxide synthase (NOS) is an enzyme involved in the activation of the glutamate/NMDA receptor-induced cascade of events. In this study we investigated the NOS activity in different rat brain regions after chronic electroconvulsive, imipramine and citalopram treatments. Chronic electroconvulsive treatment significantly increased the NOS activity (by 49%) in the cerebral cortex. However, chronic treatment with imipramine or citalopram did not alter the activity of NOS in all examined brain regions (cortex, hippocampus or cerebellum). The increased NOS activity after electroconvulsive but not pharmacologic (imipramine or citalopram) treatment may well reflect the differences between the adaptive changes of the NMDA receptor complex induced by these treatments.

Effect of kainic acid and pentetrazole administration on the activity of nitric oxide synthase in the mouse brain.

The present study examined ex vivo effect of kainic acid and pentetrazole administration on the activity of nitric oxide synthase (NOS) in the mouse brain. NOS activity was assayed by measuring the formation of [3H] citrulline from [3H]arginine in the homogenates of mouse hippocampus, neocortex and cerebellum. The highest basal activity of the enzyme was found in this latter brain region. Administration of kainic acid (30 mg/kg) increased the NOS activity in all brain regions examined. On the other hand, pentetrazole (60 mg/kg) did not evoke any significant changes in the NOS activity at 5 min after the administration. Only in cerebellum, at 10 min after administration of pentetrazole, the increase in the activity of the enzyme was observed. The obtained results indicate that the two particular convulsants used in this study differ not only in respect of behavioral signs of seizures which they evoke, but also in respect of the effect on mouse brain NOS activity.

[Optimization of bioavailability of pharmacons]. / Farmakonok biológiai hasznosíthatóságának optimálása.

The authors have investigated the optimization possibilities of bioavailability of drugs as spray-drying, spray-embedding, spray-freezing, inclusion complex formation with cyclodextrin derivatives, mineral complex formation with bentonite and in vitro diffusion of products. The bioavailability of drugs may be significantly influenced with these methods.

Chronic electroconvulsive treatment increases the activity of nitric oxide synthase in the rat brain.

Activation of the NMDA receptor complex increases the intracellular free Ca2+ concentration, which in turn influences a nitric oxide synthase (NOS) activity. In this study we investigated the NOS activity after acute and chronic electroconvulsive treatment in different rat brain regions. Chronic (10 daily treatments) but not acute (single treatment) significantly increased the NOS activity by 60% in the cerebral cortex and by 20-30% in hippocampus and cerebellum. The increased NOS activity might be a compensatory mechanism which balanced the reduced NMDA receptor complex reactivity. In fact, the adaptation of the NMDA receptor complex induced by chronic electroconvulsive treatment (and antidepressant drugs) measured at the receptor level, suggests the subsensitivity of that complex. Present results support the hypothesis of the critical role of the NMDA receptor pathway in the mechanism of antidepressant action.

Molecular characterization of a saline-soluble lectin from a parasitic fungus. Extensive sequence similarities between fungal lectins.

It has been proposed that the interactions between several parasitic and pathogenic fungi and their hosts are mediated by soluble lectins present in the fungus. We have cloned and analyzed a gene encoding such a lectin (AOL) from the nematophagous fungus Arthrobotrys oligospora (deuteromycete). The deduced primary structure of the AOL gene displayed an extensive similarity (identity 46.3%) to that of a gene encoding a lectin (ABL) recently isolated from the mushroom Agaricus bisporus (basidiomycete), but not to any other fungal, microbial, plant or animal lectins. The similarities between AOL and ABL were further demonstrated by the observation that an antibody specific for AOL cross-reacted with ABL. Together with data showing that AOL has a binding specificity that is similar to that of ABL [Rosen, S., Bergström, J., Karlsson, K.-A. & Tunlid, A. (1996) Eur. J. Biochem. 238, 830-837], these results indicate that AOL and ABL are members of a novel family of saline soluble lectins present in fungi. Southern blots indicated that there is only one AOL gene in the genome encoding a subunit (monomer) of the lectin. The primary structure of AOL did not show the presence of a typical N-terminal signal sequence. Comparison of the deduced primary structure with the molecular mass of AOL as determined by electrospray mass spectrometry (16153 Da), indicated that AOL has an acetylated N-terminal but no other post-translational modifications, and that a minor isoform is formed by deamidation. Circular dichroism (CD) spectroscopy suggested that the secondary structure of AOL contains 34% beta-sheets, 21% alpha-helix, and 45% turns and coils.

[Preparation and investigation of liposomes]. / Liposzómák elöállítása és vizsgálata.

Vesicles dispersed in an aqueous milieu and containing a phospholipid double-layer are used primarily in cosmetic and dermatological preparations, though experiments are under way to use them as carriers of diagnostics and medicines. Different parenteral and dermatological drug preparations are already in circulation worldwide. Researchers have hopes of using them for the lyophilization of lipophobic pharmacons, to prolong medicinal effects, for the active and passive targeting of drugs etc. The first steps of liposome research started in 1965 and we now know much about liposome technology and their use in therapy, but various questions remain to be answered. On the level of basic research, this paper investigates the preparation of liposomes and characteristics influencing their stability.

Formulation of diazepam containing rectal suppositories and experiences of their biopharmaceutical study.

Methodology and the results of the in vitro membrane diffusion and in vivo bioavailability studies are presented. The results confirm a correlation between in vitro and in vivo findings. Hydrophilic macrogol-mixture with great molecular mass can be recommended as the optimal vehicle for formulation of diazepam suppositories.

[Development and investigation of preparations containing kitasamycin and flumequine]. / Kitasamicin- és flumequin-tartalmú készítmények kifejlesztése és vizsgálata.

Swine dysentery and poultry cholera are very harmful animal diseases which cause great damage. Flumequine and kitasamycin are new and up-to-date preparations for the treatment of these diseases. ++ Imequyl ad us. vet. and ++ Trubin ad us. vet. are the registered medicines. The doses are 7 mg flumequine and 21 mg kitasamycin/body weight kg. The drug technological problem is that flumequine does not dissolve sufficiently in water. It dissolves well at pH = 10, but kitasamycin is unstable at this pH. It was hoped that these two components would together act as agonists, and that kitasamycin would promote the dissolution of flumequine. An injection preparation and a powder mixture for dissolution were developed. Chemical interaction between the components was conformed by IR and NMR measurements.

[Membrane diffusion of paracetamol]. / A paracetamol membrándiffúziós vizsgálata.

A study was made of how different cyclodextrin (CD) derivatives, such as alpha-CD, beta-CD, gamma-CD, dimethyl-beta-CD and random-methyl-beta-CD, influence the diffusion of paracetamol. For interpretation of the phenomena, dissolution rate investigations, measurements of surface tension and determinations of partition coefficients were also performed. It was established that paracetamol has a low diffusion ability. It was also found that the different CD derivatives exert their influence in diverse ways, which depend on, among others, the cyclodextrin ratio and the mode of preparation of the product. These complementary examinations are useful for an explanation of the phenomena.

[Formulation of diazepam suppositories, results of rheological and biopharmaceutical studies. 2. In vitro membrane diffusion and in vivo absorption results]. / Diazepám-tartalmú végbélkúpok formulálása, reológiai és biofarmáciai vizsgálatának tapasztalatai. 2. In vitro membrándiffúziós és in vivo felszívódási eredmények.

In the first part of the publication the rheological properties of the vehicles used for the production of suppositories were studied in order to determine the ideal parameters for formulation. In this part a detailed methodology and the results of the in vitro membrane diffusion and in vivo bioavailability studies, are presented. The results confirm a general correlation between the in vitro and the in vivo findings. It seems that hydrophilic macrogol-mixture with great molecular mass can be recommended as the optimal vehicle for formulation of diazepam suppositories.

Conditions of cyclodextrin complexation.

In the past 20 years, cyclodextrin (CD) research has achieved considerable results, as indicated by the large number of publications and patents, the six international symposia on CDs, the new dosage forms of medicines prepared with CDs, etc. Sufficient data have accumulated to permit a survey of the most important conditions of CD complexation. Further, an account is presented of the success of precipitation of the complex involving furosemide and beta-CD.

Preparation and investigation of inclusion complexes containing nitrazepam.

Nitrazepam is a valuable drug, being one of the often used minor tranquillizers in psychotherapy. However, its solubility characteristics are very unfavourable. Products were prepared with dimethyl-beta-cyclodextrin in different combinations (8.58%, 19.48% and 27.29%) and by several methods such as mixing, kneading, precipitation and spray-drying.

Increasing the solubility characteristics of albendazole with dimethyl-beta-cyclodextrin.

Albendazole is a veterinary anthelminthic drug with excellent effect. Since it is only slightly soluble in water, it is processed in a suspension dosage form as a drench. The solubility and bioavailability of the pharmacon were successfully increased with cyclodextrin derivatives.

Production and investigating of tablets containing furosemide and beta-cyclodextrin.

Furosemide is a very active drug with an excellent saluretic effect, but it dissolves in water only with difficulty. Furosemide products with beta-cyclodextrin (CD) have been made by five methods, and it has been established that most drugs are liberated most quickly from the kneaded product for the 12.72% combinations. The dissolution characteristics of furosemide are improved in tablets made from the kneaded product. By this means an essentially quicker effect can be achieved, a lower drug quantity is necessary for a similar effect, a smaller therapeutic risk in involved, and the technique is economical too.