[Selective depletion of alloreactive T cells and study of anti-tumor activity of specific T cell clones in patients with leukemia]. / Selektivní deplece aloreaktivních T lymfocytu a studium protinádorové aktivity specifických klonu T lymfocytu u pacientu s leuikémií.

BACKGROUND: Graft-versus-host disease (GVHD) is a severe complication of allogeneic transplantation of hematopoietic stem cells. Donor T cells play a major role in GVHD leading to the host tissue damage, mainly the skin, liver, and gastrointestinal tract. A selective depletion using an anti-CD25 immunotoxin can eliminate harmful alloreactive T cells while preserving other donor T cells with antileukemic and antiinfectious reactivity. PATIENTS AND METHODS: We performed 15 mixed lymphocyte reactions with clinical specimens from 12 patients with various types of leukemia (7x AML, 3x ALL, 1x CML, 1x CLL) and PBMC from 15 healthy volunteers from Transfusive station FN Brno Bohunice. RESULTS: In our experiments we have demonstrated, that antileukemic (GVL) effect of donor, especially CD4+ T cells was well preserved (7.46%), while unfavourable alloreactive (GVH) reaction of donor T cells was completely removed. The graft-versus-host (GVH) reactivation of donor cells was negligible ever after repeated stimulation with irradiated patient's PBMC. CONCLUSION: We have shown that anti-CD25 immunotoxin (IT), RFT5-SMPT-dgA, launched against alpha chain for human interleukin 2 (IL-2), led to long-term selective depletion of alloreactive donor T cell clones while their antileukemic activity was well preserved. Base on our results the clinical phase I/II study was designed. This study was initiated in year 2007 in three clinical centers in Czech Republic.

A study of the properties of tablets made of directly compressible maltose.

The paper deals with the study of the strength and disintegration time of tablets made of directly compressible maltose Advantose 100. It studies the differences of the effects of two types of lubricants, magnesium stearate and sodium stearylfumarate, on the above-mentioned properties, and it also tests the mixtures of the substance with microcrystalline cellulose Vivapur 102 in a ratio of 1:1 and with ascorbic and acetylsalicylic acids. The compacts are obtained by using three compression forces, excepting mixtures with active ingredients, where one compression force is used. In the compression forces of 6 and 8 kN, no statistically significant difference was found in the intervention of the lubricants into the strength of the compacts made of Advantose 100, only in the compression force of 10 kN Pruv decreased the strength more than stearate. The mixture of Advantose 100 and Vivapur 102 yielded the strongest tablets, an addition of Pruv to it decreased the strength of compacts more than stearate. The periods of disintegration time of Advantose compacts as well as those of the mixture of dry binders were longer with an addition of Pruv. The compacts with acetylsalicylic acid possessed higher strength and a longer period of disintegration than those with ascorbic acid. There was no statistically significant difference within the type of the lubricant employed, both in the case of Advantose 100 and its mixture with Vivapur 102, between the values of strength of the compacts with acetylsalicylic acid.

A study of the properties of tablets from the mixtures of directly compressible starch and directly compressible lactitol.

The paper deals with the evaluation of tablets from the mixtures of directly compressible starch Starch 1500 and directly compressible lactitol Lacty-Tab in a ratio of 3:1 and 1:1. The examination included the tensile strength and disintegration time of tablets in dependence on compression force, addition of two concentrations of sodium stearyl fumarate (Pruv) as the lubricant, and a 50% content of the model active ingredient acetylsalicylic acid. Tensile strength of tablets increased with compression force and the effect of Pruv decreased it in both mixtures. Tablets from the mixture of dry binders in a ratio 1:1 without the lubricant possessed highest values of tensile strength. After an addition of the lubricant, no statistically significant difference was found in this mixture between interventions of 0.5 and 1% Pruv concentrations into strength. Disintegration time increased with compression force; it was the shortest in tablets with 1% Pruv in the case of the mixture of Starch 1500 and lactitol 3:1; in the case of the mixture 1:1 it was the longest. Tablets containing acetylsalicylic acid possessed higher values of tensile strength in the case of the mixture of dry powders in a ratio of 1:1, the strength decreasing with increasing Pruv concentration. Tablets from this mixture also possessed a longer period of disintegration time which increased with increasing Pruv concentration.

A study of the properties of tablets from coprocessed dry binders composed of alpha-lactose monohydrate and different types of cellulose.

The paper evaluates the differences between the properties of tablets from two coprocessed dry binders based on alpha-lactose monohydrate and cellulose, MicroceLac 100 and Cellactose 80. The substances differ in the type of contained cellulose; MicroceLac 100 contains 25% of microcrystalline cellulose, Cellactose 80, 25% of powdered cellulose. The properties under study included the tensile strength and disintegration time in dependence on compression force, addition of two concentrations of the lubricant sodium stearylfumarate (Pruv) and a 50% addition of the active ingredients ascorbic acid and acetylsalicylic acid. Using one of the compression forces, the effect of Pruv and magnesium stearate on the above-mentioned properties were compared. In the compression forces of 6 and 8 kN the strength of the compacts from pure Cellactose 80 was lower than that of those from MicroceLac 100 both without and with the lubricant. The lubricant sensitivity of dry binders depended on compression force. Pruv decreased the strength of compacts less than magnesium stearate. The tablets from Cellactose 80 possessed a longer disintegration time than those from MicroceLac 100, excepting the tableting materials containing 0.4 Pruv with a compression force of 6 kN. Disintegration time was prolonged with the use of sodium stearylfumarate and it was increased with compression force much more markedly in the case of Cellactose 80. In the presence of ascorbic acid, the strength of tablets was decreased in the case of both dry binders, but it was higher with MicroceLac100, disintegration time was very short and independent of the type of the dry binder. In the case of acetylsalicylic acid, the strength of tablets was higher with a lesser influence of the type of the dry binder, and disintegration time was longer and especially in the case of Cellactose 80 increased with increasing concentration of Pruv.

[Studies of the properties of tablets made from directly compressible starch and its mixtures with directly compressible lactose]. / Studium vlastností tablet z prímo lisovatelného skrobu a jeho smesí s prímo lisovatelnou laktosou.

The paper studies the strength and disintegration time of compacts made from directly compressible Starch 1500 and its mixtures with directly compressible lactose Pharmatosa DCL 15 in different relative proportions in dependence on the added lubricant magnesium stearate and the model active ingredient ascorbic acid. The dry binders under study differ in their mechanisms of compression and thus in their sensitivity to the addition of the lubricant, which is manifested in decreased strengths of the compacts as well as the mechanism of disintegration of the compacts. The mixtures of substances under study were in the relative representations of 1:3, 1:1 and 3:1. The employed concentration of the lubricant magnesium stearate was 0.4%, that of ascorbic acid, 50%. The study has confirmed and quantitatively evaluated the sensitivity of directly compressible starch to the addition of magnesium stearate. A higher share of directly compressible lactose in the mixture decreased the sensitivity of tableting material to the addition of the lubricant and shortened disintegration time. The presence of stearate did not negatively influence disintegration time, with an exception of the mixture of Starch 1500 and Pharmatosa DCL 15 1:3. An addition of the model active ingredient ascorbic acid decreased the strength of the compacts and shortened the disintegration time in all tableting materials tested.

[A study of the properties of tablets from mixtures of two size degrees of alpha-lactose monohydrate and microcrystalline cellulose]. / Studium vlastností tablet ze smesí dvou velikostních stupnu alpha-laktosy monohydrátu a mikrokrystalické celulosy.

The paper examines the strength and disintegration time of compacts from the mixtures of two types of Tablettosas. Tablettosa 70 and Tablettosa 100 with microcrystalline cellulose represented by Vivapur 102. The mixtures of dry binders were prepared in the ratios of 3:1, 1:1, and 1:3. The effect of two concentrations of the lubricant magnesium stearate on the strength and disintegration time of compacts was also examined. Tablet strength increased with higher representation of microcrystalline cellulose in the mixture, and decreased with higher stearate concentration. The compacts from the mixtures with Tablettosa 100 showed higher strength. Disintegration time was highest in the compacts with the largest perccintage of microcrystalline cellulose, and longer in the case of the mixtures with Tablettosa 100. Stearate did not exert a negative effect on disintegration time. In the mixtures of Tablettosas with Vivapur 102 in a ratio of 1:1, the effect of the model active ingredient acetylsalicylic acid on the above-mentioned properties of tablets was tested. acetylsalicylic acid produced a further decrease in the strength of compacts and shortened the disintegration time in more instances in the cased of the mixtures with Tahlettosa 100.

[A study of the properties of compacts from a mixed dry binder on the base of alpha-lactose monohydrate and microcrystalline cellulose]. / Studium vlastností výlisku ze smesného suchého pojiva na bázi alpha-laktosy monohydrátu a mikrokrystalické celulosy.

The paper studies the tensile strength and disintegration time of compacts from the mixed dry binder MicroceLac 100. Tensile strength and disintegration time of tablets were tested in connection with the following factors: compression force, compression rate, addition of magnesium stearate, addition of ascorbic acid, the model active principle. The compression forces employed were 5, 6, and 7 kN, compression rates, 20 and 40 mm/min, stearate concentration 0, 0.4, and 0.8%, ascorbic acid concentration, 25 and 50%. With increasing addition of the stearate, the strength of compacts from MicroceLacu 100 was decreased for both compression rates, but with a higher rate, in a concentration of 0.4%, the decrease in strength was more marked. Disintegration time was increased with compression force and the addition of the stearate, but in all cases it was very short. Increased addition of ascorbic acid further intensified the decrease in the strength of compacts and decreased the disintegration time and the effect of the stearate on it. Disintegration time of compacts with ascorbic acid in a concentration of 50% did not increase with compression force.

[Study of mixed dry binders in directly compressible lactoses and microcrystalline cellulose]. / Studium smesných suchých pojiv z prímo lisovatelných laktos a mikrokrystalické celulosy.

The paper evaluated the compressibility of dry binders prepared in the ratios of 3:1, 1:1, and 1:3 from Pharmatosa DCL 15 and DCL 21 and Avicel PH 200, and the sensitivity of the mixtures to an addition of the lubricant magnesium stearate from the standpoint of the effect on the strength of tablets. Mixtures of lactoses with Avicel PH -200 in a ratio of 3:1 proved to be most advantageous. The strengths of tablets made of these mixtures oscillated in the optimal range and they showed the least sensitivity to the added lubricant. An increase in stearate concentration did not result in a marked decrease in the strength of compacts. Pharmatosa DCL 21 in a mixture with Avicel PH 200 yielded stronger compacts at lower compression force than Pharmatosa DCL 15.

[Study of the strength of compacts of mixed dry binders consisting of powdered cellulose and directly compressible lactose]. / Studium pevnosti výlisku ze smesných suchých pojiv slozených z práskové celulosy a prímo lisovatelné laktosy.

The paper studied the strength of compacts of dry binders consisting of powdered cellulose and directly compressible lactose. The powdered cellulose employed was Arbocel A300, the directly compressible lactose, Pharmatosa DCL 21. The first step of the evaluation comprised the tensile strength of compacts and sensitivity of dry binders alone to an addition of magnesium stearate. The same method of evaluation was then used for mixed dry binders from Arbocel A300 and Pharmatosa DCL 21 in ratios of 3:1, 1:1 and 1:3. The tested concentrations of magnesium stearate were 0.4 and 0.8%. Sensitivity of dry binders to an addition of the lubricant was evaluated by means of lubricant sensitivity ratio (LSR) values. The compacts with the highest strength and at the same time the lowest sensitivity to an addition of magnesium stearate were produced using a mixture of Arbocel A300 and Pharmatosa DCL 21 in a ratio of 1:3. The evaluation also included the commercially produced mixed dry binder Cellactosa 80, in which higher sensitivity to an addition of stearate than in a mixture of Arbocel A300 and Pharmatosa DCL 21 in a ratio of 1:3 was found.

[Compressibility of directly compressed forms of lactitol]. / Studium lisovatelnosti prímo lisovatelné formy laktitolu.

Lactitol ranks among sugar alcohols which are employed as dry binders in the manufacture of tablets, particularly the chewable ones. Water-granulated lactitol is the directly compacting form of this substance. The present paper studies the compressibility of the granulated form of lactitol and the effects of different concentrations of the lubricant magnesium stearate on the strength and disintegration time of the compacts from his substance. Lactitol cannot be compressed without an added lubricant. Magnesium stearate, employed in two concentrations, 0.4% and 0.8%, did not negatively interfere with the strength of the compacts. The disintegration period of tablets was prolonged with increasing stearate concentration, but independently of compression force.

[The dry binders, Vivapur 102, Vivapur 12 and the effect of magnesium stearate on the strength of tablets containing these substances]. / Suchá pojiva Vivapur 102, Vivapur 12 a vliv stearanu horecnatého na pevnost tablet z techto látek.

Vivapur is microcrystalline cellulose manufactured by the German firm J. Rettenmeier & Söhne GmbH + Co. The types Vivapur 102 and 12 enjoy priority use as dry binders for direct tablet compression. The present paper evaluates tensile strength of tablets made from these substances and the effect of an addition of the lubricant magnesium stearate in connection with its concentration and the conditions of the process of mixing, particularly the period and intensity of mixing. The tested concentrations of stearate were 0.4 and 0.8%, the tested periods of mixing being 2.5, 5, 10, and 20 minutes, intensities of mixing 17 and 34 rot./min. Sensitivity of dry binders to added stearate was evaluated by means of the LSR (lubricant sensitivity ratio) values. The results demonstrated higher sensitivity to an addition of the lubricant in Vivapur 12 than in Vivapur 102. In the first part of the paper focused on the effect of stearate concentration on tensile strength of tablets, Vivapur 102 was also compared with Avicel PH-102. Tablets from Vivapur 102 alone were stronger than those from Avicel PH-102. A concentration of stearate of 0.8% decreased the binding capacity of Vivapur 102 more than that of Avicel PH-102. With a prolonged period of mixing and increased intensity of mixing with stearate, tensile strength of tablets from both Vivapur types was decresed, and a prolonged period of mixing exerted a more marked effect on Vivapur 12 and increased intensity of mixing, on Vivapur 102.

[Effect of magnesium stearate on the tensile strength of tablets made with the binder Prosolv SMCC 90]. / Vliv stearanu horecnatého na pevnost tablet v tahu ze suchého pojiva Prosolv SMCC 90.

The present paper evaluated the tensile strength of tablets made from the dry binder Prosolv SMCC 90 and the influence of three concentrations of the lubricant magnesium stearate on the tensile strength of tablets manufactured from this material. The results were compared with the same evaluation in Avicel PH 102. The tested concentrations of the stearate were 0.4, 0.8 and 1.2%. The tablets were compressed by three press powers (3, 3.5, and 4 kN). On the basis of obtained results it can be stated that under the same press powers Prosolv SMCC 90 alone yields stronger compacts than Avicel PH 102. From the viewpoint of decreased strength of compacts by adding magnesium stearate, the dry binder Prosolv SMCC 90 is much less sensitive than Avicel PH 102. In Avicel PH 102 a marked decrease in tensile strength was recorded with an addition of 0.4%, which was not observed with Prosolv SMCC90. A more significant decrease in the strength of compacts was shown by the substance not until a stearate concentration of 0.8%. The highest employed stearate concentration of 1.2% decreases the tensile strength of tablets made from Prosolv SMCC 90 in the press powers of 3.5 and 4 kN two times less than the tensile strength of the compacts from Avicel PH 102.

[The firmness of Avicel PH 102 and Avicel PH 301 compression and the effect of magnesium stearate] ]. / Pevnost výlisku z Avicelu PH 102 a Avicelu PH 301 a její ovlivnení stearanem horecnatým.

The paper evaluated the strength of compacts made of microcrystalline cellulose of two types used as dry binders in the technology of direct compression of tablets, i.e. Avicel PH 102 and Avicel PH 301. The effect of three concentrations of the lubricant magnesium stearate (0.4; 0.8; 1.2%) on the strength of tablets made from these substances was also evaluated. Tables were compressed using three forces of compression (3; 3.5, and 4 kN). On the basis of the obtained results it can be concluded that Avicel PH 102 provides, under identical forces of compression, stronger compacts than Avicel PH 301 does. It has been further found that a magnesium stearate concentration of 0.4 markedly decreases the tensile strength of Avicel PH 102 tablets, and another marked decrease is observed with a concentration of 1.2%. The decrease in the tensile strength of Avicel PH 301 compacts due to magnesium stearate is not so marked as in Avicel PH 102 tablets, and with stearate concentrations of 0.4% and 1.2% the difference in strength is not of such importance in comparison with the previous concentrations.

[Effect of magnesium stearate on internal failure of Avicel PH 101 tablets]. / Vliv stearanu horecnatého na vnitrní poruchovost tablet z Avicelu PH 101.

The effect of the incorporation of different concentrations of magnesium stearate (0, 0.4, 0.8, and 1.2%) on the texture of the tablets from Avicel PH 101 was investigated by means of the examination of their tensile strength and the values of Weibull's modules. It has been found that with an increasing forming pressure the decrease in the tensile strength of tablets is increased. No significant difference in the decrease in tensile strength was found between stearate concentrations of 0.4 and 0.8%. The incorporation of magnesium stearate into the tableting material, by decreasing the friction between the particles, minimizes possible incidence of more marked disorders in the texture of tablets.