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The present study compares the effects of two dietary strawberry extracts rich in monomeric (ME) or dimeric (DE) ellagitannins (ETs) on gastrointestinal, blood and tissue biomarkers in Wistar rats fed high-fructose diets. Both strawberry extracts beneficially affect the antioxidant status and lipid profile of the liver and serum. The ME extract shows a greater ability to inhibit lipid peroxidation in kidneys, more effectively decreases serum and liver triglycerides, and exerts greater anti-inflammatory effects in blood serum than the DE extract. The DE extract significantly reduces the activity of microbial enzymes in the cecum. These effects might be associated with higher cecum and urine levels of ET metabolites in rats fed with ME than in rats fed with DE. In conclusion, the diet-induced fructose-related disturbances observed in biochemical parameters are regulated by both extracts; nevertheless, the beneficial effects of the ME extract are mostly associated with systemic parameters, while those of the DE extracts are associated with local microbial activity. more...

International audience; The polysaccharide composition of cell wall of sour cherry (Prunus cerasus var. Schattenmorelle) fruit and pomace was investigated. Furthermore, the alcohol insoluble solids composition of ‘Kelleriis’ and ‘Dobreczyn Botermo’ varieties were studied too. Yield of alcohol insoluble solids for fruits was lower than 10%, and for pomaces circa 50%. Uronic acid was the main pectin component of alcohol insoluble solids. Enzymes used as juice processing aids decreased the content of uronic acid. Araban and galactan side chains bonded tightly to cellulose presence was suggested by high content of arabinose and galactose in hemicellulose fraction. The process of drying at below 70 °C did not influence polysaccharide composition of sour cherry pomaces. Alcohol insoluble solids of fruits expressed higher hydration properties than of pomaces. more...

A lattice walk with all steps having the same length d is called a d-walk. In this note we examine parity properties of closed d-walks in R N in relation to N and d. We also characterize real numbers d for which in R 2 every lattice point can be the terminal point in a d-walk starting from the origin. more...

Cranes are underactuated mechanical systems with fewer control inputs than the degrees of freedom. Their usual performance goal is to execute a desired load trajectory, which is specified by as many outputs as the control inputs. A solution to the inverse simulation problem, in which the control of the underactuated system required to execute the partly specified motion is determined, is a challenging task. The inverse simulation study is usually formulated in independent variables. In this paper a dependent variable formulation is reported, advantageous in many aspects. The resultant governing equations appear as simple index-three differential-algebraic equations, and an effective numerical code for their solution is discussed. more...

SummaryAn extract obtained from industrial blackcurrant pomace was purified and fractionated on an RP C18 column, resulting in three phenolics preparations of different composition. The phenolics in the preparations were quantified by HPLC, their anti-oxidant capacity was determined, and the preparations were subjected to HPLC-MS analysis in order to identify the bioactive compounds present. The purified preparations selected for study were an anthocyanin-rich preparation, a myricetin and quercetin glycosides-containing preparation, and an aglycon-containing preparation. All three preparations were characterised by having a high content of polyphenols. The anthocyanin-rich preparation was the most concentrated in polyphenols [> 50% (w/w)], followed by the aglycon-containing preparation [> 20% (w/w)], and finally the glycosides-containing preparation [> 9% (w/w)]. The preparations were also characterised by their high anti-oxidant capacity, which was > 3,100 µM TEAC g−1 (TEAC = Trolox Equivalent Anti-oxida... more...

SummaryPomaces obtained during the production of cloudy or clear juice from scab-resistant apple cultivars (28 harvested in 2006, and 23 harvested in 2007) were studied as a source of nutritionally important components. It was shown that the average yield of pomace during the production of cloudy juice was 6.4% (w/w), and 4.9% (w/w) for clear juice pressing. The average total dietary fibre (TDF) contents were 48.4% (w/w) and 52.4% (w/w) for cloudy and clear juice pomaces, respectively. Ten pomaces from cloudy apple juice production, and 12 obtained from clear juice production, contained ≥ 2,000 mg kg−1 of polyphenols.‘Ariwa’ and ‘Rajka’ are apple cultivars suitable for juice production and their pomaces are characterised by having high contents of TDF [50.9% (w/w) and 51.1% (w/w), respectively], with aboveaverage polyphenol and quercetin glycoside concentrations. The mean contents of quercetin glycosides for pomaces from all apple cultivars was 994 mg kg−1 after clear juice production, and 908.2 mg kg−1 a... more...

The administration of fructooligosaccharides (FOS) beneficially modulates gastrointestinal functions and may enhance the metabolism of polyphenols. However, different polyphenolic components in the diet may have different influences on the activities of the digestive enzymes and microbiota in the gastrointestinal tract. Therefore, a 4-week study of forty-eight male Wistar rats was conducted to investigate the physiological response of the rat cecal environment to diets without and with FOS that contained two different strawberry polyphenolic extracts, specifically EP (polyphenolic profile 60, 35, 5, and 0% ellagitannins, proanthocyanidins, flavonols, anthocyanins, respectively) and EPA (polyphenolic profile: 50, 35, 6, and 9%, respectively). When combined with FOS, both extracts beneficially enhanced the acidification of the cecal digesta (P≤0.05 vs the groups without extracts), but the dietary combination of EPA and FOS elicited the greatest reduction in putrefactive short-chain fatty acid production and the lowest fecal β-glucuronidase activity in the cecum (P≤0.05 vs group EP). Moreover, the addition of dietary FOS elevated the metabolism of the examined strawberry extracts in the cecum and thereby increased the concentrations of the metabolites in the cecal digesta and urine (P≤0.05 vs the group with cellulose). Overall, both strawberry extracts modulated the effects of FOS in the gastrointestinal tract; however, the combination with EPA extract that contained anthocyanins exhibited greater beneficial effects in the lower gut environment than the EP extract. more...

Manipulating payloads with gantry cranes is challenging due to possible undesirable load pendulations induced by the crane motion and external perturbations. When the work environment is cluttered with obstacles, the problem gets increasingly difficult, which must be avoided, resulting in the need for appropriate load trajectory planning and more cautious craning strategy. The trajectory is first sketched by a series of points in the work space, and then approximated by spline functions. A rest-to-rest load motion along the specified trajectory is then imposed, resulting in one coordinated manoeuvre that omits the obstacles. The control of crane executing the load motion is viewed as an inverse dynamics problem, strongly influenced by the underactuated nature of the system. The arising governing differential-algebraic equations enable one for the analysis of crane dynamics and synthesis of its control in the specified motion. The open-loop control obtained this way is enhanced by a closed-loop control with feedback of the actual errors in load position to provide stable tracking of the reference trajectory in presence of perturbations and modelling inconsistencies. Some results of numerical simulations are reported. more...

There are many interesting combinatorial results and problems dealing with lattice polygons, that is, polygons in ℝ2 with vertices in the integral lattice ℤ2. Geometrically, ℤ2 is the set of corners of a tiling of ℝ2 by unit squares. Denote by H the set of corners of a tiling of the plane by regular hexagons of unit area and call a polygon P a Hex-polygon or an H-polygon if all vertices of P are in H. Our purpose is to study several combinatorial properties of H-polygons that are analogous to properties of lattice polygons. In particular we aim to find some relationships between the numbers b and i of points from H on the boundary and in the interior of an H-polygon P with the numbers v and c of vertices and the so-called boundary characteristic of P. We also pose three open problems dealing with convex Hex-polygons. more...

As many substances are poorly soluble in water and thus possess decreased bioavailability, creating orally administered forms of these substances is a challenge. The objective of this study was to determine whether the solubility of megestrol acetate, a Biopharmaceutical Classification System (BCS) class II drug, can be improved by using a newly-synthesized surfactant (Rofam 70: a rapeseed methyl ester ethoxylate) and compare it with two references surfactants (Tween 80, Pluronic F68) at three different pH values. Spectrophotometry was used to compare the solubility profiles in the presence of three tested surfactants at pH 5.0, 7.4 and 9.0. Rapeseed methyl ester ethoxylate was found to improve the solubility of the BCS Class II drug and increase its bioavailability; It increased drug solubility more effectively than Pluronic F68. Its cytotoxicity results indicate its possible value as a surfactant in Medicine and Pharmacy. more...

Background There is limited evidence indicating that specific immunotherapy in elderly patients is safe and effective. Objective To evaluate the safety and efficacy of pre-seasonal specific subcutaneous immunotherapy (SCIT) against grass pollen allergens in patients older than 65 years with seasonal allergic rhinitis and to measure the prime outcome of area under the curve for the combined symptoms and medication score during grass pollen season after 3 years of SCIT in a double-blinded, placebo-controlled trial. Methods This study included 60 65- to 75-year-old patients with seasonal allergic rhinitis and grass pollen allergy. Patients were individually randomized to the active or placebo group. Thirty-three subjects in the SCIT group and 27 subjects in the placebo group were monitored for 3 years. Patients were required to record each use of anti-allergy medication. Results Thirty-one patients completed 3 years of pre-seasonal SCIT and 24 subjects finished placebo treatment. The median area under the curve for the combined symptoms and medication score after the third grass pollen season after SCIT was significantly decreased from 7.85 (range 3.67–8.98) to 4.63 (range 3.56–7.80) in the active group and did not significantly change in the placebo group. In the active group, the combined symptoms and medication score was decreased by 41%, the symptoms score was decreased by 55%, and the medication score was decreased by 64% after 3 years of immunotherapy. Conclusion Pre-seasonal SCIT in the elderly is safe and efficacious and elicits an immune response comparable to what is found in studies of younger patients. more...

The aim of this study was to perform a 20-year post-specific immunotherapy (SIT) observational evaluation for an assessment of any manifestations of autoimmune disease or the appearance of autoantibodies in serum. In total, 1,888 patients (902 women and 986 men) were observed. The mean age of the patients was 34.1 ± 12.4 y at the start of the prospective observation after finishing SIT. New incidences of autoimmune disease and/or the presence of autoantibodies in serum were monitored. The SIT group was compared with control groups consisting of allergic patients who had very received SIT and with non-allergic subjects. There were no significant differences in the autoimmune disease prevalence between the allergic patients with or without SIT. However, significantly higher prevalence of 4 different autoimmune diseases (AID) were observed in the non-allergic patients during the same period. Additionally, the incidence of 8 different autoantibodies was significantly higher in non-allergic patients than in control subjects. Hashimoto disease was the most common autoimmune disease observed. The results of this long-term observational study indicated a lack of a significant prevalence of new instances of autoimmune disease during 20 y of observation post-SIT and at a rate lower than that of non-allergic control subjects, suggesting that SIT is safe in this regard in the long term. more...

Halitosis and gingivitis are most common pathologies (15-60% of population) which, if left untreated, lead to periodontal diseases and tooth loss.The aim of this study was to develop, based on polymers of dry sage extract and zinc gluconate, tablets intended for sucking and chewing that can be applied in the treatment of halitosis and gingivitis.Dried aqueous sage extract, zinc gluconate, Pharmagum M, Prosolv SMCC90 and SMCCHD90, Vivapur 102, sorbitol, mannitol, ludipress. Direct tableting. Testing pharmacopeial parameters and pharmaceutical availability (using basket and rotating disk methods) of tablets intended for sucking and chewing. Approximation of the obtained results.Grey and green color tablets were obtained with smooth and uniform surface, without stains, spalls or mechanical damage. The determined average mass (weight) of a tablet complied with the standard. The friability and crushing strength test revealed that tablets containing Prosolv SMCCHD90, Vivapur 102 and mannitol demonstrated the highest mechanical strength. Tablets containing these substances and intended for sucking had prolonged disintegration and release time. Tablets intended for chewing had a hardness at the level of 124 N.They demonstrated compressibility, low friability and prolonged release. The release profiles of tablets intended for sucking (v2) and those for chewing, obtained by basket and rotating disk methods, were similar.The addition of Prosolv SMCCHD90, Vivapur 102 and mannitol increased significantly the mechanical strength (higher hardness, lower friability), prolonged the disintegration time and slowed the release from the obtained tablets intended for sucking and chewing. The application of Prosolv SMCCHD90 in the formulation of tablets for chewing carries the risk for sorption of active components to the polymer structure. This process takes place in the early stage of the release. Rotating disk method used in pharmaceutical availability testing gives better results while analyzing the phenomenon than the standard basket method. The suggested and tested formulations of tablets intended for sucking and chewing may be used as an alternative to formulations containing dried titrated extracts from plants of antimicrobial activity (sage - Salvia officinalis) in combination with substances binding volatile sulfur compounds (zinc gluconate). more...

A classical problem of nonholonomic system dynamics—the motion of a sphere on the inside of a rough vertical cylinder—is extended to rolling friction. The case study is modelled in independent coordinates. Due to the nonholonomic constraints imposed on the sphere, the governing equations arise as a set of differential-algebraic equations. The results of numerical simulations show the transition of the sphere from a sinusoid path on the vertical cylinder surface to a fall with slip. The physics of the ‘paradoxical’ motion is explained in detail. more...

Aqueous solutions of homologous series of "Rofam" type surfactants (ZPC) based on rape oil fatty acids methyl esters, differing in oxyethylene segments content (n T E ), were the subjects of investigations. Content of oxyethylene segments n T E , determined by 1 H NMR, allowed to verify ZPC molecular weight and to calculate structural hydrophilic-lipophilic balance (HLB, by Davis or Griffin methods) as well as required solubility level of the balance (HLB R ) (Table 1). The following values were determined on the basis of viscometric measurements: limiting viscosity number [η], viscometric average molecular weight (Mη), specific volume (Ω) and hydrodynamic radius of micelle (Robs) (Table 2 and 3). Viscometric measurements let also calculate average number of water molecules hydrating the micelle built of "Rofam" homologous structures. Determination of critical micellar concentration (cmc) was the base for calculation of thermodynamic potential of micelle formation (ΔG 0 m ) and micellar level of hydrophilic-lipophilic balance (HLB c m c ) (Table 4, Fig. 1-3). The value of surfactant's lipophilic core upthrust over the phase boundary (A m , Fig. 4) let analyze the effect of oxyethylene segments' content in "Rofam" molecule structure on its potential solubilization properties. The results of investigations and the values calculated on this basis make clearer the mechanism of solubilization of lipophilic drugs what determines the pharmaceutical and biological availability of micellar adducts from the model forms of drugs. more...

The reactions of radiolytically generated hydroxyl radicals (OH ) with dl -o-tyrosine (o-Tyr) in 10−3 mol dm−3 aqueous solutions, saturated with N2O/O2 gas mixture (4:1, v/v), were studied in the dose range between 30 and 270 Gy. Two isomeric o-Tyr hydroxylation products, namely, 2,3-dihydroxyphenylalanine (2,3-DOPA) and 2,5-dihydroxyphenylalanine (2,5-DOPA) have been identified. The chemical structure of both products was confirmed by an electrospray ionization mass spectrometry, UV and NMR-1H spectroscopy. The quantitative analysis with the use of an electrochemical and a spectrofluorimetric detection showed that the concentration of 2,3-DOPA and 2,5-DOPA increased and the content of substrate decreased linearly with increasing radiation dose. The ratio of the yields of 2,3-DOPA and 2,5-DOPA was equal to 1.3 for the whole range of radiation dose applied. The total yield of 2,3- and 2,5-DOPAs was approximately 50% of the level of o-Tyr decomposition. more...

The paper deals with controlled mechanical systems in which the number of control inputs is equal to the number of desired system outputs, and is smaller than the number of degrees of freedom of the system. The determination of control input strategy that force the underactuated system to complete the partly specified motion is a challenging problem. In the present formulation, the outputs (performance goals), expressed in terms of system states, are treated as constraints on the system—called control or program constraints as distinct from contact constraints in the classical sense, and a mathematical resemblance of the inverse control problem to the constrained system dynamics is exploited. However, while the reactions of contact constraints act in the directions orthogonal to the respective constraint manifold, the available control reactions may have arbitrary directions with respect to the program constraint manifold, and in the extreme may be tangent. A specific methodology must then be developed to find the solution of such “singular” problems, related to a class of control tracking problems such as position control of elastic joint robots, control of cranes, and aircraft control in prescribed trajectory flight. The governing equations of the problem arise as a set of differential-algebraic equations (DAEs), and an effective method for solving the DAEs, based on backward Euler method, is proposed. The open-loop control formulation obtained this way is then extended by a closed-loop control law to provide stable tracking of the required reference trajectories in the presence of perturbations. Some examples of applications of the theory and results of numerical simulations are reported. more...

Possibility of the application of domestic surfactants (ZPC) from the,,Rofam" series (oleic acid oxyethylenated methyl esters) in a drug form technology has been investigated. The real mean number of oxyethylene units (n T E ), measured by 1 H NMR, has been used to determine the analytical level of hydrophylic-lipophylic equilibrium (HLB, H/L). The number of oxyethylene units in the,,Rofam" homologous series, declared by producer (n T E ) as well as experimentally found (n T E ), made possible verification of their molecular weights (M* and M, respectively) and calculation of the topological indices (ΣIC and ΣSIC), solubility parameters (δ * i δ) and structural level of hydrophylic-lipophylic equilibrium (HLB), using methods by Griffin or Davies, as well as HLB R (required HLB value) and H/L. Dependences between the number of oxyethylenated units in the,,Rofam" structure and HLB, H/L and the topological indices (ΣIC and ΣSIC) have been described using correlation equations. It was demonstrated that the values of structural and analytical HLB levels are similar what makes the experimental evaluation of HLB value of chosen ZPC possible. This let estimate of ZPC practical usability. "Rofam" products characterized with n T E ≥8 showed the best functional properties from the pharmaceutical point of view, as transdermal transition promotors, solubilizers and emulsifiers of oil/water type. more...

Endothelins are endothelial peptides, the properties of which have been investigated for over 25 years. They play a special role in the pathophysiology of many diseases of the cardiovascular system. Endothelin-1, which is the most explored one, is a potent vasoconstrictor. It increases renal water and sodium excretion, augments cell growth and proliferation and has proinflammatory activity, by intensifying the production of reactive oxygen and nitrogen species (ROS and RNS). ET-1 takes part in the progression of such diseases as hypertension, atherosclerosis, heart and renal failure. The physio- and pathological effects of endothelins are mediated through ETA and ETB receptors. Blocking these receptors, in particular the ETA receptor, can prevent negative effects of endothelins. Long-term efforts to create drugs which act like that have brought relevant results. Endothelin receptor antago-nists (ERA) are a new class of medicines, which are indicated in the treatment of pulmonary arterial hypertension. There are also optimistic results of trials with ERA administered in other disorders. On the basis of these data we may conclude that there will be more indications for this group of drugs. This review discusses properties and new research directions of ERA registered in pharmacotherapy. more...

Background This study evaluates the safety and efficacy of specific sublingual immunotherapy (SLIT) against grass pollen allergens in patients >60 years of age with seasonal allergic rhinitis (SAR) and/or asthma. This study sought to assess nasal symptoms during the grass pollen season, reduce medication use, and monitor adverse reactions during immunotherapy. Methods Seventy-eight 60- to 70-year-old patients with SAR and a confirmed grass pollen allergy according to skin-prick tests, nasal provocation, and measurement of serum IgE were included in the study. The patients were individually randomized to the act or placebo groups using a double-blind method. A total of 41 subjects in the SLIT group (5 grass pollen mixture) and 37 subjects in the placebo group were monitored for 3 years. The patients were required to record each use of an antiallergy medication on a diary card. Results Thirty-eight patients completed 3 years (preseasonal) of SLIT, and 34 subjects finished the placebo treatment in the same time period. The total nasal symptom score decreased by 64% in the active group and 7% in the placebo group a SLIT. This difference was only significant in the active group (p < 0.05). At the end of therapy, the total medication score of the active group decreased significantly by a maximum of 51% (p < 0.05), whereas the total medication score of the placebo group had an insignificant decrease. None of the study participants had systemic adverse reactions during the study period. Conclusions SLIT in elderly patients with a grass pollen allergy generated significant clinical improvement in the active group compared with the placebo group for grass pollen season. This therapy was well tolerated. more...

The aim of this study was to determine the surface activity parameters of novel surface active compounds, products of catalytic oxyethylation of cholic acid, and their micellar adducts with selected lipophilic therapeutic agents (diclofenac, loratadine, naproxen and rutin). High solubility of lipophilic naproxen was observed in the environment of aqueous solutions of the cholic acid oxyethylation products as suggested by determined factual solubility and the value of micellar partition coefficient (K(w)(m)). Determined surface activity of surfactants described by various physicochemical characteristics (gamma(cmc)(25), cmc, deltaG(m)(o) and A(m)) suggested their compatibility with physiological values of the surface activity of plasma (48.0-52.0 mJ/m2) and lacrimal fluid (46.0-52.0 mJ/m2). Calculated values of HLB(1)(HNMR) and n(TE) of the micellar adduct in solid phase (solid dispersion) corresponded to an increase in its hydrophilicity, and, therefore, suggested possible mechanisms and site of diclofenac, loratadine, naproxen and rutin solubilization in the micellar structure (core or palisadic layer). more...

Denote by ℤ n 3 ,n≥ 2, the lattice consisting of all pointsx in ℝ3 such thatnx belongs to the fundamental lattice ℤ3 of points with integer coordinates. Letl n be the subset of ℤ n 3 consisting of all points whose coordinates are odd multiples of 1/n. The purpose of this paper is to give several new Pick-type formulae for the volume of three-dimensional lattice polyhedra, that is, polyhedra with vertices in ℤ3. Our formulae are in terms of numbers of only thel n-points belonging to a lattice polyhedronP in contrast to already known formulae which employ numbers of all the ℤ n 3 -points inP. On our way to establishing the formulae we show that the number of points froml n belonging to a three-dimensional lattice polyhedronP has some polynomiality properties similar to those of the well-known Ehrhart polynomial expressing the number of points of ℤ n 3 inP. The paper contains also some comments on a problem of finding a volume formula which would employ only the setsl n and which would be applicable to lattice polyhedra in arbitrary dimensions. more...

The volume of a general lattice polyhedron P in ℝN can be determined in terms of numbers of lattice points from N − 1 different lattices in P Ehrhart gave a formula for the volume of “polyèdre entier” in even-dimensional spaces involving only N/2 lattices. The aim of this note is to comment on Ehrhart's formula and provide a similar volume formula applicable to lattice polyhedra that are N-dimensional manifolds in ℝN. more...

Background. Specific immunotherapy (SIT) with an ultrarush administration schedule with Purethal for tree pollen allergens has been evaluated to assess its efficacy and safety.Methods. The study group consisted of 22 patients with symptoms of allergic rhinitis and confirmed allergy to tree pollens. Patients were randomized and given an administration schedule of either ultrarush therapy or conventional preseasonal SIT. Treatment was performed during three consecutive years.Results. After three years of treatment, a similar reduction in nasal symptoms was observed; according to the visual analog scale, there was a decrease from 3.991 ± 0.804 points to 1.634 ± 0.540 in the ultrarush group and from 3.845 ± 0.265 to 1.501 ± 0.418 in the group desensitized using the conventional method (P>0.05). There was also a comparable reduction in the use of relief drugs during pollen season and an increase in the serum concentration of IgG4 to tree pollens. No significant differences in the safety profile were observed.Conclusion. An administration schedule of ultrarush SIT with Purethal Trees is a safe treatment in preliminary observations. This therapy is comparable with conventional administration of SIT in the field of efficacy and safety. more...

Solubilizing properties of aqueous solutions of a series of surface-active agents, products of oxyethylation of cholic acid, were examined in the present study. The content of oxyethylated segments determined by means of the 1H NMR method enabled the verification of the molecular mass of surfactants along with the calculation of the structural hydrophilic-lipophilic balance (HLB), the solubility parameter delta1/2, and the required solubility level of balance HLB(R). Viscosimetric measurements enabled the calculation of the limiting viscosity number, the content-average molecular mass, the effective volume, the hydrodynamic radius of the surfactant micelle and their equilibrium adducts with rutin, diclofenac and loratadine (BCS Class II and III). By means of the spectrophotometric method (UV) the amount of the solubilized diclofenac, loratadine and rutin (rutoside) was determined in the equilibrium system (saturated solution) in the environment of aqueous solutions of cholic acid derivatives of n(TE) = 20-70. The obtained results serve as a basis for determining the solubilization mechanism of lipophilic therapeutic products and indirectly for estimating the influence of the above process on pharmaceutical as well as biological availability of a micellar adduct from model drug forms (Lindbladt lithogenolitic index). more...

Pramipexole (SND 919; 2-amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydroc hlo ride) is a novel dopamine D2 family receptor agonist with a predominant action on D2 autoreceptors and with some D3 vs. D2 receptor preference. The central behavioural effects of pramipexole given subcutaneously to rats (male Wistar) and mice (Albino Swiss) are presented in this paper. Used in low doses (0.001-0.1 mg/kg), pramipexole induced locomotor hypoactivity which was antagonized by a low dose of spiperone; at higher doses (0.3, 1 mg/kg) it evoked hyperactivity which was inhibited by haloperidol, sulpiride and clozapine, but not by SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine hydrochloride). Pramipexole (0.1-1.0 mg/kg) antagonized the akinesia induced by combined pretreatment with reserpine (5 mg/kg) and alpha-methyl-p-tyrosine (250 mg/kg). Pramipexole (0.1-1 mg/kg) potentiated the hyperkinetic effect of L-DOPA (L-3,4-dihydroxyphenylalanine) (50 and 200 mg/kg, together with benserazide, 50 mg/kg) in naive and monoamine-depleted (reserpine + alpha-methyl-p-tyrosine) rats. The higher doses of pramipexole (1 and 3 mg/kg) evoked stereotypy which was antagonized by pretreatment with sulpiride or clozapine. The catalepsy induced by haloperidol, spiperone or fluphenazine was antagonized by pramipexole (1-3 mg/kg). Pramipexole (1 mg/kg) induced hypothermia in mice, which was antagonized by sulpiride. The obtained results indicate that pramipexole: (i) at low doses stimulates the dopamine D2 presynaptic autoreceptors; (ii) at higher doses stimulates dopamine D2 postsynaptic receptors. An effect on the dopamine D3 receptor cannot be excluded. At low doses pramipexole may have antipsychotic activity, and at higher ones antiparkinsonian activity. more...

Let $$\mathcal{T}$$ be the tiling of R 3 with unit cubes whose vertices belong to the fundamental lattice L 1 of points with integer coordinates. Denote by L n the lattice consisting of all points x in R 3 such that nx belongs to L 1. When the vertices of a polyhedron P in R 3 are restricted to lie in L 1 then there is a formula which relates the volume of P to the numbers of all points of two lattices L 1 and L n lying in the interior and on the boundary of P. In the simplest case of the lattices L 1 and L 2 there are 27 points in each cube from $$\mathcal{T}$$ whose relationships to the polyhedron P must be examined. In this note we present a new formula for the volume of lattice polyhedra in R 3 which involves only nine points in each cube of $$\mathcal{T}$$ : one from L 2 and eight belonging to L 4. Another virtue of our formula is that it does not employ any additional parameters, such as the Euler characteristic. more...

Metformin hydrochloride after buformin and phenformin belongs to the group of biguanid derivatives used as oral anti-diabetic drugs. The object of the study is the technological analysis and the potential effect of biodegradable macromolecular polymers on the technological and therapeutic parameters of oral anti-diabetic medicinal products with metformin hydrochloride: Siofor, Formetic, Glucophage, Metformax in doses of 500mg and 1000mg and Glucophage XR in a dose of 500 mg of modified release.Market therapeutic products containing 500 and 1000 mg of metformin hydrochloride in a normal formulation and 500 mg of metformin hydrochloride in a formulation of modified release were analyzed. Following research methods were used: technological analysis of tablets, study of disintegration time of tablets, evaluation of pharmaceutical availability of metformin hydrochloride from tested therapeutic products, mathematical and kinetic analysis of release profiles of metformin hydrochloride, statistical analysis of mean differences of release coefficients.The percentage of excipients in the XR formulation is higher and constitutes 50.5% of a tablet mass. However, in standard formulations the percentage is lower, between 5.5% and 12.76%. On the basis of the results of disintegration time studies, the analysed therapeutic products can be divided into two groups, regardless the dose. The first one are preparations with faster (not fast!) disintegration: Glucophage i Metformax. The second group are preparations with slower disintegration, more balanced in the aspect of a high dose of the biologically active substance: Formetic and Siofor. Products with a lower content of excipients (Metformax, Glucophage) disintegrate in a faster way. The disintegration rate of the products with a higher content of excipients (Formetic, Siofor) is slower. The appearance of metformin hydrochloride concentration in the gastrointestinal contents, balanced in time, caused by a slower disintegration-dissolving of a tablet, is conducive to the reduction of gastrointestinal side effects and better tolerance of the therapeutic product by a patient. The study on pharmaceutical availability indicated relevant kinetic differences between tested therapeutic products. They are particularly visible between standard formulations and the one with prolonged release (Glucophage XR500). Its release profile bears features of kinetics similar to zero-order reactions.Tested therapeutic products contain a large amount of the biologically active substance in relation to the content of excipients. A higher content of excipients in a single tablet mass distinguishes Siofor in comparison with Glucophage i Metformax. The excipients used in the formulations of tested preparations are comparable. A higher percentage of binding agents (HPMC, PVP) is observed, but there is a lack of typical disintegrants which results in a longer disintegration time up to 15 minutes. Siofor disintegrates at the same time as Formetic, but longer than Glucophage i Metformax. Considering the large content of the active substance and pharmacological properties of metformin hydrochloride, such a disintegration might have beneficial consequences, because the amount of the free active substance in the gastrointestinal tract will increase over the longer time period what will reduce the level of gastrointestinal side effects. The release profiles of metformin hydrochloride from tested therapeutic products are comparable. The Glucophage XR 500 formulation with the release kinetics of metformin hydrochloride similar to the zero-order kinetics is completely different from the others. The above is confirmed by the mathematical analysis of release profiles of metformin hydrochloride from tested preparations where equations of lines describing the release profile are characterized by similar values of correlation coefficients. more...

International audience; The aim of the present work was to characterize the pectins present in plum fruit, juice, and pomace for three plum varieties, "Promis," "Najbolja," and "Dabrowicka" (all belonging to the species Prunus domestica L). The content of dietary fiber in the pomace was 5 to 9 times higher than that in the fruit. In turn, the content of soluble fibers and readily soluble pectins (water and chelator soluble pectins) was markedly lower as compared to the fruit, and their hydrodynamic volume was decreased, especially in the case of water soluble pectins. As a result, the hydration capacity of AIS from the pomace was half of that of AIS from the fruit, but its levels were still high enough for it to be used as an ingredient in food products (WBC > 5.5 g/g). Thus, plum pomace could be an efficient source of functional fibers. more...

Introduction: Bronchial asthma is an increasing problem worldwide. The course of bronchial asthma is dependent on the type of inducing allergens. The differences between the clinical features of asthma in patients with monovalent allergies to molds and with other allergies were explored. Material and methods: Randomly selected 1910 patients (924 women and 986 men) between 18−86 years in age were analyzed according to type of allergy and asthma. The diagnosis of asthma was confirmed on the basis of GINA criteria, physical examination and spirometry. Allergy diagnosis was confirmed on the basis of medical history, a positive skin prick test and the measurement of serum-specific IgE to inhalant allergens, using an extended profile of mold allergens. Results: Patients with monovalent allergies to molds (4% of analyzed group) had significantly more frequent diagnoses of asthma than patients in the other group (53% vs. 27.1−32.4%, p < 0.05). Patients with allergies to Alternaria alternata had an odds ratio of 2.11 (95%CI: 1.86−2.32) for receiving a diagnosis of bronchial asthma. They had less control over their asthma, which was more severe compared to patients with other allergies. Patients with asthma and allergies to mold had significantly more frequent exacerbation of asthma requiring systemic corticosteroids and/or hospitalization. They used a significantly greater mean daily dose of inhaled steroids compared to other patients. Conclusions: Patients with monovalent IgE allergies to molds are at a higher risk for asthma than patients with other allergies. Their asthma is often more intense and less controlled compared to that of patients with other types of allergies. more...

Contrary to the literature statement we found that aromatic aldehydes react with diethyl phosphite and hexamethyldisilazane to give 1-(trimethylsilyloxy)-1-arylmethylphosphonates and not 1-amino-1-arylmethylphosphonate derivatives. Therefore, for preparation of diethyl N-arylidene-1-amino-1-arylmethylphosphonate, we recommend the direct reaction of hydrobenzamides with diethyl phosphite, instead of aromatic aldehydes, hexamethyldisilazane and alumina as catalyst on solid phase, as has been described previously (Sardarian, A. R.; Kaboudin, B. Tetrahedron Lett. 1997, 38, 2543–2546). more...

Diclofenac and its sodium salt is one of the best-known and popular therapeutic agents from the group of NSAIDs used in medicine in many various pharmaceutical forms. Therapeutic products containing diclofenac sodium salt in doses of 100 mg and 75 mg with a qualitatively and quantitatively diversified share of excipients and a variable dosage form of the drug (solid capsules, tablets with modified release) were subjected to technological and pharmaceutical analysis. The effect of solid formulation components of polymer character making the core and the coating of the pharmaceutical form of therapeutic products on the disintegration time and pharmaceutical availability in pharmacopoeial receptor fluids was estimated.Market therapeutic products with diclofenac sodium in doses of 75 mg and 100 mg, technological analysis of the drug dosage form was conducted, disintegration time of solid oral dosage forms of the drug with diclofenac sodium salt was examined and research on pharmaceutical availability of diclofenac sodium salt from tested therapeutic products was conducted using the acid phase and the buffer phase according to the FP standards for delayed release enteral dosage forms. The experimental data was supplemented with the statistical analysis.There are three formulations in the form of solid capsules and one formulation in the form of a coated tablet. All therapeutic products bear features of a dosage form of modified release of diclofenac sodium salt, frequently of a delayed release formula in the duodenum or the small intestine with regard to the limitation of typical undesirable effects after taking NSAIDs. Considerable diversity between solid capsules and the tablet with modified release during disintegration or hydration and swelling has been observed. In the environment of a receptor fluid--purified water (pH = 7) the capsule Dicloberl retard disintegrates at the fastest rate in 5,49 minutes, and then in the order: DicloDuo 75 mg--8,13 minutes and Olfen 100 SR--11,27 minutes. The hydration degree of gelatin walls of capsules depends on the pH of the receptor fluid. The availability of diclofenac sodium salt in given receptor fluids confirms the fact of significant connection of clinical effectiveness of the tested pharmaceutical forms with the activity of hydrogen ions (pH) of the environment in which there are therapeutic products, and excipients used for making the pharmaceutical phase.Tested therapeutic products with diclofenac sodium salt are differentiated by the type of a dosage form. Dicloberl retard contains the minimally indispensable number of simple, commonly used excipients. The research on the disintegration time may only be related to the products Dicloberl retard, Olfen 100 SR and DicloDuo 75 mg treating it as the time of deformation and disintegration of a capsule. In all three types of receptor fluids, the capsule Dicloberl retard has the fastest disintegration rate. The "acid phase" demonstrated stability of the products with a slight dissolution of diclofenac sodium salt on the level 1,3-4,18% of the Q release coefficient. In the environment of artificial intestinal juice, Dicloberl retard is more effective releasing larger amounts of diclofenac sodium salt during 4 hours of exposition (differences from 10% to 14% of the Q release coefficient). more...

The aim of the research was the application assessment of a model preparation--anti-dandruff emulsion. The experiments was conducted under in vitro conditions using of a model system of human skin, which are cellulose dialysis membranes with a standardized pore size. The behaviour of the preparation on the dialysis membrane was analyzed, and the degree of film formation performing the function of a protective barrier was evaluated after gentle rinsing with tepid water without cleaning agents. It was checked whether the product layer remaining on the membrane product layer does not block diffusion and penetration processes. Additionally, an attempt to assess the character of the layer with the use of a hydrophilic marker was made.Model anti-dandruff emulsion, Servapor Dialysis Tubing 100 dialysis membranes with a wall thickness d = 0.1 mm and a declared pore diameter phi = 25 A degrees, sodium chloride, purified water--assessment of the residue level of the analyzed preparation on the dialysis membrane. Examination on the marker diffusion through the dialysis membrane covered with the model anti-dandruff preparation, Approximation of the obtained results.The first phase of the experiment was the preparation of dialysis membranes for the adsorption process of a model anti-dandruff preparation, then its adsorption, rinsing with tepid water and the measurement of residue level of the product on the membrane control. It has been observed that the mass of the membrane on which the preparation was applied increased in relation to the membrane from a control sample. The mass increase of the membrane in a research sample is accompanied with the increase of its thickness caused by the adsorbed amount of the product and water on the membrane. The diffusion through the membrane in a control sample turned out to be slightly slower what may indicate the character of the membrane residue of the model anti-dandruff preparation. CONCLUSIONS; The technology of model anti-dandruff emulsion enables the formation of a layer forming a specific protective barrier on the surface of the dialysis membrane. The presence of the layer of model anti-dandruff emulsion on the membrane is confirmed by mean values of mass and thickness increase of the dialysis membrane. The hydrophobic diffusion layer is of a variable character. The properly applied emulsion under "in vivo" conditions might fill voids of the corneal layer of epidermis creating a structure of a film character performing the function of a protective barrier. On the basis of the in vitro assessment, the therapeutic effectiveness under in vivo conditions may be concluded. more...

Bisphosphonates are used in the treatment of osteoporosis, predominantly most often postmenopausal and glucocorticoid-induced forms. The most commonly known bisphosphonates are: derivatives of alendronic, clodronic, ibandronic, risedronic acid. Bisphosphonates have low bioavailability (1-10%) and low absorption (for more recent bisphosphonates it does not exceed 1%) after oral application (class III of BCS). The discussed group of derivatives is also a technological challenge, particularly in a situation of so difficult biopharmaceutical conditions. The above encourages compliance with the discipline of taking solid oral pharmaceutical forms (tablets), which have to be taken strictly on an empty stomach (30-60 minutes before a meal) and washed down with a glass of boiled water. The technology of oral drug forms with bisphosphonates has to minimize practically to zero the problems of potential adsorption of an active substance on excipients of a character of macromolecular polymers being part of a tablet core and a coating, at the same time providing full pharmaceutical availability. more...

Unprocessed pomace containing 61% of dietary fiber (DF) and 0.23% of polyphenols (PP) and ethanol- or ethanol/acetone-extracted pomaces containing 66% DF and 0.10% PP and 67% DF and 0.01% PP, respectively, were subjected to a 4 week study in rats. The aim of the study was assessing the advantages of dietary supplementation with the above pomaces. To measure the animal response to dietary treatments, parameters describing cecal fermentation and lipoprotein profile were assessed. The dietary use of 5% unprocessed pomace caused an increase in cecal short-chain fatty acid (SCFA) production and a decrease in blood triacylglycerols, leading to a drop in serum atherogenic index. Ethanol-extracted pomace increased the glycolytic activity of cecal microbiota and decreased cecal branched-chain fatty acid production, whereas acetone extraction led to lower cecal ammonia concentration, decreased colonic pH value, and higher HDL/total cholesterol ratio. The variations in the atherogenic index indicate flavonoids as the key pomace component in relation to blood lipid profile benefits. more...

On pharmaceutical market, beside technological variability of the forms of a drug with ibuprofen, there also occurs variability of chemical and crystallographic forms of ibuprofen itself. The above allows to use ibuprofen not only in the form of pure acid, but also forms of ibuprofen sodium salts or hydrophilic solubilized complexes of very good solubility in water. The above influences changeability of technological parameters measured with the use of methods of quality control being the pharmacopeal standard. On the basis of information collected in pharmacies, it can be also considered that pharmacological effect of identical forms of drugs with ibuprofen in the same dose is differently perceived by patients expecting comfort of the process of treatment, the result of which is to be effective. The above arguments induce undertaking studies on the estimation of differences occurring between particular market versions of the forms of a drug with ibuprofen. more...

Various methods of chromatographic analysis (GPC, HPLC, TLC) were used to estimate qualitatively and quantitatively the product of oxyethylation of rapeseed oil acid methyl esters (RME). The investigation enabled to evaluate PEG content in the product. The method of eliminating insignificant quantity of PEG found in oxyethylation products of n(TE)or = 20 was presented. The data of thin-layer chromatography obtained in the course of research constitute a point of departure for calculating n(TE) content and HLB level. more...

The famous problem of Borsuk, whether every bounded set in R n can be covered by n + 1 sets of smaller diameter, is still open for n ⩾ 4. We give an equivalent formulation of the problem. In the plane, the only sets which cannot be covered by two sets of smaller diameter are those whose completion is unique. We present a new characterization of planar sets with unique completion. more...

Nuclear factor kappa B (NF-kappaB) is essential in normal physiology, and several human disorders involve inappropriate regulation of NF-kappaB. Diets dominated by plant-based foods protect against chronic diseases, and several food derived compounds have been identified as promising NF-kappaB modulators. We investigated the effects of diets supplemented with apple, blackcurrant, or cherries on lipopolysaccharide (LPS)-induced NF-kappaB activation in transgenic NF-kappaB-luciferase mice. Whole body and organ specific NF-kappaB activities were determined. The mice had ad libitum access to the respective experimental diets for 7 days. On Day 7, all mice were given an LPS-injection (2.5 mg/kg), and NF-kappaB activation was monitored by in vivo imaging for 6 h. After imaging, blood samples were taken, the mice were euthanized, and ex vivo imaging of organs was performed. Compared to the control group, the apple and cherry groups had slightly higher whole-body NF-kappaB activation at 4 h, and all 3 experimental groups had higher NF-kappaB activation at 6 h. LPS-induced NF-kappaB activation in liver was increased with all 3 experimental diets, but no effects were observed in other organs. Our findings indicate that high intakes of lyophilized fruits modulate in vivo NF-kappaB signaling in the liver following LPS-induced stress; however, consequences of this NF-kappaB modulation in hepatic tissue needs further investigation. more...

International audience; The sugar composition in cell walls of apple and black currant pomaces was investigated with or without solvent extraction. Extraction of polyphenols by solvents changed the sugar composition of cell walls by increasing the alcohol insoluble solids (AIS) contents and increasing glucose content. Water binding capacity was increased by the ethanol extractions, but decreased again after acetone treatments. The enzyme treatments used for juice extraction increased the swelling capacity but decreased the water binding capacity, probably by loosening the cell wall structure. They resulted in decreased degrees of methylation. Pectin extractability of black currant pomaces differed between the commercial pomace (higher Water Soluble Pectins fraction and Chelator Soluble Pectins fraction), and the experimental pomaces (higher Diluted Alkali Soluble Pectins fraction) more...

When the corners of a planar polygon P are restricted to lie in the set H of vertices of a tiling of the plane by hexagons of unit area, then very often the area of P is given by the Pick-type formula A(P)=b/4+i/2+c/12-1, where b and i count the number of points of H on the boundary ∂P and in the interior of P respectively, and c is the boundary characteristic. We now characterize all primitive triangles for which this formula holds, and consider the magnitude of the error when it fails. more...

The production technology of powder cellulose (Arbocel) and microcrystaline cellulose (Vivapur) and their application in the composition of direct compression tablet mass was provided. The function of silicified microcrystaline cellulose type Prosolv in the direct compression process of dry plant extract was discussed. An analysis of the chemical structure of cellulose fiber (Vitacel) enabled determining its properties and applications in the manufacture of diet supplement, pharmaceutical and food products. more...

For the well-known Pick theorem on the area of simple lattice, polygons in the planar tiling by squares there exists an extension to nonsimple regions. All-of the authors who have considered such an extension employ the Euler characteristic of the region to modify Pick's formula. In this paper we give a new formula applicable to finding the area of nonsimple polygons. In our formula the Euler characteristic is replaced by the boundary characteristic introduced by Ding and Reay. We also apply the boundary characteristic to similar Pick-type formulas in the case of the planar tilings by regular triangles and hexagons. more...

At the Second Oklahoma Conference on Convexity and Related Combinatorial Geometry (1980) G.Sierksma posed several problems dealing with the generalised Helly and Radon numbers of a convexity space. The aim of this note is to give answers to and comment on some of Sierksma's questions. more...