Missing Link between Helical Nano- and Microfilaments in B4 Phase Bent-Core Liquid Crystals, and Deciphering which Chiral Center Controls the Filament Handedness.

The range of possible morphologies for bent-core B4 phase liquid crystals has recently expanded from helical nanofilaments (HNFs) and modulated HNFs to dual modulated HNFs, helical microfilaments, and heliconical-layered nanocylinders. These new morphologies are observed when one or both aliphatic side chains contain a chiral center. Here, the following questions are addressed: which of these two chiral centers controls the handedness (helicity) and which morphology of the nanofilaments is formed by bent-core liquid crystals with tris-biphenyl diester core flanked by two chiral 2-octyloxy side chains? The combined results reveal that the longer arm of these nonsymmetric bent-core liquid crystals controls the handedness of the resulting dual modulated HNFs. These derivatives with opposite configuration of the two chiral side chains now feature twice as large dimensions compared to the homochiral derivatives with identical configuration. These results are supported by density functional theory calculations and stochastic dynamic atomistic simulations, which reveal that the relative difference between the para- and meta-sides of the described series of compounds drives the variation in morphology. Finally, X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM) data also uncover the new morphology for B4 phases featuring p2/m symmetry within the filaments and less pronounced crystalline character.

Indication of a twist-grain-boundary-twist-bend phase of flexible core bent-shape chiral dimers.

The effect of the molecular chirality of chiral additives on the nanostructure of the twist-bend nematic (NTB) liquid crystal phase with ambidextrous chirality and nanoscale pitch due to spontaneous symmetry breaking is studied. It is found that the ambidextrous nanoscale pitch of the NTB phase increases by 50% due to 3% chiral additive, and the chiral transfer among the biphenyl groups disappears in the NTB* phase. Most significantly, a twist-grain boundary (TGB) type phase is found at c > 1.5 wt% chiral additive concentrations below the usual N* phase and above the non-CD active NTB* phase. In such a TGB type phase, the adjacent blocks of pseudo-layers of the nanoscale pitch rotate across the grain boundaries.

Functional outcome and quality of life following resection of the proximal humerus performed for musculoskeletal tumors and reconstruction done by four different methods.

INTRODUCTION: The proximal humerus is a frequent site for both primary and secondary bone tumors. Several options are currently available to reconstruct the resected humerus, but there is no consensus regarding optimal reconstruction. The aim of this retrospective study was to compare the functional outcome, complications and patient compliance following four different types of reconstructive techniques. MATERIAL AND METHODS: The authors performed 90 proximal humerus resections due to primary and secondary bone tumors over the past 21 years. Four different procedures were performed for reconstruction following the resection: fibula autograft transplantation, osteoarticular allograft implantation, modular tumor endoprosthesis (hemiarthroplasty) and reconstruction of the defect with a reverse shoulder prosthesis-allograft composite. A retrospective analysis of the complications and patient's physical status was performed. Functional outcome and life quality was evaluated by using the MSTS and SF-36 scores. RESULTS: The best range of motion was observed following arthroplasty with a reverse shoulder prosthesis-homograft composite followed by a fibula autograft reconstruction. Revision surgery was required due to major complications most frequently in the osteoarticular allograft group, followed by the reverse shoulder prosthesis-allograft composite group, the autologous fibula transplantation group; the tumor endoprosthesis hemiarthroplasty group had superior results regarding revision surgery (40, 25, 24 and 14% respectively). MSTS was 84% on average for the reverse shoulder prosthesis-allograft composite group, 70% for the autologous fibula group, 67% for the anatomical hemiarthroplasty group and 64% for the osteoartricular allograft group. Using the SF-36 questionnaire for assessment no significant differences were found between the four groups regarding quality of life. DISCUSSION: Based on the results of our study the best functional performance (range of motion and patient compliance) was achieved in the a reverse prosthesis-allograft combination group-in cases where the axillary nerve could be spared. The use of an osteoarticular allograft resulted in unsatisfying functional results and high complication rates, therefore we do not recommend it as a reconstructive method following resection of the proximal humerus due to either primary or metastatic bone tumors. Young patients who have good life expectancy but a small humerus or intramedullar cavity reconstruction by implantation of a fibula autograft is a good option. For patients with a poor prognosis (i.g. bone metastases) or in cases where the axillary nerve must be sacrificed, hemiarthroplasty using a tumor endoprosthesis was found to have acceptable results with a low complication rate. According to the MSTS and SF-36 functional scoring systems patients compliance was nearly identical following all four types of reconstruction techniques; the underlying cause may be the complexity of the shoulder girdle. However, we recommend the implantation of a reverse shoulder prosthesis-allograft whenever indication is appropriate, as it has been demonstrated to provide excellent functional outcomes, especially in young adults.

New formulation of in situ gelling Metolose-based liquid suppository.

CONTEXT: An in situ gelling liquid suppository is liquid at room temperature but forms a gel at body temperature. In our work, Metolose® SM-4000 (methylcellulose) is studied that basically shows thermal gelation at 68°C (2%, w/w). OBJECTIVE: The objective was to study the potency of different factors (concentration, pH, additives) to change the value of thermal gelation temperature (T (t)) for Metolose® to form an in situ gelling liquid suppository. MATERIALS AND METHODS: We studied the effect of Metolose® concentration, pH, and salts (sodium chloride, potassium chloride, sodium hydrogen carbonate, and sodium monohydrogen phosphate) on T (t) by viscosimetry. To choose the appropriate compound, in vitro drug release was examined. Rectal safety test was performed on rats in vivo after 12-hour application. RESULTS: Increasing the Metolose® concentrations (0.5-4%, w/w), T (t) can be decreased, but it also altered the consistency of gel. pH does not affect the T (t). The water-soluble salts allowed reducing the gelation temperature to 37°C. Sodium monohydrogen phosphate in 4.5% concentration was found to be the most appropriate. The impact of examined factors on in vitro drug release of piroxicam from the in situ-formed gel was characterized according to Fickian diffusion. Metolose® and the chosen salt did not cause any morphological damage on the rectal tissues. DISCUSSION: According to our study, Metolose® has the physical and chemical potential to be used as base for liquid suppositories.

Study on process parameters and optimization of microencapsulation based on phase separation.

As surfactants are capable of influencing the droplet formation, our study primarily aims the investigation of the effect of a nonionic surfactant e.g. Polysorbate 80 on the formation of microspheres on the course of vibrating nozzle method with coacervation. The experiments also concern the impact of the different process parameters (e.g. vibration frequency, feed rate and voltage) on the shape and size distribution of microspheres characterized by laser diffraction size determination completed with particle image analysis. The calcium-alginate microspheres were processed using freeze-drying to ensure solid state with better drug carrier capability. Addition of isomalt was advantageous in the formation of freeze-dried microspheres at low alginate concentration, which was explained by micro-CT analysis of the constructed particle structure. The internal three-dimensional network of calcium alginate demonstrated a more cancellous architecture ameliorating the roundness of microparticles.

Application of sucrose fatty acid esters in transdermal therapeutic systems.

Transdermal therapeutic systems (TTSs) were studied applying different sucrose fatty acid esters (SEs) as drug delivery agents. Matrix and membrane controlled TTSs were prepared and compared. Membrane was made from a methacrylic polymer (Eudragit NE) of pH independent permeability which can achieve diffusion controlled drug liberation. Model drug was a water soluble beta-blocker, metoprolol, which has short biological half-life, so applying it in a TTS, the duration of its action could be prolonged. Sucrose fatty acid esters of different fatty acid chain lengths and consequently different hydrophilic-lipophilic balance (HLB) values were studied considering their effect on the metoprolol release from TTSs. Different mathematical models were applied for the evaluation of the release process. The results of the in vitro studies indicated that SEs of shorter fatty acid chain length and higher HLB value increased the amount of released drug about 10 times. SEs could be promising agents in transdermal therapeutic systems to control the drug release and cutaneous absorption.

Potential application of Metolose in a thermoresponsive transdermal therapeutic system.

The purpose of the present study was to formulate a novel thermoresponsive membrane controlled therapeutic system from Metolose for possible transdermal application. Metolose gel shows thermal gelation property, which can be characterized by two (T(1), T(2)) temperatures. A sharp decrease of viscosity can be measured at T(1), but gelation can be observed at T(2). Different types of Metolose polymers were compared considering their thermoresponsive behaviour. Only thermal gelation was observed in the case of Metolose SM, while Metolose SH showed a sudden decrease of viscosity at T(1). Since this temperature is above the body temperature, so it should be shifted to the skin temperature in case of possible transdermal application. Modulation of thermoresponsibility was followed by rheological method, and the thermoresponsive drug release from Metolose gel was studied by static liberation test. Our results demonstrated that the effect of different salts (NaCl, NaHCO(3), KCl) of various concentrations in Metolose SH gel reduced T(1) to the skin temperature, which enabled enhanced drug release.

Statins Determination: A Review of Electrochemical Techniques.

The use of electroanalytical techniques for the determination of statins (Atorvastatin, Fluvastatin, Lovastatin, Pitavastatin, Pravastatin, Rosuvastatin and Simvastatin) is reviewed covering the period from 1997 to 2016. Among all of the published electrochemical methods, voltammetry and polarography are the most popular techniques for the determination of statins, and both are used for the analysis of pharmaceutical dosage forms and biological samples. The determination of statins by a potentiometric method using ion-selective electrodes is reported in only few papers. Сoulometry and conductometry have been not used for the determination of statins till date. Current trends in developing new electrochemical methods for the analysis of statins are discussed.

Quantitative estimation of film forming polymer-plasticizer interactions by the Lorentz-Lorenz Law.

Molar refraction as well as refractive index has many uses. Beyond confirming the identity and purity of a compound, determination of molecular structure and molecular weight, molar refraction is also used in other estimation schemes, such as in critical properties, surface tension, solubility parameter, molecular polarizability, dipole moment, etc. In the present study molar refraction values of polymer dispersions were determined for the quantitative estimation of film forming polymer-plasticizer interactions. Information can be obtained concerning the extent of interaction between the polymer and the plasticizer from the calculation of molar refraction values of film forming polymer dispersions containing plasticizer.

Fibrous dysplasia associated with intramuscular myxoma (Mazabraud's syndrome): a long-term follow-up of three cases.

The association between of fibrous dysplasia and intramuscular myxomas is extremely rare. The authors summarize the characteristics of Mazabraud's syndrome, as well as its clinical course on the basis of 24 cases reported in the literature and 3 cases of their own. The syndrome is quite uniform, and mostly occurs in women. Usually the presentation of poliostotic fibrous dysplasia bilaterally in the lower limbs and pelvic bones is followed by the appearance of multifocal intramuscular myxomas in the adjacent muscles, mostly decades later. These hamartomas tend to recur locally or symmetrically in the ipsilateral muscle groups and may reach enormous size without treatment. Malignant transformation (osteosarcoma, fibrosarcoma) on the basis of fibrous dysplasia in Mazabraud's syndrome has been reported in the literature. In our cases, however, in spite of the many recurrences, and the enormous size of the tumours, no malignant transformation was noted in either the fibrous dysplasias or the intramuscular myxomas during the long follow-up time (31 years for fibrous dysplasia and 16 years for myxomas). Early wide surgical excision and a careful long-term follow-up for the often very late recurrences of the myxomas is suggested in Mazabraud's syndrome.

Calcitonin therapy of aneurysmal bone cysts.

Seven aneurysmal bone cysts (ABC) were treated with the hormone calcitonin. Six of the cysts, which were hypovascular responded well to the calcitonin administered directly into the cyst. Ossification and rebuilding of the ABC occurred after some months in every case. One hypervascularized ABC, however, failed to respond either to embolo-therapy or to the calcitonin hormone treatment. The authors recommend calcitonin administration as a useful non-invasive method for the treatment of hypovascular ABC.

Multicentric extraabdominal desmoid tumour: a case report.

The very rare condition of multicentric desmoid tumours involving two distant and apparently independent sites is reported in a 17-year-old man. The tumours grew simultaneously and reached approximately equal size. No evidence of familiar polyposis or any other feature of Gardner's syndrome were noted. The proximal desmoid tumour developed from the left hip region and extended into the femoral bone, whereas the distal mass was attached to the left popliteal fossa infiltrating the flexor muscles, the nerves and vessels. On the basis of the good results published recently in the literature and our own earlier experiences, the intralesional resection of the desmoid tumours was completed with postoperative fractionated radiotherapy.

Effect of particle size and coating level on the diffuse reflectance of wax matrices.

The aim of this study was to examine the influence of particle size and extent of coating on the diffuse-reflectance spectra of wax matrices containing embedded potassium chloride. Near-infrared spectroscopy was used to analyse the diffuse-reflectance characteristics of the prepared multi-particulate matrices without destructive sample preparation. A 2-factor, 3-level face-centred central composite design was selected to construct a second-order polynomial model which described the effect of particle size and amount of coating on the intensity of the diffusely reflected light. A non-linear model was used to demonstrate the effect of the selected parameters on the intensity of the reflected light; good correlation was obtained between experimental and predicted results. The results indicated that the extent of coating and the particle size of the examined systems in the selected particle size-range modified the intensity of the reflected light. It can be concluded that near-infrared spectroscopy is a sensitive means of measuring not only the particle size of powders (substrates and their mixtures), but also that of coated multi-particulate systems.

Formulation of controlled release drug preparations with antacid effect.

Opportunities for the formulation of long-acting antacid preparations were demonstrated summarizing the results of pharmaceutical technological experiments. The telemetric intragastric data were in correlation with the in vitro measurements and demonstrated the significantly higher bioavailability of long-acting antacid preparations.

The effect of oil as a dietary component on in vitro dissolution of an acid-labile drug.

The non-benzodiazepine-like anxiolytic agent deramiclane fumarate (EGIA-3886) was used to demonstrate that the presence of high oil/fat content in dissolution media serves as a barrier against accelerated drug degradation in acidic media.

Surgical treatment and prognostic factors in giant-cell tumor of bone.

The rate of local recurrence in the giant-cell tumor of bone (GCT) is influenced by many factors. GCT aggressiveness is related to mitotic activity, aneuploidy of tumor cells, chromosomal abnormality, excessive metalloproteinase expression and alterations in different oncogenes. Statistically, there was no correlation between the recurrence rate and the size and site of tumor, stage of disease and involvement of subchondral bone. However, statistical analysis revealed that the use of adjuvants (phenol, bone cement, etc) and the type of surgical intervention (en block resection versus curettage and grafting) were factors with a prognostic value. Although recurrence or malignant transformation in GCT cannot be predicted yet, about 96% of the patients can be cured. In the majority of cases, recurrences have no fatal consequences for the patient but may lead to various degrees of disability due to repeated and more radical surgical procedures. Joint-sparing surgery and careful curettage with the use of adjuvants should be the treatment of choice whenever possible. In the future, modern instruments of molecular biology will be used to aid the evaluation of primary and recurrent tumors and will have an increasing influence on surgical planning.

[Dual fluorescence in situ hybridization analysis of synovial sarcoma]. / Synovalis sarcoma kettös jelölésü fluorescens in situ hibridizációs vizsgálata.

Synovial sarcoma have (about in 95% of the cases) the specific and characteristic reciprocal chromosomal translocation t(X; 18) (p11.2; q 11.2). Application of dual-colour fluorescence in situ hybridization (FISH) on interphase nuclei to identify the specific translocation has a diagnostic importance for daily pathological practice. For visualisation of the translocated chromosomal fragments of synovial sarcoma cells on imprint smears, chromosome X painting probes and chromosome 18 centromeric probes were used. Our present study indicates that the precise preoperative diagnosis of synovial sarcoma using dual-colour FISH is possible on smears and this possibility (to identify specific chromosomal translocations in soft tissue tumours) is a landmark in the preoperative diagnosis of soft tissue sarcomas.

[Results of limb-saving surgery and prognostic factors in patients with osteosarcoma]. / Végtagmegtartó mútétek eredményei és prognosztikai tényezók osteosarcomás betegeknél.

Ninety six patients with high-grade osteosarcoma of the extremities were treated between 1986 and 1997 in the authors institution. They were divided into three groups: in group I, all of 75 patients with non-metastatic OS received intensive chemotherapy and underwent surgery. In group II, 9 patients already had metastases at the time of referral. In group III, 12 patients received chemotherapy in delayed or suboptimal form. In group I, local recurrences occurred in 7 per cent (3 patients), metastases in 20 per cent of the patients with limb-saving, whereas these numbers were 3 per cent and 38 per cent in the amputation group. The 5-year disease free survival (DFS) was 72% v 69% in the limb-saving and amputation group, respectively. In groups II and III, 5-year DFS was extremely poor, 10 and 20% only. With univariate analysis, factors having a positive influence on the survival were: tumor volume < 60 cm3, wide or radical surgical margin, distal location of osteosarcoma, cartilagineous ground substance less than 20% and response to chemotherapy. The last 4 variables maintained their significance in the multivariate Cox model as well. Age > 30 showed indirect negative influence on the final outcome (enhanced intolerability to the drugs and less co-operability of the patients etc.). This data confirm the competence of the limb-saving surgery at certain indications beside the amputation.

[Biopharmaceutical considerations of dissolution testing used as a prognostic tool for oral drug adsorption]. / A hatóanyag orális felszívódásának elórejelzésére alkalmazott kioldódás vizsgálatok biofarmáciai vonatkozásai.

Drug dissolution is a prerequisite to drug absorption and in vivo effectiveness for almost all drugs given in oral solid dosage forms. Drug absorption depends on the dissolution and solubilization of the drug under physiological conditions, and the permeability across the gastrointestinal tract. Because of the critical nature of the first steps, in vitro dissolution may be relevant to the prediction of biological response. Dissolution tests are applied to choose between formulation factors, assess the lot-to-lot quality of a drug product according to the biobatch; and ensure continuing product quality and performance after certain changes (e.g. in the formulation and manufacturing process, site of manufacture, scale-up). The recently developed Biopharmaceutical Classification System (BCS) has several benefits for recognizing how dissolution tests can be designed and which physiological factors have to be taken into consideration for the in vitro evaluation of solid dosage forms. Choice of test conditions (composition, volume and hydrodynamics of dissolution medium) should be based on where the drug is best absorbed in the gastrointestinal tract, and on whether it is administered in fasted or fed state. Duration of test and physiologically representative media can be selected to simulate gastric and intestinal environments according to the permeability profile of the drug, but mimicking in vivo hydrodynamics remains problematic and further research is required. To provide a basis for predicting the likelihood of achieving a successful in vivo-in vitro correlation, this review summarizes the biopharmaceutical considerations of in vivo drug release in accordance with the BCS.

[Preformulation study of controlled release nitrofurantoin preparations. 2]. / Szabályozott hatóanyagleadású nitrofurantoin készítmény pre-formulálási vizsgálata. II. rész.

In their previous publications the authors rendered account of preparation and stability test of products containing controlled release nitrofurantoin in circumstances of preparing and storing. Following previous publications in vitro active principle release of developed product has been investigated by rotating basket method and by applying Sartorius Dissolution tester. Absorptions of active principle and coated pharmacon have been determined by means of Sartorius Membrane transport tester. On basis of results it can be ascertained that compressed and capsuled products coated with Eudragit L 100-55 has proved to be the most suitable concerning release of active principle as well as in vitro absorption. Taking into account probability values of absorption, active principle release and absorption of product have been properly controlled and so optimal bioavailability of the preparation can be expected.