Grain-resolved analysis of localized deformation in nickel-titanium wire under tensile load.

The stress-induced martensitic transformation in tensioned nickel-titanium shape-memory alloys proceeds by propagation of macroscopic fronts of localized deformation. We used three-dimensional synchrotron x-ray diffraction to image at micrometer-scale resolution the grain-resolved elastic strains and stresses in austenite around one such front in a prestrained nickel-titanium wire. We found that the local stresses in austenite grains are modified ahead of the nose cone-shaped buried interface where the martensitic transformation begins. Elevated shear stresses at the cone interface explain why the martensitic transformation proceeds in a localized manner. We established the crossover from stresses in individual grains to a continuum macroscopic internal stress field in the wire and rationalized the experimentally observed internal stress field and the topology of the macroscopic front by means of finite element simulations of the localized deformation.

Enhancement of the physical stability of amorphous indomethacin by mixing it with octaacetylmaltose. inter and intra molecular studies.

PURPOSE: To demonstrate a very effective and easy way of stabilization of amorphous indomethacin (IMC) by preparing binary mixtures with octaacetylmaltose (acMAL). In order to understand the origin of increased stability of amorphous system inter- and intramolecular interactions between IMC and acMAL were studied. METHODS: The amorphous IMC, acMAL and binary mixtures (IMC-acMAL) with different weight ratios were analyzed by using Dielectric Spectroscopy (DS), Differential Scanning Calorimetry (DSC), Raman Spectroscopy, X-ray Diffraction (XRD), Infrared Spectroscopy (FTIR) and Quantitative Structure-Activity Relationship (QSAR). RESULTS: Our studies have revealed that indomethacin mixed with acetylated saccharide forms homogeneous mixture. Interestingly, even a small amount of modified maltose prevents from recrystallization of amorphous indomethacin. FTIR measurements and QSAR calculations have shown that octaacetylmaltose significantly affects the concentration of indomethacin dimers. Moreover, with increasing the amount of acMAL in the amorphous solid dispersion molecular interactions between matrix and API become more dominant than IMC-IMC ones. Structural investigations with the use of X-ray diffraction technique have demonstrated that binary mixture of indomethacin with acMAL does not recrystallize upon storage at room temperature for more than 1.5 year. Finally, it was shown that acMAL can be used to improve solubility of IMC. CONCLUSIONS: Acetylated derivative of maltose might be very effective agent to improve physical stability of amorphous indomethacin as well as to enhance its solubility. Intermolecular interactions between modified carbohydrate and IMC are likely to be responsible for increased stability effect in the glassy state.

A new way of stabilization of furosemide upon cryogenic grinding by using acylated saccharides matrices. The role of hydrogen bonds in decomposition mechanism.

Recently it was reported that upon mechanical milling of pure furosemide significant chemical degradation occurs (Adrjanowicz et al. Pharm. Res.2011, 28, 3220-3236). In this paper, we present a novel way of chemical stabilization amorphous furosemide against decomposing that occur during mechanical treatment by preparing binary mixtures with acylated saccharides. To get some insight into the mechanism of chemical degradation of furosemide induced by cryomilling, experimental investigations supported by density functional theory (DFT) computations were carried out. This included detailed studies on molecular dynamics and physical properties of cryoground samples. The main thrust of our paper is that we have shown that furosemide cryomilled with acylated saccharides forms chemically and physically stable homogeneous mixtures with only one glass transition temperature, Tg. Finally, solubility measurements have demonstrated that furosemide cryomilled with acylated saccharides (glucose, maltose and sucrose) is much more soluble with respect to the crystalline form of this active pharmaceutical ingredient (API).

Dielectric studies on molecular dynamics of two important disaccharides: sucrose and trehalose.

Broadband dielectric measurements were carried out in the supercooled as well as in the glassy state of two very important disaccharides: trehalose and sucrose. Multiple relaxation processes were observed. Above the glass transition temperatures of examined disaccharides structural relaxation of cooperative origin was detected, where in the glassy state more local motions (secondary modes) appeared. Our data were discussed in light of the findings reported by other groups. We pointed out that sample preparation might impact mobility and, thus, dielectric loss spectra in a significant way. Consequently, it may lead to misinterpretation of the dielectric relaxation processes. Moreover, impact of physical aging and pressure on dynamics of two secondary relaxation processes observed in the glassy state of trehalose and sucrose has been investigated. Additionally, we have demonstrated that, in contrast to the calorimetric measurements (DSC), activation energies of the ß- and γ-relaxation processes observed in the glassy state of sucrose and trehalose do not change as a result of physical aging. Finally, we found out that the ß-relaxation process slows down as pressure increases. We interpreted this fact in view of increasing rigidity of the structures of disaccharides.

Theoretical and experimental studies on the internal mobility of two sulfonylurea agents: glibenclamide and glimepiride.

Molecular dynamics of glibenclamide and glimepiride in their glassy state were studied by means of broadband dielectric spectroscopy. In both compounds we found a γ-relaxation process, with nearly the same value of activation energy. Further, we were able to identify the origin of γ relaxation by performing calculations within the framework of density functional theory. It was found that rotation of the chain end included cyclohexyl and neighboring carbonyl group is related to the observed mode in dielectric spectra. The calculated activation energy was only a few kJ per mole lower than the energies obtained from experiment. It is demonstrated that this fast γ process is insensitive to pressure. Finally, another secondary mode in glibenclamide, predicted by computations, was confirmed from dielectric measurements at elevated pressure. Our calculations indicate that this mode should be pressure-sensitive.

Dominant GDAP1 mutations cause predominantly mild CMT phenotypes.

OBJECTIVE: Ganglioside-induced differentiation associated-protein 1 (GDAP1) mutations are commonly associated with autosomal recessive Charcot-Marie-Tooth (ARCMT) neuropathy; however, in rare instances, they also lead to autosomal dominant Charcot-Marie-Tooth (ADCMT). We aimed to investigate the frequency of disease-causing heterozygous GDAP1 mutations in ADCMT and their associated phenotype. METHODS: We performed mutation analysis in a large cohort of ADCMT patients by means of bidirectional sequencing of coding regions and exon-intron boundaries of GDAP1. Intragenic GDAP1 deletions were excluded using an allele quantification assay. We confirmed the pathogenic character of one sequence variant by in vitro experiments assaying mitochondrial morphology and function. RESULTS: In 8 Charcot-Marie-Tooth disease (CMT) families we identified 4 pathogenic heterozygous GDAP1 mutations, 3 of which are novel. Three of the mutations displayed reduced disease penetrance. Disease onset in the affected individuals was variable, ranging from early childhood to adulthood. Disease progression was slow in most patients and overall severity milder than typically seen in autosomal recessive GDAP1 mutations. Electrophysiologic changes are heterogeneous but compatible with axonal neuropathy in the majority of patients. CONCLUSIONS: With this study, we broaden the phenotypic and genetic spectrum of autosomal dominant GDAP1-associated neuropathies. We show that patients with dominant GDAP1 mutations may display clear axonal CMT, but may also have only minimal clinical and electrophysiologic abnormalities. We demonstrate that cell-based functional assays can be reliably used to test the pathogenicity of unknown variants. We discuss the implications of phenotypic variability and the reduced penetrance of autosomal dominant GDAP1 mutations for CMT diagnostic testing and counseling.

Identification of the slower secondary relaxation's nature in maltose by means of theoretical and dielectric studies.

Dielectric relaxation measurements on maltose were performed at ambient and increasing pressure. The loss spectra collected below glass transition of this disaccharide revealed presence of two well separated secondary relaxations. Activation energies determined for both modes are E(a)=73 kJ/mol and 47 kJ/mol for the slower (beta) and faster (gamma) relaxation, respectively. From high pressure measurements activation volume DeltaV=15.6 ml/mol for the slower secondary relaxation was estimated. Both quantities: activation energy and activation volume for alpha-process derived from dielectric data, were compared to those obtained from the conformational calculations with use of density functional theory (DFT). We found out satisfactory agreement between both quantities for the molecular motion related to the rotation of the two monosaccharide units around glycosidic linkage in this disaccharide.

Genotype-phenotype associations for ARX gene duplication in X-linked mental retardation.

We screened 165 mentally retarded patients for ARX gene 428-451 base pair (bp) duplication. Eighteen individuals from five families were found to carry the duplication, and all had intellectual impairment. Twelve presented with focal hand dystonia, while six patients had EEG abnormalities including seizures. Other symptoms included speech difficulties (4/18), testis enlargement (4/18), lower limb spasticity or foot dystonia (4/18), and facial telangiectasia (3/18). These features confirm the pleiotropic effect of the duplication.

Physical and developmental phenotype analyses in a boy with Wolf-Hirschhorn syndrome.

Wolf-Hirschhorn syndrome (WHS) is a rare genetic condition with characteristic facial traits, organ malformations, functional impairment and developmental delay due to partial short arm monosomy of chromosome 4. Although several hundreds of cases have been published to date, a systematic collection of its clinical symptoms and anthropological traits is missing in the literature, and reports on abilities and needs of children with WHS are scanty. Results of detailed physical and developmental phenotype analyses in a 1 10/12-year-old boy with monosomy 4p15.2-pter are presented. Physical analyses were based on systematic data acquisition. They disclosed a total of 32 clinical symptoms and 46 anthropological traits. Developmental analyses were based on the child's interactive play in an environment structured according to Montessori principles. They disclosed a total of 44 abilities and a number of needs to be satisfied by the environment for the support of the child's psychic and intellectual growth. While the physical phenotype is important for the diagnostic process, the developmental phenotype is essential for parental counseling.

Sperm chromatin structure assay of bulls qualified for artificial insemination.

The goal of our study was to find the relationship between fertility of bulls qualified for AI and the percentage of spermatozoa with abnormal chromatin structure as an independent parameter. We used the frozen semen of 8 mature bulls from one AI center. Each bull was represented by 3 ejaculates collected with at least 2-week intervals. Bull fertility was calculated on the basis of non-return ratio and was expressed as a scale where 100 points represented the average fertility of all the AI center's bulls. Bulls with lower or higher fertility received a lower or higher score respectively. Fertility scores of bulls used in the study ranged from 83 to 104 . Semen was processed according to the SCSA (sperm chromatin structure assay) method and was analyzed by flow cytometry. "Artificial" alpha(t) (alpha(t)=red/green+red fluorescence) and red fluorescence histograms were used for calculation of COMPalpha(t), SDalpha(t), %Red, %PeakR and MeanR parameters. The percentage of spermatozoa with abnormal chromatin ranged from 1.2% to 23.8%. A large variation among ejaculates was found for bulls with lower fertility. Fertility correlated significantly with COMPalpha(t) (-0.50, P < 0.05), SDalpha(t) (-0.55, P < 0.01), %Red (-0.53, P < 0.01), %PeakR (-0.58, P < 0.01) and MeanR (-0.45, P < 0.05). The SCSA method has a practical application in analyzing spermatogenesis disorders in bulls. If regularly applied, it allows us to identify and eliminate ejaculates with a high level of sperm chromatin abnormalities.

Clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18.

We report the results of detailed clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18. Classical cytogenetics and fluorescence in situ hybridization (FISH) analysis with the chromosome 18 painting probe identified five non-mosaic and two complex mosaic 46,XX,dup(18)(p11.2)/47,XX,dup(18)(p11.2),+r(18) and 46,XX,dup(18)(p11.32)/47,XX,dup(18)(p11.32),+r(18) cases. FISH analysis was performed for precise characterization of the chromosome 18 breakpoints using chromosome 18-specific short-arm paint, centromeric, subtelomeric, and a panel of fifteen Alu- and DOP-PCR YAC probes. The breakpoints were assessed with an average resolution of approximately 2.2 Mb. In all r(18) chromosomes, the 18q terminal deletions ranging from 18q21.2 to 18q22.3 ( approximately 35 and 9 Mb, respectively) were found, whereas only in four cases could the loss of 18p material be demonstrated. In two cases the dup(18) chromosomes were identified as inv dup(18)(qter-->p11.32::q21.3-->qter) and inv dup(18)(qter-->p11.32::p11.32-->p11.1: :q21.3-->qter)pat, with no evidence of an 18p deletion. A novel inter-intrachromatid mechanism of formation of duplications and ring chromosomes is proposed. Although the effect of "ring instability syndrome" cannot be excluded, the phenotypes of our patients with characteristic features of 18q- and 18p- syndromes are compared and correlated with the analyzed genotypes. It has been observed that a short neck with absence of cardiac anomalies may be related to the deletion of the 18p material from the r(18) chromosome.

[Antioxidant enzymes activity in patients suffering from laryngeal cancer]. / Aktywnosc enzymów antyoksydacyjnych u chorych na raka krtani.

The adequate activity of SOD, GPX and GR is a significant factor in oxidoreductation homeostasis maintaining. The attempt was made to estimate SOD, GPX, GR activity in full blood of 14 male patients suffering from laryngeal cancer (T2N0M0-T4N2M0). The studies were made before and in 8 and 16 week after the operation using RANDOX Company tests. The analysis of results proved that there were remarkable disorders of GR activity in comparison to a control group.

[Histological and clinical analysis of mesenchymal malignant neoplasms (soft tissue sarcomas) of head and neck region in the data of I ENT Department of Silesian Medical Academy]. / Analiza histokliniczna nowotworów zlosliwych pochodzenia mezenchymalnego (miesaków tkanek miekkich) regionu glowy i szyi na podstawie materialu operacyjnego I Katedry i Kliniki Laryngologii Slaskiej Akademii Medycznej w Katowicach.

Between the years 19890-1998 in I ENT Department of Silesian Medical Academy were treated surgically 15 patients suffering from soft tissue sarcomas of head and neck region. Patomorphological examination showed: fibrosarcoma (4 cases), haemangioendothelioma malignum (2 cases), rhabdomyosarcoma (2 cases), schwannoma malignum (2 cases), fibrohistiocytoma malignum (2 cases), tumor mixtus mesenchymalis (1 case), haemangiopericytoma malignum (1 case), extrasceletal osteosarcoma (1 case). Sarcomas were localised in paranasal sinuses (7 cases), orbita (5 cases), parapharyngeal space (1 case), parotid gland (1 case) and bucca (1 case). All those patients were treated surgically and most of them were irradiated postoperatively. The authors have presented the diagnostic and methods of treatment of soft tissue sarcomas. According to our experience and data of the literature the method of choice in treatment soft tissue sarcomas should consist of surgery and radiation therapy postoperatively.

[A contribution to the etiology of objective tinnitus: the case of arteriovenous fistula between the superficial artery and external jugular vein]. / Przyczynek do etiologii obiektywnych szumów usznych--przypadek przetoki tetniczo-zylnej tetnicy skroniowej powierzchownej i zyly szyjnej zewnetrznej.

The authors have presented a very rare case of vascular anomaly in 51-years old female with an arteriovenous fistula between the frontal branch and parietal branch of superficial temporal artery and external jugular vein with simultaneously haemangioma cavernosum of temporal region. The clinical manifestation and the diagnosis of this anomaly are discussed with particular stress laid on the role of carotid arteriography which demonstrated the presence of this abnormal arterio-venous communication. Surgical treatment and its results are discussed also. The results of diagnostic and therapeutic procedures were compared with cases described in the literature.

Agenesis of corpus callosum: clinical description and etiology.

In 135 children (aged 3 months to 15 years) with structural defects of the central nervous system found on magnetic resonance imaging, agenesis of the corpus callosum was evident in 7. The etiology of agenesis of the corpus callosum has been established in four children: partial trisomy of chromosome 13, partial duplication of the long arm of chromosome 10, Aicardi's syndrome, and intracranial bleeding during the fetal period as a result of injury. Agenesis of the corpus callosum coexisted with a Dandy-Walker malformation in one other patient, which suggests a genetic etiology. In spite of these variable etiologies, dysmorphic features were identified in all seven patients, as was psychomotor retardation. Epileptic seizures had occurred in six patients, and all manifested abnormalities on neurologic examination.

[Vascular compression syndrome of the vestibulocochlear nerve--otolaryngologic and radiologic diagnosis]. / Konflikt naczyniowo-nerwowy nerwu przedsionkowo-slimakowego--diagnostyka otolaryngologiczna i radiologiczna.

Vascular compression syndrome is the term used to classify a group of conditions though to be caused by the compression of cranial nerve by vessel. In the most cases the contact of vascular loop formed by the anterior inferior cerebellar artery (AICA) with the eight and facial nerve correlated with unilateral auditory symptoms or hemifacial spasms. The vascular compression syndrome of vestibulocochlear nerve in 8 patients treated in I ENT Clinic of Silesian Academy and MRI Department in Katowice was observed. All patients were otologic findings such as a tone audiometry, ENG, ABR and radiological diagnostics included MRI and angio MRI. The prospective analysis was performed. The results suggest that the unilateral sensorineural hearing loss, tinnitus, vestibular disorders and positive findings on magnetic resonance imaging are the most reliable evidence for the presence neurovascular compression syndrome of the eight cranial nerve. The MRI and otologic studies provided quite detailed information about topography of relationship between the blood vessels and cranial nerves in the crebellopontine cistern.

[The assessment of beta 2-microglobulin concentration in blood serum in patients with radiotherapy-treated laryngeal carcinoma]. / Ocena stezenia beta 2-mikroglobuliny w surowicy krwi u chorych na raka krtani leczonych napromienianiem.

The authors present estimation of beta 2-microglobulin concentration in blood serum in patients suffering from laryngeal cancer treated with radiotherapy in the course of treatment and 3 years after. The initial concentration of beta 2-microglobulin in the blood serum was statistically significantly higher in comparison with the control group. A significantly higher initial concentration of beta 2-microglobulin was observed in the group of patients with the recurrence of cancer in relation to the group of patients without the recurrence of cancer both immediately and 3 years after radiotherapy.

[Laryngeal carcinoma distant metastasis to the occipital bone: a case report]. / Przerzut raka do kosci potylicznej z ogniska pierwotnego w krtani.

The authors present a case of laryngeal carcinoma with rare metastasis to the occipital bone.

[The assessment of lateral orbitotomy by Krönlein-Reese-Berke in surgical treatment of primary non-malignant orbital tumors]. / Ocena dostepu bocznego do oczodolu metoda Krönleina-Reesego-Berke'a w leczeniu operacyjnym pierwotnych niezlosliwych guzów oczodolu.

AIM: The assessment of lateral orbitotomy by Krönlein-Reese-Berke was made to evaluate the possibility of radical removal of primary orbital tumors, function of visual system and cosmetic effect after lateral orbitotomy. MATERIAL AND METHODS: The authors analysed a group of 14 patients treated for primary non-malignant orbital tumors. They were treated in I ENT Clinic of Silesian Medical Academy in Katowice surgically by Krönlein-Reese-Berke lateral orbitotomy. A control examination (after 3 years) performed in all 14 patients did not show recurrence of tumor, the motility of the eye ball and visual function was normal, cosmetic effect was good. CONCLUSIONS: We suggest that in the cases of primary non-malignant tumors localised in the lateral part of the orbita, orbitotomy by Krönlein-Reese-Berke is the optimal surgical approach.

[A case of laryngeal mucoepidermoid carcinoma]. / Przypadek raka sluzowo-naskórkowego w krtani.

The authors present a very rare case of laryngeal mucoepidermoid cancer. Well separated and encysted tumor was totaly removed with Kleinsasser method.