A combined experimental and theoretical study of miconazole salts and cocrystals: crystal structures, DFT computations, formation thermodynamics and solubility improvement.

Experimental and theoretical screening of multi-component crystal forms of miconazole (MCL), an antifungal drug, with ten aliphatic dicarboxylic acids was performed. Seven multi-component molecular crystals were isolated and identified by different analytical techniques, including the powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TG), and solubility methods. The crystal structures of the MCL hemihydrate, two cocrystals with succinic ([MCL + SucAc] (2 : 1)) and fumaric acids ([MCL + FumAc] (2 : 1)) and one salt with maleic acid ([MCL + MleAc] (1 : 1)) were redetermined. The new cocrystal of MCL with adipic acid ([MCL + AdpAc] (2 : 1)) was investigated by single crystal X-ray diffractometry. It was found that the AdpAc molecule in the cocrystal has an unusual anticlinal conformation. The combination of periodic density functional theory (DFT) computations and quantum topology analysis confirmed the structure-directing role of the acid-imidazole heterosynthon for the considered crystals. The melting temperatures of all the studied multi-component crystals are between the values of the corresponding individual components except [MCL + MleAc] (1 : 1). A thermal analysis has shown that the thermodynamic and thermophysical characteristics of the considered two-component molecular crystals are strongly dependent both on specific interactions (presence of sites of donor-acceptor interactions and hydrogen bond formation) and on nonspecific interactions - molecule polarizability. Based on the sublimation thermodynamics database of molecular crystals, the standard sublimation thermodynamic functions of MCL were evaluated. The thermodynamic functions of multi-component crystal formation based on MCL were calculated and analyzed. Solubility experiments on the MCL multi-component crystals were carried out in isotonic aqueous buffer solutions at pH 1.2 and 6.8 and compared with the solubility of the MCL free base and its nitrate salt. It was found that the salt/cocrystal formation of MCL with dicarboxylic acids considerably increased the MCL solubility in pH 6.8 buffer. The biggest MCL solubility enhancement was observed in the [MCL + TartAc] (1 : 1) salt. The solubility value of MCL in the [MCL + TartAc] (1 : 1) salt is commensurate with the commercial MCL nitrate salt.

Crystal structure of a 1:1 salt of 4-amino-benzoic acid (vitamin B10) with pyrazinoic acid.

The title 1:1 salt, C7H8NO2 +·C5H3N2O2 - (systematic name: 4-carb-oxy-anilinium pyrazine-2-carboxyl-ate), was synthesized successfully by slow evaporation of a saturated solution from water-ethanol (1:1 v/v) mixture and characterized by X-ray diffraction (SCXRD, PXRD) and calorimetry (DSC). The crystal structure of the salt was solved and refined at 150 and 293 K. The salt crystallizes with one mol-ecule of 4-amino-benzoic acid (PABA) and one mol-ecule of pyrazinoic acid (POA) in the asymmetric unit. In the crystal, the PABA and POA mol-ecules are associated via COOH⋯Narom heterosynthons, which are connected by N-H⋯O hydrogen bonds, creating zigzag chains. The chains are further linked by N-H⋯O hydrogen bonds and π-π stacking inter-actions along the b axis [centroid-to-centroid distances = 3.7377 (13) and 3.8034 (13) Šat 150 and 293 K, respectively] to form a layered three-dimensional structure.

Proper-motion age dating of the progeny of Nova Scorpii AD 1437.

'Cataclysmic variables' are binary star systems in which one star of the pair is a white dwarf, and which often generate bright and energetic stellar outbursts. Classical novae are one type of outburst: when the white dwarf accretes enough matter from its companion, the resulting hydrogen-rich atmospheric envelope can host a runaway thermonuclear reaction that generates a rapid brightening. Achieving peak luminosities of up to one million times that of the Sun, all classical novae are recurrent, on timescales of months to millennia. During the century before and after an eruption, the 'novalike' binary systems that give rise to classical novae exhibit high rates of mass transfer to their white dwarfs. Another type of outburst is the dwarf nova: these occur in binaries that have stellar masses and periods indistinguishable from those of novalikes but much lower mass-transfer rates, when accretion-disk instabilities drop matter onto the white dwarfs. The co-existence at the same orbital period of novalike binaries and dwarf novae-which are identical but for their widely varying accretion rates-has been a longstanding puzzle. Here we report the recovery of the binary star underlying the classical nova eruption of 11 March AD 1437 (refs 12, 13), and independently confirm its age by proper-motion dating. We show that, almost 500 years after a classical-nova event, the system exhibited dwarf-nova eruptions. The three other oldest recovered classical novae display nova shells, but lack firm post-eruption ages, and are also dwarf novae at present. We conclude that many old novae become dwarf novae for part of the millennia between successive nova eruptions.

Controlled cholesterol efflux from the aortic smooth muscle cells triggers microheterogeneity of plasma membrane lipids and induces modification of the mitochondrial topology.

It is generally accepted that phospholipids of plasma membrane display lateral segregation into small microdomains commonly known as lipid rafts. Such lateral lipid organization is under the control of cholesterol. Cholesterol depletion evolved by methyl-beta-cyclodextrin (MCD) has been found to induce further marked perturbation in lateral lipid organization, evidenced in the high field part of electron paramagnetic resonance spectra of plasma membranes labelled with a spectroscopic probe, namely 5-doxyl-stearic acid (5DOXS). Such perturbation of surface lipid topo-logy has been found to induce distinct changes in the mitochondrial morpho-logy, i.e. switch from filamentous form into small granular form.

[Granular cell tumor of the larynx]. / Miesniak ziarnistokomórkowy krtani.

Granular cell tumor is an unusual growth of probably neuroectodermal histogenesis, first reported by Abrikossoff in 1926 with the name of myoblastenmyoma. Authors described a case of a 54 year man with laryngeal seat of granular-cell myoblastoma. In this case Abrikossoff tumor was located in the right vocal chord. The tumor was treated successfully surgically by microlaryngoscopy. The etiology, clinical features and diagnostic difficulties are discussed.

Child English pre-sentential negation as metalinguistic exclamatory sentence negation.

This paper presents a study of the spontaneous pre-sentential negations of ten English-speaking children between the ages of 1;6 and 3;4 which supports the hypothesis that child English nonanaphoric pre-sentential negation is a form of metalinguistic exclamatory sentence negation. A detailed discourse analysis reveals that children's pre-sentential negatives like No Nathaniel a king (i) are characteristically echoic, and (ii) typically express objection and rectification, two characteristic functions of exclamatory negation in adult discourse, e.g. Don't say 'Nathaniel's a king'! A comparison of children's pre-sentential negations with their internal predicate negations using not and don't reveals that the two negative constructions are formally and functionally distinct. I argue that children's nonanaphoric pre-sentential negatives constitute an independent, well-formed class of discourse negation. They are not 'primitive' constructions derived from the miscategorization of emphatic no in adult speech or children's 'inventions'. Nor are they an early derivational variant of internal sentence negation. Rather, these negatives reflect young children's competence in using grammatical negative constructions appropriately in discourse.

[Brain abscess in chronic otitis media: a case report]. / Przypadek usznopochodnego ropnia plata skroniowego mózgu.

The authors have presented a case of brain abscess during chronic otitis media. They have described a treatment, complications and reasons of failure.

[Epithelial papilloma of the nose and paranasal sinuses]. / Brodawczak nablonkowy jam nosa i zatok przynosowych.

The three rare cases of the papilloma epithelial in the nose and paranasal sinuses were described. The diagnostic difficulties, treatment and clinical course were also discussed.

Immunohistochemical localization of glutathione S-transferase in preneoplastic and neoplastic lesions of the human uterine cervix.

A mouse monoclonal antibody and a rabbit polyclonal antibody prepared against the placental form of the enzyme glutathione S-transferase (GST-pi) were used to immunohistochemically stain normal and neoplastic human uterine cervical tissues from 88 cases. Of 65 cases of preneoplastic squamous lesions and invasive carcinomas of the cervix, 94% stained with the monoclonal antibody and 100% with the polyclonal antibody. In the 23 benign tissues, staining of ectocervical squamous epithelium was generally not observed; however, areas of reserve-cell hyperplasia, immature squamous metaplasia and adjacent endocervical cells did show staining (68% with the monoclonal antibody and 95% with the polyclonal antibody). Many of the positive tissue types showed a variety of staining patterns and intensities. These findings do not support the concept that GST-pi staining can be used to distinguish preneoplastic lesions of the cervix from benign reactive or proliferative processes. These results are of interest in the investigation of cervical carcinogenesis since GST-pi may be involved in an early stage of neoplastic transformation of the cervical epithelium. The correlation of these findings with the results of human papillomavirus testing and DNA content analysis should be of interest in determining the relationship of this enzyme to cervical neoplasia.

[Case of giant meningioma of the small wing of the sphenoid bone in a 9-year-old boy]. / Przypadek olbrzymiego oponiaka skrzydla malego kosci klinowej u dziewiecioletniego chlopca

The authors report a boy aged 9 years in whom a giant meningioma of the small wing of the sphenoidal bone was removed surgically. Attention is called to the rarity of these tumours in the first decade of life. Developmental retardation, speech beginning at the age of 4 years, large head and epileptic seizures developing at the age of 7 years without signs of intracranial hypertension suggested the possibility of organic brain disease and development of massive hemiparesis, speech disturbances and choked disc in the last period of the disease were the cause of referral of the child to a neurosurgical unit. Plain skull films and angiography demonstrated changes typical of raised intracranial pressure and presence of an expanding lesion in the left cerebral hemisphere. Meningioma was found on operation hidden within the left frontal and temporal lobes but connected by means of a narrow band to the dura of the small wing of the sphenoidal bone. A good result was obtained. Follow-up examination after 2 years demonstrated slight neurological abnormalities and a very good general state of the child.