Four salts of ticagrelor, ticagrelor-3,5-dinitrobenzoic acid, ticagrelor-pyrazinamide, ticagrelor-D-proline and ticagrelor-L-proline were prepared by solvent suspension and liquid-assisted grinding to improve the solubility of ticagrelor. The compounds were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, elemental analysis, and the intermolecular salt-bonding forces were analyzed. The equilibrium solubility of salts and pure drug in hydrochloride buffer pH 1.2 and phosphate buffer pH 6.8 were measured by high-performance liquid chromatography. Ticagrelor was salted with 3,5-dinitrobenzoic acid, pyrazinamide, D-proline, L-proline all in a stoichiometric ratio of 1∶1; with the exception of ticagrelor-D-proline, the solubility of the other three salts provided significantly improved solubility in hydrochloride buffer pH 1.2, and the equilibrium solubility of ticagrelor-3,5-dinitrobenzoic acid was increased by approximately 1.7 folds as compared to pure drug. Salt-forming technology is convenient and can improve the solubility of ticagrelor.

In order to improve the poor photostability of nifedipine, this study designed a cocrystal based on the principles of crystal engineering and prepared nifedipine-imidazole cocrystal by suspension method. The new cocrystal was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TG) and infrared spectroscopy (IR) to confirm the formation of the cocrystal. The photostability of nifedipine and its cocrystal was measured by powder X-ray diffraction and high-performance liquid chromatography (HPLC). The results showed that the nifedipine-imidazole cocrystal improved the photostability of nifedipine to a certain extent. This study provides guidance for the development of nifedipine cocrystals and the improvement of its druggability.

OBJECTIVETo analyse the video-oculographic findings of positional tests and evaluate the efficacy of canalith repositioning procedure (CRP) in patients with paroxysmal positional vertigo ( BPPV) of the anterior semicircular canal (ASC).

METHODSA retrospective study of 31 patients with ASC BPPV. Then the CRP was performed.

RESULTSTwenty-two individuals (70.97%) presented a unilateral positional nystagmus during the Dix-Hallpike test, in 17 individuals had torsional nystagmus component, 5 individuals only had pure positional down beat nystagmus. Nine patients presented bilateral positional nystagmus, 7 individuals had torsional component positional nystagmus, in 2 patients the direction of the torsional component were the same during right and left Dix-Hallpike test, in 4 patients the torsional component were concurrent with positional down beat nystagmus but the direction could not be ascertained clinically, in 2 patients had pure positional down beat nystagmus. Nineteen patients (61.29%) had unilateral lesion, 11 patients had the left ASC BPPV, 8 patients had right ASC BPPV. Eleven patients had with both ASC and PSC BPPV in the ipsilateral. Twenty-one patients (67.74%) were cured, 29 patients (93.55%) were improved, 2 (6.45%) patients were inefficacy. CRP effectively resolved the nystagmus and vertigo in 14 patients (45.16%) when applied only once, The average number of CRP was 1.7 times, there were 5 patients recurrence during the follow-up.

CONCLUSIONSASC BPPV was not a common condition. The torsional nystagmus component of ASC BPPV might be weak during the Dix-Hallpike test. The positional nystagmus of ASC BPPV was triggered bilaterally. Based on these findings, CRP could be one of the most effective treatment methods for ASC BPPV.

Adult ; Aged ; Benign Paroxysmal Positional Vertigo ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Semicircular Canals ; Vertigo ; diagnosis ; therapy

BACKGROUND:Synovial mesenchymal stem cells have the ability of multilineage differentiation in vitro, which are expected to be seed cells for the treatment of cartilage defects in cartilage tissue engineering. Appropriate growth factors are critical for the chondrocyte differentiation of synovial mesenchymal stem cells.
OBJECTIVE:To study the role of secreted factors by chondrocytes to induce chondrogenesis of synovial mesenchymal stem cells.
METHODS:The synovial mesenchymal stem cells and chondrocytes were harvested from rat knee joints and cultured through the digestion method. The supernatant was col ected from chondrocytes, and centrifuged, filtered and cryopreserved. The third passage synovial mesenchymal stem cells centrifuged as pel ets were cultured in the chondrocyte supernatant for 21 days. And the cells morphology was examined and the type II col agen and aggrecan were detected through immunohistochemistry and RT-PCR.
RESULTS AND CONCLUSION:The synovial mesenchymal stem cellpel ets cultured in the chondrocyte supernatant became cartilage-like tissue after 21 days. The type II col agen was detected positively in the matrix of synovial mesenchymal stem cellpel et immunohistochemical y. RT-PCR examination showed that the type II col agen and aggrecan expressed in the synovial mesenchymal stem cellpel et cultured in the chondrocyte supernatant. It suggested that synovial mesenchymal stem cellcould be induced to differentiate into chondrocytes depending on soluble factors secreted by chondrocytes.

BACKGROUND:Articular chondrocytes with the ability of autocrine and paracrine can provide the growth factors and microenvironment for synovial mesenchymal stem cels differentiating into the chondrocyte. The
three-dimensional scaffold could provide space for cels adhesion, proliferation and differentiation.
OBJECTIVE: To study the ability of chondrogenesis by co-culturing synovial mesenchymal stem cels and chondrocytes under the three-dimensional condition.
METHODS:The synovial membrane and articular cartilage were harvested from rat knee joint. The synovial
mesenchymal stem cels and chondrocytes were obtained through the method of enzyme digestion. The passage 3 synovial mesenchymal stem cels and passage 2 chondrocytes were co-cultured in the chitosan/I colagen
composite scaffolds at the ratio of 1:2. Then, the cels/scaffold composite was harvested to be examined
morphologicaly, histologicaly and immunohistochemicaly after being cultured 21 days. The confocal laser was also employed to detect the cels distribution in the scaffold.
RESULTS AND CONCLUSION: After being cultured 72 hours, it could be observed from the cels/scaffold composite examined through the scanning electron microscope that the cels adhered on the surface of the
scaffold and extracelular matrix surrounding the cels was seen on the scaffold. After being cultured 21 days, it could be found through the confocal laser scanning that the cels were wel-distributed on the scaffold, and cels decreased gradualy. Type II colagen was positive in the extracelular matrix immunohistochamicaly. It
suggested from this study that the synovial mesenchymal stem cels could be co-cultured with chondrocytes in the chitosan/I colagen composite scaffolds and have the ability of chondrogenesis differentiation.

Piroxicam has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Analysis of the intermolecular interactions is essential to reveal the formation mechanism and differences of polymorphs. In this paper, Hirshfeld surface analysis and semi-empirical methods were used to calculate and analyze the intermolecular interactions in seven polymorphic forms of piroxicam. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions, among which H…H, O…H/H…O and N…H/H…N interactions account for 95% of the total energy. There are differences in the proportion and distribution of the forces of different crystal forms. The energy calculation shows that the lattice energy of the hydrate is significantly lower than that of the anhydrous forms, and in the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis was found that within the distance of 3.8 Å from the center of the piroxicam molecule, different crystalline forms of piroxicam molecule have different interaction energies with surrounding molecules.

China ; Clinical Trials as Topic ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Humans ; Kidney Diseases ; drug therapy ; Prospective Studies ; Retrospective Studies ; Tripterygium

OBJECTIVETo study human vestibular cerebral representations by combining right-sided ice-water stimulation at 0 degree C with blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) and to evaluate the value of this method in the functional localization of human vestibular cortex.

METHODSTwenty right-handed volunteers (12 men and 8 women) received unilateral irrigation of the right external auditory meatu for 15 s with 15 ml of water at 0 degrees C during fMRI in complete darkness. The functional imaging of brain cortex was acquired with a 1.5-T MRI scanner (Signa Infinity Twin + Excite; General Electric Co., USA). The successive functional images from each subject were analyzed as a group with statistical parametric mapping software (SPM 99).

RESULTSUltimately, data obtained from 17 subjects were analyzed (3 subjects were eliminated from data because of head movement exceeding 2 mm). The group analysis showed bilateral (particularly left-sided) cortical activation, associated with caloric stimulus involving in temporoparietal junction extending into the posterior insula, supramarginal gyrus in the inferior parietal lobe, precuneus, supplementary motor area (SMA), the ventrolateral portion of the occipital lobe, cuneus and lingual gyrus, superior temporal gyrus and cingular cortex.

CONCLUSIONSIce-water stimulation at 0 degree C in fMRI reveals a widespread cortical network involved in vestibular signal processing in human. As the functional localization of vestibular cortex could be determined precisely, ice-water stimulation at 0 degree C in fMRI would hold great promise as a sensitive and reproducible tool for the research in human vestibular cortex.

Adult ; Brain Mapping ; Cerebral Cortex ; anatomy & histology ; physiology ; Ear, Inner ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Vestibular Nuclei ; anatomy & histology ; physiology ; Young Adult

OBJECTIVELeft ventricular remodeling (LVR) following myocardial infarction (MI) is a key pathophysiological process in which MI develops into heart failure. The exact mechanism of LVR remains unclear. We performed differential proteomic analysis on the myocardia of rats with LVR after MI, to explore the mechanism of ventricular remodeling after MI.

METHODSIn the LVR group (n = 12), after the anterior descending coronary artery was ligated, the rats were fed for four weeks before the LVR models were established. Rats in the sham-operated group (n = 11) underwent thread-drawing without ligation. The hemodynamic parameters, pathological findings, and proteomics were compared between the two groups.

RESULTSIn the LVR group, the left ventricular end-diastolic pressure increased, the maximal left ventricular pressure increase/decrease ratio decreased significantly, and the left ventricular systolic pressure decreased. H-E staining and Masson staining of cardiac muscle tissues of the LVR group showed myocytolysis, disarray, and collagen proliferation. Twenty-one differentially expressed proteins were detected by proteomic analysis. We validated two proteins using western blot analysis. The differentially expressed proteins could be divided into six categories: energy metabolism-related proteins, cytoskeletal proteins, protein synthesis-related proteins, channel proteins, anti-oxidation- related proteins, and immune-related proteins.

CONCLUSIONThese differentially expressed proteins might play key roles in LVR following MI.

Animals ; Male ; Myocardial Infarction ; complications ; pathology ; Myocardium ; metabolism ; pathology ; Proteome ; analysis ; Proteomics ; Rats ; Rats, Wistar ; Ventricular Remodeling

OBJECTIVETo analyze the mutation of COL9A2 gene and investigate the molecular pathogenesis of pathological myopia in a Han Chinese population.

METHODSMutation in the coding region of the COL9A2 gene was screened by Sanger sequencing in 200 subjects with pathological myopia and 200 normal controls. The detected variants were genotyped by SNaPshot method in another 200 myopic cases and 200 normal controls.

RESULTSSanger sequencing has failed to detect the reported D281fs frameshift mutation in the 200 cases. A novel variant, c.143G>C heterozygous missense mutation in exon 2, was identified in a myopic subject, and another novel variant, c.884G>A heterozygous missense mutation in exon 17, was found in another case. Neither was found in normal controls. One SNP (rs2228564) was detected in the coding region of the COL9A2 gene, but there was no significant difference in its allelic frequencies between the two groups (P> 0.05). Genotyping of the remainder 200 cases and 200 controls by SNaPshot method has found a c.143G>C in 1 case and c.884G>A in 2 cases, though no significant difference between the two groups was detected (P> 0.05).

CONCLUSIONThe D281fs frameshift mutation in the COL9A2 gene is not associated with pathological myopia in the studied Han Chinese population. Two novel mutations, c.143G>C in exon 2 and c.884G>A in exon 17 of the COL9A2 gene, may contribute to the development of pathological myopia.

Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Collagen Type IX ; genetics ; Frameshift Mutation ; Humans ; Myopia, Degenerative ; genetics ; Sequence Analysis, DNA