Adult ; Brain Neoplasms ; pathology ; Glioblastoma ; pathology ; Humans ; Male ; Pineal Gland ; pathology

OBJECTIVETo investigate the release model of insoluble drug carbamazepine (CBM) based on HPMC matrix tablets.

METHODSCBM release profile from matrices and HPMC erosion rate were determined.

RESULTThe mathematical model by matrix erosion rate and drug release from HPMC K15M were established for the fractional HPMC and CBM released as M(P(t))/M(P(infinity))=-[0.8095ln((t))+1.2775]Meq((-0.0622t-0.305)) and M(d(t))/M(d(infinity))=-[0.1891t-0.1294]Meq(-0.9326). In comparison with the data of HPMC K4M matrix erosion and CBM release from HPMC K4M matrices, theoretical value agreed well with experimental data.

CONCLUSIONThe two mathematical models can be satisfactorily applied to insoluble drug release, which is governed by matrix erosion.

Carbamazepine ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Hypromellose Derivatives ; Methylcellulose ; administration & dosage ; analogs & derivatives ; Models, Theoretical ; Solubility ; Tablets

OBJECTIVETo study the association between the polymorphism of human monoamine oxidase type A (MAO-A) gene and Parkinson's disease(PD).

METHODSFnu4HI restriction fragment length polymorphism(RFLP) and PCR-RFLP were used to detect the mutation of MAO-A gene. The frequencies of alleles and genotypes at the MAO-A Fnu4HI locus on the X chromosome in different PD group were compared with those of the control group.

RESULTSIt was found that the frequencies of G allele in the patients with PD and controls were 0.613 and 0.527 respectively, P=0.039 "the frequencies of TT genotype were 0.303 and 0.415(P=0.014), and the frequencies of GG genotype were 0.564 and 0.451 respectively(P=0.021). When the patients were divided into two groups by age-onset, significant difference in the allelic and genotypic frequencies was observed only between early-onset PD group and control group. And when the PD patients were grouped by sex, significant difference was observed only between male PD group and male control group (the frequencies of G allele being 0.669 and 0.500 respectively, P=0.005).

CONCLUSIONThis study revealed significant differences between PD group and control group in allelic and genotypic frequencies. The findings supported the hypothesis about an association between MAO-A gene and PD, suggesting that age at onset of PD and gender predisposition might be related to the putative association, and Fnu4HI SNP be a risk factor for PD.

Alleles ; Asian Continental Ancestry Group ; Deoxyribonucleases, Type II Site-Specific ; analysis ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Monoamine Oxidase ; genetics ; Parkinson Disease ; genetics ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length

Diagnosis, Differential ; Female ; Humans ; Laparotomy ; methods ; Pregnancy ; Pregnancy, Ectopic ; diagnosis ; surgery ; Retroperitoneal Space ; diagnostic imaging ; Tomography, X-Ray Computed ; Ultrasonography

BACKGROUNDThe urokinase plasminogen activator system is believed to play an important role in degradation of the extracellular matrix associated with cartilage and bone destruction; however its precise roles in temporomandibular disorders have not yet been clarified. The aims of this study were to investigate the gene expression of fibrinolytic factors urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the articular cartilage of rabbit temporomandibular joint (TMJ) with disc displacement (DD) and to probe the relationship between fibrinolytic activity and cartilage remodeling.

METHODSDisc displacement of right joints was performed in 36 of 78 rabbits under investigation. The animals were sacrificed at 4 days and 1, 2, 4, 8 and 12 weeks after surgery, respectively. The right joints of these animals were harvested and processed for the examination of mRNA expression of uPA and PAI-1 in articular cartilage using in situ hybridization techniques.

RESULTSThe expression of uPA and PAI-1 was co-expressed weakly in the chondrocytes from transitive zone to hypertrophic zone and mineralized zone, while no hybridizing signals were shown in proliferative zone and superficial zone in control rabbits. The most striking was the up-regulation of uPA and PAI-1 mRNA in 4-day rabbits postoperatively at the onset of cartilage degeneration. The strongest hybridizing signals for uPA and PAI-1 were seen in 2-week rabbits postoperatively. After 2 weeks, the expression of uPA and PAI-1 began to decrease and reached nearly normal level at 12 weeks.

CONCLUSIONSThe expression of the uPA/PAI-1 system coincides with the pathological changes in condylar cartilage after DD. The uPA/PAI-1 system may be one of the essential mediators in articular cartilage remodeling.

Animals ; Cartilage, Articular ; metabolism ; Female ; Joint Dislocations ; metabolism ; pathology ; Male ; Mandibular Condyle ; metabolism ; pathology ; Plasminogen Activator Inhibitor 1 ; genetics ; RNA, Messenger ; analysis ; Rabbits ; Temporomandibular Joint ; metabolism ; Temporomandibular Joint Disc ; Urokinase-Type Plasminogen Activator ; genetics

OBJECTIVETo investigate the effect of anterior disc displacement on the expression of urokinase plasminogen activator and its inhibitor-1 (uPA/PAI-1) in synovial tissues.

METHODSForty Japanese white rabbits were used in this study. The animals were killed at 4 days, 1, 2, 4, 8 and 12 weeks postoperatively, respectively. In situ hybridization technology was applied to detect the expression of uPA/PAI-1 mRNA in synovial membrane.

RESULTSIn normal synovial tissues, synovial lining cells and a few fibrosblasts with mild positive staining were occasionally seen. More synovial lining cells and fibrosblasts with moderate postive signals were found 1 week after operation. Since then, the degree of staining for uPA/PAI-1 increased gradually. By the end of 12 weeks postoperatively, strong signals of uPA/PAI-1 mRNA were detected.

CONCLUSIONThere is a harmonized uPA/PAI-1 system existing in synovial tissues. The high expression of uPA and PAI-1 mRNA in synovial tissues indicates that the uPA/PAI-1 system may play an important role in the process of synovitis resulted from anterior disc displacement.

Animals ; In Situ Hybridization ; Plasminogen ; Plasminogen Activator Inhibitor 1 ; RNA, Messenger ; Rabbits ; Synovial Membrane ; Urokinase-Type Plasminogen Activator

OBJECTIVETo study (CAG) n polymorphism of the androgen receptor (AR) gene in responders and non-responders of male volunteers who received testosterone undecanoate intramuscular injection for contraception and to explore the effect of the polymorphism on hormonal male contraception.

METHODSTwenty-nine non-responders and 34 responders were enrolled in this study as a test and a control group respectively. The numbers of CAG sequence repeats were determined by PCR and DNA sequencing, and the effect of (CAG) n polymorphism on hormonal male contraception was analyzed.

RESULTSThe means of CAG repeats of the test and the control group were 23.62 and 22.97, with no significant difference in between (P > 0.05). The short CAG repeats (n < or = 22) constituted 51.7% in the test group and 50% in the control, while the long ones (n > 22) accounted for 48.3% and 50% , respectively. The short and the long group had a similar distribution. No association was found between CAG repeats and sperm concentration. With FSH > 0.2 IU/L, the probability of azoospermia in the long CAG repeat group was 1.5 times that of the short one.

CONCLUSIONCAG repeats in the AR gene presented polymorphism in the subjects, with no significant difference between the responders and non-responders. Further investigation has yet to be performed into the relationship of hormonal male contraception with CAG repeats or other factors.

Adult ; Base Sequence ; Contraception ; methods ; Gene Frequency ; Genotype ; Humans ; Injections, Intramuscular ; Male ; Molecular Sequence Data ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Receptors, Androgen ; genetics ; Sequence Analysis, DNA ; Testosterone ; administration & dosage ; analogs & derivatives ; Trinucleotide Repeats ; genetics

Apoptosis ; Caspase 3 ; Caspases ; physiology ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Isotretinoin ; pharmacology ; Melanoma ; pathology ; Receptors, Retinoic Acid ; physiology ; Retinoid X Receptors ; physiology ; Tretinoin ; pharmacology

OBJECTIVETo detect the putative association between the polymorphism of human NAD(P)H: quinone oxidoreductase (NQO1) gene and Parkinson's disease(PD).

METHODSPolymerase chain reaction-denaturing high performance liquid chromatography (PCR-DHPLC) was used to detect the polymorphism of monoamine NQO1 gene cDNA 609 site(C-->T). The frequencies of alleles and genotypes in different PD groups were compared with those of the control group.

RESULTSIt was found that the frequencies of TT genotype in the patients with PD and in the controls were 0.226 and 0.118 respectively (P=0.004), i.e., TT genotype increased the risk of PD by 2.186-fold (P=0.005). When the patients with PD were divided into two groups by the age at onset, significant difference in the genotypic frequencies was observed only between late-onset PD group and control group (the frequencies of TT genotype being 0.260 and 0.118, P=0.001) and TT genotype increased the risk of late-onset PD by 2.627-fold(P=0.001). There were no significant differences in frequencies of alleles between different PD groups and control group.

CONCLUSIONThis study revealed significant differences in genotypic frequencies between PD group and control group. The findings supported the hypothesis about an association between NQO1 gene and PD, suggesting that the age at onset of PD might be related to the putative association, and NQO1 cDNA C609T site be a risk factor for PD.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chromatography, High Pressure Liquid ; Genotype ; Humans ; Middle Aged ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; Parkinson Disease ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic

Objective:To summarize the clinical features and pathological changes of peripheral tissues from patients with neuronal intranuclear inclusion disease (NIID) diagnosed by genetic tests.Methods:Repeat-primed polymerase chain reaction was used to confirm the GGC repeated expansion in the 5′ untranslated region of the NOTCH2NLC gene in patients with suspected NIID who had visited the Department of Neurology of Peking University First Hospital from January 2018 to February 2020. The clinical data and pathological changes of peripheral tissues from patients with genetically diagnosed NIID were collected retrospectively and analysed. Immunostaining with anti-p62 and anti-ubiquitin antibody was performed on peripheral biopsy specimens.Results:Totally nine patients with NIID who had GGC repeated expansion in the NOTCH2NLC gene were found. Five patients were familial (from three faimilies), and four patients were sporadic. The age of onset was 36-61(51.33±7.12) years. The most common symptoms in this NIID group were episodic emotion and personality change (8/9), paroxysmal disturbance of consciousness (6/9) and intermitant head discomfort (6/9). Other symptoms included cognitive dysfunction, limb weakness, limb sensory disturbance, bladder dysfunction, ataxia, seizures and psychiatric symptoms. Brain magnetic resonance imaging showed high signals along the corticomedullary junction on diffusion-weighted image in eight out of nine patients. Skin biopsied samples from nine patients demonstrated the presence of eosinophilic intranuclear inclusions (IIs), appearing in the nucleus of fibroblasts, fat cells and ductal epithelial cells of sweat glands on hematoxylin-eosin staining. IIs were positive on anti-p62 and anti-ubiquitin immunostaining. Electron microscopy indicated the IIs were composed of a pile of filament materials without membrane. Muscle biopsies from two patients showed no obvious neurogenic or myogenic pathologic changes, except in one patient several rimmed vacuoles fibers were found. In one patient sural nerve biopsy showed severe demyelinating pathological changes. No IIs were found in the muscles and peripheral nerve tissue either by histological examination or by immunohistochemical staining with anti-p62 or anti-ubiquitin, while IIs were found by immunofluorescence staining with both anti-p62 and anti-ubiquitin in three patient′s tissue. Conclusions:The phenotype of this NIID patient group is adult-onset NIID, with episodic encephalopathy as the main clinical manifestation. Skin biopsy has high pathological diagnostic value for NIID. The immunofluorescence staining with anti-p62 and anti-ubiquitin is easier to detect the presence of IIs than histological staining and immumohistochemical staining.