Ataxia ; genetics ; physiopathology ; Calcium Channels ; genetics ; physiology ; Epilepsy ; genetics ; physiopathology ; Genetic Diseases, Inborn ; genetics ; physiopathology ; Humans ; Hypokalemic Periodic Paralysis ; genetics ; physiopathology ; Malignant Hyperthermia ; genetics ; physiopathology ; Migraine with Aura ; genetics ; physiopathology ; Myopathy, Central Core ; genetics ; physiopathology ; Ryanodine ; metabolism ; Spinocerebellar Ataxias ; genetics ; physiopathology

The purpose of this study is to develop glipizide push-pull osmotic pump (PPOP) tablets by using a formulation design expert system and an artificial neural network (ANN). Firstly, the expert system for the formulation design of osmotic pump of poor water-soluble drug was employed to design the formulation of glipizide PPOP, taking the dissolution test results of Glucotrol XL as the goal. Then glipizide PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. And in vivo evaluation was carried out between the samples which were similar to Glucotrol XL and the Glucotrol XL in Beagle dogs. The range of the factors of formulation and procedure, which could influence the drug release, was optimized using artificial neural network. Finally, the design space was found. It was found that the target formulation which was similar to Glucotrol XL in dissolution test could be obtained in a short period by using the expert system. The samples which were similar to Glucotrol XL were bio-equivalent to the Glucotrol XL in Beagle dogs. The design space of the key parameter coating weight gain was 9.5%-12.0%. It could be concluded that a well controlled product of glipizide PPOP was developed since the dissolution test standard of our product was more strict than that of Glucotrol XL.

Objective To investigate the diagnostic value of intraductal ultrasonography (IDUS) for unconfirmed microlithiasis under endoscopic retrograde cholangiography ( ERC). Methods The data of 22 patients who were definitely diagnosed as having microlithiasis by IDUS and endoscopic sphincterotomy (EST) from July 2007 to September 2009 were retrospectively analyzed. Microlith was defined as choledo-cholith equal to or less than 3 mm in diameter. Using IDUS plus EST findings as golden standard of bile duct microlithiasis, the accuracy of diagnosis and rate of missed diagnosis of transabdominal ultrasonography, magnetic resonance cholangiography (MRC) and ERC were evaluated and compared. Results Diagnosis rates of trans-abdominal ultrasonography, MRC and ERC for extra-hepatic duct microlithiasis were 27. 3% (6/22), 38. 5% (5/13) and 27. 3% (6/22) , respectively. Detection rates of common bile duct dilation by 3 methods were 68. 2% (15/22) , 84. 6% (11/13) and 68. 2% (15/22) , respectively. The microlithiasis in 2 patients, which manifested as repeated acute pancreatitis, were missed by transabdominal ultrasonography , MRC and ERC, and were finally confirmed by IDUS. Conclusion Sensitivity of ERC in diagnosis of extra-hepatic microlithiasis is not superior to that of transabdominal ultrasonography or MRC. IDUS is a technically easy, safe, highly sensitive and accurate procedure, which is helpful in differentiation of etiology of recurrent acute pancreatitis.

The aim of this study is to improve liposome encapsulation efficiency of water soluble drug ATP-2Na with hydrophobic ion pairing method, and evaluate its effect on tissues energy state in myocardial ischemia mice. Ion pair complex of ATP-2Na with HTAB was prepared first; then the liposomes were prepared by ethanol injection method. The size and zeta potential of ATP-2Na liposome were investigated. Its effect on tissues energy state in myocardium ischemia mice was evaluated by detecting ATP-2Na concentration in tissues and blood after injection in comparison to ATP-2Na solution. The diameters and zeta potential of ATP-2Na liposomes were (144.0 +/- 2.7) nm and (+16.2 +/- 1.6) mV, respectively. The encapsulation efficiency was (85.02 +/- 2.31) %. The in vitro drug release pattern from liposomes matches with Weibull equation. Compared with ATP-2Na solution, ATP-2Na liposome increased the ATP concentration of blood in myocardial ischemic mice very significantly; compared with blank, ATP-2Na liposome increased ATP content of myocardium and liver in myocaridal ischemic mice significantly, but ATP-2Na solution didn't show this effect. ATP-2Na liposome might have an advantage in improving tissue energy state on myocaridal ischemic animals.
Adenosine Triphosphate ; administration & dosage ; blood ; metabolism ; Animals ; Cetrimonium Compounds ; chemistry ; Drug Carriers ; Liposomes ; chemistry ; Liver ; metabolism ; Male ; Mice ; Myocardial Ischemia ; blood ; metabolism ; Myocardium ; metabolism ; Particle Size ; Random Allocation ; Surface-Active Agents ; chemistry

Objective To study the clinical value of DTI in the evaluation of high intensity focused ultra-sound (HIFU) for treating uterine fibroids by analyzing the characteristics of DTI before and after surgery. Methods DTI was performed before and after HIFU. The study included 25 patients with 30 uterine fibroids. All data were processed using GE AW4.5 Workstation. ADC,FA,VRA and T2-weighted trace of uterine fibroids before and after HIFU were recorded and analyzed. Results After HIFU,no enhancement was observed in uterine fibroids on DCE-MRI. The signal of uterine fibroids on FA,VRA map was lower after HIFU. No statistical differences were found between ADC and T2-weighted trace before and after the surgery(P>0.05). FA and VRA of uterine fibroids after HIFU were lower than those before the surgery(P<0.05). Conclusion FA and VRA can reflect micro differ-ence of uterine fibroids before and after HIFU ,which is useful for assessing the curative effect after HIFU.

Objective To study the effect of different concentration of 1,25-dihydroxyvitamin D3[1,25(OH)2D3] on cell proliferation,differentiation and the expression of vitamin D receptor (VDR) in mouse MC3T3E1 osteoblast.Methods Osteoblast were cultured in medium with different concentrations of 1,25(OH)2D3.Incubated for 48 h,cell proliferation of osteoblast were examined by MTT reduction assay (mono-nuclear cell direc cytotoxicity assay),the osteocalcin (OC) levels in cell medium were detected by ELISA,and the expression of VDR mRNA and protein were examined by using SYBR Green real-time PCR and Western blot,respectively.Results 1.After incubation with 1,25(OH)2D3 for 48 h,the number of MC3T3E1 osteoblast was significantly less than that in control group(P0.05).3.SYBR Green real-time PCR and Western blot results showed that the expression of VDR mRNA as well as VDR protein of osteoblast in 10-8,10-9 mol/L experimental groups were significantly higher than those in control group (Pa0.05).Conclusions Cell proliferation of mouse osteoblast can be inhibited,while the cell differentiation was promoted by 1,25(OH)2D3.1,25(OH)2D3 up-regulated the expression of VDR in mouse osteoblast,which suggested that the VDR signal pathway may play some role in proliferation and differentiation of osteoblast.

OBJECTIVEX-linked adrenoleukodystrophy (ALD) is a genetically determined disorder that involves the nervous system white matter, axons, adrenal cortex and testes. The typical clinical manifestations are progressive psychomotor regression, vision and/or auditory impairment and adrenal insufficiency. The clinical manifestation, biochemical change and genetic counseling work of X-linked ALD were analyzed.

METHODSThe clinical features of 29 cases with ALD were summarized and analyzed, including symptoms and signs, measurement of blood very long chain fatty acids (VLCFA), adrenal function, cranial magnetic resonance imaging (MRI) and pedigree investigation.

RESULTSAmong these 29 cases, the clinical phenotype could be classified into childhood cerebral (22 cases), adolescent cerebral (4 cases), adrenomyeloneuropathic (1 case), Addison's disease (1 case) and asymptomatic or presymptomatic (1 case) types. Nine of them had positive family history. Pedigree investigation was consistent with typical sex-linked recessive inheritance. There were 45 ALD patients in these 29 pedigrees. The neurological manifestations varied among members of the same family. Nine cases died during follow up. The causes of death were central respiratory failure or other complications of ALD and so on. Laboratory tests demonstrated abnormally high plasma levels of VLCFA in ALD patients; MRI demonstrated symmetric butterfly-like low T(1) and high T(2) signals in the parieto-occipital white matter. The impairment in the splenium of corpus callosum made the bilateral lesion region converge into one. It could progress anteriorly and injure the bilateral posterior limb of internal capsule and the temporal lobe, and could injure the brainstem inferiorly. Following intravenous injection of contrast material, thin stripe of lacelike enhancement could be observed.

CONCLUSIONSThe atypical initial symptom of ALD was seizures. The MRI showed abnormal signal in the cerebellar white matter. This disease can influence the normal development of children, this was more pronounced in the childhood cerebral ALD type. It tended to progress rapidly with dementia, vegetative state or death. Since antenatal diagnostic method is available now, emphasis should be made on the antenatal examination in order to make an early diagnosis and abort pregnancy if necessary.

Adolescent ; Adrenoleukodystrophy ; blood ; diagnosis ; therapy ; Child ; Child, Preschool ; China ; Fatty Acids ; blood ; Female ; Follow-Up Studies ; Humans ; Male ; Pedigree ; Treatment Outcome

Objective To evaluate magnifying endoscopy combined with narrow-band imaging ( ME-NBI) for diagnosis of early gastric cancer (EGC).Methods A total of 150 focal lesions from 143 patients over 35 years old identified by white light endoscopy (WLE) from March 2010 to December 2010 in our tertiary referential institution were recruited in the prospective study with written informed consent.Focal lesions were defined as any small local mucosa with abnormal shape or color based on an assessment of findings of WLE without any specified criteria, including superficial, depressed and elevated lesions.The patients with local advanced gastric cancer, submucosal lesions and history of gastrectomy were excluded from the study.All the patients received ME-NBI.Based on literature, national criteria of early diagnosis with ME-NBI were established.All the lesions underwent biopsy and pathological examination.Diagnostic accuracy of ME-NBI for EGC was assessed with reference to histopathology.Results In 150 focal lesions, 19 were pathologically diagnosed as EGC, 8 of which were treated by endoscopic resection and 11 were resected surgically.The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of conventional WLE for diagnosing EGC were 94.7%, 53.4%, 22.8%, 98.6% and 58.7%, respectively.The counterparts of ME-NBI for diagnosing EGC were 73.7%, 99.2%, 93.3%, 96.3% and 96.0%, respectively.The diagnostic accuracy of ME-NBI was significantly better than that of conventional WLE (96.0% vs.58.7%, P＜0.05).With regard to the findings of EGC on ME-NBI, irregular or absent microsurface pattern and microvascular pattern were characteristic features of EGC.Conclusion Conventional WLE is still an important and mandatory screening modality, which is significant for further procedures of suspected lesions, preferably accompanied with biopsy.ME-NBI achieved superior accuracy in the differential diagnosis of focal lesions detected with conventional WLE, but needs further verification.

Despite a few genes that do not encode ion channels have been identified as implicating some kinds of human idiopathic epilepsies(IE) in recent years, but genetic discoveries have shown the ion channels to play a central role in genetic pathomechanism of IE. The gene mutations of ion channels are a common cause of some rare monogenic IE which could be so-called as channelopathies, and able to be applied to account for the questioned epileptic syndrome to minority of families and sporadic cases. However, more frustrating has been from the genetic research on more common IE with complex inheritance due to the unknown mode of inheritance, the phenotypic heterogeneity and the uncertainty of genetic overlap among syndrome subtypes, which have limited gene mapping. Absence epilepsy is a kind of common IE subtype and shows a complex way to inherit. Evidences from heredity investigation indicate that eleven genes are correlated with absence epilepsy, of which four encode the neuronal calcium channel subunits. Therefore, calcium channel genes may be considered as important candidates for involving in absence epilepsy. To focus the genetics research on calcium channel genes of absence epilepsy may be opening an optimal gate to the pathogenetic study of more common IE with complex inheritance, and benefit to elucidate the molecular mechanisms of absence epilepsy finally, one of the more common IE subtypes with complex inheritance.
Calcium ; metabolism ; Calcium Channels ; genetics ; physiology ; Epilepsy, Absence ; genetics ; physiopathology ; Genetic Predisposition to Disease ; genetics ; Humans ; Models, Biological

OBJECTIVETo investigate mutations of ABCD1 gene in X- linked adrenoleukodystrophy (ALD) patients in China.

METHODSPolymerase chain reaction and DNA direct sequencing were employed to analyze the 10 exons of ABCD1 gene in 25 ALD patients.

RESULTSSeventeen mutations in different exons (except exons 4, 9 and 10) were identified in 18 of 25 patients. Most of the mutations were missense mutations, including R182P, G266R, H283D, S404P, N509I, R518G, L520Q, Q556R, S606L and R617C, four (H283D, S40 4P, N509I, R518G) of 10 missense mutations were novel. Also identified were 3 nonsense mutations (W132X, W242X, W595X), 1 dinucleotides deletion mutation (1414 del AG) resulting in frameshift, and 1 base pair deletion at splice acceptor site (IVS5-6 del C). Two synonymous mutations (L516L and V349V) appeared simultaneously in 2 unrelated patients, and no other mutations could be found with them in all 10 exons screened.

CONCLUSIONThere were no hot spot mutations in ABCD1 gene in China. Mutations in gene were found over 70% of patients with ALD in China. The ABCD1 gene mutations identified revealed no obvious correlation between the type of mutation and phenotype.

ATP Binding Cassette Transporter, Sub-Family D, Member 1 ; ATP-Binding Cassette Transporters ; genetics ; Adrenoleukodystrophy ; genetics ; pathology ; Age of Onset ; Base Sequence ; China ; Codon, Nonsense ; DNA ; chemistry ; genetics ; DNA Mutational Analysis ; Humans ; Male ; Mutation ; Mutation, Missense