ABSTRACT
Oral formulations of nanoemulsions (NE) were systematically designed, and then their effects on oral absorption of raloxifene (RAL), including their absorption mechanisms were investigated. RAL solubility in water and various excipients of NE and oil-water partition coefficient[P(O/W)] of RAL were examined. Next the optimal compatibility between emulsifiers and oils in NE were ascertained by emulsification ability. Proportions of each component and optimal RAL-NE were fully confirmed by a pseudo-ternary phase diagram and drug loading, respectively. RAL-NE quality was evaluated by particle size, zeta potential, morphology, entrapment efficiency and stability in simulated gastrointestinal fluid. A MDCK cell model was used to study the in vitro transport mechanism of RAL-NE. Oral bioavailability of RAL-NE was eventually performed in SD rats. RAL can be classified as BCSⅡ based on the solubility and P(O/W). The best formulation of RAL-NE was composed of linoleic acid (LOA):isopropyl palmitate (IPP):cremophor RH40 (RH40):alcohol as 1.67:3.33:3:2. Drug loading in pre-nanoemulsion was 15 mg·g-1 andentrapment efficiency of RAL in NE was (79.4 ±0.4)%. The particle size, zeta potential and drug content of RAL-NE were maintained in the simulated gastrointestinal fluid. The in vitro transport mechanism of RAL-NE in MDCK cells was mainly clathrin-mediated endocytosis. The oral bioavailability of RAL in RAL-NE relative to RAL-suspension was 171.9%. The best formulation of RAL-NE studied systematically was confirmed to significantly improve the RAL absorption by in vitro and in vivo evaluations (P < 0.05). This paper provides references for oral NE research and development.
ABSTRACT
The development and metastasis of uterine tumors depend highly on tumor angiogenesis. Multiphase dynamic contrast-enhanced magnetic resonance imaging can quantitatively describe the hemodynamic changes of uterine tumors based on a variety of tracer kinetic models and time-signal curves and by simulating the distribution of contrast inside and outside the blood vessels. Functional parameters can accurately and noninvasively assess tumor angiogenesis. It provides a non-invasive functional evaluation method for the differential diagnosis,staging,response evaluation,and prognostic prediction of uterine tumors.
ABSTRACT
<p><b>OBJECTIVE</b>To establish double antibody sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of human soluble VE-cadherin in human plasma and to investigate its value in clinical use.</p><p><b>METHODS</b>The monoclonal antibodies against human VE-cadherin were prepared from BALB/c mice immunized with prokaryotic expression recombinant proteins, and the best combination of double antibodies was selected by checkerboard titration method. Double antibody sandwich ELISA for the determination of human VE-cadherin was established by using HRP-labeled McAb as a detection antibody and a capture antibody. The methodology performance was evaluated. The plasma concentrations of VE-cadherin in 28 healthy subjects and 60 patients with cancer were determined.</p><p><b>RESULTS</b>The double antibody sandwich ELISA for the determination of human VE-cadherin was established by selecting the combination of double antibodies. The detection limit was 24.7 pg/ml, the coefficients of variation for inner-batch and inter-batch were 4.1%-7.7% and 8.7%-10.8% respectively. The average recovery was 96.7%. The plasma level of soluble VE-cadherin in normal controls was 262.1±11.75 pg/ml. The plasma level of soluble VE-cadherin was 173.9±17.98 pg/ml in 24 patients with leukemia, 311.7±25.24 pg/ml in 14 patients with stomach cancer, 206.8±25.01 pg/ml in 11 patients with lung cancer, and 310.7±11.82 pg/ml in others patients(9 patients with breast cancer, 1 patients with gliomas, 1 patients with liver cancer).</p><p><b>CONCLUSION</b>The developed ELISA kit has better sensitivity and specificity, and can be used in detection of human soluble VE-cadherin in human plasma, therefore, it can provide a new mathod for diagnosis of cancer patients.</p>
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<p><b>OBJECTIVE</b>To investigate whether the plasma level of platelet auto- antibodies in ITP patients is related to that of co-stimulatory molecules sB7-H2 and sB7-H3.</p><p><b>METHODS</b>A total of 61 ITP patients and 25 healthy controls from the First Affiliated Hospital of Soochow University from June 2012 to August 2013 were enrolled in this study. The expression levels of platelet auto-antibodies against 5 glycoproteins (GPIX, GP Ib, GP IIIa, GPIIb and P-selectin) in plasma were detected by flow cytometric immuno-beads array, and the expression of soluable co-stimulatory molecules sB7-H2 and sB7-H3 was measured by ELISA.</p><p><b>RESULTS</b>The plasma levels of 5 auto-antibodies against platelet membrance glycoproteins significantly increased in ITP patiens (P < 0.01). Compared with healthy controls, sB7-H2 levels increased (P < 0.05), while the sB7-H3 level did not significantly change (r = 0.13, P > 0.05). However, the correlation analysis showed that sB7-H3 negatively correlated with platelet P-selectin auto-antibody (r = -0.46, P < 0.05), and sB7-H2 and sB7-H3 significantly reduced in ITP patients with positive P-selectin auto-antibody (P < 0.01). In ITP patients, platelet counts negatively correlated with sB7-H2 (r = -0.3907, P < 0.01), but did not correlate with sB7-H3.</p><p><b>CONCLUSION</b>Soluble costimulatory molecule sB7-H2 elevates in ITP patients, and the level of sB7-H3 is associated with auto-antibodies against P-selectin, suggesting that costimulatory molecules B7-H2 and B7-H3 may be involved in the pathogenesis of immune regulation abnormality in ITP.</p>
Subject(s)
Humans , Autoantibodies , B7 Antigens , Blood Platelets , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Platelet Membrane Glycoproteins , Purpura, Thrombocytopenic, IdiopathicABSTRACT
<p><b>OBJECTIVE</b>To summarize the experience with duodenal perforations to determine a systematic management approach.</p><p><b>METHODS</b>A total of 11 250 patients who received endoscopic retrograde cholangiopancreatography(ERCP) in The First People's Hospital of Hangzhou from January 2005 to December 2011 and 15(0.13%) patients developed duodenal perforation. The clinical data of these 15 cases were analyzed.</p><p><b>RESULTS</b>There were 6 males and 9 females. The age ranged from 45 to 87 years. Seven patients developed perforation after sphincterotomy of the duodenal papilla. Five patients perforated due to the endoscope, and 3 due to guide wire and net basket. All the patients presented varying degree of abdominal pain and distention. CT scan of the upper abdomen showed peripancreatic and retroperitoneal air or fluid. Diagnosis was confirmed in 7 patients using abdominal X-ray. Eight patients developed postoperative abdominal pain and distention, subcutaneous emphysema, and fever 3 hours to 5 days after surgery, and diagnosis was confirmed using plain abdominal X-ray or upper abdominal CT scan. Nine patients were managed conservatively, 4 of whom were diagnosed within 3 hours after perforation and were managed by endoscopic metal clip and nasobiliary drainage and no abdominal abscesses developed. The length of hospital stay ranged from 10 to 15 days. Five patients were diagnosed 10 hour to 5 days after perforation, of whom 2 had intestinal fistula, 4 had abscess, and one died, the length of hospital stay ranged from 15 to 105 days. Six patients were managed surgically, 4 received surgery within 4 to 8 hours after perforation and no abscess developed, and the length of hospital stay ranged from 18 to 21 days. The other 2 patients were operated at 24 hours and 30 hours after perforation respectively, one of whom had recurrent intra-abdominal bleeding after surgery and one died from intra-abdominal abscess and multiple organ failure.</p><p><b>CONCLUSIONS</b>For duodenal perforations related to ERCP, early diagnosis can be made by prompt intraoperative identification and postoperative CT scan. Endoscopic metal clip and nasobiliary drainage should be considered aside from surgical intervention.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Cholangiopancreatography, Endoscopic Retrograde , Duodenal Diseases , Diagnosis , Therapeutics , Intestinal Perforation , Diagnosis , Therapeutics , Retrospective StudiesABSTRACT
Meckel diverticulum (MD), a congenital gastrointestinal anomaly, is often involved in pediatrics, but less in the adult population. The patient in this report was a 69-year-old female presented with massive gastrointestinal bleeding causing hemorrhagic shock due to MD containing ectopic pancreatic tissue. A review of the literature revealed that gastrointestinal bleeding from MD containing ectopic pancreatic tissue is rare in adults and difficult to be identified preoperation. MD should be considered as one of the differential diagnosis for lower gastrointestinal bleeding, although scarce in adults, especially when the patient has massive painless bleeding.
Subject(s)
Aged , Female , Humans , Choristoma , Diagnosis , Gastrointestinal Hemorrhage , Diagnosis , Meckel Diverticulum , Diagnosis , Pancreas , PathologyABSTRACT
<p><b>OBJECTIVE</b>Essential hypertension (EH) was a complex disease resulted from the interaction of cumulative effect of multiple genetic and environment factors. The relationship between the genetic polymorphisms in the transforming growth factor-beta1 (TGF-beta1), the blood levels and EH have been investigated, but the conclusions were different. Therefore, we investigate the relationship between the tagging single nucleotide polymorphisms (tSNPs) (rs1800469, rs2241716, rs11466345, rs2241715, rs4803455) in TGF-beta1 gene, blood levels and EH in the Han nationality population in Xinjiang, to clarity the pattern of linkage disequilibrium (LD) and the feature of the structure of haplotype.</p><p><b>METHODS</b>Based on the case-control study,we selected 732 (365 EH patients,367 controls) Han Chinese population from the Boertonggu countryside of Shawan region in the Xinjiang Uygur Autonomous Region of China by random cluster sampling. After questionnaire and physical examination, we collected blood samples, and the blood levels of TGF-beta1 were quantified using sandwich ELISA. The polymorphisms of TGF-beta1 gene in the study groups were detected with SNaPshot system. The case-control study in a large group was carried out separately for each of the tSNP and followed up by haplotypes analyses to determine the relation between tSNPs of TGF-beta1 gene and EH in the Han population.</p><p><b>RESULTS</b>(1) The frequencies of alleles A, G of rs11466345 of TGF-beta1 gene in EH group and control group were as follows: 69.7%, 30.3%, 74.4%, 25.6%, respectively. It was demonstrated that the G allele of the rs11466345 polymorphism occurred at a significantly higher frequency in EH patients than in healthy controls (30.3% vs. 25.6%, P < 0.05). The rs11466345G-allele carriers had a significantly increased risk of EH compared to rs11466345A-allele carrier (OR = 1.261; P < 0.05). The frequencies of genotypes and alleles of the other tSNPs of TGF-beta1 gene had no difference between EH patients and controls (P > 0.05). (2)Except the site of rs11466345, the other tSNPs were in strong LD, and no statistical differences were observed in haplotypes distribution in the followup study between case-control groups (P > 0.05). (3) There were no difference of TGF-beta1 levels between the different genotypes and alleles in tSNPs of TGF-beta1 gene (P > 0.05).</p><p><b>CONCLUSIONS</b>(1) These results suggested that TGF-beta1 gene rs11466345 G allele was likely to be a genetic susceptibility factor for EH in the Xinjiang Han population, the other tSNPs perhaps had no association with EH of in the study groups. (2) Except rs11466345, the other tSNPs were in strong LD, and the haplotypes reconstructed by tSNPs might not be associated with EH in the Han nationality populations. (3) There was no association between the tSNP of TGF-beta1 gene and TGF-beta1 blood levels in the Xinjiang Han nationality population.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Alleles , Asian People , Genetics , China , Epidemiology , Gene Frequency , Genotype , Haplotypes , Hypertension , Epidemiology , Genetics , Polymorphism, Single Nucleotide , Risk Factors , Transforming Growth Factor beta1 , Blood , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the association of the transforming growth factor- beta 1 (TGF- beta 1) gene polymorphisms and blood TGF- beta 1 level with essential hypertension (EH) in Kazakh Chinese.</p><p><b>METHODS</b>The polymorphisms of TGF- beta 1 gene in 354 Kazakh EH patients and 435 healthy controls were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. The blood level of TGF- beta 1 was quantified using specific sandwich ELISA.</p><p><b>RESULTS</b>The frequencies of genotypes GG, GC and alleles G and C of +915G/C in Xinjiang Kazakh were 97.9%, 2.1% and 98.77%, 1.23%, respectively. No significantly difference was found between EH patients and controls (P>0.05). The frequencies of genotypes TT, TC, CC and alleles T and C of +869T/C in controls was 25.97%, 46.67%, 27.36%, 49.3% and 50.7%, respectively, the CC genotype or C allele in EH patients had significantly higher frequencies than controls [41.60% vs. 27.36%, and 62.2% vs. 50.7%, respectively (P<0.05)]. It was also shown that TGF- beta 1 +869 C allele carriers had significantly increased risk of EH compared with T allele carriers (OR=1.60, P=0.00). There was linkage disequilibrium (LD) between the two polymorphisms. The frequency of haplotype C-G in the EH group was significantly higher than that in controls (61.6% vs. 49.8%, P<0.05). There were no differences in TGF- beta 1 level among different genotypes or alleles in both +869T/C and +915G/C loci (P>0.05).</p><p><b>CONCLUSION</b>The frequency of +915G/C variation of the TGF- beta 1 gene was very low in Kazakh and there was no homozygous variation. The +869 C allele was likely the genetic susceptibility factor for EH in the population. There was linkage disequilibrium in the polymorphisms of +869T/C and +915G/C. Haplotype C-G was the risk factor of EH.</p>