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Find video protocols related to scientific articles indexed in Pubmed.
Anxiety- and depressive-like behaviors in olfactory deficient Cnga2 knockout mice.
Behav. Brain Res.
PUBLISHED: 09-01-2014
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There is a close neuroanatomical connection between odor and emotional processing. Olfactory dysfunction is found in various neurodegenerative and neuropsychiatric disorders. Here, mice take the cyclic nucleotide gated channel 2 mutant gene (Cnga2), which is critical for olfactory sensory neurons to generate odor induced action potentials were used. The Cnga2 mice were congenitally anosmic. Adult mice were tested in a series behavioral paradigm such as open field, light/dark box, forced swim test and Y-maze. Our study found that Cnga2 mice showed increased anxiety- and depressive-like behaviors than their wide type siblings. However, Cnga2 mice showed no difference from the wide types when tested in the two-trial recognition Y-maze. The results indicate that innate olfactory deficiency might modulate emotional behaviors in mice.
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[Clinical significance of Sokal, Hasford and EUTOS prognostic scoring systems in chronic myeloid leukemia].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 08-26-2014
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To compare the validity of three currently used chronic myeloid leukemia (CML) scoring systems (Sokal CML prognostic scoring system, Hasford prognostic scoring system, and EUTOS prognostic scoring system) in chronic phase CML (CP-CML) patients.
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[Preliminary study of the inhibitory effect and mechanism of B16F10-ESAT-6-gpi/IL-21 vaccine on the pulmonary metastasis in mouse models of melanoma].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 07-04-2014
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To investigate the effect and mechanism of B16F10-ESAT-6-gpi/IL-21 tumor cell vaccine on pulmonary metastasis in mouse model of melanoma.
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Alzheimer's disease and methanol toxicity (part 2): lessons from four rhesus macaques (Macaca mulatta) chronically fed methanol.
J. Alzheimers Dis.
PUBLISHED: 05-03-2014
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A recently established link between formaldehyde, a methanol metabolite, and Alzheimer's disease (AD) pathology has provided a new impetus to investigate the chronic effects of methanol exposure. This paper expands this investigation to the non-human primate, rhesus macaque, through the chronic feeding of young male monkeys with 3% methanol ad libitum. Variable Spatial Delay Response Tasks of the monkeys found that the methanol feeding led to persistent memory decline in the monkeys that lasted 6 months beyond the feeding regimen. This change coincided with increases in tau protein phosphorylation at residues T181 and S396 in cerebrospinal fluid during feeding as well as with increases in tau phosphorylated aggregates and amyloid plaques in four brain regions postmortem: the frontal lobe, parietal lobe, temporal lobe, and the hippocampus. Tau phosphorylation in cerebrospinal fluid was found to be dependent on methanol feeding status, but phosphorylation changes in the brain were found to be persistent 6 months after the methanol feeding stopped. This suggested the methanol feeding caused long-lasting and persistent pathological changes that were related to AD development in the monkey. Most notably, the presence of amyloid plaque formations in the monkeys highlighted a marked difference in animal systems used in AD investigations, suggesting that the innate defenses in mice against methanol toxicity may have limited previous investigations into AD pathology. Nonetheless, these findings support a growing body of evidence that links methanol and its metabolite formaldehyde to AD pathology.
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Alzheimer's disease and methanol toxicity (part 1): chronic methanol feeding led to memory impairments and tau hyperphosphorylation in mice.
J. Alzheimers Dis.
PUBLISHED: 05-03-2014
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Although methanol toxicity is well known for acute neurological sequelae leading to blindness or death, there is a new impetus to investigate the chronic effects of methanol exposure. These include a recently established link between formaldehyde, a methanol metabolite, and Alzheimer's disease (AD) pathology. In the present study, mice were fed with methanol to revisit the chronic effects of methanol toxicity, especially as it pertains to AD progression. Three groups of mice (n = 9) were given either water as a control or a methanol solution (concentrations of 2% or 3.8%) over a 6-week period. The methanol-fed mice were found to have impaired spatial recognition and olfactory memory in Y-maze and olfactory memory paradigms. Immunohistochemical analysis of the mouse brains found increased neuronal tau phosphorylation in the hippocampus and an increased cellular apoptotic marker in hippocampal CA1 neurons (~10% of neurons displayed chromatin condensation) in the methanol-fed groups. Two additional in vitro experiments in mouse embryonic cerebral cortex neurons and mouse neuroblastoma N2a cells found that formaldehyde, but not methanol or the methanol end product formic acid, induced microtubule disintegration and tau protein hyperphosphorylation. The findings of the behavioral tests and immunohistochemical analysis suggested that the methanol-fed mice presented with partial AD-like symptoms. The in vitro experiments suggested that formaldehyde was most likely the detrimental component of methanol toxicity related to hippocampal tau phosphorylation and the subsequent impaired memory in the mice. These findings add to a growing body of evidence that links formaldehyde to AD pathology.
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Synthesis and biological activity of anthrapyrazoles derivatives as potential antitumor agents.
Med Chem
PUBLISHED: 04-04-2014
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We have synthesized a series of anthrapyrazoles derivatives. The biological results indicated that these derivatives exhibited potent in vitro cytotoxicity against different cancer cell lines (human hepatocellular carcinoma HepG2 and BEL-7402, human colonic carcinoma HCT-116 and HT-29) and drug-resistant human hepatoma cell line (SMMC-7721). Among them, the polyamine-based anthrapyrazole derivatives 4c and 4f-g showed superior cytotoxicity than that of Mitoxantrone both on cancer cell lines and the drug-resistant subline. However, the DNA relaxation assay revealed that they had insignificant topoisomerase II inhibition. These results clearly indicate that polyamine side chains will have a profound effect on the cytotoxicity of anthrapyrazoles derivatives.
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Percutaneous Transhepatic Biliary Metal Stent for Malignant Hilar Obstruction: Results and Predictive Factors for Efficacy in 159 Patients from a Single Center.
Cardiovasc Intervent Radiol
PUBLISHED: 04-01-2014
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To investigate and compare the efficacy and safety of percutaneous transhepatic biliary stenting (PTBS) using a one- or two-stage procedure and determine the predictive factors for the efficacious treatment of malignant hilar obstruction (MHO).
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Increased expression of TIGIT on CD4+ T cells ameliorates immune-mediated bone marrow failure of aplastic anemia.
J. Cell. Biochem.
PUBLISHED: 03-08-2014
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Aplastic anemia (AA) is an autoimmune disease in which T cell activation is suspected to play an important role. T cell immunoglobulin and ITIM (immunoreceptor tyrosine-based inhibition motif) domain (TIGIT) is an inhibitory receptor, which exhibits inhibitory functions on the immune response. However, its role in AA has not been clearly determined. In the current study, we showed that the frequency of TIGIT-positive CD4(+) T cells was reduced in the vast majority of AA patients (85%, 17/20). In TIGIT-silenced human CD4(+) T cells, stimulation of agonistic anti-TIGIT monoclonal antibody significantly facilitated cell proliferation, increased production of IL-2 and IFN-?, and inhibited production of IL-10. However, in TIGIT-overexpressed human CD4(+) T cells, cell proliferation and the production of IL-2, IFN-?, and TNF-? were significantly hindered; in contrast, the secretion of IL-10 was improved. RT-PCR and Western blotting showed that T-bet expression in human CD4(+) T cells was significantly decreased by TIGIT overexpression, but only slightly altered by TIGIT knockdown. In mouse models, lentivirus-mediated TIGIT-overexpressed CD4(+) T cell transfer significantly rescued the decreased red blood cell count, attenuated the increase in serum INF-? and TNF-? levels, and lengthened the median survival time. The mRNA levels of CD34, stem cell factor (SCF), and granulocyte/macrophage-colony-stimulating factor (GM-CSF) in bone marrow mononuclear cells were also up-regulated. In conclusion, increased expression of TIGIT could inhibit the function of CD4(+) T cells in vitro and ameliorate immune-mediated bone marrow failure of AA in vivo providing a new potential strategy for the treatment of AA.
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Expression of GRP78 predicts taxane-based therapeutic resistance and recurrence of human gastric cancer.
Exp. Mol. Pathol.
PUBLISHED: 02-19-2014
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Cancer cells adapt to chronic stress in the tumor microenvironment by inducing the expression of glucose-regulated protein 78 (GRP78), a major endoplasmic reticulum chaperone with Ca(2+)-binding and antiapoptotic properties. The effect in and potential role of its expression in progression of and prognosis for gastric cancer (GC) are unclear. In the present study, we investigated the clinical value of GRP78 expression in judgment of the severity of and prognosis for GC in a retrospective cohort study of 160 patients who underwent D2 radical gastrectomy and adjuvant chemotherapy. GRP78 expression was detected using immunohistochemistry. The relationships of GRP78 expression with age, sex, differentiation, invasion depth, disease stage, lymph node metastasis, and time to recurrence (TTR) were analyzed. The GRP78 expression was higher in tumors from patients with deep tumor infiltration, with poor differentiation, at late disease stages, and with lymph node metastasis than that in tumors from patients without. Also, GRP78 positivity was associated with short TTR (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.07-4.85; P=0.041). Subgroup analysis revealed that the HR in the GRP78-high group increased significantly in patients who did not receive taxane-containing regimens (HR, 2.21; 95% CI, 1.23-7.36; P=0.038). In contrast, in the patients who received taxane-based chemotherapy, the association between GRP78 positivity and increased risk of recurrence was not statistically significant (HR, 1.16; 95% CI, 0.81-2.98; P=0.111). In the patients with GRP78 expression, those who underwent taxane-containing chemotherapy had longer median TTRs than did those who did not undergo this treatment (P=0.017). Downregulation of GRP78 expression markedly inhibited proliferation of the GC cells at the G1 phase, whereas GRP78 overexpression promoted cell-cycle progression. These findings suggest that GRP78 overexpression promotes GC cells proliferation and is an independent indicator of poor prognosis for GC.
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Highly potent HCV NS4B inhibitors with activity against multiple genotypes.
J. Med. Chem.
PUBLISHED: 02-18-2014
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The exploration of novel inhibitors of the HCV NS4B protein that are based on a 2-oxadiazoloquinoline scaffold is described. Optimization to incorporate activity across genotypes led to a potent new series with broad activity, of which inhibitor 1 displayed the following EC50 values: 1a, 0.08 nM; 1b, 0.10 nM; 2a, 3 nM; 2b, 0.6 nM, 3a, 3.7 nM; 4a, 0.9 nM; 6a, 3.1 nM.
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Structure-activity relationships of diamine inhibitors of cytochrome P450 (CYP) 3A as novel pharmacoenhancers. Part II: P2/P3 region and discovery of cobicistat (GS-9350).
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-14-2014
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The HIV protease inhibitor (PI) ritonavir (RTV) has been widely used as a pharmacoenhancer for other PIs, which are substrates of cytochrome P450 3A (CYP3A). However the potent anti-HIV activity of ritonavir may limit its use as a pharmacoenhancer with other classes of anti-HIV agents. Ritonavir is also associated with limitations such as poor physicochemical properties. To address these issues a series of compounds with replacements at the P2 and/or P3 region was designed and evaluated as novel CYP3A inhibitors. Through these efforts, a potent and selective inhibitor of CYP3A, GS-9350 (cobicistat) with improved physiochemical properties was discovered.
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A functional MiR-124 binding-site polymorphism in IQGAP1 affects human cognitive performance.
PLoS ONE
PUBLISHED: 01-01-2014
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As a product of the unique evolution of the human brain, human cognitive performance is largely a collection of heritable traits. Rather surprisingly, to date there have been no reported cases to highlight genes that underwent adaptive evolution in humans and which carry polymorphisms that have a marked effect on cognitive performance. IQ motif containing GTPase activating protein 1 (IQGAP1), a scaffold protein, affects learning and memory in a dose-dependent manner. Its expression is regulated by miR-124 through the binding sites in the 3'UTR, where a SNP (rs1042538) exists in the core-binding motif. Here we showed that this SNP can influence the miR-target interaction both in vitro and in vivo. Individuals carrying the derived T alleles have higher IQGAP1 expression in the brain as compared to the ancestral A allele carriers. We observed a significant and male-specific association between rs1042538 and tactile performances in two independent cohorts. Males with the derived allele displayed higher tactual performances as compared to those with the ancestral allele. Furthermore, we found a highly diverged allele-frequency distribution of rs1042538 among world human populations, likely caused by natural selection and/or recent population expansion. These results suggest that current human populations still carry sequence variations that affect cognitive performances and that these genetic variants may likely have been subject to comparatively recent natural selection.
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A new method for piercing the tentorium cerebelli for implanting fragile electrodes into the brain stem in the rhesus monkey (Macaca mulatta).
J. Neurophysiol.
PUBLISHED: 12-11-2013
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Recent developments in neuron recording techniques include the invention of some fragile electrodes. The fragility of these electrodes impedes their successful use in deep brain recordings because it is difficult to penetrate the electrodes through the dura mater, especially the tentorium cerebelli (TC) enclosing the cerebellum and brain stem. This paper reports a new method to pierce the tentorium cerebelli for inserting fragile electrodes into the inferior colliculus of rhesus monkeys. Briefly, a unique tool kit, consisting of needles with sharp tips, a guide tube and an "impactor," was used in a multi-step protocol to pierce the TC. The "impactor" provided a brief force that quickly thrust the needles through the meninges without causing significant damage to the brain tissue under the TC. Using this novel approach, tetrodes were successfully implanted into the inferior colliculus of a rhesus monkey and neuronal discharge signals were recorded. This method, which is simple, convenient and economical, allows neurophysiologists to study the electrophysiological characteristics of deep brain structures under the tentorium cerebelli with advanced, albeit fragile, electrodes.
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Identification of a primary biliary cirrhosis associated protein as lysosome-associated membrane protein-2.
J Proteomics
PUBLISHED: 06-09-2013
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Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown etiology and abnormality of hepatobiliary transport might contribute to its pathogenesis. In this study, we aimed to isolate and identify new molecules associated with PBC. With hepatocyte canalicular membrane vesicles (CMVs) of PBC patients as immunogens, we screened the monoclonal antibody 1F9 (mAb1F9), whose antigen dominantly recognized the subapical domains in hepatocytes in normal livers. Immunohistochemistry revealed that the expression of mAb1F9 antigen (mAb1F9-Ag) significantly increased in PBC livers compared with control groups including normal livers, cirrhosis or cholestasis other than PBC. Interestingly, the augmented expression of mAb1F9-Ag was correlated with the severity of PBC, and ursodeoxycholic acid treatment may significantly improve the recovery of mAb1F9-Ag. In addition, redistribution of mAb1F9-Ag was found in 46% of PBC. mAb1F9-Ag was isolated and analyzed with mass spectrometry, which indicated lysosome-associated membrane protein 2 (LAMP-2) as the candidate. Further studies showed that mAb1F9 recognized LAMP-2 immunoprecipitates and vice verse, mAb1F9 reacted with recombinant LAMP-2. mAb1F9 and LAMP-2 antibody exhibited similar staining pattern and displayed similar subcellular localization. Together, the identity of mAb1F9-Ag is LAMP-2, suggesting that LAMP-2 may assist in the differentiation of PBC and predict a poor outcome in patients with PBC.
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Cognitive impairments in Hashimotos encephalopathy: a case-control study.
PLoS ONE
PUBLISHED: 02-08-2013
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Hashimotos encephalopathy is considered as a treatable dementia, but it is often misdiagnosed. We investigated cognitive impairment and the MRI pathology of Hashimotos encephalopathy patients.
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Effects of morphine on associative memory and locomotor activity in the honeybee (Apis mellifera).
Neurosci Bull
PUBLISHED: 02-06-2013
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Morphine can modulate the processes underlying memory in vertebrates. However, studies have shown various modulations by morphine: positive, negative and even neutral. The honeybee is a potential platform for evaluating the effects of drugs, especially addictive drugs, on the nervous system. However, the involvement of morphine in learning and memory in insects or other invertebrates is poorly understood. The current work evaluated whether morphine affects memory acquisition, consolidation and retrieval in honeybees, using the proboscis extension response (PER) paradigm. We demonstrated that morphine treatment (5 ?g/bee) before training decreased the percentage of correct PERs and the response latency related to aversive rather than rewarding odors when tested after 1 or 24 h. Morphine treatment after training also caused a decrease in this latency when tested after 24 h. Meanwhile, morphine treatment reduced the ambulation distance when tested after 30 min. Our findings suggest that morphine impairs the acquisition of short- and long-term associative memory and slightly disrupts the consolidation of long-term memory in honeybees. These negative effects cannot be explained by reduced locomotion but by impaired memory associated with aversion.
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Whole-brain CT perfusion and CT angiography assessment of Moyamoya disease before and after surgical revascularization: preliminary study with 256-slice CT.
PLoS ONE
PUBLISHED: 01-24-2013
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The 256-slice CT enables the entire brain to be scanned in a single examination. We evaluated the application of 256-slice whole-brain CT perfusion (CTP) in determining graft patency as well as investigating cerebral hemodynamic changes in Moyamoya disease before and after surgical revascularization.
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A retrospective analysis on the diagnostic value of ultrasound-guided percutaneous biopsy for peritoneal lesions.
World J Surg Oncol
PUBLISHED: 01-15-2013
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Routine examinations have a low specificity and a low positive rate for the diagnosis of peritoneal lesions. This study aimed to evaluate the diagnostic value and safety of ultrasound-guided percutaneous peritoneal lesion biopsies in patients with ascites and/or abdominal distension with unclear causes.
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Synthesis, structure-activity relationship and biological activity of acridine derivatives as potent MDR-reversing agents.
Curr. Med. Chem.
PUBLISHED: 01-15-2013
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Multidrug resistance (MDR) mediated by P-glycoprotein is one of the best characterized transporter-mediated barriers to successful cancer chemotherapy. In an attempt to find MDR-reversing agents, a series of novel acridine derivatives were synthesized and evaluated for their in vitro antiproliferative activities against K562 and K562/ADM cells. Some of these compounds showed superior MDR-reversing activities than Amsacrine, the reference compound. Structure-activity relationships (SAR) of these compounds indicated that the N, N-diethylamine moiety had an affect on the in vitro antiproliferative activity. Interestingly, the compounds bearing N, N-diethylamine moiety showed higher growth-inhibitory activity against K562/ADM cells than K562 cells. The high duplex DNA binding affinity and inhibition of topoisomerase of these acridine compounds are maintained which were confirmed by fluorescent quenching and DNA topoisomerase II cleavage assay, respectively. Moreover, several compounds were examined for their ability to increase the accumulation of rhodamine 123 in K562 and K562/ADM cells, and the result suggested that they may be inhibitors for P-glycoprotein. Our study suggested that acridine framework is a potentially interesting scaffold for developing novel MDR-reversing agents.
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Randomized-controlled trials of levetiracetam as an adjunctive therapy in epilepsy of multiple seizure types.
J Clin Neurosci
PUBLISHED: 01-10-2013
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This meta-analysis aimed to systematically collect and synthesize the current evidence regarding the efficacy and tolerability of levetiracetam (LEV) as an adjunctive therapy for adults and children suffering from idiopathic and secondary epilepsy of multiple seizure types. We selected randomized-controlled trials (RCT) of LEV as an adjunctive therapy in epilepsy according to predefined criteria. Outcome measures included a ?50% reduction in seizure frequency, seizure freedom, and adverse events. Thirteen RCT were analyzed. Results showed that the efficacy of adjunctive LEV was superior to placebo both in achieving ?50% reduction in seizure frequency (pooled odds ratio [OR] 3.36, 95% confidence interval [CI] 2.78-4.07, Z=12.46; p<0.00001) and seizure freedom (pooled OR 4.72, 95% CI 2.96-7.54, Z=6.50; p<0.00001). The heterogeneity was mild (chi-squared=12.28, I(2)=2% in ?50% reduction in seizure frequency, and chi-squared=0.49, I(2)=0% in seizure freedom). Subgroup analysis suggested similar effects across different dosages in adults. The incidence of adverse reactions was not significantly different between the LEV group and the placebo group. The adverse events of relatively high incidence in the LEV group included somnolence, agitation, dizziness, asthenia, and infection. Incidence of serious adverse reaction such as rash and white blood cells and platelets decreasing was quite low. Adjunctive therapy with LEV was superior to placebo in reducing the frequency of seizures in patients with partial and idiopathic generalized epilepsy with effect in both adults and children, and demonstrated good tolerance in patients with epilepsy.
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Transjugular intrahepatic portosystemic shunt for the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis: study protocol for a randomised controlled trial.
BMJ Open
PUBLISHED: 01-01-2013
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Portal vein thrombosis (PVT) increases the risk of variceal rebleeding in liver cirrhosis. However, the strategy for preventing variceal rebleeding in cirrhotic patients with PVT has not been explored. This study aims to evaluate whether the transjugular intrahepatic portosystemic shunt (TIPS) or conventional therapy is preferable for the prevention of variceal rebleeding in liver cirrhosis patients with PVT.
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The powerful applications of polyunsaturated fatty acids in improving the therapeutic efficacy of anticancer drugs.
Expert Opin Drug Deliv
PUBLISHED: 12-16-2011
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Tumor-targeting delivery of drugs has received much attention in the field of drug development. Traditional antitumor agents are often nonspecific for tumor cells; therefore, tumor-targeting drug-delivery design is a promising approach to improve the therapeutic efficacy of chemotherapy. Polyunsaturated fatty acids (PUFAs), such as linoleic acid, ?-linolenic acid, arachidonic acid and docosahexaenoic acid, are naturally occurring essential substances which play important roles in cell growth. Due to their lipophilic nature, PUFAs are readily incorporated into the lipid bilayer of cells, especially tumor cells. Therefore, PUFAs can be used as an applicable carrier to increase the therapeutic efficacy of anticancer drugs. In this review, several PUFA-drug conjugates with potent antitumor activities are summarized, and the bright prospects of PUFAs in drug development are also proposed. A general design strategy of PUFA-drug conjugates is provided, as well as a discussion of the recent progress in PUFA-drug conjugates and preclinical therapies. The tumor growth-related PUFAs are expected to play an important role in the development of more efficacious antitumor agents.
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[Effects of different compatibility proportion of jiaotai pills on treating type 2 diabetes mellitus in rats].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 11-22-2011
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To study the effects of different compatibility proportion of Jiaotai pills on treating type 2 diabetes mellitus (T2DM) in rats.
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Maternal separation produces lasting changes in cortisol and behavior in rhesus monkeys.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-15-2011
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Maternal separation (MS), which can lead to hypothalamic pituitary adrenal axis dysfunction and behavioral abnormalities in rhesus monkeys, is frequently used to model early adversity. Whether this deleterious effect on monkeys is reversible by later experience is unknown. In this study, we assessed the basal hair cortisol in rhesus monkeys after 1.5 and 3 y of normal social life following an early separation. These results showed that peer-reared monkeys had significantly lower basal hair cortisol levels than the mother-reared monkeys at both years examined. The plasma cortisol was assessed in the monkeys after 1.5 y of normal social life, and the results indicated that the peak in the peer-reared cortisol response to acute stressors was substantially delayed. In addition, after 3 y of normal social life, abnormal behavioral patterns were identified in the peer-reared monkeys. They showed decreases in locomotion and initiated sitting together, as well as increases in stereotypical behaviors compared with the mother-reared monkeys. These results demonstrate that the deleterious effects of MS on rhesus monkeys cannot be compensated by a later normal social life, suggesting that the effects of MS are long-lasting and that the maternal-separated rhesus monkeys are a good animal model to study early adversity and to investigate the development of psychiatric disorders induced by exposure to early adversity.
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Transjugular intrahepatic portosystemic shunt for portal cavernoma with symptomatic portal hypertension in non-cirrhotic patients.
Dig. Dis. Sci.
PUBLISHED: 06-08-2011
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Portal cavernoma is regarded as a contraindication to transjugular intrahepatic portosystemic shunt (TIPS).
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Correlation between osteopontin messenger RNA expression and microcalcification shown on sonography in papillary thyroid carcinoma.
J Ultrasound Med
PUBLISHED: 06-03-2011
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The aims of this study were to investigate the correlation between osteopontin expression and microcalcification seen on sonograms of human papillary thyroid carcinoma and to explore the mechanism of microcalcification in these tumors.
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Genistein reverses free fatty acid-induced insulin resistance in HepG2 hepatocytes through targeting JNK.
J. Huazhong Univ. Sci. Technol. Med. Sci.
PUBLISHED: 04-20-2011
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This study investigated the effects and molecular mechanisms of genistein in improving insulin resistance induced by free fatty acids (FFAs) in HepG2 hepatocytes. A model of insulin resistance in HepG2 cells was established by adding palmitic acid (0.5 mmol/L) to the culture medium and the cells were treated by genistein. Glucose consumption of HepG2 cells was determined by glucose oxidase method. The levels of c-jun N-terminal kinase (JNK) phosphorylation, insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation, JNK, IRS-1, phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 1 (GLUT1) proteins were detected by Western blotting. The results showed that after the treatment with palmitic acid for 24 h, the insulin-stimulated glucose transport in HepG2 cells was inhibited, and the glucose consumption was substantially reduced. Meanwhile, the expressions of IRS-1, PI-3K p85 protein and GLUT1 were obviously reduced, while the levels of JNK phosphorylation and IRS-1 Ser307 phosphorylation and the expression of JNK protein were significantly increased, as compared with cells of normal control. However, the aforementioned indices, which indicated the existence of insulin resistance, were reversed by genistein at 1-4 ?mol/L in a dose-dependent manner. It was concluded that insulin resistance induced by FFAs in HepG2 hepatocytes could be improved by genistein. Genistein might reverse FFAs-induced insulin resistance in HepG2 cells by targeting JNK.
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Dissociable modulation of overt visual attention in valence and arousal revealed by topology of scan path.
PLoS ONE
PUBLISHED: 03-01-2011
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Emotional stimuli have evolutionary significance for the survival of organisms; therefore, they are attention-grabbing and are processed preferentially. The neural underpinnings of two principle emotional dimensions in affective space, valence (degree of pleasantness) and arousal (intensity of evoked emotion), have been shown to be dissociable in the olfactory, gustatory and memory systems. However, the separable roles of valence and arousal in scene perception are poorly understood. In this study, we asked how these two emotional dimensions modulate overt visual attention. Twenty-two healthy volunteers freely viewed images from the International Affective Picture System (IAPS) that were graded for affective levels of valence and arousal (high, medium, and low). Subjects heads were immobilized and eye movements were recorded by camera to track overt shifts of visual attention. Algebraic graph-based approaches were introduced to model scan paths as weighted undirected path graphs, generating global topology metrics that characterize the algebraic connectivity of scan paths. Our data suggest that human subjects show different scanning patterns to stimuli with different affective ratings. Valence salient stimuli (with neutral arousal) elicited faster and larger shifts of attention, while arousal salient stimuli (with neutral valence) elicited local scanning, dense attention allocation and deep processing. Furthermore, our model revealed that the modulatory effect of valence was linearly related to the valence level, whereas the relation between the modulatory effect and the level of arousal was nonlinear. Hence, visual attention seems to be modulated by mechanisms that are separate for valence and arousal.
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Cognitive impairment in mild general paresis of the insane: AD-like pattern.
Dement Geriatr Cogn Disord
PUBLISHED: 02-22-2011
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We investigated the clinical and cognitive features of patients with mild general paresis of the insane (GPI) in comparison to Alzheimers disease (AD) patients, mild frontotemporal dementia (FTD) patients and normal elderly individuals.
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Effect of morphine on conditioned place preference in rhesus monkeys.
Addict Biol
PUBLISHED: 02-11-2011
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In rodents, a conditioned place preference (CPP) can be induced by morphine. In the current study, we designed a biased place conditioning paradigm to test the rewarding effects of morphine in freely moving rhesus monkeys. Five monkeys were first placed in three serial rooms with the doors open between them for three days. After this habituation period, during which baseline preference for each of the two end rooms was measured, CPP conditioning occurred when the monkeys were injected intramuscularly with morphine at an increasing dose (1.5, 3, 4.5 mg/kg) before they entered the non-preferred room and on alternate days, with saline before they entered the preferred room. Morphine and saline treatment lasted for six days, respectively. CPP was tested 24 hours after the end of CPP training. The result showed that in all five monkeys, CPP was induced by the morphine treatment. The preference lasted for at least 15.3 ± 1.7 months.
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Effects of beta-adrenergic antagonist, propranolol on spatial memory and exploratory behavior in mice.
Neurosci. Lett.
PUBLISHED: 01-21-2011
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The beta-adrenergic system has been suggested to be involved in novelty detection and memory modulation. The present study aimed to investigate the role of beta-adrenergic receptors on novelty-based spatial recognition memory and exploratory behavior in mice using Y-maze test and open-field respectively. Mice were injected with three doses of beta-adrenergic receptor antagonist, propranolol (2, 10 and 20 mg/kg) or saline at three different time points (15 min prior to training, immediately after training and 15 min before test). The results showed that higher doses of propranolol (10 and 20 mg/kg) given before the training trial impaired spatial recognition memory while those injected at other two time points did not. A detailed analysis of exploratory behavior in open-field showed that lower dose (2 mg/kg) of propranolol reduced exploratory behavior of mice. Our findings indicate that higher dose of propranolol can impair acquisition of spatial information in the Y-maze without altering locomotion, suggesting that the beta-adrenergic system may be involved in modulating memory processes at the time of learning.
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Distinguishing crystallographic misorientations of lanthanum zirconate epilayers on nickel substrates by electron backscatter diffraction.
Ultramicroscopy
PUBLISHED: 01-07-2011
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Electron backscatter diffraction (EBSD) was used for distinguishing crystallographic orientations and local lattice misfits of a La(2)Zr(2)O(7) (LZO) buffer layer epitaxially grown on a cube textured Ni-5.%W (Ni-W) substrate for a YBCO superconductor film. Orientation data were obtained from the LZO epilayer using low energy primary electrons (5keV) and from the Ni-W substrate by increasing the voltage to 15keV. In-plane and out-of-plane orientations of the LZO epilayer were revealed with respect to its Ni-W substrate. A strong {100} ?011? rotated-cube texture in the LZO epilayer was formed on the {100} ?001? cube-textured Ni-W substrates. LZO and Ni in-plane crystallographic axes are related by an expected 45° rotation. The step-misorientations and the local misfit strains between the LZO epilayer and the substrate were also analyzed.
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Synthesis and bioevaluation of aryl-guanidino polyamine conjugates targeting the polyamine transporter.
Bioorg. Med. Chem. Lett.
PUBLISHED: 08-10-2010
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Aryl-guanidino polyamine conjugates were prepared to evaluate their recognition for polyamine transporter (PAT) via a-difluoromethylornithine (DFMO) and spermidine (SPD)-treated B16 cell lines. The potent synergistic effects of DFMO on guanidino polyamine conjugates indicated that the presence of DFMO strongly facilitates the transport of conjugates into cells via PAT on cell membrane. The apoptotic mechanisms of triamine conjugates 10 and 1 (with and without guanidine groups) revealed that they induced apoptosis of Hela cells through the mitochondrial pathway associated with lysosomes, while DFMO strongly synergizes the function of 10 without changing the apoptotic route. Taken together, guanidino polyamine conjugates can target PAT for transport as normal polyamine ones, and the presence of guanidine in the polyamine vectors does not seem to alter the cellular targets of the conjugates, which may depend mainly on the pharmacophore.
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Antitumor conjugates with polyamine vectors and their molecular mechanisms.
Expert Opin Drug Deliv
PUBLISHED: 07-20-2010
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A polyamine conjugate is a special polyamine derivative composed of polyamine vectors appended directly or by a linker to a cargo with specific biological functions. In recent years, extensive researches have emphasized the fact that polyamine conjugates acting as promising antitumor candidates are becoming increasingly important in the polyamine field.
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A new MRI approach for accurately implanting microelectrodes into deep brain structures of the rhesus monkey (Macaca mulatta).
J. Neurosci. Methods
PUBLISHED: 04-21-2010
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The accurate implantation of microelectrodes is a significant difficulty facing many neurophysiologists. This paper reports on a new method used to promote the precise positioning of electrode implantation through magnetic resonance imaging (MRI), allowing both the relevant brain structure and the MRI-visible external markers anchored on the skull (in this case rigid glass tubes with a 0.5mm internal diameter) to be displayed. By referencing these markers, the coordinates of the brain target were calculated. Using this novel approach, recording electrodes were successfully implanted into the superior colliculus (SC) of rhesus monkeys, with an error <1mm, and its neuronal discharge signals were obtained. This new method allows neurophysiologists to precisely target the small deep brain structures of monkeys and study their electrophysiological characteristics in detail.
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Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with symptomatic portal hypertension in liver cirrhosis.
J. Hepatol.
PUBLISHED: 03-31-2010
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Data on the management of portal vein thrombosis (PVT) in patients with decompensated cirrhosis are extremely limited, particularly in the cases of the transjugular intrahepatic portosystemic shunt (TIPS). We assessed the outcome of TIPS for PVT in patients with cirrhosis and symptomatic portal hypertension and determined the predictors of technical success and survival.
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Chronic morphine treatment decreases acoustic startle response and prepulse inhibition in rats.
Sci China Life Sci
PUBLISHED: 02-03-2010
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The reward-related effects of addictive drugs primarily act via the dopamine system, which also plays an important role in sensorimotor gating. The mesolimbic dopamine system is the common pathway of drug addiction and sensorimotor gating. However, the way in which addictive drugs affect sensorimotor gating is currently unclear. In previous studies, we examined the effects of morphine treatment on sensory gating in the hippocampus. The present study investigated the effects of morphine on sensorimotor gating in rats during chronic morphine treatment and withdrawal. Rats were examined during treatment with morphine for 10 successive days, followed by a withdrawal period. Acoustic startle responses to a single startle stimulus (115 dB SPL) and prepulse inhibition responses were recorded. The results showed that acoustic startle responses were attenuated during morphine treatment, but not during withdrawal. PPI was impaired in the last 2 morphine treatment days, but returned to a normal level during withdrawal.
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N1-Alkyl pyrimidinediones as non-nucleoside inhibitors of HIV-1 reverse transcriptase.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-11-2010
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A series of N1-alkyl pyrimidinediones were designed, synthesized and evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Our efforts identified compound 10b, which represents the lead compound in this series with pharmacokinetics and antiviral potency that may support once-daily dosing.
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N1-Heterocyclic pyrimidinediones as non-nucleoside inhibitors of HIV-1 reverse transcriptase.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-11-2010
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A series of N1-heterocyclic pyrimidinediones were extensively evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Inhibitor 1 is active against NNRTI-resistant viruses including RT mutant K103N. The co-crystal structure of inhibitor 1 with HIV-1 RT revealed that H-bonds are formed with K101 and K103. Efforts to improve the suboptimal pharmacokinetic profile of 1 resulted in the discovery of compound 13, which represents the lead compound in this series with improved pharmacokinetics and similar potency as inhibitor 1.
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Environmental enrichment and chronic restraint stress in ICR mice: effects on prepulse inhibition of startle and Y-maze spatial recognition memory.
Behav. Brain Res.
PUBLISHED: 01-04-2010
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In most studies regarding the improving or therapeutical effects induced by enriched environment (EE), EE was performed after the stress treatment or in patients with certain diseases. In the current study, the effects of chronic restraint stress (6h/day) in mice living in an enriched environment or standard environment (SE) were tested. Mice were randomly divided into 4 groups: non-stressed or stressed mice housed in SE or EE conditions (SE, stress+SE, EE, stress+EE). Prepulse inhibition (PPI) of startle was tested after the 2 weeks or 4 weeks stress and/or EE treatment and 1 or 2 weeks withdrawal from the 4 weeks treatment. After the 4 weeks treatment, spatial recognition memory in Y-maze was also tested. The results showed that EE increased PPI in stressed and non-stressed mice after 2 weeks treatment. No effect of EE on PPI was found after the 4 weeks treatment. 4 weeks chronic restraint stress increased PPI in mice housed in standard but not EE conditions. Stressed mice showed deficits on the 1h delay version of the Y-maze which could be prevented by living in an enriched environment. Our results indicated that living in an enriched environment reversed the impairing effects of chronic restraint stress on spatial recognition memory. However, EE did not change the effects of stress on PPI.
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Function of PrPC (1-OPRD) in biological activities of gastric cancer cell lines.
J. Cell. Mol. Med.
PUBLISHED: 02-04-2009
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Approximately 10-15% of the human prion disease is inherited and one of the important genetic mutations occurs in the octapeptide repeat region of prion protein gene. One of the variants, one octapeptide repeat deletion (1-OPRD), existed in several gastric cancer cell lines and its mutation frequency was higher in gastric cancer cases. However, the biological functions of it remain unknown. Wild-type and mutation forms of PrP(C) were cloned and transfected into gastric cancer cells. Cell apoptosis, adhesion, invasion, multidrug resistance (MDR) and proliferation were, respectively, investigated. Different expressed genes were screened by gene array and proved by PT-PCR. Further, luciferase report assay was used to explore the transcriptional activation of target genes. Forced overexpression PrP(C) (1-OPRD) could promote the gastric cancer cells SGC7901 growth through facilitating G1- to S-phase transition in the cell cycle. PrP(C) (1-OPRD) could also inhibit apoptosis, and promote adhesion, invasion and MDR in SGC7901. However, it exhibited no significant difference between wild-type PrP(C) (1-OPRD) and PrP(C) on apoptosis, invasion or MDR effects. Further experiments indicated that PrP(C) (1-OPRD) could trigger the transactivation of cyclinD3 besides cyclinD1 to promote cell transition and proliferation. Overexpression of PrP(C) (1-OPRD) might promote the proliferation of gastric cancer cells at least partially through transcriptional activation of cyclinD3 to accelerate the G1-/S-phase transition. The promoting proliferation effect of PrP(C) (1-OPRD) was more than that of wild-type PrP(C). However, they showed no difference on apoptosis, adhesion, invasion or MDR effects of gastric cancer cells.
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Inhibition of PI3K/Akt partially leads to the inhibition of PrP(C)-induced drug resistance in gastric cancer cells.
FEBS J.
PUBLISHED: 01-16-2009
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Cellular prion protein (PrP(C)), a glycosyl-phosphatidylinositol-anchored membrane protein with unclear physiological function, was previous found to be upregulated in adriamycin (ADR)-resistant gastric carcinoma cell line SGC7901/ADR compared to its parental cell line SGC7901. Overexpression of PrP(C) in gastric cancer has certain effects on drug accumulation through upregulation of P-glycoprotein (P-gp), which is suggested to play an important role in determining the sensitivity of tumor cells to chemotherapy and is linked to activation of the phosphatidylinositol-3-kinase/Akt (PI3K/Akt) pathway. In the present study, we further investigate the role of the PI3K/Akt pathway in PrP(C)-induced multidrug-resistance (MDR) in gastric cancer. Immunohistochemistry and confocal microscope detection suggest a positive correlation between PrP(C) and phosphorylated Akt (p-Akt) expression in gastric cancer. Using established stable PrP(C) transfectant cell lines, we demonstrated that the level of p-Akt was increased in PrP(C)-transfected cells. Inhibition of PrP(C) expression by RNA interference resulted in decreased p-Akt expression. Inhibition of the PI3K/Akt pathway by one of its specific inhibitors, LY294002, or by Akt small interfering RNA (siRNA) resulted in decreased multidrug resistance of SGC7901 cells, partly through downregulation of P-gp induced by PrP(C). Taken together, our results suggest that PrP(C)-induced MDR in gastric cancer is associated with activation of the PI3K/Akt pathway. Inhibition of PI3K/Akt by LY2940002 or Akt siRNA leads to inhibition of PrP(C)-induced drug resistance and P-gp upregulation in gastric cancer cells, indicating a possible novel mechanism by which PrP(C) regulates gastric cancer cell survival.
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[Study on the compatibility optimization of categorized formulas of Chinese medicine based on support vector regression].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
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Prediction on pharmacodynamic action of categorized formulas is presented with the theory of support vector regression (SVR) in this paper. A prediction model of pharmacodynamic action of categorized formulas based on SVR was set up in order to predict the law of the compatibility of the categorized formulas. Pharmacodynamic action of various categorized formulas could be predicted based on this model. It is very significient to optimize the compatibility of categorized formulas and clinical practice. This model was applied to the research of the law of compatibility in three categorized formulas for tonifying kidney yang which contains shenqi pill, yougui pill and yougui drink. As indicated in the model prediction, pharmacodynamic actions of several compatibilities of the categorized formulas are superior to that of the three original formulas for tonifying kidney yang.
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Epigenetic considerations and the clinical reevaluation of the overlap syndrome between primary biliary cirrhosis and autoimmune hepatitis.
J. Autoimmun.
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Epigenetic changes are of crucial importance in the etiopathogenesis of autoimmune liver diseases. Among these, there is limited agreement on the definitions and treatment of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) overlap syndromes, we evaluated a large series of consecutive patients with PBC (n = 565) and AIH (n = 196) to identify a group of patients with corticosteroid-responsive PBC-AIH overlap syndrome. Within this series, a total of 490 patients were biopsied based upon staging or diagnostic needs. Review of the biopsies in conjunction with the International AIH Group criteria identified 80 patients with suspected overlap syndrome and 52 patients agreed to participate in the study and were prospectively treated with corticosteroids. Of these, 40/52 (77%) achieved a complete biochemical response (i.e. normal ALT, AST, and IgG) within 12 months of treatment. A survey of pre-treatment characteristics of the 40 responders revealed more severe interface hepatitis. Serum IgG levels ?1.3x the upper limit of normal had 60% sensitivity and 97% specificity rates for steroid-responsiveness while the use of a higher threshold (?2.0x) reduced sensitivity to 10%. When the Paris criteria for PBC-AIH were applied to the steroid-responsive patients, 29/40 (73%) cases fulfilled at least two of the three Paris criteria. Applying the recently designed simplified IAIHG scoring system, 35/40 (88%) had a "definite" diagnosis of AIH. This study supports the hypothesis that a complete response to corticosteroids may denote a variant of a PBC-AIH overlap syndrome which could be identified prior to treatment by modified Paris criteria in concert with the simplified IAIHG scoring system.
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Observation on therapeutic efficacy of ursodeoxycholic acid in Chinese patients with primary biliary cirrhosis: a 2-year follow-up study.
Front Med
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The efficacy of ursodeoxycholic acid (UDCA) on long-term outcome of primary biliary cirrhosis (PBC) has been less documented in Chinese cohort. We aimed to assess the therapeutic effect of UDCA on Chinese patients with PBC. In the present study, 67 patients with PBC were treated with UDCA (13-15 mg·kg(-1)·day(-1)) and followed up for 2 years to evaluate the changes of symptoms, laboratory values and histological features. As the results indicated, fatigue and pruritus were obviously improved by UDCA, particularly in patients with mild or moderate symptoms. The alkaline phosphatase and ?-glutamyl transpetidase levels significantly declined at year 2 comparing to baseline values, with the most profound effects achieved in patients at stage 2. The levels of alanine aminotransferase and aspartate aminotransferase significantly decreased whereas serum bilirubin and immunoglobulin M levels exhibited no significant change. Histological feature was stable in patients at stages 1-2 but still progressed in patients at stages 3-4. The biochemical response of patients at stage 2 was much better than that of patients at stages 3-4. These data suggest that, when treated in earlier stage, patients in long-term administration of UDCA can gain favorable results not only on symptoms and biochemical responses but also on histology. It is also indicated that later histological stage, bad biochemical response and severe symptom may be indicators of poor prognosis for UDCA therapy.
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[The influence of methacryloxy propyl trimethoxyl silane on shear bond strength of three kinds metal and Filtek resin].
Hua Xi Kou Qiang Yi Xue Za Zhi
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To study the influence of three different metal alloy surfaces treated with primer methacryloxy propyl trimethoxyl silane (gamma-MPS) coupling agent on the bond strength of Filtek Z350 resin.
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Percutaneous recanalization for Budd-Chiari syndrome: an 11-year retrospective study on patency and survival in 177 Chinese patients from a single center.
Radiology
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To evaluate the long-term outcomes of percutaneous recanalization and determine the predictors of patency and survival in a large case series of Chinese patients with Budd-Chiari syndrome (BCS).
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[Effect of gallnut extract on nasopharyngeal carcinoma 5-8F cells and its mechanism].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
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To determine the biological activity of ellagic acid extracted from gallnut against nasopharyngeal carcinoma and its molecular mechanism.
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Synthesis, cytotoxicity, and cell death profile of polyaminoanthraquinones as antitumor agents.
Chem Biol Drug Des
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Investigation on designed polyaminoanthraquinones revealed that the anthraquinones bearing triamine motifs are generally more potent than their counterparts with diamine or tetramine motifs. Compared with the reference drug mitoxantrone (MTX), 9b and 9c exhibited better inhibitory activity on cancerous HepG2 cells and preferable cell selectivity in the further screen of normal QSG7701 cells, although they were not assimilated by cancer cells via the polyamine transporter. The presence of polyamine motifs elevated the interaction of compounds 9b and 9c with lysosomes and resulted in distinct mode of cell death. 9c and MTX could cause caspases-dependent HepG2 cell apoptotic death involving in mitochondrial membrane potential (MMP) loss, cytochrome c release, and caspase-3 activation. However, 9b, which contained only one less methylene group in the polyamine tail, produced cytotoxicity by necrosis. In conclusion, the modification of anthraquinones with polyamines may furnish potent anticancer drug candidates against hepatocellular carcinoma undergoing distinct cell death mechanisms.
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Transjugular intrahepatic portosystemic shunt may be superior to conservative therapy for variceal rebleeding in cirrhotic patients with non-tumoral portal vein thrombosis: a hypothesis.
Med. Sci. Monit.
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The presence of occlusive portal vein thrombosis (PVT) greatly changes the natural history of liver cirrhosis, because it not only significantly increases the incidence of variceal rebleeding but also negatively influences the survival. However, due to the absence of strong evidence, no standard treatment algorithm for the secondary prophylaxis of variceal bleeding in cirrhotic patients with non-tumoral PVT has been established. Previous randomized controlled trials have demonstrated that transjugular intrahepatic portosystemic shunt (TIPS) can significantly decrease the incidence of variceal rebleeding in cirrhotic patients without PVT, compared with conservative therapy (i.e., endoscopic plus pharmacological therapy). Further, several large cohort studies have confirmed that TIPS can effectively prevent variceal rebleeding in cirrhotic patients with non-tumoral PVT. On the other hand, TIPS can facilitate recanalizing the thrombosed portal vein by endovascular manipulations, even in the presence of cavernous transformation of the portal vein (CTPV). More importantly, successful TIPS insertions can maintain the persistent portal vein patency, and avoid thrombus extension into the portal venous system. By comparison, anticoagulation therapy can achieve portal vein recanalization only in patients with partial PVT, but not in those with occlusive PVT or CTPV, and the use of anticoagulants may aggravate the risk of variceal bleeding in cirrhotic patients with a history of variceal bleeding. Collectively, we hypothesize that TIPS may be superior to conservative therapy for the prevention of variceal rebleeding in cirrhotic patients with non-tumoral PVT. Randomized controlled trials should be conducted to evaluate the survival benefit of TIPS in these patients.
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Interactive effects of morphine and scopolamine, MK-801, propanolol on spatial working memory in rhesus monkeys.
Neurosci. Lett.
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Opiate, cholinergic, glutamatergic and beta-adrenergic neurotransmitters play key roles in learning and memory in humans and animals. Dysfunction of the interactions between these neurotransmitters may induce human diseases. In the present study, the interactions of morphine and acetylcholine (ACh), NMDA, and beta-adrenergic receptor antagonist (scopolamine, MK-801, and propanolol) were evaluated in a single-blind design by co-administrations of morphine and these drugs in a delayed response in rhesus monkeys. The results indicated that: (1) Co-administration of morphine and scopolamine deteriorated spatial working memory. (2) Co-treatment of morphine and MK-801 restored impairment caused by morphine and MK-801 in a dose-depending pattern. (3) Morphine plus propranolol impaired spatial working memory. High dose of morphine (0.01 mg/kg) reversed impaired spatial working memory induced by single propranolol and morphine treatment. These data suggested that the interactions of morphine and AChergic, NMDAergic and beta-adrenergic compounds were involved in spatial working memory in rhesus monkeys.
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[Decision rules model for studying the law of compatibility of categorized formula based on rough set].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
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The theory of rough set was applied to the law of compatibility of categorized formulas research, and the decision rules model of the law of compatibility of categorized formulas was set up in order to explore the correlation between the compatibility of the categorized formula and the syndrome indexes. Based on this model, the core herbs of categorized formula were obtained through attribute reduction, the interaction of each herb in categorized formula could be analyzed by the effective decision rules, and the efficacy of the categorized formula could be predicted by decision rules. It would be very significant to optimize the compatibility of categorized formula and guide the clinical-practice.
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Synthesis and Preliminary Biological Evaluation of Polyamine-aniline Acridines as P-glycoprotein Inhibitors.
Med Chem
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We have synthesized a series of polyamine-based anilinoacridine derivatives. The preliminary biological evaluation indicated that the 9-anilinoacridine-polyamine derivatives had low or insignificant in vitro cytotoxicity against K562 cell line and K562/ADM, the drug-resistant cell line. However, the evaluation for P-gp modulation showed that they held potent P-gp inhibitory ability. Among them, the effect of compound 7c on P-gp was even greater than that of Verapamil, the known P-gp modulator. The results suggest that 9-anilinoacridine-polyamine derivatives can be employed as effective P-gp modulators.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.