ABSTRACT
A hyperspectral imaging system (HIS) is a helpful tool that acquires spatial and spectral information from a target. This study developed a coaxial heterogeneous HIS (CHHIS) to collect spectral images with wavelengths ranging from 400 to 1700 nm. In this system, a visible (VIS) spectrometer and a short-wave infrared (SWIR) spectrometer are combined with a coaxial optical path to share the same field of view. This structure reduces the complexity of spatial registration and maintains the scanning duration of two spectrometers as that of a single spectrometer. The spectrometers are also replaceable for extending the detecting spectral range of the system. The calibration methodologies, including spatial correction, spectral calibration, and reflectance calibration, were developed for this system. The signal-to-noise ratio of VIS and SWIR spectrometers in the CHHIS was up to 40 and 60 dB when the exposure time of the VIS and SWIR imaging sensors was 1000 and 10 ms, respectively. When the target distance was at 600 mm, the spatial error of VIS and SWIR images in the scanning direction was less than 1 pixel; these results proved that the system was stable.
Subject(s)
Diagnostic Imaging , Hyperspectral Imaging , CalibrationABSTRACT
OBJECTIVE: To investigate the effects of long non-coding ribonucleic acid (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on the high glucose-induced proliferation, apoptosis, migration and angiogenesis of endothelial cells and its potential mechanism. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were divided into 3 groups, including control group (medium with 5.5 mmol/L glucose), high glucose group (HG group, medium with 33.5 mmol/L glucose) and lncRNA MALAT1 knockdown group [HG + MALAT1 small interfering RNA (siRNA) group, medium with 33.5 mmol/L glucose]. Cell Counting Kit-8 (CCK-8) assay was performed to observe the proliferation of HUVECs in each group at different time points. Meanwhile, the wound-healing assay was applied to detect the migratory ability of HUVECs in each group at 0 h and 24 h. The apoptosis rate of each group of cells was measured by means of flow cytometry, and the expression of Bcl-2-associated X protein (Bax) was detected via immunofluorescence at the same time. In addition, the amount of neovascularization in each group of cells was observed through the tube formation assay. Finally, Western blotting was utilized to determine the expression level of proteins in phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in each group of cells. RESULTS: Compared with that in the control group, the expression level of lncRNA MALAT1 in the HG group was elevated markedly (p<0.05). The proliferative capacity of HUVECs in the HG group was increased notably after knocking down lncRNA MALAT1 with siRNA (p<0.05). According to wound-healing assay, the knockdown of lncRNA MALAT1 could prominently reverse the declined HUVECs migratory ability induced by high glucose (p<0.05). Flow cytometry results manifested that the apoptosis level of HUVECs in the HG group was increased markedly, but inhibition on lncRNA MALAT1 could lower the apoptosis level evidently (p<0.05). The results of immunofluorescence showed that the expression of Bax in the HG + MALAT1 siRNA group was remarkably lower than that in the HG group (p<0.05). It was revealed in Western blotting that the knockdown of lncRNA MALAT1 could reverse the inhibition of high glucose on the PI3K/Akt signaling pathway in HUVECs (p<0.05). CONCLUSIONS: Inhibiting lncRNA MALAT1 can promote endothelial cell proliferation, migration and angiogenesis and repress endothelial cell apoptosis simultaneously, whose mechanism may be related to the activation of the PI3K/Akt signaling pathway.
Subject(s)
Apoptosis/drug effects , Glucose/pharmacology , Neovascularization, Pathologic/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Long Noncoding/metabolism , Cell Movement/drug effects , Cell Proliferation/drug effects , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Neovascularization, Pathologic/pathology , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , RNA, Long Noncoding/antagonists & inhibitors , RNA, Long Noncoding/genetics , RNA, Small Interfering/pharmacology , Signal Transduction/drug effectsABSTRACT
Objective: To evaluate the preliminary efficacy and safety of penetrating canaloplasty for treating primary angle-closure glaucoma (PACG). Methods: It is a prospective interventional case series study. Twenty-two patients (24 eyes) with PACG were treated with penetrating canaloplasty (video attached) at the Eye Hospital of Wenzhou Medical University from June 2015 to August 2018. This modified canaloplasty was performed by making a window at the corneal-scleral bed. Aqueous was redirected to the opening of Schlemm's canal after the canaloplasty with intension sutures. Postoperative follow-up was made at 1 day, 7 days, 1 month, 3 months, and 6 months. Surgical success was defined as intraocular pressure (IOP) ≤ 21 mmHg (1 mmHg=0.133 kPa) with glaucoma medication (quantified success) and without any glaucoma medication (complete success). Main outcome measures included IOP, number of medication, surgical success rate, complications, and filtering bleb status. One-way repeated measure ANOVA and rank sum test were used in statistical analysis. Results: Due to the failure of circumferential catheterization of the canal, 4 eyes converted to trabeculectomy. A total of 19 PACG patients (20 eyes) achieved the successful 360-degree catheterization of the canal, including 11 males and 8 females. The mean age was (54±7) years old (range: 41-65 years old), and the mean angle-closure range was (326.3±46.6) degrees. The mean preoperative IOP was (38.0±11.9) mmHg with the median medication number of 3 (range: 2-5). The mean postoperative IOP was (14.5±11.1), (16.1±6.0), (17.7±5.5), (15.7±5.0), and (15.4±3.7) mmHg at 1 day, 7 days, 1 month, 3 months, and 6 months, respectively. There was significant difference in IOP between postoperative and preoperative (all P<0.01). The median medication number (range) was 0 (0-3), 0 (0-2), 0(0-3), 0(0-2), and 0 (0-2) at the 5 time points, respectively. There was significant difference in medication number between postoperative and preoperative (all P<0.01). The quantified success rate was 95%(19/20), and the complete success rate was 90%(18/20) at 6 months. Postoperative complications were observed in 7 eyes (35%) of 20 PACG eyes, including 3 eyes (15%) with hyphema, 2 eyes (10%) with shallow anterior chamber, 1 eye (5%) with Descemet membrane detachment, and 1 eye (5%) with filtration obstruction at the trabeculum ostium. According to the results of slit lamp and ultrasound biomicroscopy examinations, 70% of the eyes (14/20) had no filtering bleb. Eight eyes (40%) with IOP spike were observed. Conclusion: Preliminary study shows penetrating canaloplasty is safe and effective in the treatment of PACG, but needs a longer follow-up. (Chin J Ophthalmol, 2019, 55: 448-453).
Subject(s)
Glaucoma, Angle-Closure , Glaucoma, Open-Angle , Trabeculectomy , Adult , Aged , Female , Glaucoma, Angle-Closure/surgery , Glaucoma, Open-Angle/surgery , Humans , Intraocular Pressure , Male , Middle Aged , Prospective Studies , Visual AcuityABSTRACT
Hypomorphic RAG1 mutations allowing residual T- and B-cell development have been found in patients presenting with delayed-onset combined immune deficiency with granulomas and/or autoimmunity (CID-G/AI) and abnormalities of the peripheral T- and B-cell repertoire. To examine how hypomorphic Rag1 mutations affect the earliest stages of lymphocyte development, we used CRISPR/Cas9 to generate mouse models with mutations equivalent to those found in patients with CID-G/AI. Immunological characterization showed partial development of T and B lymphocytes, with persistence of naïve cells and preserved serum immunoglobulin but impaired antibody responses and presence of autoantibodies, thereby recapitulating the phenotype seen in patients with CID-G/AI. By using high-throughput sequencing, we identified marked skewing of Igh V and Trb V gene usage in early progenitors, with a bias for productive Igh and Trb rearrangements after selection occurred and increased apoptosis of B-cell progenitors. Rearrangement at the Igk locus was impaired, and polyreactive immunoglobulin M antibodies were detected. This study provides novel insights into how hypomorphic Rag1 mutations alter the primary repertoire of T and B cells, setting the stage for immune dysregulation frequently seen in patients.
Subject(s)
Cell Differentiation/genetics , Genes, RAG-1 , Lymphopoiesis/genetics , Mutation , Alleles , Animals , B-Lymphocytes/cytology , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Biomarkers , Disease Susceptibility/immunology , Gene Editing , Gene Expression Regulation , Genetic Predisposition to Disease , Immunity, Humoral , Immunophenotyping , Mice , Mice, Transgenic , Phenotype , T-Lymphocytes/cytology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , V(D)J RecombinationABSTRACT
Objective: To understand the underreporting of death cases and related factors in disease surveillance system of Fujian province. Methods: We carried out a field underreporting survey in 20 disease surveillance sites selected through stratified cluster random sampling during 2012-2014. The related factors of underreporting were analyzed by using logistic regression method. Propensity score weighting method was used to calculate the underreporting rate in different groups classified by year, urban/rural areas, gender, age and death cause variables. Results: The overall underreporting rate was 9.21%(95%CI: 9.06%-9.39%) after adjusting by propensity score weighting method. The underreporting rate was higher in rural area (11.55%, 95%CI: 11.30%-11.81%) than in urban area (6.64%, 95%CI: 6.50%-6.78%). The underreporting rate was highest in age group 0-14 years (36.29%, 95% CI: 34.23%-38.67%) and lowest in age group ≥65 years (7.91%, 95% CI: 7.78%-8.03%). The underreporting rate was higher in people died of perinatal disease, congenital anomalies and injury. Conclusion: The underreporting rates were different between different groups classified by urban/rural areas, age and death cause variables. Propensity score weighting method can be used to adjust underreporting rate of death cases in mortality surveillance in Fujian.
Subject(s)
Cause of Death , China , Humans , Propensity Score , Rural Population , Urban PopulationABSTRACT
SUMMARY STATEMENT: Intravitreal high dose (2 mg) ranibizumab may lead to quicker resolution of choroidal neovascularization (CNV) and associated retinal pigment epithelial detachment in eyes with exudative age-related macular degeneration, although it may possibly correlate with RPE tears in certain cases. PURPOSE: This prospective study compared the outcomes of 0.5 vs 2.0 mg intravitreal ranibizumab injections (RI) for treating vascularized pigment epithelial detachment (vPED) due to age-related macular degeneration. METHODS: Patients with vPED were randomized to receive 2.0 vs 0.5 mg RI monthly for 12 months or for 4 months and then repeated on a pro-re nata basis. Optical coherence tomography, fundus photography, and fluorescein and indocyanine-green angiography were obtained at baseline and subsequent specific intervals. Outcome measures were best-corrected standardized visual acuities, central 1-mm thickness, surface area (SA), greatest linear diameter (GLD), heights (PED and CNV), and amount of subretinal fluid (SRF) and cystoid macular edema (CME). RESULTS: Both groups yielded reductions of the central 1-mm thickness, PED and CNV SA and PED height and GLD, SRF, and CME. Vision improvement and reduction in SRF and PED height occurred earlier for eyes receiving the 2.0 mg dose. Cataract progression was similar but RPE tears developed more often with the 2.0 mg dose. CONCLUSIONS: There were similar visual and anatomical outcomes at the end of the study; however, the higher dose yielded more rapid reductions and more complete resolution of the PED, although there was possible increased tendency for an RPE tear with the higher dose.
Subject(s)
Angiogenesis Inhibitors/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Retinal Detachment/drug therapy , Retinal Neovascularization/drug therapy , Retinal Pigment Epithelium/blood supply , Wet Macular Degeneration/drug therapy , Aged , Aged, 80 and over , Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Coloring Agents , Contrast Sensitivity , Female , Fluorescein Angiography , Humans , Indocyanine Green , Intravitreal Injections , Male , Prospective Studies , Ranibizumab , Retinal Detachment/diagnosis , Retinal Detachment/physiopathology , Retinal Neovascularization/diagnosis , Retinal Neovascularization/physiopathology , Risk Assessment , Sickness Impact Profile , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/physiology , Wet Macular Degeneration/diagnosis , Wet Macular Degeneration/physiopathologyABSTRACT
MicroRNA-based short hairpin RNAs (shRNAs) are natural inducers of RNA interference and have been increasingly used in shRNA expression strategies. In the present study, we compared the efficiencies of exogenous green fluorescence protein (GFP) and endogenous glyceraldehyde-3-phosphate dehydrogenase (GAPDH) knockdown and red fluorescent protein (RFP) indicator expression mediated by three differently designed plasmids. RFP was introduced either at the 5' end, at the 3' end of the human mir155-based target gene (TG) (e.g., GFP or GAPDH) shRNA expression cassette (EC), or at the 3' end of the chimeric intron-containing TG shRNA EC. Comparisons with the control vector showed an obvious reduction of GFP or GAPDH expression with the various shRNA expression plasmids (P < 0.05). When RFP was located at the 5' end or at the 3' end of the TG shRNA EC, RFP expression was low; whereas when RFP was connected with the chimeric intron-containing TG shRNA EC, RFP expression was high. Taken together, this study demonstrated an efficient plasmid design for both TG silencing induced by microRNA-based shRNA and indicator gene expression in vitro.
Subject(s)
Gene Expression Regulation , Gene Silencing , Genetic Techniques , MicroRNAs/metabolism , RNA, Small Interfering/metabolism , Base Sequence , Cell Line , Glyceraldehyde-3-Phosphate Dehydrogenases/genetics , Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Humans , Luciferases/metabolism , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , MicroRNAs/chemistry , MicroRNAs/genetics , Molecular Sequence Data , Nucleic Acid Conformation , Plasmids/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transfection , Red Fluorescent ProteinABSTRACT
In this report, we describe an improved method for the establishment of reproducible congestive heart failure (CHF) in a rat model. The area of myocardial infarction (MI) after ligation of the left anterior descending (LAD) coronary artery was quantified. Histological changes, heart function detected by echocardiography and isolated Langendorff perfusion, and selected biochemical factors were monitored after ligation of the LAD. Contrary to previous beliefs, thoracotomy in the second intercostal space provided a much better visualization of and easier access to the LAD and significantly reduced the mortality rate. Surface electrocardiogram (ECG) showed that the S-T interval was arched raised upward immediately after ligation. Typical morphological and functional changes of CHF were observed after LAD ligation. Cardiomyocytes in the infarcted zone were depleted and deranged. Biochemical analysis and enzyme-linked immunosorbent assay (ELISA) showed that superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and nitric oxide (NO) levels were significantly lowered in rats with MI than in the normal and sham groups, whereas serum malondialdehyde (MDA), MB isoenzyme of creatine kinase (CK-MB), cardiac troponin (cTnT) and C-reactive protein (CRP) levels were elevated. After MI, N-terminal pro-brain natriuretic peptide (NT-proBNP) was increased but insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF) in culture supernatant were lower than in the normal and sham groups. We present an improved model for maximal reproducibility of experimental CHF in rats which allows the study of molecular and physiological variables in relation to CHF.
Subject(s)
Disease Models, Animal , Heart Failure/physiopathology , Myocardial Infarction/complications , Animals , Chronic Disease , Electrocardiography , Heart Failure/etiology , Insulin-Like Growth Factor I/metabolism , Male , Myocardial Infarction/physiopathology , Myocytes, Cardiac/pathology , Natriuretic Peptide, Brain/metabolism , Peptide Fragments/metabolism , Rats , Rats, Sprague-Dawley , Thoracotomy/methods , Vascular Endothelial Growth Factor A/metabolismABSTRACT
The RNA interference (RNAi) technique has been widely used in gene function studies. It is typical to screen for effective siRNAs by knocking down targeted genes since a single gene can be suppressed by several siRNAs to varying degrees. The miRNA-based short hairpin RNA (shRNA) is a natural inducer of RNAi and has been used in siRNA expression strategies. We investigated the potential application of multiple putative microRNA-based shRNAs for gene silencing and studied the inhibition efficiency of exogenous GFP and firefly luciferase (luc) by triple human mir155-based shRNA expression vectors. A total of three candidate siRNA sequences targeted against GFP or luc were selected based on an online prediction program. Single and triple miRNA-155-based shRNAs targeted against GFP or luc were transfected into HEK293 cells mediated by the pcDNA(3) vector with an RNA polymerase II-type CMV (cytomegalovirus) promoter. Comparisons with negative control shRNAs revealed that GFP levels were markedly reduced by the triple miRNA-155-based GFP shRNA by fluorescent microscopy. Consistent results from the dual luciferase assay and real-time quantitative RT-PCR revealed that the triple miRNA-155-based GFP shRNA significantly suppressed GFP expression (P < 0.01), without significant differences from the most effective single miRNA-155-based GFP shRNA (P > 0.05). Results from the dual luciferase assay and real-time quantitative RT-PCR revealed that the triple miRNA-155-based luc shRNA significantly suppressed luc expression as the most effective single miRNA-155-based luc shRNA (P < 0.05). These studies demonstrated the gene silencing efficiency mediated by the triple putative miRNA-155-based shRNAs. This suggested that multiple miRNA-based shRNAs are quick and valuable strategies for gene silencing.
Subject(s)
Gene Silencing , Gene Targeting/methods , MicroRNAs , Nucleic Acid Conformation , RNA Interference , RNA, Small Interfering , Animals , Cell Line , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Promoter Regions, Genetic , RNA, Small Interfering/chemistry , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolismABSTRACT
BACKGROUND AND PURPOSE: Macrophage migration inhibitory factor (MIF) is now known to be a pro-inflammatory cytokine associated with insulin resistance. Our aim was to investigate whether angiotensin converting enzyme 2 (ACE2) could modulate the expression of MIF and the insulin/Akt-endothelial nitric oxide (NO) synthase (eNOS) signalling in a human endothelial cell line (EAhy926). EXPERIMENTAL APPROACH: A recombinant plasmid encompassing human ACE2 gene was constructed and transfected into the EAhy926 cells. The mRNA, phosphorylation and protein levels of p22phox, MIF, Akt and eNOS in endothelial cells were determined by real-time PCR and Western blot analysis, respectively. KEY RESULTS: Gene transfer of ACE2 suppressed the expression of p22phox and MIF induced by angiotensin (Ang) II and Ang IV, accompanied by a decreased level of malondialdehyde in cells. In addition, Ang II diminished insulin-stimulated phosphorylation of Akt (at Ser(473)) and eNOS (at Ser(1177)) and NO generation, effects which were reversed by ACE2 gene transfer and anti-MIF treatment in endothelial cells. CONCLUSIONS AND IMPLICATIONS: The results reveal that gene transfer of ACE2 regulated Ang II-mediated impairment of insulin signalling and involved the Akt-eNOS phosphorylation pathway. These beneficial effects of ACE2 overexpression appear to result mainly from blocking MIF expression in endothelial cells, suggesting that the ACE2 gene may be a novel therapeutic target for diseases related to inflammation and insulin resistance.
Subject(s)
Insulin/pharmacology , Macrophage Migration-Inhibitory Factors/antagonists & inhibitors , Peptidyl-Dipeptidase A/physiology , Proto-Oncogene Proteins c-akt/physiology , Signal Transduction/physiology , Angiotensin II/analogs & derivatives , Angiotensin II/pharmacology , Angiotensin-Converting Enzyme 2 , Cells, Cultured , Cloning, Molecular , Humans , Insulin Resistance , Macrophage Migration-Inhibitory Factors/genetics , Malondialdehyde/analysis , NADPH Oxidases/analysis , Peptidyl-Dipeptidase A/genetics , RNA, Messenger/analysisABSTRACT
PURPOSE: To describe the unusual complication of retinal pigment epithelial (RPE) tear after intravitreal ranibizumab (Lucentis) for subfoveal fibrovascular pigment epithelial detachment (PED) and its effective management. METHODS: Chart review for case report of RPE tear after ranibizumab. RESULTS: An inferior RPE tear was documented by fluorescein angiography, fundus photography, and optical coherence tomography (OCT) 1 month after receiving repeat ranibizumab injection in the right eye of a patient with bilateral subfoveal fibrovascular PED. He had undergone multiple bevacizumab followed by ranibizumab injections for neovascular age-related macular degeneration (AMD) in both eyes, starting 6 months previously. Subsequent antivascular endothelial growth factor (VEGF) therapy improved vision of right eye from 20/200 to 20/40, despite RPE tear. CONCLUSIONS: RPE tear may form after anti-VEGF therapy, including ranibizumab injection. Further anti-VEGF therapy may preserve or improve vision. To the authors' knowledge, this is first case report of effective suppression of neovascular activity with bevacizumab after an RPE tear following ranibizumab therapy.
Subject(s)
Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal/adverse effects , Pigment Epithelium of Eye/drug effects , Retinal Detachment/drug therapy , Retinal Perforations/chemically induced , Aged , Antibodies, Monoclonal, Humanized , Fluorescein Angiography , Humans , Injections , Macular Degeneration/drug therapy , Male , Pigment Epithelium of Eye/pathology , Ranibizumab , Retinal Perforations/diagnosis , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity , Vitreous BodyABSTRACT
Reentrant condensation of DNA in the presence of spermidine (SPD) is studied by gel electrophoresis (GEP). It is found that the reentrant condensation of DNA induced by SPD can produce a reentrant jamming of DNA molecules at the liquid-gel interface during GEP. However, not all the DNA are jammed at the interface indicating that there are different forms of condensed DNA. A model of condensed DNA consisting of two conformations can be used to explain the experimental observations. A phase diagram of the reentrant condensation based on the jamming states of DNA in terms of the length of DNA (L) and concentration of SPD is constructed. Furthermore, no charge inversion is observed during the reentrant transition.
ABSTRACT
There is an increasing use of herbal medicines worldwide, and the extracts from the root of Salvia miltiorrhiza are widely used in the treatment of angina and stroke. In this study, we investigated the mechanism for the intestinal absorption of tanshinone IIB (TSB), a major constituent of S. miltiorrhiza. The oral bioavailability of TSB was about 3% in rats with less proportional increase in its maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC) with increasing dosage. The time to C(max) (T(max)) was prolonged at higher oral dosage. In a single pass rat intestinal perfusion model, the permeability coefficients (P(app)) based on TSB disappearance from the lumen (P(lumen)) were 6.2- to 7.2-fold higher (p < 0.01) than those based on drug appearance in mesenteric venous blood (P(blood)). The uptake and efflux of TSB in Caco-2 cells were also significantly altered in the presence of an inhibitor for P-glycoprotein (PgP) or for multi-drug resistance associated protein (MRP1/2). TSB transport from the apical (AP) to basolateral (BL) side in Caco-2 monolayers was 3.3- to 5.7-fold lower than that from BL to AP side, but this polarized transport was attenuated by co-incubation of PgP or MRP1/2 inhibitors. The P(app) values of TSB in the BL-AP direction were significantly higher in MDCKII cells over-expressing MDR1 or MRP1, but not in cells over-expressing MRP2-5, as compared with the wild-type cells. The plasma AUC(0-24hr) in mdr1a and mrp1 gene-deficient mice was 10.2- to 1.7-fold higher than that in the wild-type mice. Furthermore, TSB significantly inhibited the uptake of digoxin and vinblastine in membrane vesicles containing PgP or MRP1. TSB also moderately stimulated PgP ATPase activity. Taken collectively, our findings indicate that TSB is a substrate for PgP and MRP1 and that drug resistance to TSB therapy and drug interactions may occur through PgP and MRP1 modulation.
Subject(s)
ATP-Binding Cassette Transporters/metabolism , Anticoagulants/pharmacokinetics , Intestinal Absorption/drug effects , Intestinal Mucosa/metabolism , Phenanthrenes/pharmacokinetics , Salvia miltiorrhiza/chemistry , ATP-Binding Cassette Transporters/antagonists & inhibitors , Abietanes , Animals , Anticoagulants/chemistry , Anticoagulants/pharmacology , Biological Transport/drug effects , Biological Transport/physiology , Caco-2 Cells , Diterpenes/chemistry , Diterpenes/pharmacokinetics , Diterpenes/pharmacology , Humans , Intestinal Absorption/physiology , Intestines/cytology , Male , Mice , Mice, Knockout , Phenanthrenes/chemistry , Phenanthrenes/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
Esmolol is a unique cardioselective, intravenous, ultra-short acting, beta1-adrenergic blocking agent. It has been widely applied in treating ventricular and supraventricular arrhythmias, especially in emergency situations. In this study the effects of esmolol on sodium current (I(Na)) were investigated by the whole cell patch-clamp recording technique in isolated adult rat ventricular myocytes. The results indicated that esmolol reversibly inhibited I(Na) in a concentration-dependent manner, with an IC50 of 74.2 +/- 0.60 micromol l(-1) with a Hill coefficient of 1.02 +/- 0.04. This inhibition was voltage- and frequency-dependent. Esmolol decreased the peak of the I-V relationship curve at -35 mV from 16.97 +/- 1.68 pA/pF to 6.96 +/- 0.51 pA/pF. The steady-state inactivation curve of I(Na) was shifted to more negative potentials, the voltage at half-inactivation changing from -78.75 +/- 2.3 mV in control to -85.94 +/- 3.2 mV in the presence of esmolol. The development of resting inactivation from closed states was accelerated by esmolol, the time constant was shortened from 62.75 +/- 3.21 ms to 24.93 +/- 2.43 ms, whereas the activation curve was not altered. I(Na) from inactivation could not be recovered completely in the presence of esmolol. These results suggest that esmolol inhibits I(Na) through sodium channel in rat ventricular myocytes by mechanisms involving preferential interaction with the inactivated state and acceleration of the development of inactivation directly from resting state. Therefore, the effect of inhibitory sodium of esmolol may play a vital role in its antiarrhythmic efficacy.
Subject(s)
Adrenergic beta-Antagonists/pharmacology , Anti-Arrhythmia Agents/pharmacology , Myocytes, Cardiac/drug effects , Propanolamines/pharmacology , Sodium Channel Blockers/pharmacology , Animals , Heart Ventricles/cytology , In Vitro Techniques , Male , Membrane Potentials/drug effects , Myocytes, Cardiac/physiology , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Sodium/physiology , Sodium Channels/drug effects , Sodium Channels/physiologyABSTRACT
AIMS: Analysis of highly myopic eyes (mean myopia -11 D) with post-LASIK vitreoretinal complications (breaks, retinal detachment) that also had pre-LASIK vitreoretinal pathology (lattice, breaks). METHODS: Retrospective case series. RESULTS: 67 eyes in 56 patients with pre-LASIK retinal examination developed post-LASIK vitreoretinal complications. 17 of the 67 eyes (25.4%) had pre-LASIK vitreoretinal pathology. 10 of the 17 eyes that underwent pre-LASIK prophylactic retinal treatment still developed post-LASIK lesions. They developed adjacent to pre-LASIK lesions for 15 of 17 eyes (88.2%), and outside of quadrant(s) of pre-LASIK lesions for five eyes (29.4%). CONCLUSION: Pre-LASIK retinal examination may predict locations of certain post-LASIK retinal lesions that may develop in highly myopic eyes with pre-LASIK vitreoretinal pathology, but prophylactic treatment may not prevent all post-LASIK vitreoretinal complications.
Subject(s)
Keratomileusis, Laser In Situ/adverse effects , Myopia/surgery , Retina/pathology , Retinal Perforations/pathology , Adult , Female , Humans , Male , Middle Aged , Myopia/pathology , Retina/surgery , Retinal Perforations/etiology , Retinal Perforations/surgery , Retrospective StudiesABSTRACT
OBJECTIVE: To observe the clinical effect of Sini Decoction (SND) on ischemia/reperfusion injury in acute myocardial infarction (AMI). METHODS: Randomized case-control clinical trial was conducted to observe the change of Holter monitoring in 22 cases of AMI treated with thrombolytic therapy before and after treatment. RESULTS: The lasting time of acute ST segment, total burden of myocardial infarction, QRS score, QT dispersion and occurrence of reperfusion arrhythmia in patients received SND treatment were lower than those untreated with SND (P < 0.05). CONCLUSION: SND is helpful in improving reperfusion injury of thrombolytic therapy in AMI patients.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/prevention & control , Phytotherapy , Thrombolytic Therapy , Aged , Electrocardiography, Ambulatory , Female , Humans , Male , Middle Aged , Myocardial Infarction/physiopathology , Myocardial Reperfusion Injury/etiology , Thrombolytic Therapy/adverse effects , Urokinase-Type Plasminogen Activator/adverse effects , Urokinase-Type Plasminogen Activator/therapeutic useABSTRACT
Macrophage migration inhibitory factor (MIF) has been shown to play an important role in macrophage-mediated diseases. We investigate the potential role of MIF in atherogenesis using a hypercholesterolemic rabbit model. New Zealand White rabbits fed with a 2% cholesterol diet developed hypercholesterolemia and early fatty streaks at 1 month. The lesions became advanced at 3 months and were associated with de novo MIF expression by vascular endothelial cells (VECs) and smooth muscle cells (SMCs), as demonstrated by immunohistochemistry, reverse transcriptase-polymerase chain reaction, and in situ hybridization. By contrast, there was no increase in MIF levels in rabbits fed a normal diet. In early atherogenesis, marked upregulation of MIF mRNA and protein by VECs and some intimal cells were closely associated with CD68(+) monocyte adhesion onto and subsequent migration into subendothelial space. Of significance, the accumulation of macrophages was exclusively localized to areas of strong MIF expression, which may be associated with the macrophage-rich fatty streak lesion formation. Upregulation of MIF by SMCs is transient during atherogenesis. Importantly, strong MIF expression by activated macrophages may be responsible for the development of foam cell-rich lesions. Finally, the ability of MIF to induce intercellular adhesion molecule-1 expression by VECs implicates its pathogenic role in atherogenesis. In conclusion, the present study provides the first demonstration that MIF is markedly upregulated during atherogenesis. Upregulation of MIF by VECs and SMCs may play a role in macrophage adhesion, transendothelial migration, accumulation, and, importantly, transformation into foam cells. Furthermore, strong MIF expression by macrophages may both initiate and amplify the atherogenesis process.
Subject(s)
Arteriosclerosis/metabolism , Macrophage Migration-Inhibitory Factors/biosynthesis , Macrophages/metabolism , Animals , Arteries/metabolism , Arteriosclerosis/pathology , Cell Movement , Cells, Cultured , Disease Models, Animal , Endothelium, Vascular/metabolism , Foam Cells/metabolism , Hypercholesterolemia/etiology , Hypercholesterolemia/metabolism , Intercellular Adhesion Molecule-1/biosynthesis , Macrophages/physiology , Muscle, Smooth/metabolism , RNA, Messenger/biosynthesis , Rabbits , Up-RegulationABSTRACT
AIM: To assess the inhibitory effect of c-sis antisense oligodeoxynucleotides (ODN) on vascular smooth muscle cells (VSMC) proliferation and c-sis proto-oncogene mRNA expression. METHODS: The VSMC were cultured with Dulbecco's modified Engle's medium (DMEM) containing synthesized c-sis antisense or sense oligomers, [3H]thymidine (TdR) incorporation into DNA was determined by liquid scintillation counter and the numbers of cells were counted by cell counting plate, the mRNA level was observed by using of reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: C-sis antisense ODN 2, 4, 6, 8, and 10 mumol.L-1 inhibited VSMC proliferation (10.3% +/- 0.7%, 22.6% +/- 0.9%, 31.0% +/- 1.1%, 35.4% +/- 0.9%, and 43.3% +/- 1.2%) and [3H]TdR incorporation (6.8% +/- 0.3%, 9.7% +/- 0.7%, 29.0% +/- 0.6%, 32.0% +/- 0.7%, and 50.6% +/- 1.3%) in a concentration-dependent manner. When VSMC were treated with antisense ODN 10 mumol.L-1 for 4 d, the highest inhibitory rate of VSMC growth and that of [3H]TdR incorporation were 60.3% +/- 1.0% and 56.3% +/- 0.9%, respectively. RT-PCR showed that c-sis proto-oncogene antisense ODN downregulated c-sis mRNA expression obviously, while c-sis sense ODN did not inhibit VSMC proliferation and expression of c-sis proto-oncogene mRNA. CONCLUSION: The c-sis antisense ODN inhibited VSMC proliferation and downregulated c-sis mRNA level.
Subject(s)
Muscle, Smooth, Vascular/cytology , Oligodeoxyribonucleotides, Antisense/pharmacology , Proto-Oncogenes , Animals , Cell Division/drug effects , Cells, Cultured , Down-Regulation , Gene Expression Regulation/drug effects , Male , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , RabbitsABSTRACT
AIM: To study the pharmacokinetics of atenolol (Ate) stereoisomers in Chinese. METHOD: A single oral dose of 100 mg of racemic Ate tablets were given to 12 healthy volunteers of Han nationality. Plasma and urine concentrations were determined by the reversed phase HPLC method. RESULTS: The disposition of d-Ate and l-Ate was conformed to one-compartment model. Maximal plasma concentration (Cmax): l-Ate (331 +/- 79) micrograms.L-1, d-Ate (342 +/- 78) micrograms.L-1. Area under blood concentration-time curve (AUC): d-Ate (2635 +/- 610) micrograms.h.L-1, l-Ate (2442 +/- 588) micrograms.h.L-1. Renal clearance (Clr): l-Ate (6.9 +/- 1.2) L.h-1, d-Ate (6.5 +/- 1.3) L.h-1. CONCLUSION: The disposition of Ate stereoisomers is of stereoselectivity.