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1.
Nanoscale ; 15(34): 14205-14214, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37594187

ABSTRACT

Renewable energy has been a focus in recent years. Triboelectric nanogenerators (TENGs) have potential for converting mechanical energy into electricity. However, there are restrictions on the use of biological materials and bionanocomposites, such as the high cost and complexity of the synthesis process, poor stability, and inadequate output performance. To overcome the constraints of TENGs, we have turned to hydroxyapatite, a biological substance with great biocompatibility and high mechanical strength that can be manufactured from waste materials. We successfully developed a negative triboelectric bionanocomposite hydroxyapatite (HA) loaded polydimethylsiloxane (PDMS) to harness energy from biomechanical sources such as wearable devices. A TENG (2 × 2 cm2) with a pushing force of 2 N and different amounts of HA in PDMS can produce highly stable output voltage, current, surface charge density, and power density values of 300 V, 22.4 µA, 90.36 µC m-2, and 27.34 W m-2, which are 6, 9, and 10 times higher than those without HA, respectively. These improvements were attributed to the highest observed surface potential of 1512 mV. After 20 000 cycles of contact-separation, the HA/PDMS-TENG shows exceptionally stable performance. Furthermore, adding HA improves the mechanical properties and the stretchability of the bionanocomposite. The HA/PDMS bionanocomposite exhibits remarkable stretchability of more than 290%. Effectively harvesting energy from body movements, the TENG gadget may be used to charge multiple commercial capacitors, drive up to 100 LEDs, and power a low-power electronic device. Self-powered sensing and wearable devices are made possible by the HA/PDMS-TENG, which allows their large-scale preparation and deployment.

2.
J Clin Pathol ; 76(5): 339-344, 2023 May.
Article in English | MEDLINE | ID: mdl-34844950

ABSTRACT

AIMS: The aim of this study was to determine common variants in F8, including intron 22 inversion (Inv22), intron 1 inversion (Inv1) and point mutations, the transmission of these variants between patients with haemophilia A (HA) and their family members. METHODS: Genetic analysis was conducted in 71 patients who were clinically diagnosed with HA and 152 related female members in South Vietnam by a combination of inversion PCR (I-PCR), multiplex PCR and direct sequencing. RESULTS: Variants in F8, including Inv22, point mutations (with 37 genotypes) and two novel variants, occupied 60 patients with HA. Among severe patients, the rate of Inv22 was 44%. Missense was the common point mutation of over 50% in patients with moderate HA and mild HA. Inv1 was absent in all patients. F8 variants were also found in 119 female carriers (FCs) (78.3%) from families related to patients with HA. There were 56 mothers (93.3%) carrying F8 variants and passing the same variants to their sons. CONCLUSIONS: These findings were the first to provide important information about the presence of Inv22 and point mutation in Vietnamese patients with HA, the mothers and their female family members. It demonstrated that genetic diagnosis and counselling for HA carriers were essential factors for future improvements in comprehensive and equitable healthcare polices for patients with HA and FCs in Vietnam.


Subject(s)
Hemophilia A , Humans , Female , Hemophilia A/diagnosis , Hemophilia A/genetics , Factor VIII/genetics , Vietnam , Family , Chromosome Inversion , Multiplex Polymerase Chain Reaction , Mutation
3.
Lancet Reg Health West Pac ; 27: 100543, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35874914

ABSTRACT

The competency-based undergraduate curriculum reform at the University of Medicine and Pharmacy at Ho Chi Minh City, Faculty of Medicine (UMP-FM) is detailed and reviewed in reference to the instructional and institutional reforms, and enabling actions recommended by the Lancet 2010 Commission for Health Professional Education. Key objectives are to: revise the overall 6-year curriculum to be more integrated and competency-based; reinforce students' knowledge application, problem-solving, clinical competence, self-directed learning and soft skills; develop a comprehensive and performance-based student assessment programme; and establish a comprehensive quality monitoring programme to facilitate changes and improvements. New features include early introduction to the practice of medicine, family- and community-based medicine, professionalism, interprofessional education, electives experiences, and a scholarly project. Institutional reform introduces a faculty development programme, joint planning mechanism, a "culture of critical inquiry", and a transparent faculty reward system. Lessons learnt from the curriculum reform at UMP-FM could be helpful to medical schools from low- and middle-income countries considering transitioning from a traditional to a competency-based curriculum. Funding: This work receives no external funding.

4.
Front Artif Intell ; 5: 831841, 2022.
Article in English | MEDLINE | ID: mdl-35481282

ABSTRACT

In response to a call for help during a surge in coronavirus disease-19 (COVID-19) cases in Ho Chi Minh City in July 2021, the University of Medicine and Pharmacy at Ho Chi Minh City developed and implemented a community care model for the management of patients with COVID-19. This was based on three main principles: home care; providing monitoring and care at a distance; and providing timely emergency care if needed. One team supported patients at home with frequent contacts and remote monitoring, while a second team transferred and cared for patients requiring treatment at field emergency care facilities. COVID-19-related mortality rates at the two districts where this approach was implemented (0.43% and 0.57%) were substantially lower than the overall rate in Ho Chi Minh City over the same period (4.95%). Thus, utilization of a community care model can increase the number of patients with COVID-19 who can be effectively managed from home, and use of field emergency care facilities limited the number of patients that had to be referred for tertiary care. Importantly, the community care model also markedly reduced the mortality rate compared with traditional methods of COVID-19 patient management.

5.
Molecules ; 27(6)2022 Mar 14.
Article in English | MEDLINE | ID: mdl-35335249

ABSTRACT

Triterpenoids are among the bioactive components of Chaga, the sterile conk of the medicinal fungus Inonotus obliquus. Supercritical fluid extraction of Chaga triterpenoids was carried out with supercritical CO2, while a modified Folch method was used as a comparison. Three temperature-pressure combinations were tested varying between 314-324 K (40-50 °C) and 281-350 bars, using time- and volume-limited extractions. Six triterpenoids were identified with GC-MS and quantified with GC-FID: ergosterol, lanosterol, ß-sitosterol, stigmastanol, betulin, and inotodiol. The Folch extraction resulted in recovery of trametenolic acid, which was not extracted by supercritical CO2. Inotodiol was the major triterpenoid of all the extracts, with a yield of 87-101 mg/100 g and 139 mg/100 g, for SFEs and the Folch method, respectively. The contents of other major triterpenoids, lanosterol and ergosterol, varied in the ranges 59-63 mg/100 g and 17-18 mg/100 g by SFE, respectively. With the Folch method, the yields were 81 mg/100 g and 40 mg/100 g, respectively. The highest recovery of triterpenoids with SFE in relation to Folch was 56% and it was obtained at 324 K (50 °C) and 350 bar, regardless of extraction time or volume of CO2. The recoveries of lanosterol and stigmastanol were unaffected by SFE conditions. Despite the lower yield, SFE showed several advantages including shorter extraction time and less impact on the environment. This work could be a starting point for further studies on green extraction methods of bioactive triterpenoids from Chaga.


Subject(s)
Chromatography, Supercritical Fluid , Triterpenes , Carbon Dioxide , Chromatography, Supercritical Fluid/methods , Ergosterol , Inonotus
6.
Mol Genet Genomic Med ; 9(8): e1732, 2021 08.
Article in English | MEDLINE | ID: mdl-34114358

ABSTRACT

BACKGROUND: X-linked hyper-IgM syndrome (XHIGM) is a rare primary immunodeficiency caused by CD40 ligand defects. METHODS: We identified three patients with XHIGM in Ho Chi Minh City, Vietnam. Whole-exome sequencing, immunological analyses and western blot were performed to investigate phenotypic and genotypic features. RESULTS: Despite showing symptoms typical of XHIGM, including recurrent sinopulmonary infections, oral ulcers and otitis media, the diagnosis was significantly delayed. One patient developed anti-phospholipid syndrome, which has been documented for the first time in XHIGM syndrome. Two patients had elevated IgM levels and all of them had low IgG levels. Exome sequencing revealed mutations in the CD40LG gene: one novel splicing mutation c.156+2T>A and two previously characterised mutations (non-frameshift deletion c.436_438delTAC, stop-gain c.654C>A). Due to these mutations, the CD40 ligand was not expressed in any of the three patients, as demonstrated by western blot analysis. CONCLUSION: This is the first report of XHIGM syndrome in Vietnam indicates that an effective diagnostic strategy, such as sequencing analysis, contributes to reliable diagnosis and subsequent therapy.


Subject(s)
Antiphospholipid Syndrome/genetics , CD40 Ligand/genetics , Hyper-IgM Immunodeficiency Syndrome, Type 1/genetics , Phenotype , Adolescent , Adult , Antiphospholipid Syndrome/etiology , Antiphospholipid Syndrome/pathology , Child , Humans , Hyper-IgM Immunodeficiency Syndrome, Type 1/complications , Hyper-IgM Immunodeficiency Syndrome, Type 1/pathology , Male , Mutation
7.
Research (Wash D C) ; 2021: 6426130, 2021.
Article in English | MEDLINE | ID: mdl-33796861

ABSTRACT

Since the first invention of triboelectric nanogenerators (TENGs) in 2012, many mechanical systems have been applied to operate TENGs, but mechanical contact losses such as friction and noise are still big obstacles for improving their output performance and sustainability. Here, we report on a magnet-assembled cam-based TENG (MC-TENG), which has enhanced output power and sustainability by utilizing the non-contact repulsive force between the magnets. We investigate the theoretical and experimental dynamic behaviors of MC-TENGs according to the effects of the contact modes, contact and separation times, and contact forces (i.e., pushing and repulsive forces). We suggest an optimized arrangement of magnets for the highest output performance, in which the charging time of the capacitor was 2.59 times faster than in a mechanical cam-based TENG (C-TENG). Finally, we design and demonstrate a MC-TENG-based windmill system to effectively harvest low-speed wind energy, ~4 m/s, which produces very low torque. Thus, it is expected that our frictionless MC-TENG system will provide a sustainable solution for effectively harvesting a broadband of wasted mechanical energies.

8.
Mol Genet Genomic Med ; 8(5): e1216, 2020 05.
Article in English | MEDLINE | ID: mdl-32154999

ABSTRACT

BACKGROUND: Lipopolysaccharide-responsive and beige-like anchor (LRBA) deficiency is a rare autosomal recessive common variable immunodeficiency (CVID), affecting 1:25,000-1:50,000 people worldwide. Biallelic mutations in the gene LRBA have been implicated in affected individuals. METHODS: We report a 16-year-old Vietnamese, male patient with recurrent CVID symptoms including chronic diarrhea, interstitial pneumonia, cutaneous granulomatous lesions, hepatosplenomegaly, and finger clubbing. Immunological analyses and whole exome sequencing (WES) were performed to investigate phenotypic and genotypic features. RESULTS: Immunological analyses revealed hypogammaglobulinemia and low ratios of CD4+/CD8+ T cells. Two novel compound heterozygous stop-gain mutation in LRBA were identified: c.1933C > T (p.R645X) and c.949C > T (p.R317X). Sanger sequencing confirmed the segregation of these variants from the intact parents. The abolished LRBA protein expression was shown by immunoblot analysis. Subsequent treatment potentially saves the child from the same immune thrombocytopenia which led to his brother's untimely death; likely caused by the same LRBA mutations. CONCLUSION: This first report of LRBA deficiency in Vietnam expands our knowledge of the diverse phenotypes and genotypes driving CVID. Finally, the utilization of WES shows great promise as an effective diagnostic for CVID in our setting.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Codon, Nonsense , Common Variable Immunodeficiency/genetics , Adolescent , Common Variable Immunodeficiency/pathology , Heterozygote , Humans , Male
9.
Sci Rep ; 9(1): 8223, 2019 Jun 03.
Article in English | MEDLINE | ID: mdl-31160678

ABSTRACT

Ambient vibration energy is highly irregular in force and frequency. Triboelectric nanogenerators (TENG) can convert ambient mechanical energy into useable electricity. In order to effectively convert irregular ambient vibrations into electricity, the TENG should be capable of reliably continuous operation despite variability in input forces and frequencies. In this study, we propose a tandem triboelectric nanogenerator with cascade impact structure (CIT-TENG) for continuously scavenging input vibrations with broadband frequencies. Based on resonance theory, four TENGs were explicitly designed to operate in tandem and cover a targeted frequency range of 0-40 Hz. However, due to the cascade impact structure of CIT-TENG, each TENG could produce output even under non-resonant conditions. We systematically studied the cascade impact dynamics of the CIT-TENG using finite element simulations and experiments to show how it enables continuous scavenging from 0-40 Hz even under low input accelerations of 0.2 G-0.5 G m/s2. Finally, we demonstrated that the CIT-TENG could not only scavenge broadband vibrations from a single source such as a car dashboard, but it could also scavenge very low frequency vibrations from water waves and very high frequency vibrations from air compressor machines. Thus, we showed that the CIT-TENG can be used in multiple applications without any need for redesign validating its use as an omnipotent vibration energy scavenger.

10.
Micromachines (Basel) ; 9(8)2018 Aug 17.
Article in English | MEDLINE | ID: mdl-30424340

ABSTRACT

Triboelectric nanogenerators (TENGs) are used as self-power sources for various types of devices by converting external waves, wind, or other mechanical energies into electric power. However, obtaining a high-output performance is still of major concern for many applications. In this study, to enhance the output performance of polydimethylsiloxane (PDMS)-based TENGs, highly dielectric TiO2-x nanoparticles (NPs) were embedded as a function of weight ratio. TiO2-x NPs embedded in PDMS at 5% showed the highest output voltage and current. The improved output performance at 5% is strongly related to the change of oxygen vacancies on the PDMS surface, as well as the increased dielectric constant. Specifically, oxygen vacancies in the oxide nanoparticles are electrically positive charges, which is an important factor that can contribute to the exchange and trapping of electrons when driving a TENG. However, in TiO2-x NPs containing over 5%, the output performance was significantly degraded because of the increased leakage characteristics of the PDMS layer due to TiO2-x NPs aggregation, which formed an electron path.

11.
J Endod ; 44(4): 659-664, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29459151

ABSTRACT

INTRODUCTION: Pericervical dentin (PCD) loss may increase root fracture propensity in root-filled teeth. This study evaluated the impacts of bonding PCD with composite resin (CR) on radicular microstrain distribution and load at failure of root-filled maxillary premolars. METHODS: Ten single-canal maxillary premolars decoronated 2 mm coronal to the cementoenamel junction (CEJ) had canals enlarged with ProTaper Universal instruments (Dentsply Tulsa Dental Specialties, Tulsa, OK) to F3. They were root filled with gutta-percha (GP) to the CEJ and restored with Cavit (3M Deutschland GmbH, Neuss, Germany) (GP group, n = 5) or 6 mm apical to the CEJ and restored with bonded CR to simulate bonding of PCD (bonded PCD group, n = 5). Digital moiré interferometry was used to evaluate pre- and postoperative whole-field microstrain distribution in the root dentin under physiologically relevant loads (10-50 N). Another 30 premolars, similarly treated as groups 1 and 2 or left untreated as controls (n = 10/group), were subjected to cyclic loads (1.2 million cycles, 45 N, 4 Hz) followed by uniaxial compressive load to failure. Mechanical data were analyzed with 1-way analysis of variance and the post hoc Tukey test at a 5% level of significance. RESULTS: Microstrain distribution showed bending and compressive patterns at the coronal and apical root dentin, respectively. In the GP group, microstrain distribution was unaltered. In the bonded-PCD group, different microstrain distribution suggested stiffening at the PCD. The load at failure did not differ significantly for the GP, bonded PCD, and control groups (P > .05). CONCLUSIONS: CR bonding of PCD might impact the biomechanical responses in maxillary premolar roots at low-level continuous loads. The effect of this impact on root fracture loads when subjected to cyclic load warrants further investigation.


Subject(s)
Bicuspid/physiology , Dental Bonding/adverse effects , Dentin/physiology , Tooth, Nonvital/physiopathology , Biomechanical Phenomena , Composite Resins/adverse effects , Composite Resins/therapeutic use , Dental Stress Analysis , Humans , Maxilla , Root Canal Therapy/adverse effects , Root Canal Therapy/methods , Tooth Fractures/etiology , Tooth Fractures/prevention & control
12.
RSC Adv ; 8(10): 5233-5242, 2018 Jan 29.
Article in English | MEDLINE | ID: mdl-35542441

ABSTRACT

Supercritical fluid was applied to extract volatile compounds from Finnish wild mushrooms (Craterellus tubaeformis). The effects of extraction pressure, temperature and supercritical carbon dioxide volume on extraction yield and the content of mushroom alcohols in the extracts were investigated in the range from 80 to 95 bar, 35 to 55 °C and 30 to 70 mL, respectively. The correlation between extracted volatile compounds and supercritical fluid extraction parameters was studied and prediction models of ten extracted aroma compounds were established by partial least squares regression (PLSR). The calibrated and validated models of 2-octen-1-ol (R _cal = 0.96, R _cal 2 = 0.91, R _val = 0.94, R _val 2 = 0.88) and geranyl acetone (R _cal = 0.96, R _cal 2 = 0.92, R _val = 0.95, R _val 2 = 0.90) were satisfactory, and had the predictive capability of 88% and 92%, respectively. Moreover, the predictive equations for other extracted aroma compounds were also proved to be sufficiently accurate. Hence, the present study provides useful reference for extraction of volatile compounds from mushrooms using supercritical fluid for further industrial applications.

13.
Stem Cells Int ; 2016: 5720413, 2016.
Article in English | MEDLINE | ID: mdl-26839564

ABSTRACT

Because of self-renewal, strong proliferation in vitro, abundant sources for isolation, and a high differentiation capacity, mesenchymal stem cells are suggested to be potentially therapeutic for liver fibrosis/cirrhosis. In this study, we evaluated the treatment effects of mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) on mouse liver cirrhosis induced by carbon tetrachloride. Portal and tail vein transplantations were examined to evaluate the effects of different injection routes on the liver cirrhosis model at 21 days after transplantation. BM-MSCs transplantation reduced aspartate aminotransferase/alanine aminotransferase levels at 21 days after injection. Furthermore, BM-MSCs induced positive changes in serum bilirubin and albumin and downregulated expression of integrins (600- to 7000-fold), transforming growth factor, and procollagen-α1 compared with the control group. Interestingly, both injection routes ameliorated inflammation and liver cirrhosis scores. All mice in treatment groups had reduced inflammation scores and no cirrhosis. In conclusion, transplantation of BM-MSCs via tail or portal veins ameliorates liver cirrhosis in mice. Notably, there were no differences in treatment effects between tail and portal vein administrations. In consideration of safety, we suggest transfusion of bone marrow-derived mesenchymal stem cells via a peripheral vein as a potential method for liver fibrosis treatment.

14.
Br J Clin Pharmacol ; 79(3): 429-40, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25099492

ABSTRACT

AIMS: Acute lymphoblastic leukemia (ALL) is the most common of all paediatric cancers. Aside from predisposing to ALL, polymorphisms could also be associated with poor outcome. Indeed, genetic variations involved in drug metabolism could, at least partially, be responsible for heterogeneous responses to standardized leukemia treatments, hence requiring more personalized therapy. The aims of this study were to (a) to determine the prevalence of seven common genetic polymorphisms including those that affect the folate and/or thiopurine metabolic pathways, i.e. cyclin D1 (CCND1-G870A), γ-glutamyl hydrolase (GGH-C452T), methylenetetrahydrofolate reductase (MTHFR-C677T and MTHFR-A1298C), thymidylate synthase promoter (TYMS-TSER), thiopurine methyltransferase (TPMT*3A and TPMT*3C) and inosine triphosphate pyrophosphatase (ITPA-C94A), in Caucasian (n = 94, age < 20) and Vietnamese (n = 141, age < 16 years) childhood ALL and (b) to assess the impact of a multilocus genetic risk score (MGRS) on relapse-free survival (RFS) using a Cox proportional-hazards regression model. RESULTS: The prevalence of MTHFR-677TT genotype was significantly higher in Caucasians (P = 0.008), in contrast to the prevalence of TYMS-TSER*3R/3R and ITPA-94AA/AC genotypes which were significantly higher in Vietnamese (P < 0.001 and P = 0.02, respectively). Compared with children with a low MGRS (≤ 3), those with a high MGRS (≥ 4) were 2.06 (95% CI = 1.01, 4.22; P = 0.04) times more likely to relapse. Adding MGRS into a multivariate Cox regression model with race/ethnicity and four clinical variables improved the predictive accuracy of the model (AUC from 0.682 to 0.709 at 24 months). CONCLUSION: Including MGRS into a clinical model improved the predictive accuracy of short and medium term prognosis, hence confirming the association between well determined pharmacogenotypes and outcome of paediatric ALL. Whether variants on other genes associated with folate metabolism can substantially improve the predictive value of current MGRS is not known but deserves further evaluation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Asian People/genetics , Pharmacogenetics , Polymorphism, Genetic , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , White People/genetics , Adolescent , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Child , Child, Preschool , Disease-Free Survival , Gene Frequency , Humans , Infant , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/enzymology , Predictive Value of Tests , Proportional Hazards Models , Young Adult
15.
J Pediatr Hematol Oncol ; 36(7): 534-40, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24322500

ABSTRACT

AIM OF THIS STUDY: To compare the relapse-free survival (RFS) in Vietnamese (n=141) and white (n=94) children living in Vietnam and Belgium, respectively, and treated in their own country for acute lymphoblastic leukemia according to the same FRALLE 2000 protocol. RESULTS: RFS was significantly worse in Vietnamese children (hazards ratio=4.48; 95% confidence interval [CI], 2.16-9.3; P<0.01). The 5-year RFS was 83.8% (95% CI, 76.3%-92.0%) and 47.8% (95% CI, 35.6%-64.2%) for white and Vietnamese children, respectively. In the latter group, relapses occurred in bone marrow and cerebrospinal fluid at a much earlier stage. The outcome was compared at first relapse only because of different treatments afterward, according to the country. Both series were similar for sex, age at diagnosis, initial white blood cell count, cytogenetic abnormalities, and corticosensitivity at day 8. Higher frequency of L2-acute lymphoblastic leukemia (P<0.001) but lower frequency of T-acute lymphoblastic leukemia (P=0.004) were observed in Vietnamese children. CONCLUSIONS: Several factors may contribute to the poor RFS in Vietnamese children, which include the time interval before the first intrathecal therapy and differences in the management of drug-related toxicity. However, additional contribution of socioeconomic factors and/or variations in pharmacogenetic polymorphisms in Vietnamese patients cannot currently be ruled out.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Asian People/statistics & numerical data , Precursor Cell Lymphoblastic Leukemia-Lymphoma , White People/statistics & numerical data , Adolescent , Antimetabolites, Antineoplastic/therapeutic use , Belgium/epidemiology , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Mercaptopurine/therapeutic use , Methotrexate/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/ethnology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Proportional Hazards Models , Treatment Outcome , Vietnam/epidemiology , Young Adult
16.
Cancer Genet Cytogenet ; 168(1): 59-68, 2006 Jul 01.
Article in English | MEDLINE | ID: mdl-16772122

ABSTRACT

During the Vietnam War, southern Vietnam was exposed to a large amount of dioxin, a strong human carcinogen. Although we have observed much shorter survival in southern Vietnamese chronic myeloid leukemia (CML) patients, the cause remains to be clarified. Here, we report cytogenetic and molecular findings for 47 CML patients. Cytogenetically, the Philadelphia (Ph) chromosome was found in 44 patients (93.6%); of the remaining 3 patients with Ph-negative CML, 2 exhibited BCR/ABL transcripts but no BCR/ABL FISH fusion signals, suggesting the existence of two clones, with and without the BCR/ABL fusion gene. Surprisingly, in 17 patients (36.2%) (4 at diagnosis, 11 during chronic phase, and 2 in accelerated phase), we found several unique secondary chromosome abnormalities including trisomy 13, partial trisomy 13, and abnormalities of 1p, 3p, 6p, 7p, 10p, and 11p, which are different from the so-called additional chromosome abnormalities (extra Ph, +8, i(17q), +19, and +21) observed in blastic phase CML. FISH analysis revealed the Ph translocation with der(9) deletion in 11 patients (23.4%). Of these, 2 had two clones, with and without der(9) deletion, suggesting that der(9) deletion would occur in a subset of patients during disease progression. These observations point to preexisting genetic instability that induces various secondary chromosome abnormalities and multiple clones, resulting in shorter survival.


Subject(s)
Chromosome Aberrations , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Chromosomes, Human, Pair 13/genetics , Female , Fusion Proteins, bcr-abl/genetics , Gene Deletion , Humans , In Situ Hybridization, Fluorescence , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/genetics , Male , Middle Aged , Philadelphia Chromosome , RNA, Messenger/analysis , Translocation, Genetic/genetics , Trisomy/genetics , Vietnam
17.
J Vasc Res ; 42(6): 455-62, 2005.
Article in English | MEDLINE | ID: mdl-16155361

ABSTRACT

Metabolic syndrome is a risk factor for atherosclerosis and restenosis. In metabolic syndrome, insulin resistance coexists with hyperinsulinemia and hyperlipidemia. Hyperlipidemia has growth-promoting effects, whereas insulin has both growth-promoting and growth-inhibitory effects on vascular smooth muscle cells in vitro. The objective of this study was to investigate the effects of hyperlipidemia and hyperinsulinemia on vascular cell growth in vivo after arterial injury. Rats fed a low-fat diet were treated with either subcutaneous blank (LFC) or insulin (LFI) implants. Rats fed a high-fat diet also received blank (HFC) or insulin (HFI) implants. After 3 days, rats received balloon carotid injury, and 14 days later they were sacrificed to measure neointimal area and proliferation. Hyperinsulinemia was present in LFI and HFI and hyperlipidemia was present in HFC and HFI. Neointimal area was higher in HFC (0.153 +/- 0.009 mm(2), p < 0.05) but lower in LFI (0.098 +/- 0.005, p < 0.01) than LFC (0.127 +/- 0.005). In HFI (0.142 +/- 0.008, p < 0.05) neointimal area was not different from HFC or LFC. In conclusion, insulin reduced neointimal growth, but the effect of insulin was diminished by the high-fat diet. Thus, our results demonstrate an anti-atherogenic effect of insulin in vivo and suggest that in metabolic syndrome insulin resistance rather than hyperinsulinemia is the atherogenic risk factor.


Subject(s)
Atherosclerosis/prevention & control , Insulin/pharmacology , Animals , Carotid Arteries/pathology , Carotid Artery Injuries/complications , Carotid Artery Injuries/etiology , Carotid Artery Injuries/pathology , Carotid Artery Injuries/physiopathology , Catheterization , Cell Division/drug effects , Dietary Fats/administration & dosage , Dietary Fats/pharmacology , Dose-Response Relationship, Drug , Drug Implants , Hyperinsulinism/complications , Hyperlipidemias/complications , Insulin/administration & dosage , Male , Rats , Rats, Sprague-Dawley , Tunica Intima/drug effects , Tunica Intima/pathology
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