RESUMO
Microspheres are beneficial for filling defects of various shapes and provide a large surface area for cell attachment. Porous microspheres have attracted particular attention because they can deliver cells and bioactive molecules such as growth factors. In this study, BCP-collagen composite microspheres were developed for growth factor delivery in bone regeneration. Firstly, porous biphasic calcium phosphate (BCP) microspheres were fabricated by applying a water-in-oil emulsion technique using camphene as a pore generator. Then, porous BCP-collagen composite microspheres were fabricated by repetitively dip coating the microspheres in a collagen solution to effectively deliver growth factor to bone defects. Characterization of the microspheres and in vitro studies were conducted to investigate the effect of collagen infiltration on bone regeneration. In addition, in vitro evaluation demonstrated the sustained bone morphogenetic protein-2 (BMP-2) delivery of the microspheres and the effect of cell differentiation, and in vivo assessment with rabbits revealed that the microspheres filled the defect well and that bone could be regenerated through the microspheres. Moreover, the composite system was more effective for bone regeneration than the bare BCP microspheres because of the drug retention of collagen. These findings indicate that the porous microspheres are effective for tissue regeneration by continuous growth factor delivery.
Assuntos
Fosfatos de Cálcio/química , Microesferas , Alicerces Teciduais/química , Animais , Proteína Morfogenética Óssea 2/química , Regeneração Óssea/fisiologia , Masculino , Osteogênese/fisiologia , Polímeros/química , Porosidade , CoelhosRESUMO
Polymeric vascular grafts have been widely used in the vascular regeneration field because of their ease of application. However, synthetic polymer grafts have the severe problem of low biocompatibility, which may cause delayed endothelialization and hyperplasia. In this study, we fabricated a linear hydroxyapatite (HA) pattern on a silicon wafer and then transferred the pattern to a poly(L-lactic)-acid (PLLA) film for use as a tubular vascular graft. The HA pattern with its characteristic needle-like shape was successfully embedded into the PLLA. The HA-patterned PLLA film exhibited superior mechanical stability compared with that of a HA-coated PLLA film under bending, elongation, and in vitro circulation conditions, suggesting its suitability for use as a tubular vascular graft. In addition, the HA pattern guided rapid endothelialization by promoting proliferation of endothelial cells and their migration along the pattern. The hemocompatibility of the HA-patterned PLLA was also confirmed, with substantially fewer platelets adhered on its surface. Overall, in addition to good mechanical stability, the HA-patterned PLLA exhibited enhanced biocompatibility and hemocompatibility compared with pure PLLA.
Assuntos
Durapatita/química , Teste de Materiais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Plaquetas/citologia , Plaquetas/metabolismo , Adesão Celular/efeitos dos fármacos , Durapatita/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Poliésteres/química , Alicerces Teciduais/química , Enxerto Vascular/métodosRESUMO
For hydrogel injection applications, it is important to improve the strength and biostability of the hydrogel as well as its injectability to pass easily through the needle. Making gel microspheres is one approach to achieve these improvements. Granulization of a bulk hydrogel is a common procedure used to form microsized particles; however, the nonuniform size and shape cause an uneven force during injection, damaging the surrounding tissue and causing pain to the patients. In this study, injectable hyaluronic acid (HA)-based hybrid hydrogel microspheres were fabricated using a water-in-oil emulsion process. The injectability was significantly enhanced because of the relatively uniform size and spherical shape of the hydrogel formulates. In addition, the biostability and mechanical strength were also increased owing to the increased cross-linking density compared with that of conventionally fabricated gel microparticles. This tendency was further improved after in situ calcium phosphate precipitation. Our findings demonstrate the great potential of HA-based hydrogel microspheres for various clinical demands requiring injectable biomaterials.
RESUMO
Thiolated biodegradable polyurethane (TG-DPU) was synthesized using a one-pot reaction with thioglycerol adopted as a functionalized chain extender. After characterization of the chemical structure of TG-DPU using proton nuclear magnetic resonance spectroscopy, bone morphogenetic protein (BMP-2) was loaded in the TG-DPU under oxidative conditions to form disulfides between the free thiol of TG-DPU and BMP-2. The interaction between TG-DPU and BMP-2, so-called bioconjugates, was investigated using X-ray photoelectron spectroscopy analysis; the appearance of disulfide (S-S) linkage indicated the formation of a polymer/growth factor conjugate system. The covalently linked bioconjugates provided stability with minimal loss during the drug delivery with prolonged release performance in in vitro release tests. The effects of the drugs delivered by TG-DPU were also confirmed by in vitro alkaline phosphatase tests using pre-osteoblasts and in vivo bone regeneration tests. The drugs effectively induced cell differentiation and promoted mature bone recovery.
Assuntos
Proteína Morfogenética Óssea 2/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Preparações de Ação Retardada/química , Glicerol/análogos & derivados , Poliuretanos/química , Animais , Materiais Biocompatíveis/química , Proteína Morfogenética Óssea 2/farmacologia , Linhagem Celular , Glicerol/química , Camundongos , Osteogênese/efeitos dos fármacos , Porosidade , Coelhos , Nanomedicina Teranóstica , Engenharia TecidualRESUMO
In this work, highly lubricous hyaluronic acid-silica (HA-SiO2) nanohybrid coatings were fabricated through a sequential process consisting of a sol-gel followed by electrophoretic deposition (EPD). SiO2 nanoparticles were uniformly distributed in the coating layers, and the coating thickness was identified as approximately 1-2⯵m regardless of the amount of SiO2. Incorporation of SiO2 into the HA polymer matrix enhanced the mechanical stability of the nanohybrid coatings, indicating greater interfacial bonding strength compared to HA coating layers alone. In addition, due to improved stability, the nanohybrid coatings showed excellent biolubrication properties, which were evaluated with a tribological experiment. These results indicate that the nanohybrid coatings have great potential to be used in biomedical applications that require superior biolubrication properties.
Assuntos
Tecnologia Biomédica , Ácido Hialurônico/química , Hidrogéis/química , Nanopartículas/química , Dióxido de Silício/química , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
The medical applications of porous Mg scaffolds are limited owing to its rapid corrosion, which dramatically decreases the mechanical strength of the scaffold. Mimicking the bone structure and composition can improve the mechanical and biological properties of porous Mg scaffolds. The Mg structure can also be coated with HA by an aqueous precipitation coating method to enhance both the corrosion resistance and the biocompatibility. However, due to the brittleness of HA coating layer, cracks tend to form in the HA coating layer, which may influence the corrosion and biological functionality of the scaffold. Consequently, in this study, hybrid poly(ether imide) (PEI)-SiO2 layers were applied to the HA-coated biomimetic porous Mg to impart the structure with the high corrosion resistance associated with PEI and excellent bioactivity with SiO2. The porosity of the Mg was controlled by adjusting the concentration of the sodium chloride (NaCl) particles used in the fabrication via the space-holder method. The mechanical measurements showed that the compressive strength and stiffness of the biomimetic porous Mg increased as the portion of the dense region increased. In addition, following results show that HA/(PEI-SiO2) hybrid-coated biomimetic Mg is a promising biodegradable scaffold for orthopedic applications. In-vitro testing revealed that the proposed hybrid coating reduced the degradation rate and facilitated osteoblast spreading compared to HA- and HA/PEI-coating scaffolds. Moreover, in-vivo testing with a rabbit femoropatellar groove model showed improved tissue formation, reduced corrosion and degradation, and improved bone formation on the scaffold. STATEMENT OF SIGNIFICANCE: Porous Mg is a promising biodegradable scaffold for orthopedic applications. However, there are limitations in applying porous Mg for an orthopedic biomaterial due to its poor mechanical properties and susceptibility to rapid corrosion. Here, we strategically designed the structure and coating layer of porous Mg to overcome these limitations. First, porous Mg was fabricated by mimicking the bone structure which has a combined structure of dense and porous regions, thus resulting in an enhancement of mechanical properties. Furthermore, the biomimetic porous Mg was coated with HA/(PEI-SiO2) hybrid layer to improve both corrosion resistance and biocompatibility. As the final outcome, with tunable mechanical and biodegradable properties, HA/(PEI-SiO2)-coated biomimetic porous Mg could be a promising candidate material for load-bearing orthopedic applications.
Assuntos
Materiais Biomiméticos , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos , Materiais Revestidos Biocompatíveis , Magnésio , Teste de Materiais , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Substitutos Ósseos/química , Substitutos Ósseos/farmacologia , Linhagem Celular , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Força Compressiva , Corrosão , Magnésio/química , Magnésio/farmacologia , Masculino , Camundongos , Osteogênese/efeitos dos fármacos , Porosidade , CoelhosRESUMO
Poly(lactic acid) (PLA) is the most utilized biodegradable polymer in orthopedic implant applications because of its ability to replace regenerated bone tissue via continuous degradation over time. However, the poor osteoblast affinity for PLA results in a high risk of early implant failure, and this issue remains one of the most difficult challenges with this technology. In this study, we demonstrate the use of a new technique in which plasma immersion ion implantation (PIII) is combined with a conventional DC magnetron sputtering. This technique, referred to as sputtering-based PIII (S-PIII), makes it possible to produce a tantalum (Ta)-implanted PLA surface within 30 s without any tangible degradation or deformation of the PLA substrate. Compared to a Ta-coated PLA surface, the Ta-implanted PLA showed twice the surface roughness and substantially enhanced adhesion stability in dry and wet conditions. The strong hydrophobic surface properties and biologically relatively inert chemical structure of PLA were ameliorated by Ta S-PIII treatment, which produced a moderate hydrophilic surface and enhanced cell-material interactions. Furthermore, in an in vivo evaluation in a rabbit distal femur implantation model, Ta-implanted PLA demonstrated significantly enhanced osseointegration and osteogenesis compared with bare PLA. These results indicate that the Ta-implanted PLA has great potential for orthopedic implant applications.
Assuntos
Poliésteres/química , Tantálio/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Fêmur/diagnóstico por imagem , Fêmur/patologia , Íons/química , Camundongos , Osseointegração/efeitos dos fármacos , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Próteses e Implantes , Coelhos , Propriedades de Superfície , Molhabilidade , Microtomografia por Raio-XRESUMO
The creation of a moist environment and promotion of cell proliferation and migration together with antibacterial property are critical to the wound-healing process. Alginate (Alg) is an excellent candidate for injectable wound dressing materials because it can form a gel in a mild environment. Taking advantage of its gelation property, an injectable nano composite hydrogel containing nano-sized (about 90â¯nm) calcium fluoride (CaF2) particles was developed using in-situ precipitation process. The amount of released fluorine (F-) ion from the nanocomposite hydrogel increased with increasing CaF2 content inside the composite hydrogel and the ions stimulated both the proliferation and migration of fibroblast cells in vitro. The antibacterial property of the composite hydrogel against E. coli and S. aureus was confirmed through colony formation test where the number of bacterial colonies significantly decreased compared to Alg hydrogel. The in vivo results based on a full-thickness wound model showed that the nanocomposite hydrogel effectively enhanced the deposition of the extracellular matrix compared to that of the Alg hydrogel. This study demonstrates the potential of this nanocomposite hydrogel as a bioactive injectable wound-dressing material with the ability to inhibit bacterial growth and stimulate cell proliferation and migration for accelerated wound healing.
Assuntos
Alginatos/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Flúor/farmacologia , Hidrogéis/química , Injeções , Nanocompostos/química , Animais , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Precipitação Química , Reagentes de Ligações Cruzadas/química , Escherichia coli/efeitos dos fármacos , Inflamação/patologia , Íons , Masculino , Camundongos , Nanocompostos/ultraestrutura , Ratos Sprague-Dawley , Reologia , Staphylococcus aureus/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Difração de Raios XRESUMO
In this study, we report the development of a hyaluronic acid (HA)-based composite hydrogel containing calcium fluoride (CaF2) with good biocompatibility and antibacterial properties for multifunctional wound dressing applications. CaF2 was newly selected for incorporation within HA because it can release both Ca2+ and F- ions, which are well-known ions for affecting cell proliferation and inhibiting bacterial growth, respectively. In particular, an in situ precipitation process enables easy control over the released amount of F- ions by simply adjusting the precursor solutions (calcium chloride (CaCl2) and ammonium fluoride (NH4F)) used for the CaF2 precipitation. CaF2 particles were uniformly embedded within a HA-based pure hydrogel using an in situ precipitation process. Through variation of the CaCl2 and NH4F concentrations used in the precipitation as well as the precipitation time, composite hydrogels with different ion-release profiles were obtained. By controlling the precipitation time, especially for 10 min and after 30 min, large differences in the ion-release profiles as a function of CaF2 concentration were observed. A shorter precipitation time resulted in faster release of fluoride, whereas for the 30 min and 1 h samples, sustained ion release was achieved. Colony tests and live/dead assays using Escherichia coli and Staphylococcus aureus revealed a lower density of bacteria on the CaF2 composite hydrogels than on the pure hydrogel for both strains. In addition, improved cellular responses such as cell attachment and proliferation were also observed for the CaF2 composite hydrogels compared to those for the pure hydrogel. Furthermore, the composite hydrogels exhibited excellent wound healing efficiency, as evidenced by an in vitro cell migration assay. Finally, monitoring of the wound closure changes using a full-thickness wound in a rat model revealed the accelerated wound healing capability of the CaF2 composite hydrogels compared with that of the pure hydrogel. Based on our findings, these CaF2 composite hydrogels show great potential for application as advanced hydrogel wound dressings with antibacterial properties and accelerated wound-healing capabilities.
RESUMO
This study reports the development of a bilayered scaffold with aligned channels produced via a sequential coextrusion and unidirectional freezing process to facilitate upward bone-marrow stem-cell migration. The biomimetic scaffold with collagen and biphasic calcium phosphate (BCP) layers is successfully fabricated with matching of the cartilage and bone layers. The aligned structure results in an enhancement of the compressive strength, and the channels enable tight anchoring of the collagen layers on the BCP scaffolds compared with a randomly structured porous scaffold. An in vitro evaluation demonstrates that the aligned channels guide the cells to attach on the surface in highly stretched shapes and migrate upward faster than the random structure. In addition, in vivo assessment reveals that the aligned channels yield superior osteochondral tissue regeneration compared with the random structure. Moreover, the channel diameter greatly affects the tissue regeneration, and the scaffold with a channel diameter of ≈270 µm exhibits the optimal regeneration because of sufficient nutrient supply and adequate tissue ingrowth. These findings indicate that the introduction of aligned channels to a bilayered scaffold provides an effective approach for osteochondral tissue regeneration.
Assuntos
Regeneração Óssea , Colágeno/química , Hidroxiapatitas/química , Engenharia Tecidual , Alicerces Teciduais , Animais , Biomimética , Cartilagem , Processamento de Imagem Assistida por Computador , Masculino , Porosidade , CoelhosRESUMO
Radiotherapy (RT) has been used for decades as one of the main treatment modalities for cancer patients. The therapeutic effect of RT has been primarily ascribed to DNA damage leading to tumor cell death. Besides direct tumoricidal effect, RT affects antitumor responses through immune-mediated mechanism, which provides a rationale for combining RT and immunotherapy for cancer treatment. Thus far, for the combined treatment with RT, numerous studies have focused on the immune checkpoint inhibitors and have shown promising results. However, treatment resistance is still common, and one of the main resistance mechanisms is thought to be due to the immunosuppressive tumor microenvironment where myeloid-derived suppressor cells (MDSCs) play a crucial role. MDSCs are immature myeloid cells with a strong immunosuppressive activity. MDSC frequency is correlated with tumor progression, recurrence, negative clinical outcome, and reduced efficacy of immunotherapy. Therefore, increasing efforts to target MDSCs have been made to overcome the resistance in cancer treatments. In this review, we focus on the role of MDSCs in RT and highlight growing evidence for targeting MDSCs in combination with RT to improve cancer treatment.
RESUMO
Environmental toxicants such as toxic metals can alter epigenetic regulatory features such as DNA methylation, histone modification, and non-coding RNA expression. Heavy metals influence gene expression by epigenetic mechanisms and by directly binding to various metal response elements in the target gene promoters. Given the role of epigenetic alterations in regulating genes, there is potential for the integration of toxic metal-induced epigenetic alterations as informative factors in the risk assessment process. Here, we focus on recent advances in understanding epigenetic changes, gene expression, and biological effects induced by toxic metals.
Assuntos
Adamantano/análogos & derivados , Trifosfato de Adenosina/metabolismo , Benzamidas/farmacologia , Melaninas/biossíntese , Antagonistas do Receptor Purinérgico P2X/farmacologia , Pigmentação da Pele/efeitos dos fármacos , Adamantano/farmacologia , Células Cultivadas , Humanos , Melaninas/análise , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Cultura Primária de Células , Receptores Purinérgicos P2X7/metabolismo , Pigmentação da Pele/fisiologia , Antígeno gp100 de Melanoma/metabolismoRESUMO
PURPOSE: To determine failure patterns and survival outcomes of T4N0-1 non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. MATERIALS AND METHODS: Ninety-five patients with T4N0-1 NSCLC who received definitive radiotherapy with or without chemotherapy from May 2003 to October 2014 were retrospectively reviewed. The standard radiotherapy scheme was 66 Gy in 30 fractions. The main concurrent chemotherapy regimen was 50 mg/m2 weekly paclitaxel combined with 20 mg/m2 cisplatin or AUC 2 carboplatin. The primary outcome was overall survival (OS). Secondary outcomes were failure patterns and toxicities. RESULTS: The median age was 64 years (range, 34 to 90 years). Eighty-eight percent of patients (n = 84) had an Eastern Cooperative Oncology Group performance status of 0-1, and 42% (n = 40) experienced pretreatment weight loss. Sixty percent of patients (n = 57) had no metastatic regional lymph nodes. The median radiation dose was EQD2 67.1 Gy (range, 56.9 to 83.3 Gy). Seventy-one patients (75%) were treated with concurrent chemotherapy; of these, 13 were also administered neoadjuvant chemotherapy. At a median follow-up of 21 months (range, 1 to 102 months), 3-year OS was 44%. The 3-year cumulative incidences of local recurrence and distant recurrence were 48.8% and 36.3%, respectively. Pretreatment weight loss and combined chemotherapy were significant factors for OS. Acute esophagitis over grade 3 occurred in three patients and grade 3 chronic esophagitis occurred in one patient. There was no grade 3-4 radiation pneumonitis. CONCLUSION: Definitive radiotherapy for T4N0-1 NSCLC results in favorable survival with acceptable toxicity rates. Local recurrence is the major recurrence pattern. Intensity modulated radiotherapy and radio-sensitizing agents would be needed to improve local tumor control.
Assuntos
Humanos , Área Sob a Curva , Carboplatina , Carcinoma Pulmonar de Células não Pequenas , Cisplatino , Tratamento Farmacológico , Esofagite , Seguimentos , Incidência , Linfonodos , Paclitaxel , Pneumonite por Radiação , Radioterapia , Recidiva , Estudos Retrospectivos , Redução de PesoRESUMO
The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family of cytokines. TRAIL selectively induces apoptotic cell death in various tumors and cancer cells, but it has little or no toxicity in normal cells. Agonism of TRAIL receptors has been considered to be a valuable cancer-therapeutic strategy. However, more than 85% of primary tumors are resistant to TRAIL, emphasizing the importance of investigating how to overcome TRAIL resistance. In this report, we have found that nemadipine-A, a cell-permeable L-type calcium channel inhibitor, sensitizes TRAIL-resistant cancer cells to this ligand. Combination treatments using TRAIL with nemadipine-A synergistically induced both the caspase cascade and apoptotic cell death, which were blocked by a pan caspase inhibitor (zVAD) but not by autophagy or a necrosis inhibitor. We further found that nemadipine-A, either alone or in combination with TRAIL, notably reduced the expression of survivin, an inhibitor of the apoptosis protein (IAP) family of proteins. Depletion of survivin by small RNA interference (siRNA) resulted in increased cell death and caspase activation by TRAIL treatment. These results suggest that nemadipine-A potentiates TRAIL-induced apoptosis by down-regulation of survivin expression in TRAIL resistant cells. Thus, combination of TRAIL with nemadipine-A may serve a new therapeutic scheme for the treatment of TRAIL resistant cancer cells, suggesting that a detailed study of this combination would be useful.
Assuntos
Humanos , Apoptose , Autofagia , Canais de Cálcio Tipo L , Morte Celular , Citocinas , Regulação para Baixo , Felodipino , Necrose , Receptores do Ligante Indutor de Apoptose Relacionado a TNF , Interferência de RNA , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: Geriatric depression is a disease, that possibly can cause serious problems, in case it is not detected and treated. As the mean age of patients on Sorok Island increases, possibility of depression along with dementia rises, but up to date prevalence of this disease in this population has not been studied. This study identifies dementia and depression in patients on Sorok Island via a questionnaire survey, to incorporate the results in future treatment. METHOD: Two hundred thirty-six Sorok Island residents (142 male, 94 female) were enrolled in this survey including Geriatric depression scale (GDS), Korean modified Mini Mental Status Exam (k-mMMSE), and Global Deterioration Scale (GDS). RESULTS: Suspicious group of depression was found in 25% and Certain group of depression in 17%, which adds up to a high overall prevalence of 42%. There was no gender difference in Suspicious group of depression, but Certain group of depression was significantly more prevalent in women compared to men. Suspicious group of depression detected with k-mMMSE and GDS showed a prevalence of 30% and 35%, respectively, and prevalence was higher in women. Comparing depression group to non-depression group, a significantly higher prevalence of depression group was detected in patients with symptoms of dementia. CONCLUSION: The results, compared to prevalence studies in other populations, showed a higher prevalence of depression and dementia in patients on Sorok Island. This may be due to the relatively higher mean age or due to a realtively lower functional level of the patients. Possiblity of dementia accompanied by depression is high, and in geriatric patients, the denial of depression or misinterpretation of it as somatic disorders is common. Thus, implication of these results in treatment may yield an improvement of future outcome.
Assuntos
Feminino , Humanos , Masculino , Estudos Transversais , Demência , Negação em Psicologia , Depressão , Estudos Epidemiológicos , Hanseníase , Prevalência , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To determine the effect of hormone replacement therapy on bone mineral density and biochemical marker of bone metabolism in postmenopausal women receiving hormone replacement therapy. METHOD: We have treated two groups of menopausal women for 4 years; Group 1 received Conjugated Equine Estrogen 0.625 mg (Premarin(R)); Group 2 received Cyclic combined therapy, estrogen and progestin, (Premarin(R) 0.625 mg per day, Provera(R) 10mg per day for 12days), Group 1 was hysterectomized women, received Conjugated Equine Estrogen 0.625 mg per day. We compared the change of bone marker, osteocalcin and bone mineral density during therapy. RESULT: The data demonstrated a beneficial effect in bone marker, osteocalcin decreased in two groups from the baseline values. And hormone replacement therapy shows the beneficial effect in bone mineral densities. Spine BMD increased in two groups by 3.67%, 3.04% after 4years. Femur BMD increased in two groups by 5.34%, 5.25% from the initial value after 4 years. CONCLUSION: Our study results suggest that single estrogen therapy and cyclic combined therapy have benificial effect on increased BMD and decreased bone marker, osteocalcin. Their effects were not signigicantly different between two groups.
Assuntos
Feminino , Humanos , Biomarcadores , Densidade Óssea , Estrogênios , Fêmur , Terapia de Reposição Hormonal , Metabolismo , Osteocalcina , Coluna VertebralRESUMO
OBJECTIVES: Alcohol-induced oxidative stress has been known to injure various tissues or organs. This stress is related with free radicals which are produced as the result of long-term alcohol consumption. Malonyldialdehyde(MDA) is produced by the interaction of free radicals and cell membrane lipids, and indicates the degree of lipid peroxidation indirectly. The purpose of this study was to investigate the relationship between red blood cell(RBC) membrane lipid peroxidation by free radicals, and associated hepatic injuries and hematologic changes. METHODS: Thirty-three subjects diagnosed as alcohol dependence according to DSM-IV diagnostic criteria were evaluated within 72 hours after discontinuing alcohol drinking. Clinical characteristics were evaluated by CAGE questionnaire and Korean Michigan Alcoholism Screening Test(MAST). RBC membrane MDA level was measured as the marker of RBC membrane lipid peroxidation. Aspartate aminotransferase(AST), alanine aminotransferase(ALT) and gamma-glutamyltransferase(GGT) were used as the biochemical markers of liver damage due to alcohol ingestion. The alcohol-induced hematologic change was assessed by mean corpuscular volume(MCV). RESULTS: The results were as follows. Clinical characteristics were not different between two groups having normal and abnormal levels of AST, ALT, GGT or MCV. The levels of MDA were not correlated with the clinical characteristics and serum levels of AST, ALT and GGT. However, there was a significant correlation between the levels of MDA and the value of MCV(p=0.017). CONCLUSIONS: These findings suggest that oxidative stress in alcohol dependence may not be reflected in liver enzyme markers such as AST, ALT and GGT, but may be reflected in MCV.
Assuntos
Humanos , Alanina , Consumo de Bebidas Alcoólicas , Alcoolismo , Aspartato Aminotransferases , Ácido Aspártico , Biomarcadores , Manual Diagnóstico e Estatístico de Transtornos Mentais , Ingestão de Alimentos , Índices de Eritrócitos , Eritrócitos , Radicais Livres , Peroxidação de Lipídeos , Fígado , Programas de Rastreamento , Lipídeos de Membrana , Membranas , Michigan , Estresse Oxidativo , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: This study was performed to compare the clinical characteristics of benign and malignant tumor in postmenopausal woman. METHODS: We reviewed the chart of 91 postmenopausal women over 50 years of age, operated and confirmed by postoperative histopathologic study at Department of Obstetrics and Gynecology, Soonchunhyang Chunan Hospital, from January 1st 1995 to December 31th 1998. RESULTS: Benign ovarian tumor was found in 85.7% (78 cases) and malignant ovarian tumor was found in 14.3% (13 cases). Age distribution of malignant ovarian tumors showed the highest frequency in the age group 61-65 years compared to benign ovarian tumor. In the larger than 10 cm in tumor size, there were 7 benign (58.3%) and 5 malignant (41.7%) lesion. There was no evidence of malignant tumor according to the parity. In malignant lesion, stage I was seen in 15.4%, stage II in 30.7%, stage III in 7.7%, stage IV in 23.0% and unexplored in 23.0%. Tumor marker of CA 125 in malignant lesion was increased in 69.2%. As the subjective symptoms of benign lesions, no symptom was noticed in 38.4%, but in malignant lesions, lower abdominal pain was noticed in 38.4% as the most common. Bilaterality in benign lesions was noted in 29.4% and the same in malignant lesions was 15.3%. CONCLUSIONS: Considering the above results, as the tumor size increases, the risk of malignancy increases.
Assuntos
Feminino , Humanos , Dor Abdominal , Distribuição por Idade , Ginecologia , Obstetrícia , ParidadeRESUMO
Although adenosine (Ado) is being recently recognized as a potent inducer of apoptosis, molecular mechanism of apoptosis by Ado remains to be elucidated. In this study we observed that c-Myc was rapidly down-regulated in the apoptosis in human promyelocytic leukemia HL-60 cells treated with Ado. To establish the molecular and biochemical mechanisms of apoptosis, we tested the specific effects of several antagonists of Ado receptors or inhibitors of Ado transporter on the induction of apoptosis. Treatment of dipyridamole (DPD), an Ado transport inhibitor, effectively suppressed both c-Myc reduction and DNA fragmentation, suggesting that the induction of apoptosis and down-regulation of c-Myc is mediated by active Ado transporter. It was another evidence supporting the entrance of Ado into cells undergoing apoptosis that Ado cytotoxicity was potentiated by a addition of methylation cycle intermediates. These results suggest that the active Ado transporter-mediated Ado entrance into HL-60 cells leads to the induction of apoptosis through down-regulation of c-Myc.