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This study aimed to determine the influence of psychiatric training and hands-on learning with individuals with mental illness on increasing medical students' benevolent attitudes towards psychiatry and psychiatric patients. The cross-sectional study compares medical students' attitudes before and after a compulsory psychiatry curriculum and psychiatric bedside training at Hanoi Medical University with those of non-medical students who have yet to undergo similar training. Two validated scales regarding the attitudes toward psychiatry and psychiatric patients were evaluated. Analysis of the Medical Conditions Regard Scale[1] revealed a significant difference, indicating that medical students displayed more accepting and benevolent attitudes towards psychiatry and psychiatric patients after completing the curriculum and bedside training than medical students before participation. Most stigmatising and rejecting attitudes were found among non-medical students. This study is the first to examine medical students' attitudes toward psychiatry and psychiatric patients compared to non-medical students in Vietnam. It can guide the development of the medical curriculum to increase benevolence towards psychiatric patients and interest in the psychiatric field of work in Vietnam and Southeast Asia, aiming to improve the mental health care sector.
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Transtornos Mentais , Estudantes de Medicina , Humanos , Estudos Transversais , Estigma Social , Estudantes de Medicina/psicologia , Vietnã , Inquéritos e Questionários , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Currículo , Atitude do Pessoal de SaúdeRESUMO
Lithium-ion batteries lay the foundation for satisfying the fast-growing demand of portable electronics and electric vehicles. However, due to the complexity of material syntheses, high fabrication temperature condition, and toxic gas emission, high volume manufacturing of lithium-ion batteries is still challenging. Here, we propose a modified coprecipitation method to synthesize Li1.0Ni0.6Mn0.2Co0.2O2 (NMC622-MCP) as a cathode material in a simple, cost-effective, and environmentally friendly approach. We demonstrate that the proposed method can be operated in a lower temperature environment, with respect to the requirement of conventional synthesis methods. Furthermore, only CO2 gas is emitted during synthesis. We also employed first-principles simulations to evaluate the crystallinity of the synthesized materials via X-ray diffractometer patterns. During charge/discharge processes, the obtained cathode materials induce outstanding electrochemical performance with a maximum specific capacity of up to 206.9 mAh g-1 at 0.05 C and a retention capacity of 83.22% after 100 cycles. Thus, the simple, cost-effective, environmentally friendly, and highly electrochemical performance of the newly acquired material envisages the modified coprecipitation method as a promising tool to manufacture cathode materials for lithium-ion batteries.
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PURPOSE: To determine the role of Doppler ultrasonography when combined with B-mode ultrasonography in diagnosing uterine intracavitary pathologies (UIPs) in perimenopausal and postmenopausal bleeding women. METHODS: This multicentre prospective observational study included 150 women aged > 40 years with abnormal uterine bleeding (AUB), who were hospitalised at Hospital X and Hospital Y between June 2016 and June 2019. All participants underwent transvaginal B-mode ultrasound and transvaginal Doppler ultrasound, and the results of sonography were compared to histopathological endpoint. RESULTS: The morphological features, structure, margin, border line of the endometrial-mass lesion, intracavitary uterine fluid, and Doppler signal clearly differed between benign and malignant intracavitary pathologies (p < 0.0001). However, echogenicity had a limited value in differentiating among UIPs (p = 0.1). The sensitivity and specificity of the pedicle sign in diagnosing endometrial polyps were 50.0% and 97.6%; for the circular pattern in endometrial fibroids were 46.2% and 100.0%; for the multiple vessel pattern in endometrial cancer were 64.0% and 96.0%; and for the scattered vessel pattern in endometrial hyperplasia were 43.96% and 56.43%, respectively. The additional value of Doppler ultrasound was greater than that of separate B-mode ultrasound in assessing UIPs in our study. CONCLUSIONS: B-mode ultrasound used in combination with Doppler as a noninvasive tool was significantly valuable in the diagnostic procedures for UIPs in perimenopausal and postmenopausal bleeding women. Doppler ultrasound and B-mode transvaginal ultrasound should be used together routinely for discrimination between malignant diseases and benign endometrial changes. Further studies are needed to better understand the benefits of combining Doppler ultrasound and B-mode ultrasound in routine sonographic practice.
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Pós-Menopausa , Doenças Uterinas , Feminino , Humanos , Perimenopausa , Vietnã , Ultrassonografia , Hemorragia Uterina/diagnóstico por imagem , Hemorragia Uterina/patologia , Ultrassonografia Doppler/métodos , Sensibilidade e EspecificidadeRESUMO
Objectives: To determine the role of B-mode ultrasonography combined with Doppler ultrasonography in diagnosing uterine intracavitary pathology in perimenopausal and postmenopausal women with abnormal uterine bleeding (AUB). Patients and Methods: This prospective observational study included 150 women aged >40 years with AUB hospitalized at Hue University Hospital and Hue Central Hospital between 6/2016 and 6/2019. All participants were investigated by B-mode transvaginal ultrasound and Doppler transvaginal ultrasound, and the result of sonography was compared to the histopathological endpoint. Results: The morphological features, structure, margin, border line of the endometrial-mass lesion, intracavitary uterine fluid, and Doppler signal clearly differed between benign and malignant intracavitary pathologies (P < 0.0001). However, echogenicity had a limited value in distinguishing between uterine intracavitary pathologies (P = 0.1). The sensitivity and specificity of the pedicle sign in diagnosing endometrial polyps were 50.0% and 97.6%, respectively; for the circular pattern in subendometrial fibroids were 46.2% and 100.0%, respectively; for the multiple vessel pattern in endometrial cancer were 64.0% and 96.0%, respectively, and for the scattered-vessel pattern in endometrial hyperplasia were 43.96% and 56.43%, respectively. Conclusions: Ultrasound B-mode combined with Doppler as a noninvasive tool was significantly valuable in the diagnostic procedures for uterine intracavitary pathology in perimenopausal and postmenopausal women with AUB. It could also help differentiate malignant diseases from benign endometrial changes.
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BACKGROUND AND PURPOSE: Delayed wound healing is among the deleterious consequences of over-activation of the mineralocorticoid receptor (MR) induced by topical dermocorticoids. The role of dermal inflammation and angiogenesis in the benefits of MR blockade is unknown. EXPERIMENTAL APPROACH: Skin wounds were made on C57Bl6 mice after topical pretreatment with the dermocorticoid clobetasol. The impact of topical MR blockade by canrenoate on inflammation, angiogenesis, and the wound macrophage phenotype was analysed 5 days post-wounding. Similar experiments were conducted on mice with genetic deletion of the MR in myeloid cells. KEY RESULTS: Topical inhibition of the MR with canrenoate improved delayed wound healing through the resolution of prolonged inflammation in glucocorticoid-pretreated mouse skin. This effect was associated with a higher ratio of anti-inflammatory macrophages versus pro-inflammatory macrophages in wounds treated by canrenoate. Furthermore, MR blockade led to upregulated expression of pro-angiogenic factors and improved impaired angiogenesis in wounds of glucocorticoid-pretreated skin. Finally, deletion of MR expression by myeloid cells reproduced the benefits of topical pharmacological MR blockade. CONCLUSION AND IMPLICATIONS: Topical MR antagonism facilitates the switching of macrophages towards an anti-inflammatory phenotype, which improves prolonged inflammation and induces angiogenesis to accelerate wound healing delayed by glucocorticoid treatment.
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Glucocorticoides , Receptores de Mineralocorticoides , Camundongos , Animais , Receptores de Mineralocorticoides/metabolismo , Glucocorticoides/farmacologia , Glucocorticoides/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Cicatrização , Pele/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismoRESUMO
OBJECTIVE: To determine the value of endometrial thickness (ET) and Doppler indices of uterine artery (UtA) as sonographic markers in predicting endometrial cancer (EC) among postmenopausal bleeding (PMB) women in low-resource settings as Vietnam. METHODS: This cross-sectional study was conducted at the Hue University Hospital and Hue Central Hospital between June 2016 and June 2019. The study enrolled all women who complained of PMB and were followed by transvaginal Doppler ultrasound. Their definitive histopathological examination was the gold standard for comparison. RESULTS: The UtA Doppler indices, including resistance index (RI), pulsatility index (PI), and peak systolic velocity (PSV), were significantly lower in the malignant group than in the benign group. The threshold values of the UtA, RI ≤0.73 and PI ≤1.42, were found with an area under receiver operating characteristic curve (AUC) of 0.85-0.88, and the sensitivity and specificity were 91.3% and 83.3%, respectively. Unlike PSV, the diagnostic value was the lowest, with an AUC of 0.72. ET was a good predictor for the diagnosis of EC, with an AUC of 0.89. In women with PMB, when using the cutoff value of EC more than 12.5 mm, the sensitivity and specificity were 93.8% and 77.8%, respectively. In addition, the higher the stage of EC, the lower the RI and PI and the greater the EC. CONCLUSION: ET, and RI, PI, and PSV of the UtA could help in differentiating malignant from benign endometrial changes. Pulsed ultrasonic Doppler velocimetry seems to play a role in predicting the higher stages of EC. Further studies are needed to confirm these findings.
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Background: Intracavitary uterine pathologies (IUPs) may be resulting in vaginal bleeding in perimenopausal and postmenopausal women. Especially, malignant disease needed to be investigated due to its adverse impact on the quality of mid-life women as well as the burden of health-care costs in low- and middle-income countries such as Vietnam. Objective: Thereby, through this study, we aimed to assess the major clinical features of IUPs in women with perimenopausal and postmenopausal bleeding women. Materials and Methods: This was a cross-sectional observational study at Hue University Hospital and Hue Central Hospital from June 2016 to June 2019. The study enrolled 150 women above 40 years old involving with intrauterine bleeding. Results: The mean age of the study population was 51.51 ± 7.65. The most common symptom in perimenopausal women was menorrhagia, up to 62.2% of cases. In addition to intrauterine bleeding, there were 54.7% of cases had at least one other functional symptom, they were pale skin (35.9%), and lower abdominal pain (31.3). Endometrial hyperplasia (EH) was the most common pathology in both groups with perimenopausal and postmenopausal bleeding (PMB), respectively, 66.7% and 51.7%. In PMB group, endometrial cancer (EC) occupied approximately 38.3% following EH. Our study revealed age, menstrual characteristics, and diabetes in relation to malignant disease. Other factors seemed to be less associated with EC. Conclusions: Menorrhagia was the most common type of abnormal uterine bleeding in perimenopausal women. Besides vaginal bleeding, others symptoms such as pale skin, pelvic pain, and fatigue were also common. Length day and blood loss before hospitalization in perimenopausal women were greater significantly than that in postmenopausal women. Age, menstrual characteristics, and diabetes increased the risk of EC in women with PMB.
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The ankle-brachial index (ABI) is a fast, simple, noninvasive method that provides accurate results in the early diagnosis of peripheral artery disease. Microalbuminuria is considered a predictor of renal and cardiovascular complications in patients with diabetes. This study was conducted to determine the correlation between ABI and microalbuminuria with certain risk factors in patients with type 2 diabetes. SUBJECTS AND RESEARCH METHODS: A cross-sectional descriptive study was performed on 62 inpatients with type 2 diabetes. All patients were measured for ABI as well as microalbuminuria, HbA1c, glucose and lipidemia in the blood. RESULTS: The study results showed that in patients with dyslipidemia, the risk of having microalbuminuria (+) increased 5.7 times and ABI ≤0.90 increased 8.6 times (P = 0.004 and 0.021, respectively). Fasting blood glucose >7.2 mmol/L had 5.7 times higher microalbuminuria (+) risk and 8.6 times higher ABI ≤0.90 (P = 0.004 and 0.021, respectively). Patients with HbA1c ≥7% were 2.9 times more likely to have microalbuminuria (+) and ABI ≤0.90 (P = 0.043 and 0.048, respectively). CONCLUSIONS: Peripheral vascular disease risk factors such as hypertension, dyslipidemia and waist circumference and the effectiveness of fasting blood glucose and HbA1c control increased the risk of high microalbuminuria and ABI in patients with type 2 diabetes.
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BACKGROUND AND AIMS: Herein, we aim to examine the prevalence of depression in type 2 diabetic patients at a provincial general hospital located in the Northeast region of Vietnam and to explore its relationship with some sociodemographic, lifestyle and medical history characteristics. MATERIALS AND METHODS: This was a single-centre cross-sectional descriptive study. The patients of both sexes who were at the age of 18 years or above, were treated at our institution and were diagnosed with type 2 diabetes mellitus, previously or during the study period. A total of 220 patients were included in the study. RESULTS: Depression prevalence was 32.27% according to ICD-10. The severity of depression was categorized as mild in 77.46% patients, moderate in 19.72% patients and severe in 2.82% patients. The odds of depression was 0.18 (95%CI 0.05-0.69, p = 0.012) less for those known as the upper social class compared with those in lower social class. Those who were not on insulin treatment had significantly higher odds of depression than those on treatment with insulin (OR 2.06, 95%CI: 1.01-4.21). Individuals on treatment without oral diabetes drugs had higher odd of depression compared to those being treated with oral diabetes drugs (OR 2.77, 95%CI: 1.14-6.73). Also, hypertension was an increasing contributor to the depression prevalence (OR 2.32, 95%CI: 1.10-4.90). CONCLUSIONS: A high prevalence of depression among type 2 diabetic patients was documented. Only significant factors for depression were lower social class, co-morbid hypertension and none of the insulin treatment or oral diabetes drugs.
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Biomarcadores/sangue , Glicemia/análise , Depressão/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Depressão/sangue , Depressão/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Vietnã/epidemiologiaRESUMO
BACKGROUND: Postherpetic neuralgia (PHN) is the most common and bearable complication of herpes zoster (HZ). This pain may have negative impact on the patient's all aspects of daily life and health-related quality of life (HRQOL). Despite numerous advances in treatment, many patients remain resistant to the current therapy options. It is the first time subcutaneous injection of methylprednisolone acetate and lidocaine has been used to treat refractory PHN. We report the results of this treatment evaluating pain relief and HRQOL improvement in this disorder. METHODS: A total of 43 patients with refractory PHN was enrolled in the observational study. All patients received daily subcutaneous injection of methylprednisolone acetate and lidocaine for 10 consecutive days. The severity of pain was assessed by using Visual Analog Scale (VAS), and 36-Item Short Form Survey (SF-36) was applied to evaluate HRQOL. Assessment of the pain and HRQOL was carried out at baseline and posttreatment at 4 weeks as well as 6 and 12 months. RESULTS: At baseline, all patients experienced severe PHN with average VAS scores of 8.44 ± 0.85 (minimum 7; maximum 10). At 4 weeks, 6 months, and 12 months after treatment, the pain had significantly decreased (P < .001), and all subjects showed significant improvement in all eight domains of HRQOL. No major adverse events associated with the subcutaneous injection were observed. CONCLUSIONS: Our results indicate that subcutaneous injection of methylprednisolone acetate and lidocaine can be an effective and safe treatment for PHN.
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Skin ulcers resulting from impaired wound healing are a serious complication of diabetes. Unresolved inflammation, associated with the dysregulation of both the phenotype and function of macrophages, is involved in the poor healing of diabetic wounds. Here, we report that topical pharmacological inhibition of the mineralocorticoid receptor (MR) by canrenoate or MR small interfering RNA can resolve inflammation to improve delayed skin wound healing in diabetic mouse models; importantly, wounds from normal mice are unaffected. The beneficial effect of canrenoate is associated with an increased ratio of anti-inflammatory M2 macrophages to proinflammatory M1 macrophages in diabetic wounds. Furthermore, we show that MR blockade leads to downregulation of the MR target, LCN2, which may facilitate macrophage polarization toward the M2 phenotype and improve impaired angiogenesis in diabetic wounds. Indeed, diabetic LCN2-deficient mice showed improved wound healing associated with macrophage M2 polarization and angiogenesis. In addition, recombinant LCN2 protein prevented IL-4-induced macrophage switch from M1 to M2 phenotype. In conclusion, topical MR blockade accelerates skin wound healing in diabetic mice via LCN2 reduction, M2 macrophage polarization, prevention of inflammation, and induction of angiogenesis.
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Ácido Canrenoico/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Macrófagos/fisiologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Úlcera Cutânea/prevenção & controle , Pele/patologia , Animais , Diferenciação Celular , Células Cultivadas , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Modelos Animais de Doenças , Feminino , Humanos , Lipocalina-2/genética , Lipocalina-2/metabolismo , Camundongos , Camundongos Knockout , RNA Interferente Pequeno/genética , Receptores de Mineralocorticoides/genética , Úlcera Cutânea/etiologia , Cicatrização/efeitos dos fármacosRESUMO
Background: Mental health risk-factors for Asian migrants have been studied almost exclusively in the US, Canada, and Australia but not in European countries. Therefore, we aimed to identify sociodemographic, clinical, and migration-surrounding factors associated with experienced mental distress among Vietnamese migrants in Germany. Method: 305 Vietnamese migrants utilizing Germany's first Vietnamese psychiatric outpatient clinic filled out at admission the Brief-Symptom-Inventory 18 (BSI-18) as well as a questionnaire on 22 potential mental health determinants. Using a multiple linear regression model, we identified those sociodemographic, clinical, and migration-surrounding factors that were significantly related to the Global Severity Index (GSI) of the BSI-18. Results: The factors unemployment (B = -6.32, p = 0.014), financial problems (B = -10.71, p < 0.001), no or only little religious involvement (B = -3.23, p = 0.002), no psychiatric precontact (B = -7.35, p = 0.004), previous migration experiences (B = 8.76, p = 0.002), and perceived discrimination (B = 6.58, p = 0.011) were found to significantly increase the level of mental distress according to the BSI-GSI. Conclusion: Based on these results, we were able to construct a mental health risk-profile for Vietnamese migrants in Germany, which aims to detect candidates for psychiatric problems earlier and supply them with customized prevention and therapy options.
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BACKGROUND: In Vietnam, the mental health care infrastructure is on the verge of transformation with an increase in the demand for access to adequate and effective mental health care services. Public attitudes towards mental illness, as well as corresponding treatment options influence help-seeking behaviors of patients and caregivers, affecting the course of their treatment. This study assesses attitudes towards treatment options for depression and schizophrenia, as the two most common psychiatric disorders in Vietnam, accounting for at least 75% of all psychiatric inpatients. METHODS: A general population-based survey was conducted in Hanoi, Vietnam between April and August 2013. Participants received a description of a person with symptoms of either depression (n = 326) or schizophrenia (n = 403) and were asked to give recommendations for adequate sources of mental health support and treatment options. Multiple analyses on a single item level compared the likelihood of recommendation between schizophrenia and depression. RESULTS: Overall, respondents recommended health care services, ranging from seeking mental health care professionals, psychotherapists, and psychiatrists for both disorders. Psychotherapy was the most favored treatment method, whereas further treatment options, such as concentration and relaxation exercises, meditation or yoga and psychotropic medication were also endorsed as helpful. For the schizophrenia vignette condition, psychotherapy, visiting a psychiatrist or psychotherapist received stronger endorsement rates as compared to the depression vignette. Furthermore, ECT, Feng Shui-based practices, praying and visiting natural healers were recommended less by respondents for the depression vignette in comparison with the schizophrenia vignette. CONCLUSIONS: The Vietnamese public endorsed evidence-based treatment recommendations from a variety of treatments options. Differences in the treatment recommendations between depression and schizophrenia reflected the perceived severity of each disorder. Further developments of the Vietnamese mental health care system concerning mental health care providers, as well as the legal regulations surrounding the provision of psychotherapy are needed.
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Two new cycloartanes, named dolichandrone A (1) and dolichandrone B (2), as well as two new iridoids, named [6-O-[(E)-4-methoxycinnamoyl]-1ß-hydroxy-dihydrocatalpolgenin (3) and 6-O-[(E)-4-methoxycinnamoyl]-1α-hydroxy-dihydrocatalpolgenin (4), together with four known iridoids (5-8), were isolated from the leaves and barks of Dolichandrone spathacea. Their structures were elucidated by means of extensive analysis of their HRESIMS, 1D and 2D NMR spectroscopic data. All of these compounds have been isolated for the first time from this plant. Compounds 1, 2, 5, and 7 were evaluated for their cytotoxic activity in vitro against four human cancer cell lines KB, Lu, HepG2, and MCF7. The results showed that only compound 2 exhibited a good cytotoxicity against KB cell line with IC50 of 18.77 µM.
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Iridoides/química , Magnoliopsida/química , Triterpenos/química , Áreas Alagadas , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Modelos Moleculares , Estrutura Molecular , VietnãRESUMO
We recently demonstrated that blockade of the mineralocorticoid receptor (MR) effectively ameliorated GC-induced skin atrophy in healthy human skin explants and epidermal MR knockout mice. However, whether MR blockade improves the therapeutic index of glucocorticoids (GCs) in skin pathology was not investigated. We assessed the effects of GCs, MR antagonists (MRA) or both, in SDS-treated human skin explants. All treatments restored SDS-augmented epidermal thickness but only GC plus MRA restored the expression of COL1A1. However, MRA alone or in combination with GCs may exert a dual role in regulating inflammatory cytokines. Thus, although combined treatment may be beneficial to improve irritative skin, extensive in vivo testing is required to establish whether the anti-inflammatory effects of GCs are maintained in the presence of MRA.
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Anti-Inflamatórios/farmacologia , Atrofia/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Pele/efeitos dos fármacos , Animais , Atrofia/induzido quimicamente , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Epiderme/metabolismo , Glucocorticoides/farmacologia , Humanos , Queratinócitos/metabolismo , Camundongos , Camundongos Knockout , Receptores de Mineralocorticoides , Pele/metabolismo , Pele/patologiaRESUMO
Chirita drakei Burtt (now accepted as Primzina drakei (B.L.Burtt) Mich.M61ler & A.Weber) is growing on limestone mountain slopes of Ha Long Bay islands in Vietnam. The chemical investigation of the aerial parts of C. drakei led to the isolation and structural elucidation of two new compounds named chiridrakoside A (1) and chiridrakoside B (2) besides twelve known compounds comprising five phenylethanoid glycosides (3-7), two lignans (8, 9), a phenyl propanoid (10), an anthraquinone (11), a furan derivative (12) and two triterpenes (13, 14). All described compounds, except 4, 5 and 11, were obtained for the first time from the genera Chirita or Primulina. The cytotoxic activity of the isolated compounds was evaluated against the four human cancer cell lines KB (mouth epidermal carcinoma), HepG2 (hepatocellular carcinoma), Lu (lung carcinoma) and MCF7 (breast carcinoma). Epoxyconiferyl alcohol (10) exhibited cytotoxic activity against the tested cell lines (IC50 from 46 to 128 µM).
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Antineoplásicos Fitogênicos/química , Magnoliopsida/química , Extratos Vegetais/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacocinética , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , VietnãRESUMO
Impaired cutaneous wound healing is a social burden. It occurs as a consequence of glucocorticoid treatment in several pathologies. Glucocorticoids (GC) bind not only to the glucocorticoid receptor but also to the mineralocorticoid receptor (MR), both expressed by keratinocytes. In addition to its beneficial effects through the glucocorticoid receptor, GC exposure may lead to inappropriate MR occupancy. We hypothesized that dermatological use of MR antagonists (MRA) might be beneficial by overcoming the negative impact of GC treatment on pathological wounds. The potent GC clobetasol, applied as an ointment to mouse skin, or added to cultured human skin explants, induced delayed wound closure and outgrowth of epidermis with reduced proliferation of keratinocytes. Delayed wound re-epithelialization was rescued by local MRA application. Normal skin was unaffected by MRA. The benefit of MR blockade is explained by the increased expression of MR in clobetasol-treated mouse skin. Blockade of the epithelial sodium channel by phenamil also rescued cultured human skin explants from GC-impaired growth of the epidermis. MRA application over post-biopsy wounds of clobetasol-treated skin zones of healthy volunteers (from the Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy clinical trial) also accelerated wound closure. In conclusion, we propose repositioning MRA for cutaneous application to improve delayed wound closure occurring in pathology.
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Clobetasol/farmacologia , Glucocorticoides/farmacologia , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Reepitelização/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Administração Cutânea , Amilorida/análogos & derivados , Amilorida/farmacologia , Animais , Clobetasol/administração & dosagem , Epiderme/efeitos dos fármacos , Epiderme/patologia , Glucocorticoides/administração & dosagem , Humanos , Queratinócitos/metabolismo , Camundongos , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Pomadas , Receptores de Mineralocorticoides/efeitos dos fármacos , Receptores de Mineralocorticoides/metabolismo , Pele/efeitos dos fármacos , Pele/patologiaRESUMO
Leg ulcers are a major complication of sickle cell disease that occur in 2.5-40% of patients. Leg ulcers are responsible for frequent complications because they are often long-lasting and are highly resistant to therapy. Although their occurrence is associated with hyperhemolysis, the mechanisms underlying sickle cell ulcers remain poorly understood. In this study, we show that skin wound healing is severely altered in old SAD sickle cell mice but is normal in young animals, consistent with reports in humans. Alterations of wound healing were associated with impaired blood and lymphatic angiogenesis in the wound beds and poor endothelial progenitor cell mobilization from the bone marrow. CXCL12 secretion by keratinocytes and inflammatory cells was low in the wounds of SAD mice. Local therapy with endothelial progenitor cells or recombinant CXCL12 injections restored wound angiogenesis and rescued the healing defect together with mobilization of circulating endothelial progenitor cells. To our knowledge, this is a previously unreported study of the cellular and molecular mechanisms of sickle cell ulcers in a murine model that provides promising therapeutic perspectives for clinical trials.
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Anemia Falciforme/complicações , Quimiocina CXCL12/metabolismo , Neovascularização Patológica/fisiopatologia , Úlcera Cutânea/patologia , Cicatrização/fisiologia , Anemia Falciforme/patologia , Animais , Proliferação de Células , Modelos Animais de Doenças , Células Progenitoras Endoteliais/transplante , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Úlcera Cutânea/fisiopatologia , Úlcera Cutânea/cirurgia , Transplante de Células-Tronco/métodos , Fatores de TempoRESUMO
BACKGROUND: The purpose of this pilot study is to investigate the effects of local application of minocycline hydrochloride ointment (MHO) and erythromycin eye ointment (EEO) on wound healing after flapless implant surgery. METHODS: Forty patients with flapless implant surgery were enrolled and assigned randomly to three groups: 1) MHO group (n = 17); 2) EEO group (n = 18); and 3) control group (n = 5). All of them took systemic antibiotics; the control group did not receive the application of topical antibiotics. Three days after the surgical operation, clinical parameters, peri-implant crevicular fluid volume, and crevicular lipopolysaccharide (LPS) levels of all patients were collected, measured, and analyzed. RESULTS: Clinical outcomes of the two treatment groups were superior to results of the control group, indicating the effectivity of local antibiotics application in promoting early wound healing after flapless implant surgery. There was no obviously different effect between EEO and MHO in the early stages of healing. In addition, there were significant correlations between LPS level and all clinical parameters. CONCLUSIONS: The local application of antibiotics along with the systemic antibiotics could reduce the inflammatory response in wound healing after implant surgery. The EEO and MHO were equally effective in early wound healing. Compared to the MHO, the EEO has advantages of higher cost efficiency and convenience. Therefore, it is recommended to use the EEO in topical antibiotic prophylaxis for wound healing after flapless implant surgery.