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BACKGROUND AND AIMS: Endoscopic therapy of gastroesophageal reflux disease (GERD) overcomes the "treatment gap" for patients with refractory GERD, who are not willing to go into surgery. We propose an easy and efficient technique that is referred to as anti-reflux mucosectomy (ARMS) using cap-assisted endoscopic mucosal resection (EMR-C) which could be called ARMS-C. This study aimed to investigate the short-term outcomes of ARMS-C in GERD patients. METHODS: From December 2016 to February 2018, we performed ARMS-C in 33 patients with pathologic reflux disease and esophageal hypersensitivity. ARMS-C involved endoscopic mucosal resection at the circumference of the esophagogastric junction (EGJ), resulting in narrowing of the hiatal opening after healing. The GERD symptoms, 24-h pH monitoring results, manometry, endoscopy, and EGJ distensibility were compared before and after the procedure. RESULTS: Six months after ARMS-C, 63% of patients discontinued the use of pump inhibitors (PPIs), while 30% patients reduced their PPI dose. The GERD questionnaire scores significantly decreased after ARMS-C, from 11.0 to 6.0 (P < 0.001). The median DeMeester score and acid exposure time based on pH monitoring also improved after ARMS-C. Furthermore, the median flap valve grade and EGJ distensibility decreased from 3.0 to 1.0 (P < 0.001) and from 19.0 to 13.9 (P < 0.001), respectively. Two patients were treated with balloon dilation due to stricture, but no other serious adverse events were encountered. CONCLUSION: ARMS-C may be an effective and safe treatment method for GERD in terms of short-term outcomes.
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Ressecção Endoscópica de Mucosa , Refluxo Gastroesofágico/cirurgia , Junção Esofagogástrica/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare (C. quadrangulare) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.
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Combretum/química , Dermatite Atópica/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pele/efeitos dos fármacos , Pele/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Citocinas/metabolismo , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/etiologia , Dermatite Atópica/patologia , Modelos Animais de Doenças , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Pele/patologiaRESUMO
BACKGROUND AND AIM: Diabetic gastropathy is associated with loss of interstitial cells of Cajal and autonomic neuropathy. Effective management for diabetic gastropathy is still unavailable. This study was aimed to confirm the pathogenetic changes in diabetic gastropathy and to examine the effect of treatment with placental-derived mesenchymal stem cells (PDMSCs) in stomachs of animal models. METHODS: Fourteen non-obese diabetic/ShiLtJ mice of 8 weeks were bled until week 30. Diabetes mellitus developed in 10 out of 14 mice, which all survived with insulin. The mice were grouped into three groups: nondiabetic group (n = 4), diabetic sham group (n = 5), and diabetic PDMSC group (n = 5) all of which were treated with intraperitoneal PDMSCs injection at week 30. All mice were killed at week 34, and the stomachs were examined by immunohistochemical stain with c-kit and neuronal nitric oxide synthase antibodies. RESULTS: The number of c-kit positive cells in stomach decreased significantly in the diabetic sham group compared with that in the nondiabetic group (21.2 ± 6.7 vs 88.0 ± 29.3, P = 0.006) but increased with PDMSC treatment (21.2 ± 6.7 vs 64.0 ± 15.1, P = 0.02). The positive rate of neuronal nitric oxide synthase in neural plexus was also significantly lower in the diabetic sham group than in the nondiabetic group (22.3% ± 18.5% vs 48.0% ± 22.7%, P = 0.003) but increased with PDMSC treatment (22.3% ± 18.5% vs 43.3% ± 20.5%, P = 0.03). CONCLUSIONS: Interstitial cells of Cajal and neural plexus decreased in stomachs of mice with diabetes mellitus but were significantly repaired with intraperitoneal injection of PDMSC.
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Diabetes Mellitus Tipo 1/complicações , Mucosa Gástrica/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Placenta/citologia , Gastropatias/etiologia , Gastropatias/terapia , Estômago/patologia , Animais , Autoanticorpos/metabolismo , Biomarcadores/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Modelos Animais de Doenças , Estudos de Viabilidade , Feminino , Imuno-Histoquímica , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos NOD , Óxido Nítrico Sintase Tipo I/imunologia , Gravidez , Proteínas Proto-Oncogênicas c-kit/metabolismo , Estômago/inervação , Gastropatias/metabolismoRESUMO
The exact pathogenesis of diarrhea-dominant irritable bowel syndrome (IBS) is not known, but the abnormal microbiota of the gastrointestinal tract is considered to be one of the important contributing factors as in other gastrointestinal diseases such as inflammatory bowel disease, antibiotic-associated diarrhea, and colorectal cancer as well as systemic diseases. Though diverse trials of probiotics had been continued in the treatment of diarrhea-IBS, only a few proved by randomized clinical trial. To prove the efficacy of Lactobacillus gasseri BNR17 isolated from breast milk in patients with diarrhea-IBS, prospective, randomized, placebo controlled clinical trial was done including health related-quality of life analysis, colon transit time, and the changes of fecal microbiota. BNR17 significantly improved the symptoms of diarrhea compared to control group. Health related-QOL analysis showed significant improvement of abdominal pain, distension, disturbed daily life, and mean defecation frequency with BNR17. On comparative CTT before and after BNR17, 6 out of 24 subjects showed significant correction of rapid colon transit pattern, while only 2 out of 24 in placebo (p<0.01). Upon fecal microbiota analysis, BNR17 significantly increased B. fecalis, E. rectale, C. aerofaciens, F. prausnitzil and B. steroris. Conclusively, Lactobacillus gasseri BNR17 can be a potential probiotics to ameliorate diarrhea-IBS.
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BACKGROUND AND AIM: There is controversy about the surveillance interval after colonoscopy when 5-10 adenomas have been found on index colonoscopy. This study aimed to investigate the risk of colorectal neoplasm (CRN) according to the number of adenomas at index colonoscopy. METHODS: A retrospective, multicenter study was conducted at 10 university hospitals in Korea. We included 1394 patients with ≥ 3 adenomas at index colonoscopy. The risk of advanced CRN was compared according to the number of adenomas (intermediate risk group, 3-4 small adenomas or at least one ≥ 10 mm, and high risk group, ≥ 5 small adenomas or ≥ 3 at least one ≥ 10 mm). RESULTS: Overall, 164 (11.8%) developed an advanced CRN after a mean of 4.0 years from baseline colonoscopy. The 3-year and 5-year risk of advanced CRN was 2.1% (95% CI 2.09-2.11) and 14.4% (95% CI 14.36-14.44) in intermediate risk group and 3.2% (95% CI 3.19-3.21) and 23.3% (95% CI 19.15-19.25) in high risk group (P = 0.01). Having ≥ 5 adenomas (OR = 1.57, 95% CI 1.11-2.23, P = 0.01) detected at index colonoscopy was a significant risk factor for developing advanced CRN. CONCLUSIONS: Although risk of advanced CRN in patients with 5-10 adenomas was significantly higher than that in patients with 3-4 adenomas, the cumulative risk at 3 years was low at 3.2%. Thus, we suggest that a 3-year surveillance interval might be appropriate for the patients with 5-10 adenomas, and further prospective studies are needed to investigate whether more intensive surveillance is needed in this group.
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Adenoma/diagnóstico , Adenoma/epidemiologia , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/epidemiologia , Adenoma/prevenção & controle , Idoso , Neoplasias Colorretais/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Risco , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVES: With advances in diagnostic endoscopy, the detection of rectal neuroendocrine tumors (NETs) has increased. However, clinical outcomes, especially after endoscopic treatment, are still unclear. The aim of this study was to determine the long-term clinical outcomes of endoscopically resected rectal NETs according to the pathologic status after initial resection. METHODS: In this large, multicenter, retrospective cohort study, we analyzed the medical records of patients who underwent endoscopic resection of rectal NETs and were followed for ≥24 months at 16 university hospitals. The outcomes of interest were local or distant recurrence and metachronous lesions. RESULTS: On the pathologic assessment of 407 patients, the resection margin status was positive in 76 (18.7%) and indeterminate in 72 (17.7%) patients. Patients whose rectal NETs were diagnosed or suspected as NETs before resection showed a much higher complete resection rate than those whose tumors were resected as polyps and then diagnosed (P<0.001). Fourteen patients received salvage treatment at 1.9±2.8 months after initial treatment. During a median follow-up period of 45.0 months, local recurrence occurred in 3 (0.74%) patients, but there was no recurrence in the lymph nodes or distant organs. Metachronous rectal NETs were diagnosed in 3 (0.74%) patients. According to the pathologic status after initial resection, local recurrence and metachronous lesions occurred in 1 (0.4%) and 2 (0.8%) patients, respectively, in the pathologic tumor-free group, whereas they occurred in 2 (1.4%) and 1 (0.7%) patients, respectively, in the indeterminate group. CONCLUSIONS: Considering the long-term prognosis including that for recurrences or metachronous lesions, endoscopic resection is an efficient and a safe modality for the treatment of rectal NETs. This treatment may result in favorable clinical outcomes in patients with tumors of indeterminate pathology, as well as in pathologic tumor-free cases after initial resection.
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Ressecção Endoscópica de Mucosa/métodos , Pólipos Intestinais/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Retais/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colonoscopia , Feminino , Humanos , Pólipos Intestinais/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Prognóstico , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECT: As nonmicrobial dietary approach is capable of controlling Helicobacter pylori infection, we evaluated the efficacy of long-term dietary administration of Artemisia and/or green tea extracts on H. pylori-initiated, high-salt-promoted chronic atrophic gastritis and gastric tumorigenesis mouse model. METHODS: Helicobacter pylori-infected and high-salt-diet-administered C57BL/6 mice were administered with Artemisia extracts (MP group) and/or green tea extracts (GT group) for 36 weeks in addition to the control group (ES group, gastroprotective drug, ecabet sodium 30 mg/kg, diet pellet). Gross and pathological gastric lesions were evaluated after 24 and 36 weeks, respectively, and their underlying molecular changes were measured in gastric homogenates. Detailed mechanisms were further evaluated in in vitro cell models. RESULTS: The erythematous and nodular changes and mucosal ulcerative and erosive lesions were noted in the control group at 24 weeks. MP, GT, MPGT, and ES groups all showed significantly ameliorated pathologic lesion compared to the control group (p < .05). After the 36 weeks, scattered nodular masses with some central ulcers and thin gastric surface were noted in the control stomach, whereas no tumorous lesion and milder atrophic changes were observed in all MP, GT, and MPGT groups except ES group (p < .05). On molecular analysis, increased expressions of COX-2, TNF-α, IL-6, lipid peroxide, and activated STAT3 relevant to H. pylori infection were significantly decreased with MPGT administration (p < .01), whereas HSP70 was significantly increased. PGDH expressions, core tumor suppressor involved in carcinogenesis, were significantly decreased with H. pylori infection (p < .05), but significantly increased in MPGT group (p < .05). Increased mucosal apoptotic index noted in the control group was significantly decreased with MP and/or GT along with significantly preserved gastric gastroprotective mediators (p < .01) such as mucins, HSP27, and HSP70. H. pylori-induced serum TNF-α and NF-κB activations were significantly decreased with MPGT administration (p < .05). CONCLUSION: Long-term dietary intake of MP and/or GT can be an effective strategy either to rejuvenate H. pylori atrophic gastritis or to suppress tumorigenesis.
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Artemisia/química , Camellia sinensis/química , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Neoplasias Gástricas/prevenção & controle , Animais , Carcinogênese/efeitos dos fármacos , Feminino , Gastrite Atrófica/genética , Gastrite Atrófica/metabolismo , Gastrite Atrófica/microbiologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/crescimento & desenvolvimento , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: The <80 % Helicobacter pylori eradication rate with sequential therapy is unsatisfactory. Modified bismuth quadruple therapy, replacing metronidazole with amoxicillin, could be promising because H. pylori resistance to tetracycline or to amoxicillin is relatively low. A 14-day modified bismuth quadruple protocol as first-line H. pylori treatment was compared with 10-day sequential therapy. METHODS: In total, 390 H. pylori-infected subjects participated in the randomized clinical trial: 10-day sequential therapy (40 mg pantoprazole plus 1 g amoxicillin twice a day for 5 days, then 40 mg pantoprazole and 500 mg clarithromycin twice a day and 500 mg metronidazole three times a day for 5 days) or 14-day modified bismuth quadruple therapy (40 mg pantoprazole, 600 mg bismuth subcitrate, 1 g tetracycline, and 1 g amoxicillin, twice a day). (13)C-urea breath test, rapid urease testing, or histology was performed to check for eradication. RESULTS: Intention-to-treat (ITT) eradication rates of 10-day sequential and 14-day quadruple therapy were 74.6 % and 68.7 %, respectively, and the per-protocol (PP) rates were 84.2 and 76.5 %, respectively. The eradication rate was higher in the sequential therapy group, but neither the ITT nor the PP analyses had a significant difference (P = 0.240 and P = 0.099, respectively). However, the adverse events were significantly lower in the modified bismuth quadruple therapy group than the sequential therapy group (36.9 vs. 47.7 %, P = 0.040). CONCLUSIONS: Ten-day sequential therapy appears to be more effective despite frequent adverse events. However, both 10-day SQT and 14-day PBAT did not reach the excellent eradication rates that exceed 90 %. Additional trials are needed to identify a more satisfactory first-line eradication therapy. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02159976 ); Registration date: 2014-06-03, CRIS ( KCT0001176 ); Registration date: 2014-07-23.
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Amoxicilina/uso terapêutico , Antiácidos/uso terapêutico , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Gastrite/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Tetraciclina/uso terapêutico , Amoxicilina/efeitos adversos , Antiácidos/efeitos adversos , Antibacterianos/efeitos adversos , Bismuto/efeitos adversos , Esquema de Medicação , Farmacorresistência Bacteriana , Quimioterapia Combinada , Feminino , Gastrite/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Prospectivos , Tetraciclina/efeitos adversos , Falha de TratamentoRESUMO
BACKGROUND AND AIM: Advanced adenoma (> 10 mm in diameter, villous structure, or high-grade dysplasia) in young patients may have different characteristics and prognosis compared with those in older patients. We aimed to compare the incidence of colorectal neoplasms in young patients with older patients after removing high-risk adenoma (advance adenoma or ≥ 3 adenomas). METHODS: A retrospective, multicenter study was conducted at 13 university hospitals in Korea. The 1479 patients who removed high-risk adenoma at index colonoscopy and followed by surveillance colonoscopy ≥ 2.5 years after were included. The cumulative incidence of overall and advanced colorectal neoplasms was compared according to the age groups (group 1: < 50 years, group 2: 50-70 years, and group 3: ≥ 70 years). RESULTS: The prevalence of advance adenoma detected at index colonoscopy was significantly higher in group 1 than in groups 2 and 3 (85.4%, 78.1%, and 77.2%, respectively; P = 0.035). The 5 years cumulative incidence of overall and advanced colorectal neoplasms were 61.9%, 67.9%, and 74.7% (P < 0.001), and 11.7%, 17.9%, and 27.1% (P = 0.001) in groups 1, 2, and 3, respectively. In multivariate analysis, age > 70 years was a significant risk factor for developing overall (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.12-1.82, P = 0.004) and advanced colorectal neoplasms (HR = 2.56, 95% CI 1.43-4.59, P = 0.002). CONCLUSION: The cumulative incidence of overall and advanced colorectal neoplasms was significantly higher in older patients than in young patient groups. Age was a significant risk factor for developing colorectal neoplasms after removing high-risk adenoma.
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Adenoma/cirurgia , Colonoscopia , Neoplasias Colorretais/epidemiologia , Adenoma/epidemiologia , Fatores Etários , Idoso , Estudos de Coortes , Colonoscopia/métodos , Neoplasias Colorretais/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Prevalência , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Risco , Fatores de Risco , TempoRESUMO
BACKGROUND: Data regarding outcomes for patients with multiple findings for high-risk adenomas are scarce. AIM: To compare the risk for colorectal neoplasm (CRN) recurrence according to the number of high-risk findings. METHODS: This was a retrospective and multicenter study. Patients who had one or more high-risk adenomas at the index colonoscopy and underwent follow-up colonoscopy 2.5 or more years after the index colonoscopy were included. The number of high-risk findings was defined as follows: number of adenomas larger than 1 cm + number of adenomas with HGD + number of adenomas with a villous component + existence (counted as 1) or nonexistence (counted as 0) of three or more adenomas. RESULTS: A total of 1646 patients were included, and the mean duration between index and follow-up colonoscopy was approximately 4 years. The cumulative incidence rate of recurrent advanced CRN in patients with three or more high-risk findings was higher than that in patients with one or two high-risk findings (p < 0.001). However, the difference in 3-year cumulative incidence rates of recurrent advanced CRN between the two groups was not great, although it was statistically significant (4.8 vs. 2.3 %, p = 0.039). CONCLUSIONS: A 3-year surveillance interval for patients with multiple high-risk findings, regardless of the number of high-risk findings, appears reasonable.
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Adenoma/patologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Adenoma/epidemiologia , Idoso , Colonoscopia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
PURPOSE: There are no effective treatment methods with which to control complications of radiation proctitis with fistula or recurrent bleeding following radiation treatment for prostate, cervical, or rectal cancer. Mesenchymal stem cells (MSCs) can induce immune modification, resulting in tissue repair and regeneration. Therefore, we used a rat model of radiation-induced proctitis and observed the effects of using human placenta-derived (PD) and adipose tissue-derived (AD) MSCs. MATERIALS AND METHODS: Female Sprague Dawley rats were irradiated at the pelvic area with 25 Gy. We injected 1×106 cells of human PD-MSCs, human AD-MSCs, human foreskin fibroblasts, and control media into the rectal submucosa following irradiation. We sacrificed rats for pathologic evaluation. RESULTS: Fibrosis on the rectum was reduced in both MSC groups, compared to the control group. Mucosal Ki-67 indices of both MSC injected groups were higher than those in the control group. Although caspase-3 positive cells in the mucosa gradually increased and decreased in the control group, those in both MSC injected groups increased rapidly and decreased thereafter. CONCLUSION: We demonstrated the effects of regional MSC injection treatment for radiation-induced proctitis in rats. MSC injection reduced fibrosis and increased proliferation in rat mucosa. Human AD-MSCs and PD-MSCs had similar effectiveness.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Proctite , Humanos , Masculino , Ratos , Feminino , Animais , Ratos Sprague-Dawley , Proctite/etiologia , Proctite/terapia , Proctite/patologia , Reto , Células-Tronco Mesenquimais/patologia , Fibrose , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
In the last few decades, numerous studies have focused on designing suitable hydrophilic materials to inhibit surface-induced fog or frost under extreme conditions. As fogging and condensation frosting on a film involves molecular interaction with water prior to forming discrete droplets on the surface, it is essential to control the extent of a film to strongly bind with water molecules for antifogging coatings. While the water contact angle measurement is commonly used to probe the hydrophilicity of a film, it oftentimes fails to predict the antifogging and antifrosting performance as this value only reflects the wettability of a given surface to water droplet. In this work, a polysaccharide-based film composed of chitosan (CHI) and carboxymethyl cellulose (CMC) is used as the model system and oligo(ethylene glycol) (OEG) moieties are additionally introduced to study the effect of OEG moieties on antifogging and condensation frosting. We show that the film containing OEG-grafted CHI exhibits excellent frost-resistant capability due to the OEG moieties in the film that serve as active sites for water molecules to strongly interact in a nonfreezable state.
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Based upon the fact that L-nucleosides have been generally known to be less cytotoxic than D-counterparts, L-bicyclo[3.1.0]hexenyl carbanucleoside derivatives with a fixed north conformation were designed and synthesized by employing a novel synthetic strategy starting from (R)-epichlorohydrin in order to search for new anti-HIV agents with high potency and less cytotoxicity. A tandem alkylation, γ-lactonization, a chemoselective reduction of ester in the presence of γ-lactone functional group, a RCM reaction, and a Mitsunobu coupling reaction were used as key reactions. D-Counterpart nucleosides were also prepared according to the same synthetic method. Among the synthesized carbanucleosides, D-thymine nucleoside, D-2 and L-thymine nucleoside, L-2 exhibited excellent anti-HIV-1 and -2 activities, in MT-4 cells, which were higher than those of ddI, an anti-AIDS drug. Whereas D-2 exhibited high cytotoxicity in MT-4 cell lines, L-2 did not show any discernible cytotoxicity in all cell lines tested, reflecting that L-2 may be a good candidate for an anti-AIDS drug. L-2 also showed weak anti-HSV-2 activity without cytotoxicity. However, none of the synthesized nucleosides exhibited antiviral activities against RNA viruses including coxsakie, influenza, corona and polio viruses, maybe due to their 2',3'-dideoxy structure. Potent antiviral effects of D-2 and L-2 indicate that nucleosides belonging to a class of D4Ns can be an excellent candidate for anti-DNA virus agents. This research strongly supports L-nucleosides of a class of D4Ns to be a very promising candidate for antiviral agents due to its low cytotoxicity and a good antiviral activity.
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Antivirais/síntese química , Compostos Bicíclicos com Pontes/química , Nucleosídeos/química , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/toxicidade , Antivirais/química , Antivirais/toxicidade , Linhagem Celular , Vírus de DNA/efeitos dos fármacos , Epicloroidrina/química , Humanos , Nucleosídeos/síntese química , Nucleosídeos/toxicidade , Vírus de RNA/efeitos dos fármacos , EstereoisomerismoRESUMO
Toxoplasma gondii Korean isolate (KI-1) tachyzoites were inoculated intraduodenally to BALB/c mice using a silicon tube, and the course of infection and immune responses of mice were studied. Whereas control mice, that were infected intraperitoneally, died within day 7 post-infection (PI), the intraduodenally infected mice survived until day 9 PI (infection with 1 × 10(5) tachyzoites) or day 11 PI (with 1 × 10(6) tachyzoites). Based on histopathologic (Giemsa stain) and PCR (B1 gene) studies, it was suggested that tachyzoites, after entering the small intestine, invaded into endothelial cells, divided there, and propagated to other organs. PCR appeared to be more sensitive than histopathology to detect infected organs and tissues. The organisms spread over multiple organs by day 6 PI. However, proliferative responses of splenocytes and mesenteric lymph node (MLN) cells in response to con A or Toxoplasma lysate antigen decreased significantly, suggesting immunosuppression. Splenic CD4(+) and CD8(+) T-lymphocytes showed decreases in number until day 9 PI, whereas IFN-γ and IL-10 decreased slightly at day 6 PI and returned to normal levels by day 9 PI. No TNF-α was detected throughout the experimental period. The results showed that intraduodenal infection with KI-1 tachyzoites was successful but did not elicit significant mucosal immunity in mice and allowed dissemination of T. gondii organisms to systemic organs. The immunosuppression of mice included reduced lymphoproliferative responses to splenocytes and MLN cells to mitogen and low production of cytokines, such as IFN-γ, TNF-α, and IL-10, in response to T. gondii infection.
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Toxoplasma/imunologia , Toxoplasmose Animal/imunologia , Animais , Proliferação de Células , Citocinas/metabolismo , Modelos Animais de Doenças , Duodeno/imunologia , Duodeno/parasitologia , Duodeno/patologia , Células Endoteliais/parasitologia , Histocitoquímica , Tolerância Imunológica , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase , Doenças dos Roedores/imunologia , Doenças dos Roedores/parasitologia , Doenças dos Roedores/patologia , Subpopulações de Linfócitos T/imunologia , Toxoplasma/patogenicidade , Toxoplasmose Animal/parasitologia , Toxoplasmose Animal/patologiaRESUMO
Toxoplasma gondii KI-1, a recent new isolate from Korea, shows similar pathogenicity and infectivity to mice compared to the virulent RH strain. To understand characteristics of host immunity, including immune enhancement or suppression, we investigated proliferative responses and phenotypes of spleen cells. In addition, kinetics of IFN-γ, a Th1 cytokine, was examined in BALB/c mice up to day 6 post-infection (PI). Intraperitoneal injection of mice with 10(3) KI-1 tachyzoites induced significant decreases (P < 0.05) in proliferative responses of spleen cells. This occurred at days 2-6 PI even when concanavalin A (con A) was added and when stimulated with KI-1 antigen, suggesting suppression of the immunity. CD4(+) T-cells decreased markedly at day 2 PI (P < 0.05), whereas CD8(+) T-cells, NK cells, and macrophages did not show significant changes, except a slight, but significant, increase of CD8(+) T-cells at day 6 PI. The capacity of splenocytes to produce IFN-γ by con A stimulation dropped significantly at days 2-6 PI. These results demonstrate that intraperitoneal injection of KI-1 tachyzoites can induce immunosuppression during the early stage of infection, as revealed by the decrease of CD4(+) T-cells and IFN-γ.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Tolerância Imunológica , Baço/imunologia , Toxoplasma/imunologia , Toxoplasma/patogenicidade , Animais , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células , Feminino , Interferon gama/metabolismo , Células Matadoras Naturais/imunologia , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Scent is one of the most important economic traits in Freesia hybrida. "Shiny Gold", a popular cultivar in South Korea, is widely cultivated for its scent. The relative scent intensity of "Shiny Gold" was approximately 16% higher in full-bloomed flower when compared to the yellow bud stage, while tissue-specifically, tepals showed higher intensity in electronic-nose (e-nose) analysis. E-nose analysis also showed that the scent intensity of "Shiny Gold" was higher and lower than "10C3-424" and "10C3-894", respectively, and was similar to "Yvonne". These results correlated to those of the olfactory tests. In total, 19 volatile compounds, including linalool, ß-ocimene, D-limonene, trans-ß-ionone were detected in gas chromatography-mass spectrometry analysis. Among these, linalool was the major volatile compound, accounting for 38.7% in "Shiny Gold". Linalool synthase and TPS gene expression corresponded to the scent intensity of the four cultivars, with the lowest expression in the "10C3-424". TPS 2, TPS 3, TPS 5, TPS 6 and TPS 8 were highly expressed in both bud and flower in "Shiny Gold", while the expression of TPS 4 was lower, relative to other TPS genes in both the flowering stages. These results may aid in enhancing scent composition in Freesia cultivars using marker-assisted selection.
RESUMO
BACKGROUND: Skin grafting is a commonly performed procedure, but studies of changes in the levels of cytokines after skin grafting have not been reported. OBJECTIVE: We examined changes in cytokines and the degree of erythema after skin grafting in pigs in the control group. Interferon alpha (IFN-alpha) was injected to reduce erythema, and subsequent changes in cytokines and the degree of erythema were examined in the experimental group. METHODS: Vascular endothelial growth factor (VEGF), thrombospondin-1 (TSP1), and CD31 were examined using Western blot analysis and immunohistochemistry. The degree of erythema was measured at 2, 4, and 8 weeks using a chromometer. RESULTS: In the control group, VEGF increased at 2 weeks and decreased at 4 and 8 weeks. TSP1 increased over time. CD31 increased to 4 weeks and decreased at 8 weeks. In the experimental group, VEGF was lower at 2 weeks and higher at 8 weeks than in the control group, TSP1 was higher at 2 weeks and lower at 8 weeks, and CD31 was lower at 4 and 8 weeks. Erythema in the experimental group was lower than that in the control group at 2 and 8 weeks. CONCLUSION: IFN-alpha may be one of the agents that reduces erythema by suppressing excessive revascularization.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Eritema/prevenção & controle , Interferon-alfa/administração & dosagem , Transplante de Pele/efeitos adversos , Animais , Citocinas/análise , Eritema/etiologia , Interferon alfa-2 , Modelos Animais , Neovascularização Fisiológica , Proteínas Recombinantes , Pele/química , SuínosRESUMO
Intramural hematoma of the duodenum is a relatively unusual complication associated with the endoscopic treatment of bleeding peptic ulcers. Intramural hematomas are typically resolved spontaneously with conservative treatment alone. We report a case of an intramural duodenal hematoma following endoscopic hemostasis with epinephrine injection therapy, which was associated with transient obstructive jaundice in a patient undergoing hemodialysis. The patient developed biliary sepsis due to obstruction of the common bile duct secondary to the huge hematoma. He was treated with fluoroscopy-guided drainage catheter insertion, which spontaneously resolved the biliary sepsis through conservative treatment in 6 weeks. Fluoroscopy-guided drainage may impact the treatment of intramural hematomas that involve life-threatening complications.