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Interprofessional geriatric education programs enhance trainees' knowledge of older adults, and the valuable contributions health and social care practitioners make to their well-being when specialists work collaboratively. In response to the 2020 COVID-19 pandemic restrictions, in-person geriatric interprofessional education (IPE) programs were redesigned for virtual delivery. Nineteen virtual programs were held between September 2020 and December 2022. Of the 369 health and social care trainees who participated, 67.2% completed both pre- and post-program surveys. Survey instruments included the Interprofessional Collaborative Competency Attainment Survey (ICASS), which measures perceptions associated with patient-centered, team-based, collaborative care. Significant differences were obtained across ICASS domains, including communication, conflict management/resolution, and team functioning, suggesting that virtual programs may enhance attitudes and perceived abilities for interprofessional collaborative practice. Furthermore, participants' perceived understanding of older adult needs improved, as did their interest in geriatrics. Results illustrate that virtual geriatric interprofessional (IP) programs may be viable alternatives to in-person opportunities.
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COVID-19 , Avaliação Geriátrica , Geriatria , Equipe de Assistência ao Paciente , Humanos , COVID-19/epidemiologia , Equipe de Assistência ao Paciente/organização & administração , Geriatria/educação , Avaliação Geriátrica/métodos , Masculino , Feminino , SARS-CoV-2 , Idoso , Educação Interprofissional/organização & administração , Educação Interprofissional/métodos , Relações Interprofissionais , Educação a Distância/métodos , Educação a Distância/organização & administração , Comportamento Cooperativo , Pessoal de Saúde/educação , Adulto , Pandemias , Inquéritos e QuestionáriosRESUMO
The present study examined the underlying mechanisms of mechanical allodynia and thermal hyperalgesia induced by the intracisternal injection of angiotensin (Ang) II. Intracisternal Ang II injection decreased the air puff threshold and head withdrawal latency. To determine the operative receptors for each distinct type of pain behavior, we intracisternally injected Ang II receptor antagonists 2 h after Ang II injection. Losartan, an Ang II type 1 receptor (AT1R) antagonist, alleviated mechanical allodynia. Conversely, PD123319, an Ang II type 1 receptor (AT2R) antagonist, blocked only thermal hyperalgesia. Immunofluorescence analyses revealed the co-localization of AT1R with the astrocyte marker GFAP in the trigeminal subnucleus caudalis and co-localization of AT2R with CGRP-positive neurons in the trigeminal ganglion. Intracisternal pretreatment with minocycline, a microglial inhibitor, did not affect Ang II-induced mechanical allodynia, whereas L-α-aminoadipate, an astrocyte inhibitor, significantly inhibited Ang II-induced mechanical allodynia. Furthermore, subcutaneous pretreatment with botulinum toxin type A significantly alleviated Ang II-induced thermal hyperalgesia, but not Ang II-induced mechanical allodynia. These results indicate that central Ang II-induced nociception is differentially regulated by AT1R and AT2R. Thus, distinct therapeutic targets must be regulated to overcome pain symptoms caused by multiple underlying mechanisms.
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Purpose: The purpose of this study was to use targeted next-generation sequencing (NGS) to identify possible causative genes for isolated and sporadic human mesiodens. Methods: The targeted panel consisted of 101 target genes related to tooth development. NGS of this panel was initially performed on a discovery set (39 cases and 27 controls); association tests were performed after genotyping of nine selected variants in a validation set (57 cases and 56 controls). Results: Among these nine variants, a synonymous variant, ACVR2A (rs1128919) associated with mesiodens was identified. Moreover, in silico analysis was performed and demonstrated the instability of mRNA with the G allele. Conclusions: The formation of isolated and sporadic human mesiodens is associated with a synonymous variation in ACVR2A (rs1128919).
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Sequenciamento de Nucleotídeos em Larga Escala , Dente Supranumerário , Humanos , Dente Supranumerário/genéticaRESUMO
Despite the increasing prevalence of overweight or obesity in the global population, most of the approved drugs for obesity are still not ideal for long-term use due to severe cardiovascular and/or neurological side effects. Therefore, we designed a library-implemented virtual screening (VS) approach to discover new anti-obesity agents without significant toxicity. The Bayesian classification and 3D pharmacophore model for the VS process were built by using the screening results of our in-house library of natural piper amide-like compounds, which possess a wide range of biological activities and relatively low toxicities. The VS process identified six compounds of different classes with enhanced inhibitory activities against lipid accumulation and without toxicity. Moreover, the most active compound with an oxadiazole scaffold resulted in weight loss and improved the fatty liver condition of mice with overnutrition in animal experiments.
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INTRODUCTION: This study compared the stemness and differentiation potential of stem cells derived from the apical complex (apical complex cells [ACCs]) and coronal pulp (dental pulp stem cells [DPSCs]) of human immature permanent teeth with the aim of determining a more suitable source of stem cells for regeneration of the dentin-pulp complex. METHODS: ACC and DPSC cultures were established from 13 human immature permanent teeth using the outgrowth method. The proliferation capacity and colony-forming ability of ACCs and DPSCs were evaluated. ACCs and DPSCs were analyzed for mesenchymal stem cell markers using flow cytometry. The adipogenic and osteogenic differentiation potential of ACCs and DPSCs were evaluated using the quantitative real-time polymerase chain reaction and histochemical staining. ACCs and DPSCs were transplanted subcutaneously in immunocompromised mice using macroporous biphasic calcium phosphate as a carrier. The histomorphologic characteristics of the newly formed tissues were verified using hematoxylin-eosin staining and immunohistochemical staining. Quantitative alkaline phosphatase analysis and quantitative real-time polymerase chain reaction using BSP, DSPP, POSTN, and ColXII were performed. RESULTS: ACCs and DPSCs showed similar cell proliferation potential and colony-forming ability. The percentage of mesenchymal stem cell markers was similar between ACCs and DPSCs. In the in vitro study, ACCs and DPSCs showed adipogenic and osteogenic differentiation potential. In the in vivo study, ACCs and DPSCs formed amorphous hard tissue using macroporous biphasic calcium phosphate particles. The quantity and histomorphologic characteristics of the amorphous hard tissue were similar in the ACC and DPSC groups. Formation of periodontal ligament-like tissue, positive to Col XII, was observed in ACC transplants, which was absent in DPSC transplants. CONCLUSIONS: ACCs and DPSCs showed similar stemness, proliferation rate, and hard tissue-forming capacity. The notable difference was the periodontal ligament-like fiber-forming capacity of ACCs, which indicates the presence of various lineages of stem cells in the apical complex compared with the coronal pulp. Regarding regeneration of the dentin-pulp complex, the coronal pulp can be a suitable source of stem cells considering its homogenous lineages of cells and favorable osteo/odontogenic differentiation potential.
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Diferenciação Celular , Polpa Dentária , Osteogênese , Células-Tronco , Animais , Moléculas de Adesão Celular , Proliferação de Células , Células Cultivadas , Dentina , Humanos , Camundongos , Proteínas/metabolismo , RegeneraçãoRESUMO
PURPOSE: The purpose of this study was to construct and test a hypothetical model of clinical decision-making ability of nurses based on the Decision Making Process model and the Cognitive Continuum theory. METHODS: The data were collected from nurses working at 11 hospitals in Busan, Daejeon, and South Gyeongsang Province from June 30 to August 1, 2017. Finally, the data from 323 nurses were analyzed. RESULTS: The goodness-of-fit of the final model was at a good level (χ²/df=2.46, GFI=.87, AGFI=.84, IFI=.90, CFI=.90, SRMR=.07, RMSEA=.07) and 6 out of 10 paths of the model were supported. The clinical decision-making ability was both directly and indirectly affected by task complexity and indirectly affected by experiences, autonomy, and work environment. Specifically, it was strongly directly affected by analytical competency but was insignificantly affected by intuitive competency. These variables accounted for 66.0% of clinical decision-making ability. CONCLUSION: The nurses' clinical decision-making ability can be improved by improving their analytical competency. Therefore, it is necessary to organize nursing work, create a supportive work environment, and develop and implement various education programs.
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Tomada de Decisão Clínica , Modelos Teóricos , Recursos Humanos de Enfermagem Hospitalar/psicologia , Adulto , Competência Clínica , Feminino , Humanos , Masculino , Inquéritos e Questionários , Local de TrabalhoRESUMO
Annona muricata L., known as graviola, is an evergreen plant of the tropical regions and is a rich source of natural products. Graviola has various biological activities, and it is best known for its anticancer activity. This study aimed to investigate the effects of crude graviola extract in vitro on breast cancer cells; in particular, we aimed to identify an agent against triple negative breast cancer (TNBC). We used the TNBC MDA-MB-231 cell line as the experimental model and the ER(+) non-TNBC MCF-7 breast cancer cell line as the control. We identified annonaceous acetogenins, including annonacin isomers, characteristic to this plant by using liquid chromatography tandem mass spectrometry (LC/MS/MS). We observed a significant decrease in the cell viability in both cell lines within 48 h, whereas impaired cell motility and invasiveness were observed only in the MDA-MB-231 cell line. While the MCF-7 cells showed an ER-dependent mechanism of apoptosis, the apoptosis of MDA-MB-231 cells was governed by an intrinsic apoptotic pathway triggered by graviola leaf extract (GLE).
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Cantharidin is an active constituent of blister beetles (cantharides) which have traditionally been used for cancer treatment. Several studies have shown that cantharidin has a cytotoxic effect on various cancer cells. However, few studies have examined the effect of cantharidin on signal transducer and activator of transcription 3 (STAT3) signaling in cancer. In this study, we isolated cantharidin from cantharides by bioassay-guided fractionation and examined its inhibitory effect on STAT3 activation in human breast cancer MDA-MB-231 cells, expressing high level of phosphorylated STAT3. Cantharides were extracted with acetonitrile and separated into hexane, methylene chloride/acetonitrile, and water fractions. The methylene chloride/acetonitrile fraction was further separated into four fractions by preparative high-throughput high-performance liquid chromatography. Cantharidin was then isolated from the third fraction by countercurrent chromatography and structurally determined by comparing nuclear magnetic resonance and high-resolution mass spectrometry data. Cantharidin inhibited STAT3 tyrosine phosphorylation in MDA-MB-231 cells. Cantharidin suppressed epidermal growth factor (EGF)-induced STAT3 and PI3K/Akt signaling pathways through inhibition of EGF receptor phosphorylation. Moreover, cantharidin reduced cell proliferation and induced apoptosis with downregulation of STAT3 target genes, such as Bcl-2, COX-2, and cyclin D1. Taken together, this study provides evidence that cantharidin may be a potential therapeutic agent for triple-negative breast cancer by reducing EGFR-mediated STAT3 and Akt signaling pathways.
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Cantaridina/química , Receptores ErbB/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Antineoplásicos , Besouros , Humanos , Transdução de SinaisRESUMO
OBJECTIVE: The aim of this study was to investigate the epidemiology of delayed tooth development (DTD) and the link between DTD and tooth agenesis (TA). DESIGN: The dental maturity of all of the developing permanent teeth of 4611 children (2417 males and 2194 females) was evaluated from panoramic radiographs. The prevalence of DTD and TA was analyzed, and gender difference for DTS and TA was investigated. The correlation of DTD and TA was investigated in intra-fields and inter-fields. RESULTS: The total prevalence of DTD among the 4611 children was 3.40%. The maxillary second premolar was the most frequently delayed tooth (1.02%), followed by the maxillary second molar (0.88%) and the mandibular second premolar (0.74%). DTD significantly correlated with TA in both intra-fields and inter-fields (p<0.05). CONCLUSIONS: The field of delayed development exhibited a significant correlation with that of TA.
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Anodontia/epidemiologia , Anormalidades Dentárias/epidemiologia , Erupção Dentária/fisiologia , Determinação da Idade pelos Dentes , Anodontia/diagnóstico por imagem , Criança , Feminino , Humanos , Masculino , Odontogênese , Prevalência , Radiografia Panorâmica/métodos , República da Coreia/epidemiologia , Anormalidades Dentárias/diagnóstico por imagemRESUMO
PURPOSE: The aim of this study was to evaluate the tissue stiffness of solid pancreatic lesions by using acoustic radiation force impulse (ARFI) elastography to differentiate benign from malignant pancreatic lesions. METHODS: ARFI elastography was performed in 26 patients who had 27 focal solid pancreatic lesions, including 8 benign lesions (mass-forming pancreatitis, 5; autoimmune pancreatitis, 3) and 19 malignant lesions (pancreatic adenocarcinoma, 16; metastasis from colorectal cancer, 2; malignant neuroendocrine tumor, 1). On the elastographic images of virtual touch tissue imaging (VTI), the echogenicity of the mass was categorized on a 5-grade scale. On the elastographic image of virtual touch tissue quantification (VTQ), the shear wave velocities (SWVs) of the lesion and surrounding parenchyma were measured. RESULTS: On the VTI images, the mean echogenicity score of the malignant lesions (3.7±1.0) was higher than that of the benign lesions (3.1±0.4; P=0.023). On the VTQ images, there were no statistical differences in the mean SWV between the benign (2.4±1.1 m/sec) and malignant (3.3±1.0 m/sec) lesions (P=0.101). However, the mean SWV difference values between the lesion and background parenchyma of the malignant lesions (1.5±0.8 m/sec) were higher than those of the benign lesions (0.4±0.3 m/sec; P=0.011). CONCLUSION: ARFI elastography can determine the relative stiffness between a lesion and the background pancreatic parenchyma using VTI and VTQ, which is helpful in the differentiation between benign and malignant solid pancreatic lesions.
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Ionizing radiation has become an inevitable health concern emanating from natural sources like space travel and from artificial sources like medical therapies. In general, exposure to ionizing radiation such as γ-rays is one of the methods currently used to stress specific model systems. In this study, we elucidated the long-term effect of acute and fractionated irradiation on DCX-positive cells in hippocampal neurogenesis. Groups of two-month-old C57BL/6 female mice were exposed to whole-body irradiation at acute dose (5 Gy) or fractional doses (1 Gy × 5 times and 0.5 Gy × 10 times). Six months after exposure to γ-irradiation, the hippocampus was analyzed. Doublecortin (DCX) immunohistochemistry was used to measure changes of neurogenesis in the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). The number of DCX-positive cells was significantly decreased in all acute and fractionally irradiation groups. The long-term changes in DCX-positive cells triggered by radiation exposure showed a very different pattern to the short-term changes which tended to return to the control level in previous studies. Furthermore, the number of DCX-positive cells was relatively lower in the acute irradiation group than the fractional irradiation groups (approximately 3.6-fold), suggesting the biological change on hippocampal neurogenesis was more susceptible to being damaged by acute than fractional irradiation. These results suggest that the exposure to γ-irradiation as a long-term effect can trigger biological responses resulting in the inhibition of hippocampal neurogenesis.
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Giro Denteado/efeitos da radiação , Raios gama , Neurogênese/efeitos da radiação , Animais , Giro Denteado/citologia , Giro Denteado/metabolismo , Relação Dose-Resposta à Radiação , Proteínas do Domínio Duplacortina , Proteína Duplacortina , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Neuropeptídeos/metabolismo , Irradiação Corporal TotalRESUMO
Obesity is a global health problem. It is also known to be a risk factor for the development of metabolic disorders, type 2 diabetes, systemic hypertension, cardiovascular disease, dyslipidemia, and atherosclerosis. In this study, we elucidated that Buddleja officinalis Maximowicz extract significantly inhibited lipid accumulation during 3T3-L1 adipocyte differentiation. Furthermore, Buddleja officinalis Maximowicz extract reduced the body weight gain induced through feeding a high-fat diet to C57BL/6 mice. The treatment of Buddleja officinalis Maximowicz extract significantly reduced the adipose tissue weight to 2.7/100 g of body weight in high-fat mice. When their adipose tissue morphology was investigated for histochemical staining, the distribution of cell size in the high-fat diet groups was hypertrophied compared with those from Buddleja officinalis Maximowicz extract-treated mice. In addition, in Buddleja officinalis Maximowicz extract-treated mice, a significant reduction of serum triglyceride and T-cholesterol was observed at to 21% and 17%, respectively. The discovery of bioactive compounds from diet or dietary supplementation is one of possible ways to control obesity and to prevent or reduce the risks of various obesity-related diseases. These results support that Buddleja officinalis Maximowicz extract is expected to create the therapeutic interest with respect to the treatment of obesity.
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Adipócitos/efeitos dos fármacos , Fármacos Antiobesidade/administração & dosagem , Buddleja , Obesidade/tratamento farmacológico , Extratos Vegetais , Células 3T3-L1 , Animais , Peso Corporal/efeitos dos fármacos , Buddleja/química , Diferenciação Celular/efeitos dos fármacos , Dieta Hiperlipídica , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Triglicerídeos/sangue , Aumento de Peso/efeitos dos fármacosRESUMO
AIMS: To investigate nociceptive behavior and the immunoreactivity of microglia and phosphorylated-p38 (p-p38) mitogen-activated protein kinase (MAPK) following intracisternal administration of SB203580, a p38 MAPK inhibitor, or minocycline, a microglia inhibitor, in rats with temporomandibular joint (TMJ) inflammation. METHODS: The number of nociceptive behavioral responses was recorded for nine successive 5-minute intervals following formalin injections into the left TMJ. SB203580 or minocycline was administered intracisternally 2 hours prior to the formalin injection. Statistical analysis used one-way analysis of variance followed by least significant difference post-hoc analysis. RESULTS: The intra-articular injection of formalin increased the expression of p-p38 MAPK in the ipsilateral medullary dorsal horn. Most of the p-p38 MAPK co-localized with OX42, a microglial marker, but not with GFAP, an astrocyte marker. Intracisternal injections of SB203580 (0.5, 1, or 5 Μg) attenuated the number of nociceptive behavioral responses and the expression of p-p38 MAPK in the medullary dorsal horn. Intracisternal injections of minocycline (25 or 50 Μg) also attenuated the responses and the expression of OX42 and p-p38 MAPK in the medullary dorsal horn. CONCLUSION: These findings suggest that p38 MAPK in microglia plays an important role in the central processing of inflammatory TMJ nociception in rats. The data further indicate that a targeted blockade of the microglial p38 MAPK pathway is a potentially important new treatment strategy for inflammatory TMJ nociception.
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Artralgia/enzimologia , Microglia/enzimologia , Nociceptividade/efeitos dos fármacos , Transtornos da Articulação Temporomandibular/enzimologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Análise de Variância , Animais , Cisterna Magna/efeitos dos fármacos , Determinação de Ponto Final , Formaldeído/administração & dosagem , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Injeções Intra-Articulares , Masculino , Microglia/efeitos dos fármacos , Minociclina/administração & dosagem , Minociclina/farmacologia , Atividade Motora/efeitos dos fármacos , Fosforilação , Células do Corno Posterior/enzimologia , Inibidores de Proteases/administração & dosagem , Inibidores de Proteases/farmacologia , Piridinas/administração & dosagem , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Articulação Temporomandibular/inervação , Transtornos da Articulação Temporomandibular/induzido quimicamente , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/químicaRESUMO
In this study, we elucidated the inhibitory effect of fucoidan from marine brown algae on the lipid accumulation in differentiated 3T3-L1 adipocytes and its mechanism. The treatment of fucoidan in a dose-dependent manner was examined on lipid inhibition in 3T3-L1 cells by using Oil Red O staining. Fucoidan showed high lipid inhibition activity at 200 µg/mL concentration (P < 0.001). Lipolytic activity in adipocytes is highly dependent on hormone sensitive lipase (HSL), which is one of the most important targets of lipolytic regulation. Here, we examined the biological response of fucoidan on the protein level of lipolysis pathway. The expressed protein levels of total hormone sensitive lipase (HSL) and its activated form, phosphorylated-HSL were significantly increased at concentration of 200 µg/mL fucoidan. Furthermore, insulin-induced 2-deoxy-D-[³H] glucose uptake was decreased up to 51% in fucoidan-treated cells as compared to control. Since increase of HSL and p-HSL expression and decrease of glucose uptake into adipocytes are known to lead to stimulation of lipolysis, our results suggest that fucoidan reduces lipid accumulation by stimulating lipolysis. Therefore, these results suggest that fucoidan can be useful for the prevention or treatment of obesity due to its stimulatory lipolysis.
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Metabolismo dos Lipídeos/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Phaeophyceae/química , Polissacarídeos/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Glucose/metabolismo , Insulina/metabolismo , Lipólise/genética , Camundongos , Obesidade/metabolismo , Polissacarídeos/isolamento & purificação , Esterol Esterase/metabolismoRESUMO
Mechanical allodynia is a common symptom found in neuropathic patients. Hyperpolarization-activated cyclic nucleotide-gated channels and their current, I(h), have been suggested to play an important role in neuropathic pain, especially in mechanical allodynia and spontaneous pain, by involvement in spontaneous ectopic discharges after peripheral nerve injury. Thus, I(h) blockers may hold therapeutic potential for the intervention of mechanical allodynia under diverse neuropathic conditions. Here we show that eugenol blocks I(h) and abolishes mechanical allodynia in the trigeminal system. Eugenol produced robust inhibition of I(h) with IC(50) of 157 µM in trigeminal ganglion (TG) neurons, which is lower than the dose of eugenol that inhibits voltage-gated Na channels. Eugenol-induced I(h) inhibition was not mediated by G(i/o)-protein activation, but was gradually diminished by an increase in intracellular cAMP concentration. Eugenol also inhibited I(h) from injured TG neurons which were identified by retrograde labeling with DiI and reversed mechanical allodynia in the orofacial area after chronic constriction injury of infraorbital nerve. We propose that eugenol could be potentially useful for reversing mechanical allodynia in neuropathic pain patients.
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Canais de Cátion Regulados por Nucleotídeos Cíclicos/antagonistas & inibidores , Eugenol/farmacologia , Eugenol/uso terapêutico , Hiperalgesia/tratamento farmacológico , Gânglio Trigeminal/lesões , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Canais de Cátion Regulados por Nucleotídeos Cíclicos/fisiologia , Relação Dose-Resposta a Droga , Hiperalgesia/fisiopatologia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Masculino , Canais de Potássio/fisiologia , Ratos , Ratos Sprague-Dawley , Gânglio Trigeminal/efeitos dos fármacos , Gânglio Trigeminal/fisiopatologiaRESUMO
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract, but also occurs at a lower frequency in extra-gastrointestinal regions such as omentum, mesentery, retroperitoneum and undefined abdominal sites. This tumor is called extragastrointestinal stromal tumor (EGIST). EGIST is mostly diagnosed as a cystic mass, but rarely occurs as a disseminated abdominal tumor. We experienced a 70-year-old man with primary EGIST presenting as peritoneal dissemination. Abdominal CT showed diffuse peritoneal thickening with a large amount of ascites, but no definite mass lesion. Laparoscopic biopsy was performed and histologic findings showed tumor composed of epithelioid cells. In the results of immunohistochemical stains, the tumor showed positive reactivity with CD117 (c-kit), CD34, vimentin and actin, but negative reactivity with desmin and S-100 protein. On account of unresectability and histologic parameters of malignant behavior, he was started on imatinib.
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Tumores do Estroma Gastrointestinal/diagnóstico , Neoplasias Peritoneais/diagnóstico , Actinas/metabolismo , Idoso , Antígenos CD34/metabolismo , Tumores do Estroma Gastrointestinal/patologia , Humanos , Laparoscopia , Masculino , Neoplasias Peritoneais/secundário , Tomografia por Emissão de Pósitrons , Proteínas Proto-Oncogênicas c-kit/metabolismo , Tomografia Computadorizada por Raios X , Vimentina/metabolismoRESUMO
A hydrophobic and water-insoluble platinum(II) compound, cis-(cha)(2)Pt(NO(3))(2) was encapsulated by macromolecular micelles self-assembled from an amphiphilic cyclotriphosphazene [NP(MPEG750)(GlyPheLeu)(2)Et](3) (CP750). The micelle-encapsulated platinum(II) compound exhibited outstanding pharmacokinetics in rats by showing long blood circulation and much larger systemic exposure (AUC=43.5 µgh/ml) compared with the free carboplatin (AUC=4.32 µgh/ml). Biodistribution study of the micellar platinum(II) compound using male Sprague-Dawley rats has shown excellent tumor to tissue ratios of 4.03 at 2h post injection and 4.67 at 24h post injection. Furthermore, the micellar platinum(II) compound exhibited more than 6 times higher cellular uptake in human cervical (HeLa) and lung (A549) tumor cells compared with the free platinum compound. Also it is surprising that the micellar platinum(II) compound displayed specifically high cytotoxicity against the stomach tumor cells (SNU638), which are one of the least responsive to chemotherapeutic agents currently in clinical use. The acute toxicity study has shown that the LD(50) values of free and the micellar cis-(cha)(2)Pt(NO(3))(2) are approximately 70 mg/kg and 90 mg/kg, respectively. Thus the platinum compound encapsulated by cyclotriphosphazene micelles is a promising candidate for preclinical studies.
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Antineoplásicos/administração & dosagem , Portadores de Fármacos/química , Compostos Organoplatínicos/administração & dosagem , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Disponibilidade Biológica , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Dose Letal Mediana , Masculino , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Micelas , Compostos Organoplatínicos/farmacocinética , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/toxicidade , Ratos , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
AIMS: To examine the antinociceptive effects of N-Methyl-D-aspartate (NMDA) receptor NR2 subunit antagonists in a rat model of the facial formalin test. METHODS: Experiments were carried out on adult male Sprague-Dawley rats weighing 220 to 280 g. Anesthetized rats were individually mounted on a stereotaxic frame and a polyethylene tube was implanted for intracisternal injection and, 72 hours later, formalin tests were performed. NMDA receptor antagonists were administered intracisternally 10 minutes prior to subcutaneous injection of 5% formalin (50 MicroL) into the vibrissal pad. RESULTS: The intracisternal administration of 25, 50, or 100 Microg of memantine, an antagonist that acts at the NMDA ion channel site, significantly suppressed the number of scratches in the second phase of the behavioral responses to formalin. Intracisternal administration of a range of doses of 5,7-dichlorokynurenic acid, a glycine site antagonist, or DL-2-amino-5-phosphonopentanoate (AP-5), a nonselective NMDA site antagonist, produced significant antinociceptive effects in the second phase. Intracisternal administration of 1, 2.5, or 5 Microg of (2R,4S)-4-(3 Phosphonopropyl)-2-piperidine_carboxylic acid (PPPA), a competitive NR2A antagonist, significantly suppressed the number of scratches in the second phase, while only the highest dose of PPPA (5 Microg) significantly suppressed the number of scratches in the first phase. The antinociceptive effects of intracisternal injection of (alphaR, betaS)-alpha-(4Hydroxyphenyl)-_ methyl-4-(phenylmethyl)-1-Piperidinepropanol maleate(Ro 25-6981), a selective NR2B antagonist, were similar to those of PPPA. Injection of memantine, AP-5, Ro 25-6981, or vehicle did not result in any motor dysfunction. A low dose of PPPA (1 microg) or 5,7-dichlorokynurenic acid (2.5 microg) did not affect motor function. However, higher doses of PPPA and 5,7-dichlorokynurenic acid produced motor dysfunction. CONCLUSION: The present results suggest that central NR2 subunits play an important role in orofacial nociceptive transmission. Moreover, this data also indicate that targeted inhibition of the NMDA receptor NR2 subunit is a potentially important new treatment approach for inflammatory pain originating in the orofacial area.
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Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Dor Facial/prevenção & controle , Formaldeído/efeitos adversos , Memantina/uso terapêutico , Nociceptores/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Comportamento Animal/efeitos dos fármacos , Cisterna Magna , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Dor Facial/induzido quimicamente , Formaldeído/administração & dosagem , Injeções , Injeções Subcutâneas , Ácido Cinurênico/análogos & derivados , Ácido Cinurênico/uso terapêutico , Masculino , Memantina/administração & dosagem , Atividade Motora/efeitos dos fármacos , Fenóis/uso terapêutico , Piperazinas/uso terapêutico , Piperidinas/uso terapêutico , Prurido/prevenção & controle , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/administração & dosagem , Transmissão Sináptica/efeitos dos fármacos , Fatores de Tempo , Vibrissas/efeitos dos fármacosRESUMO
Cyclotriphosphazenes grafted with equimolar amounts of a hydrophilic polyethylene glycol and a hydrophobic oligopeptide in cis-nongeminal way form a new class of tripodal amphiphiles allowing both intra- and intermolecular hydrophobic interactions that differ from linear block copolymer amphiphiles. It has been found in this study that the tripodal amphiphiles can be tuned for self-assembly from micelles to bilayered polymersomes by controlling the hydrophobicity of the oligopeptide grafted. For instance, the tripodal amphiphiles with an intermediate hydrophobicity (0
Assuntos
Micelas , Oligopeptídeos/química , Tensoativos/química , Animais , Sistemas de Liberação de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oligopeptídeos/farmacocinética , Compostos Organofosforados/química , Compostos Organofosforados/farmacocinética , Tensoativos/farmacocinéticaRESUMO
BACKGROUND/AIMS: The cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), the proteins that have the role in the gastric carcinogenesis, are stimulated by H. pylori infection in the gastric mucosa. The aim of this study was to evaluate the expression of COX-2 and iNOS proteins one year after the eradication of H. pylori. METHODS: Gastric antral mucosa from fifty eight patients with chronic gastritis who were all infected with H. pylori was examined for the expression of COX-2 and iNOS proteins before and one year after the eradication of H. pylori by immunohistochemical stain. RESULTS: COX-2 and iNOS proteins were expressed in the epithelial cells and interstitial inflammatory cells of gastric mucosa. Percent expressions of COX-2 and iNOS were significantly decreased one year after the eradication in the patients with cured infection, but not in those having persistent H. pylori. COX-2 and iNOS expressions were well correlated with H. pylori density, acute and chronic inflammation of gastric mucosa. CONCLUSIONS: The eradication of H. pylori can decrease the expression of COX-2 and iNOS in the gastric mucosa in long-term period. This seems to be due to the removal of H. pylori itself and related regression of gastric inflammation.