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1.
Proc Natl Acad Sci U S A ; 120(21): e2218506120, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37192168

RESUMO

Novel genes have the potential to drive the evolution of new biological mechanisms, or to integrate into preexisting regulatory circuits and contribute to the regulation of older, conserved biological functions. One such gene, the novel insect-specific gene oskar, was first identified based on its role in establishing the Drosophila melanogaster germ line. We previously showed that this gene likely arose through an unusual domain transfer event involving bacterial endosymbionts and played a somatic role before evolving its well-known germ line function. Here, we provide empirical support for this hypothesis in the form of evidence for a neural role for oskar. We show that oskar is expressed in the adult neural stem cells of a hemimetabolous insect, the cricket Gryllus bimaculatus. In these stem cells, called neuroblasts, oskar is required together with the ancient animal transcription factor Creb to regulate long-term (but not short-term) olfactory memory. We provide evidence that oskar positively regulates Creb, which plays a conserved role in long-term memory across animals, and that oskar in turn may be a direct target of Creb. Together with previous reports of a role for oskar in nervous system development and function in crickets and flies, our results are consistent with the hypothesis that oskar's original somatic role may have been in the insect nervous system. Moreover, its colocalization and functional cooperation with the conserved pluripotency gene piwi in the nervous system may have facilitated oskar's later co-option to the germ line in holometabolous insects.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Fatores de Transcrição/genética , Células Germinativas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Insetos/genética , Memória de Longo Prazo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo
2.
J Ultrasound Med ; 43(2): 385-395, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37994205

RESUMO

The intermittent injection of teriparatide, a recombinant fragment of human parathyroid hormone (PTH 1-34), activates anabolic activity on bone turnover. However, the PTH administration period is limited to 2 years. Thus, sequential therapy after discontinuation of PTH is required. Low-intensity pulsed ultrasound (LIPUS) has been widely used for bone fracture healing. In this study, we examined the effects of LIPUS on bone mass after PTH withdrawal in ovariectomized (OVX) model mice. The LIPUS-non-irradiated femoral trabecular bone mineral density (BMD) in the treated after PTH withdrawal was significantly decreased. Meanwhile, the femoral BMD in the OVX + PTH-LIPUS group was remarkably higher than that of the OVX group. Additionally, mRNA expression of Runx2, Osterix, Col1a1, and ALP increased significantly following LIPUS irradiation after PTH withdrawal. These results suggest that LIPUS protected against femoral trabecular BMD loss and up-regulated the osteogenic factors following PTH withdrawal in OVX mice.


Assuntos
Densidade Óssea , Hormônio Paratireóideo , Humanos , Camundongos , Animais , Feminino , Hormônio Paratireóideo/farmacologia , Osteogênese , Ondas Ultrassônicas , Ovariectomia
3.
FASEB J ; 36(11): e22593, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36251357

RESUMO

In eukaryotes, CREB-binding protein (CBP), a coactivator of CREB, functions both as a platform for recruiting other components of the transcriptional machinery and as a histone acetyltransferase (HAT) that alters chromatin structure. We previously showed that the transcriptional activity of cAMP-responsive element binding protein (CREB) plays a crucial role in neuronal plasticity in the pond snail Lymnaea stagnalis. However, there is no information on the molecular structure and HAT activity of CBP in the Lymnaea central nervous system (CNS), hindering an investigation of its postulated role in long-term memory (LTM). Here, we characterize the Lymnaea CBP (LymCBP) gene and identify a conserved domain of LymCBP as a functional HAT. Like CBPs of other species, LymCBP possesses functional domains, such as the KIX domain, which is essential for interaction with CREB and was shown to regulate LTM. In-situ hybridization showed that the staining patterns of LymCBP mRNA in CNS are very similar to those of Lymnaea CREB1. A particularly strong LymCBP mRNA signal was observed in the cerebral giant cell (CGC), an identified extrinsic modulatory interneuron of the feeding circuit, the key to both appetitive and aversive LTM for taste. Biochemical experiments using the recombinant protein of the LymCBP HAT domain showed that its enzymatic activity was blocked by classical HAT inhibitors. Preincubation of the CNS with such inhibitors blocked cAMP-induced synaptic facilitation between the CGC and an identified follower motoneuron of the feeding system. Taken together, our findings suggest a role for the HAT activity of LymCBP in synaptic plasticity in the feeding circuitry.


Assuntos
Proteína de Ligação a CREB , Lymnaea , Animais , Proteína de Ligação a CREB/genética , Proteína de Ligação a CREB/metabolismo , Sistema Nervoso Central/metabolismo , Cromatina/metabolismo , Lymnaea/genética , Lymnaea/metabolismo , RNA Mensageiro/metabolismo , Proteínas Recombinantes/metabolismo
4.
Ann Nutr Metab ; 77(5): 289-298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34569491

RESUMO

INTRODUCTION: Although several approaches for approximating daily Na intake and the Na/K ratio using casual urine are available, the most useful method remains unclear during daily practice and at home. METHODS: Twenty-seven participants measured their casual urinary Na/K ratio repeatedly using a Na/K ratio monitor and also measured overnight urine once daily using a monitoring device which delivers on-site feedback to estimate their salt intake under unrestricted, low-salt (LS) (6 g/day), and high-salt (HS) (12 g/day) diets. RESULTS: The monitoring method utilizing overnight urine to estimate daily Na remained insensitive, resulting in significant overestimation during the LS diet and underestimation during the HS diet periods; estimated salt intake during the LS and HS diet periods plateaued at 7-8 g/day and 9-10 g/day within 3 day; mean estimated salt intake was 11.3 g/day, 7.9 g/day, and 9.8 g/day on the last day of the unrestricted, LS, and HS diets; the coefficient of variation (CV) of the estimated Na intake was 0.23 and 0.17 in the latter half of the low- and high-salt diet periods, respectively. The mean urinary Na/K molar ratio was 5.6, 2.5, and 5.3 on the last day of the unrestricted, LS, and HS diets; the CV of the daily mean Na/K ratio was 0.41 and 0.36 in the latter half of the LS and HS diet periods, respectively. The urinary Na/K ratio during the LS and HS diet periods plateaued within 2 days. The monitoring method based on the daily mean of the casual urinary Na/K ratio reflected the actual change in Na intake, and the estimated value tracked the actual changes in salt intake with smaller difference than the overnight urine estimates when using the estimation coefficient set at 2; estimated salt intake during the LS and HS diet periods plateaued at 5-6 g/day and 10-12 g/day within 2-3 day; mean estimated salt intake was 11.0 g/day, 5.7 g/day, and 10.7 g/day on the last day of the unrestricted, LS, and HS diets, respectively. DISCUSSION/CONCLUSION: Estimates of daily Na intake derived from overnight urine may remain insensitive during dietary interventions. The urinary Na/K ratio reflects the actual change in Na intake during dietary modification and may serve as a practical marker, particularly during short-term interventions. Conversion from the urinary Na/K ratio to estimated salt intake may be useful, if the coefficient was set appropriate by further investigations.


Assuntos
Cloreto de Sódio na Dieta , Sódio na Dieta , Dieta Hipossódica , Humanos , Japão , Refeições , Voluntários
5.
Ann Diagn Pathol ; 52: 151739, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33862415

RESUMO

We investigated the expression of LGR5, the most robust and reliable known cancer stem cell (CSC) marker of colorectal cancer, and PD-L1 in tumor budding (TB), as well as clinicopathological features. Tissue microarrays (TMAs) were generated from TB samples from 32 stage II/III colorectal adenocarcinoma patients, and LGR5 expression in TMAs was evaluated by RNAscope, an extremely sensitive RNA in situ hybridization technique. LGR5 expression was significantly lower in the PD-L1-positive group than in the PD-L1-negative group (P = 0.0256). In the PD-L1-positive group, the tumor-infiltrating lymphocytes (TILs) score tended to be higher while the TNM stage was lower compared with the PD-L1 negative group (P = 0.0822 and P = 0.0765, respectively). There was no significant difference in Overall Survival between the PD-L1-positive and PD-L1-negative groups (log-rank test, P = 0.8218). This study showed that PD-L1-positive patients are a unique population with low LGR5 expression, and that LGR5-positive cells may be a promising therapeutic target in PD-L1-negative patients.


Assuntos
Adenocarcinoma/metabolismo , Antígeno B7-H1/metabolismo , Estadiamento de Neoplasias/métodos , Receptores Acoplados a Proteínas G/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Estadiamento de Neoplasias/estatística & dados numéricos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Prognóstico , RNA/genética , Análise Serial de Tecidos/métodos
6.
Nihon Shokakibyo Gakkai Zasshi ; 118(7): 679-685, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34248081

RESUMO

This case report describes a 73-year-old woman with pancreatic adenocarcinoma who had undergone a colectomy for colorectal cancer in 1995 and a right mastectomy and axillary dissection for breast cancer in 2013. In January 2019, a tumor, approximately 20mm in diameter, was detected in the pancreatic body. It contained a cyst noted to have delayed perfusion towards the center on abdominal computed tomography. On T1-weighted magnetic resonance imaging (MRI), almost the entire tumor exhibited low intensity. On T2-weighted MRI, however, the tumor center displayed high intensity, the tumor wall displayed low intensity, and the outermost layer displayed high intensity. On endoscopic ultrasound, the tumor center displayed low echo density, the tumor wall had a slightly elevated echo density, and the outermost layer had a low echo density. A distal pancreatectomy was performed for a suspected metastatic pancreatic cancer, pancreatic neuroendocrine neoplasm, or invasive ductal carcinoma without tubular adenocarcinoma. Histopathological examination revealed that the tumor cells had formed atypical tubular gland ducts with a fibrous stroma in the background. The lesion differed from the histopathological findings of her previous colorectal and breast cancers, and it was ultimately diagnosed as a pancreatic ductal adenocarcinoma. The lumen of the cyst was covered with tumor cells identical to those of the atypical tubular gland ducts in the tumor parenchyma, suggesting that the cyst was a dilated tubular gland duct.


Assuntos
Adenocarcinoma , Neoplasias da Mama , Carcinoma Ductal Pancreático , Cistos , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Idoso , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Feminino , Humanos , Mastectomia , Pancreatectomia , Ductos Pancreáticos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia
7.
Biochem Biophys Res Commun ; 530(4): 665-672, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768187

RESUMO

The role of sphingosine 1-phosphate (S1P) and its sphingosine-1-phosphate receptors (S1PRs) in non-alcoholic steatohepatitis (NASH) is unclear. We aimed to analyze the role of S1P/S1PRs in a Melanocortin-4 receptor (Mc4r)-deficient NASH murine model using FTY720, the functional antagonist of S1PR1, S1PR3, S1PR4, and S1PR5, and JTE-013, the antagonist of S1PR2. We observed that, compared to that in the control, the mRNA of S1pr1 tended to decrease, whereas those of S1pr2 and S1pr3 significantly increased in Mc4r-knockout (KO) mice subjected to a Western diet (WD). While the fat area did not differ, fibrosis progression differed significantly between control mice and mice in which liver S1PRs were blocked. Lipidomic and metabolomic analysis of liver tissues showed that JTE-013-administered mice showed elevation of S-adenosyl-l-methionine level, which can induce aberrant methylation due to reduction in glycine N-methyltransferase (GNMT) and elevation in diacylglycerol (DG) and triacylglycerol (TG) levels, leading to increased susceptibility to hepatocellular carcinoma (HCC). These phenotypes are similar to those of Gnmt-KO mice, suggesting that blocking the S1P/S1PR2 axis triggers aberrant methylation, which may increase DG and TG, and hepatocarcinogenesis. Our observations that the S1P/S1PR2 axis averts HCC occurrence may assist in HCC prevention in NASH.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Receptores de Esfingosina-1-Fosfato/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Regulação da Expressão Gênica , Glicina N-Metiltransferase/genética , Glicina N-Metiltransferase/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptor Tipo 4 de Melanocortina/genética , Receptor Tipo 4 de Melanocortina/metabolismo , Receptores de Esfingosina-1-Fosfato/antagonistas & inibidores , Receptores de Esfingosina-1-Fosfato/genética
8.
Pancreatology ; 20(6): 1062-1068, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32800575

RESUMO

BACKGROUND/OBJECTIVES: Patients with autoimmune pancreatitis (AIP) sometimes progress to chronic pancreatitis (CP). We evaluated the ability of corticosteroids to prevent the progression to CP. METHODS: We defined patients with definitive findings of CP (stones in the main pancreatic duct [MPD] or multiple pancreatic calcifications) as having severe calcification (SC). A total of 145 AIP patients were enrolled. We measured the duration between AIP diagnosis and SC development and retrospectively compared the time to SC development between patients with and without steroids. Multivariate analysis for factors associated with SC were performed. RESULTS: Nineteen (13%) patients progressed to SC. Since 95 patients had pancreatic head swelling and SC was found in these patients only, our analysis focused mainly on these at-risk populations. In Kaplan-Meier analysis limited to patients with pancreatic head swelling, the incidence of SC was significantly lower in patients with steroids than in those without (hazard ratio [HR] 0.18, 95% confidence interval [CI] 0.07-0.52; p < 0.001). Multivariate testing of patients with pancreatic head swelling confirmed that steroid therapy was significantly associated with a lower incidence of SC (HR 0.11, 95% CI 0.03-0.34; p < 0.001), while MPD dilation at AIP diagnosis was related to a higher incidence of SC (HR 4.02, 95% CI 1.43-11.7; p = 0.009). CONCLUSIONS: Corticosteroids appeared to prevent progression to CP in AIP patients, especially in those with pancreatic head swelling. Patients with both pancreatic head swelling and MPD dilation at diagnosis have a higher incidence of progression to CP. Steroid therapy is suggested for these high-risk cases.


Assuntos
Corticosteroides/uso terapêutico , Pancreatite Autoimune/tratamento farmacológico , Pancreatite Crônica/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcinose/tratamento farmacológico , Calcinose/etiologia , Progressão da Doença , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Ductos Pancreáticos , Pancreatite Crônica/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
9.
Scand J Gastroenterol ; 54(6): 773-779, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31164010

RESUMO

Objectives: Autoimmune pancreatitis (AIP) sometimes becomes complicated with pancreatic cysts, although their detailed characteristics and management strategy have not been fully determined. We aimed to clarify the efficiency of steroid therapy and the risk factors for cyst formation and cyst-related complications. Methods: One hundred sixty-three AIP patients were retrospectively analyzed for relevant factors of cyst formation. We compared subjects with and without steroids to evaluate drug effectiveness on cyst size change and investigated the factors associated with cyst-related complications. Results: Thirty-two patients (19.6%) had complicating pancreatic cyst formation, and 40 cystic lesions of ≥10 mm in size were detected. Multivariate analysis revealed a drinking habit, abdominal/back pain, and elevated serum amylase to be significantly associated with cyst formation. Steroid-treated cysts became significantly reduced in size in the short-term and disappeared significantly more frequently within 1-year as compared with non-treated ones, which was confirmed by multivariate analysis. Six of 40 cysts exhibited cyst-related complications significantly associated with multilocular morphology and larger size. Conclusions: Steroid therapy is an effective choice for cysts developing in AIP to promote the release of pancreatic juice stasis. Larger lesions with multilocular morphology should be monitored closely for cyst-related complications and be considered strong candidates for steroid therapy.


Assuntos
Pancreatite Autoimune/complicações , Cisto Pancreático/tratamento farmacológico , Cisto Pancreático/etiologia , Esteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
10.
Neurobiol Learn Mem ; 148: 20-29, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29294381

RESUMO

The pond snail Lymnaea stagnalis learns conditioned taste aversion (CTA) and consolidates it into long-term memory (LTM). How well they learn and form memory depends on the degree of food deprivation. Serotonin (5-HT) plays an important role in mediating feeding, and insulin enhances the memory consolidation process following CTA training. However, the relationship between these two signaling pathways has not been addressed. We measured the 5-HT content in the central nervous system (CNS) of snails subjected to different durations of food deprivation. One-day food-deprived snails, which exhibit the best learning and memory, had the lowest 5-HT content in the CNS, whereas 5-day food-deprived snails, which do not learn, had a high 5-HT content. Immersing 1-day food-deprived snails in 5-HT impaired learning and memory by causing an increase in 5-HT content, and that the injection of insulin into these snails reversed this impairment. We conclude that insulin rescues the CTA deficit and this may be due to a decrease in the 5-HT content in the CNS of Lymnaea.


Assuntos
Aprendizagem da Esquiva/fisiologia , Comportamento Animal/fisiologia , Sistema Nervoso Central/metabolismo , Disfunção Cognitiva , Condicionamento Psicológico/fisiologia , Privação de Alimentos/fisiologia , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Lymnaea/fisiologia , Memória de Longo Prazo/fisiologia , Serotonina/metabolismo , Percepção Gustatória/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Condicionamento Psicológico/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Lymnaea/efeitos dos fármacos , Lymnaea/metabolismo , Memória de Longo Prazo/efeitos dos fármacos , Percepção Gustatória/efeitos dos fármacos , Fatores de Tempo
11.
Neurobiol Learn Mem ; 141: 189-198, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28450080

RESUMO

The pond snail Lymnaea stagnalis is capable of learning taste aversion by pairing presentations of a sucrose solution and an electric shock and consolidating it into long-term memory (LTM), which is referred to as conditioned taste aversion (CTA). We asked here if the neurotransmitter octopamine is involved in CTA. We first determined the levels of octopamine and its catabolites in the central nervous system (CNS) of snails with varying degrees of food deprivation, because CTA grades are correlated with degrees of food deprivation. We next manipulated the octopamine signaling using both an agonist and an antagonist of octopamine receptors and correlated their respective effects with CTA grades. We found that snails with the least amount of food-deprivation obtained the best CTA grade and had low levels of octopamine; whereas the most severely food-deprived snails did not form CTA and had the highest CNS octopamine levels. In modestly food-deprived snails, octopamine application increased the basal level of feeding response to a sucrose solution, and it did not obstruct CTA formation. Application of phentolamine, an octopamine receptor antagonist, to the most severely food-deprived snails decreased the basal level of feeding elicited by sucrose, but it did not enhance CTA formation. We conclude that octopamine involvement in CTA formation in Lymnaea is at best weak, and that the changes in CNS octopamine content are an epiphenomenon.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Octopamina/metabolismo , Paladar/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/fisiologia , Privação de Alimentos/fisiologia , Lymnaea/efeitos dos fármacos , Lymnaea/fisiologia , Octopamina/farmacologia , Fentolamina/farmacologia , Receptores de Amina Biogênica/agonistas , Receptores de Amina Biogênica/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Paladar/fisiologia
12.
Pancreatology ; 17(4): 567-571, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28506431

RESUMO

PURPOSE: To compare three-dimensional magnetic resonance cholangiopancreatography (MRCP) with/without partial maximum intensity projection (MIP) and endoscopic retrograde cholangiopancreatography (ERCP) in patients with autoimmune pancreatitis (AIP). MATERIALS AND METHODS: Three-dimensional MRCP and ERCP images were retrospectively analyzed in 24 patients with AIP. We evaluated the narrowing length of the main pancreatic duct (NR-MPD), multiple skipped MPD narrowing (SK-MPD), and side branches arising from the narrowed portion of the MPD (SB-MPD) using four MRCP datasets: 5 original images (MIP5), 10 original images (MIP10), all original images (full-MIP), and a combination of these three datasets (a-MIP). The images were scored using a 3- or 5-point scale. The scores of the four MRCP datasets were statistically analyzed, and the positive rate of each finding was compared between MRCP and ERCP. RESULTS: The median scores for SB-MPD on MIP5 and a-MIP were significantly higher than those on MIP10 and full-MIP. In other words, partial MIP is superior to full-MIP for visualization of detailed structures. The positive rate for SB-MPD on full-MIP was significantly lower than that on ERCP, whereas the positive rate on MIP5, MIP10, and a-MIP was not significantly different from that on ERCP. Moreover, the positive rate for NR-MPD and SK-MPD on the MRCP images was significantly higher than that on the ERCP images. CONCLUSION: Partial MIP is useful for evaluating the MPD and is comparable with ERCP for diagnosing AIP.

13.
J Exp Biol ; 220(Pt 17): 3026-3038, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28855319

RESUMO

Cannabinoids are hypothesized to play an important role in modulating learning and memory formation. Here, we identified mRNAs expressed in Lymnaeastagnalis central nervous system that encode two G-protein-coupled receptors (Lymnaea CBr-like 1 and 2) that structurally resemble mammalian cannabinoid receptors (CBrs). We found that injection of a mammalian CBr agonist WIN 55,212-2 (WIN 55) into the snail before operant conditioning obstructed learning and memory formation. This effect of WIN 55 injection persisted for at least 4 days following its injection. A similar obstruction of learning and memory occurred when a severe traumatic stimulus was delivered to L. stagnalis In contrast, injection of a mammalian CBr antagonist AM 251 enhanced long-term memory formation in snails and reduced the duration of the effects of the severe traumatic stressor on learning and memory. Neither WIN 55 nor AM 251 altered normal homeostatic aerial respiratory behaviour elicited in hypoxic conditions. Our results suggest that putative cannabinoid receptors mediate stressful stimuli that alter learning and memory formation in Lymnaea This is also the first demonstration that putative CBrs are present in Lymnaea and play a key role in learning and memory formation.


Assuntos
Canabinoides/farmacologia , Lymnaea/efeitos dos fármacos , Receptores Acoplados a Proteínas G/genética , Animais , Benzoxazinas/farmacologia , Condicionamento Operante , Aprendizagem/efeitos dos fármacos , Lymnaea/genética , Lymnaea/fisiologia , Memória/efeitos dos fármacos , Morfolinas/farmacologia , Naftalenos/farmacologia , Piperidinas/farmacologia , Pirazóis/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo
14.
Lipids Health Dis ; 16(1): 122, 2017 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-28646901

RESUMO

BACKGROUND: Lowering cholesterol levels decreases the risk of atherosclerotic diseases. Effective ways to stably reduce LDL-C level are warranted in type 2 diabetic patients, a high-risk population for CVD, with various anti-diabetic therapeutic background. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles. We evaluated long-term ezetimibe add-on therapy in T2DM patients with hypercholesterolemia. METHODS: In a randomized, multicenter, open-label, prospective study, a total of 109 T2DM patients not attaining LDL-C target value despite first-line dose statin (10 mg of atorvastatin or 1 mg of pitavastatin) therapy in Japan were recruited. We investigated the difference in cholesterol lowering effect between ezetimibe (10 mg) add-on statin (EAT) group and double-dose statin (DST) group. Changes of parameters related to atherosclerotic event risks were assessed. RESULTS: The reduction of LDL-C was larger in the EAT group (28.3%) than in the DST group (9.2%) at 52 weeks as well as the primary endpoint of 12 weeks. EAT achieved significant lower levels of TC and apo B, respectively. Both treatments attained significant reduction in sd-LDL-C or hsCRP on this long-term basis. Notably, sd-LDL-C in EAT reduced as low as 36.1 ± 14.9 mg/dl to reach near the threshold (35.0 mg/dl) for atherosclerosis with significantly higher achievement rate (55.6%) than DST treatment. Simultaneously, hsCRP reduction by EAT attained as low value as 0.52 ± 0.43 mg/l. CONCLUSIONS: In the present 52-week long-term period, ezetimibe add-on therapy showed a robust advantage in lowering LDL-C and in attaining target LDL-C values compared with the doubling of statin dose. Moreover, it's meaningful that sd-LDL, powerfully atherogenic lipoprotein, exhibited prominent decrease consistently prominently by ezetimibe add-on therapy. DM patients with hypercholesterolemia are at high risk for CAD, and adding ezetimibe onto usual-dose statin treatment in Japan has been suggested as the first-line therapy for those DM patients who failed to attain the target LDL-C value (UMIN000002593).


Assuntos
Anticolesterolemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ezetimiba/uso terapêutico , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Estudos Prospectivos
15.
Biochem Biophys Res Commun ; 478(2): 1014-9, 2016 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-27392711

RESUMO

Specific genes quickly transcribed after extracellular stimuli without de novo protein synthesis are known as immediate early genes (IEGs) and are thought to contribute to learning and memory processes in the mature nervous system of vertebrates. A recent study revealed that the homolog of Early growth response protein-1 (Egr-1), which is one of the best-characterized vertebrate IEGs, shared similar properties as a neural activity-dependent gene in the adult brain of insects. With regard to the roles of vertebrate Egr-1 in neural development, the contribution to the development and growth of visual systems has been reported. However, in insects, the expression dynamics of the Egr-1 homologous gene during neural development remains poorly understood. Our expression analysis demonstrated that AmEgr, a honeybee homolog of Egr-1, was transiently upregulated in the developing brain during the early to mid pupal stages. In situ hybridization and 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry revealed that AmEgr was mainly expressed in post-mitotic cells in optic lobes, the primary visual center of the insect brain. These findings suggest the evolutionarily conserved role of Egr homologs in the development of visual systems in vertebrates and insects.


Assuntos
Abelhas/crescimento & desenvolvimento , Evolução Biológica , Sequência Conservada , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Olho/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Metamorfose Biológica/genética , Vertebrados/genética , Animais , Abelhas/genética , Encéfalo/citologia , Encéfalo/metabolismo , Proliferação de Células , Proteína 1 de Resposta de Crescimento Precoce/genética , Éxons/genética , Olho/metabolismo , Perfilação da Expressão Gênica , Hibridização In Situ , Lobo Óptico de Animais não Mamíferos/citologia , Lobo Óptico de Animais não Mamíferos/metabolismo , Pupa/metabolismo , Homologia de Sequência de Aminoácidos
16.
Dig Endosc ; 28(5): 607-10, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26946036

RESUMO

The natural history of Barrett's esophagus (BE) is unclear. We herein describe a case of Barrett's adenocarcinoma (BAC) in which we could closely observe marked morphological changes in BE over a long follow-up period of 15 years. A man in his seventies received routine esophagogastroduodenoscopy (EGD) and was diagnosed as having reflux esophagitis and short-segment BE. The BE gradually became elongated, and BAC was detected 9 years following the initial EGD examination with continued administration of a proton pump inhibitor. We witnessed that BE elongated sporadically over time and mucosal breaks of reflux esophagitis were detectable several years before elongation. The patient underwent endoscopic submucosal dissection for BAC and has been monitored by EGD every year thereafter. These remarkable morphological changes may be representative of the natural history of BE and aid in deciding long-term disease management.


Assuntos
Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Endoscopia Gastrointestinal , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/patologia , Adenocarcinoma/cirurgia , Idoso , Neoplasias Esofágicas/cirurgia , Seguimentos , Humanos , Masculino , Fatores de Tempo
17.
J Exp Biol ; 218(Pt 11): 1699-704, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25883377

RESUMO

Food deprivation for 1 day in the pond snail Lymnaea stagnalis before aversive classical conditioning results in optimal conditioned taste aversion (CTA) and long-term memory (LTM) formation, whereas 5-day food deprivation before training does not. We hypothesize that snails do in fact learn and form LTM when trained after prolonged food deprivation, but that severe food deprivation blocks their ability to express memory. We trained 5-day food-deprived snails under various conditions, and found that memory was indeed formed but is overpowered by severe food deprivation. Moreover, CTA-LTM was context dependent and was observed only when the snails were in a context similar to that in which the training occurred.


Assuntos
Lymnaea/fisiologia , Animais , Aprendizagem da Esquiva , Condicionamento Clássico , Privação de Alimentos , Memória de Longo Prazo , Paladar/fisiologia
18.
BMC Gastroenterol ; 15: 28, 2015 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-25887404

RESUMO

BACKGROUND: Although most patients with autoimmune pancreatitis (AIP) respond favorably to prednisolone therapy, some individuals who later suffer from pancreatic calculi may require additional extracorporeal shock wave lithotripsy (ESWL) treatment. This study compares the efficacy of ESWL for calculi in AIP with that in ordinary chronic pancreatitis (CP) and proposes a new treatment approach for pancreatic duct stones occurring in AIP. METHODS: We examined the clinical records of 8 patients with chronic stage AIP and 92 patients with ordinary CP who received ESWL for pancreatic calculi. RESULTS: The AIP group was significantly older than the CP group (69.0 vs. 56.5 years, P = 0.018). With regard to the indications for ESWL, chronic pain was significantly less frequent in the chronic stage AIP group (0% vs. 45.7%, P = 0.001), whereas preservation of pancreatic function was significantly more frequent (75% vs. 19.6%, P = 0.001). Compared with the CP group, the AIP group tended to exhibit pancreatic duct stenosis proximal to pancreatic calculi and had a lower rate of complete extraction of stones from the main pancreatic duct. Histopathological analysis of a patient with chronic stage AIP revealed widely distributed nodular pancreatitis, which was characteristic of ordinary CP, along with isolated areas of lymphoplasmacytic sclerosing pancreatitis. CONCLUSIONS: Different approaches are needed for the treatment of pancreatic calculi in chronic stage AIP and ordinary CP. Specifically, it appears that intensive ESWL therapy can be avoided or delayed in AIP if the patient displays: (1) advanced age, (2) little or no chronic pain or pancreatitis, and (3) pancreatic duct stenosis proximal to pancreatic stones. In such cases, the benefit of ESWL treatment may be outweighed by the risks involved in this procedure.


Assuntos
Doenças Autoimunes/complicações , Cálculos/terapia , Litotripsia , Pancreatopatias/terapia , Pancreatite Crônica/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/patologia , Cálculos/complicações , Dor Crônica/etiologia , Constrição Patológica/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatopatias/complicações , Ductos Pancreáticos/patologia , Pancreatite Crônica/imunologia , Pancreatite Crônica/patologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 70(8): 793-8, 2014 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-25142390

RESUMO

The array spatial sensitivity encoding technique (ASSET) is a form of parallel imaging (PI). Another scan, called a reference scan (Ref) is required before acquiring the ASSET image. However, artifacts tend to interfere with recognition of the object due to differences between the ASSET scan and Ref. scan. This is because the liver is in contact with the diaphragm, making it susceptible to respiratory motion. Further, since the liver upper edge is surrounded by the lung field, there is a risk of susceptibility artifacts. The purpose of this study was to reduce the accompanied deployment failure artifact using a thick slice sensitivity map. Our data showed it was possible to reduce accompanied deployment failure artifacts, as well as to suppress noise, by increasing the slice thickness of the Ref scan.


Assuntos
Artefatos , Imageamento por Ressonância Magnética/métodos , Fígado/patologia , Imageamento por Ressonância Magnética/instrumentação , Imagens de Fantasmas , Sensibilidade e Especificidade
20.
PNAS Nexus ; 3(4): pgae162, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38689705

RESUMO

Many animals use multicomponent sex pheromones for mating, but the specific function and neural processing of each pheromone component remain unclear. The cockroach Periplaneta americana is a model for studying sex pheromone communication, and an adult female emits major and minor sex pheromone components, periplanone-B and -A (PB and PA), respectively. Attraction and courtship behaviors (wing-raising and abdominal extension) are strongly expressed when adult males are exposed to PB but weakly expressed when they are exposed to PA. When major PB is presented together with minor PA, behaviors elicited by PB were impaired, indicating that PA can both promote and suppress courtship behaviors depending on the pheromonal context. In this study, we identified the receptor genes for PA and PB and investigated the effects of knocking down each receptor gene on the activities of PA- and PB-responsive sensory neurons (PA- and PB-SNs), and their postsynaptic interneurons, and as well as effects on courtship behaviors in males. We found that PB strongly and PA weakly activate PB-SNs and their postsynaptic neurons, and activation of the PB-processing pathway is critical for the expression of courtship behaviors. PA also activates PA-SNs and the PA-processing pathway. When PA and PB are simultaneously presented, the PB-processing pathway undergoes inhibitory control by the PA-processing pathway, which weakens the expression of courtship behaviors. Our data indicate that physiological interactions between the PA- and PB-processing pathways positively and negatively mediate the attraction and courtship behaviors elicited by sex pheromones.

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