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1.
J Evol Biol ; 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39031072

RESUMO

Exploring the evolutionary architecture of female sexual traits and their potential evolvability is important to understand their possible role as post-mating sexual signals. Egg colouration has been proposed to be one of these post-mating sexual signals, honestly advertising female quality in birds, especially in blue-green laying species. In this study, we used an animal model in a Bayesian framework to estimate the evolvability of multiple descriptors of blue-green egg colouration and egg size in a wild long-term monitored population of spotless starlings (Sturnus unicolor). Our results show low to moderate heritability (h2 = 0.31 - 0.44) for three egg colour descriptors (blue-green chroma, chroma and lightness) and egg size. Using the coefficient of additive genetic variance (CVA) and the evolvability (IA) as proxies of evolutionary potential of all components of this trait, we found low values of CVA for all these variables, suggesting a small evolutionary potential of these phenotypic traits, contrasting to previous results reported in another blue-green egg laying species. Our results indicate a modest raw genetic material of this trait on which sexual selection can act upon and, therefore, a small probability for these traits to respond easily to selection.

2.
Obes Surg ; 33(8): 2420-2427, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37351763

RESUMO

PURPOSE: Laparoscopic sleeve gastrectomy (LSG) is the most popular primary bariatric metabolic procedure worldwide but severe complications are still reported, and there is no ideal technique to avoid them. This study analyses the impact of oversewing (OS) and gastropexy (GP) on complication rate, early dyspeptic and late de novo GERD symptoms after LSG. MATERIAL AND METHOD: A case-control study was conducted on patients with obesity who underwent LSG. The total cohort was divided in group A (control group) - patients with no oversewing (OS) or gastropexy (GP), group B - patients with OS but no gastropexy and group C - patients with both OS and GP performed during LSG. RESULTS: We included 272 patients with obesity with a mean BMI 42.9±6.94 kg/m2, 96 patients in group A, 90 patients in group B and 86 in group C with no statistical differences between them. We had 5 cases of postoperative hemorrhage (4 in group A) and three patients who developed leaks (2 in group A and one in group B). Prolonged and severe early dyspeptic episodes and after 6 months reflux symptoms were significantly more in groups A and B (p<0.05). The operative time was longer in group B and C (p<0.05) but with no difference in procedure -related morbidity and in hospital length of stay. CONCLUSION: Adding both OS and GP to LSG reduce complications rate with no influence on procedure-related postoperative morbidity and in-hospital length of stay. GP reduces early postoperative dyspeptic and de novo GERD symptoms after LSG.


Assuntos
Refluxo Gastroesofágico , Laparoscopia , Obesidade Mórbida , Humanos , Estudos de Casos e Controles , Obesidade Mórbida/cirurgia , Laparoscopia/métodos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Obesidade/cirurgia , Refluxo Gastroesofágico/cirurgia , Refluxo Gastroesofágico/etiologia , Resultado do Tratamento , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia
3.
Minerva Obstet Gynecol ; 75(4): 371-378, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35420290

RESUMO

Survival rates after cancer diagnosis and treatment have been raising through the last decades. Nowadays, oncofertility represents a useful strategy for young women affected by cancer to preserve their ovarian function and their family planning opportunity. Apart from more diffused techniques as cryopreservation of mature oocytes after controlled ovarian stimulation and gonadal downregulation with gonadotropin-releasing hormone agonist depots, the cryopreservation of the cortical region of the ovarian tissue, which contains 90% of the follicular reserve, and later autologous transplant represent a possible and intriguing strategy. Nonetheless, the safety of the procedure is still a matter of debate and is a topic of great interest in both oncologic and reproductive fields. Especially, in order to improve the efficacy of the strategy the open questions are: 1) how to search for malignant cells; 2) slow freezing vs. vitrification; 3) state of the art on the "artificial ovary." The aim of this review was to summarize the recent advances in ovarian tissue cryopreservation and present future perspectives.


Assuntos
Criopreservação , Preservação da Fertilidade , Neoplasias , Ovário , Humanos , Feminino , Neoplasias/complicações , Ovário/patologia , Infertilidade Feminina/prevenção & controle
4.
Photochem Photobiol Sci ; 21(6): 949-958, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35157258

RESUMO

Many microorganisms produce specific structures, known as spores or cysts, to increase their resistance to adverse environmental conditions. Scientists have started to produce biomimetic materials inspired by these natural membranes, especially for industrial and biomedical applications. Here, we present biological data on the biocompatibility of a polydopamine-based artificial coating for diatom cells. In this work, living Thalassiosira weissflogii diatom cells are coated on their surface with a polydopamine layer mimicking mussel adhesive protein. Polydopamine does not affect diatoms growth kinetics, it enhances their resistance to degradation by treatment with detergents and acids, and it decreases the uptake of model staining emitters. These outcomes pave the way for the use of living diatom cells bearing polymer coatings for sensors based on living cells, resistant to artificial microenvironments, or acting as living devices for cells interface study.


Assuntos
Diatomáceas , Microalgas , Diatomáceas/metabolismo , Indóis/química , Indóis/farmacologia , Polímeros/química
5.
Memory ; 30(3): 230-247, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34762020

RESUMO

Age deficits in memory for individual episodes are well established. Less is known about how age affects another key memory function: the ability to form new conceptual knowledge. Here we studied age differences in concept formation in a category-learning paradigm with face-blend stimuli, using several metrics: direct learning of category members presented during training, generalisation of category labels to new examples, and shifts in perceived similarity between category members that often follow category learning. We found that older adults were impaired in direct learning of training examples, but that there was no significant age deficit in generalisation once we accounted for the deficit in direct learning. We also found that category learning affected the perceived similarity between members of the same versus opposing categories, and age did not significantly moderate this effect. Lastly, we compared traditional category learning to categorisation after a learning task in which a category label (shared last name) was presented alongside stimulus-specific information (unique first names that individuated category members). We found that simultaneously learning stimulus-specific and category information resulted in decreased category learning, and that this decrement was apparent in both age groups.


Assuntos
Generalização Psicológica , Aprendizagem , Idoso , Formação de Conceito , Humanos , Conhecimento , Percepção
6.
J Neurosci ; 42(5): 865-876, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-34937702

RESUMO

Category learning, learning to sort a set of stimuli into categories or groups, can induce category biases in perception such that items in the same category are perceived as more similar than items from different categories. To what degree category bias develops when learning goals emphasize individuation of each stimulus and whether the bias emerges spontaneously during learning itself rather than in response to task demands is unclear. Here, we used functional MRI (fMRI) during encoding to test for category biases in neural representations of individual stimuli during learning. Human participants (males and females) encountered face-blend stimuli with unique first names and shared family names that indicated category membership. Participants were instructed to learn the full name for each face. Neural pattern classification and pattern similarity analyses were used to track category information in the brain. Results showed that stimulus category could be decoded during encoding across many frontal, parietal, and occipital regions. Furthermore, two stimuli from the same category were represented more similarly in the prefrontal cortex than two stimuli from different categories equated for physical similarity. These findings illustrate that a mere presence of category label can bias neural representations spontaneously during encoding to emphasize category-relevant information, even in the absence of explicit categorization demands and when category-irrelevant information remains relevant for task goals.SIGNIFICANCE STATEMENT Entities belonging to the same category are perceived as being more similar than entities belonging to different categories. Here, we show that neural representations highlighting category-relevant information form spontaneously during encoding. Notably, the presence of a category label led to neural category bias although participants focused on remembering individual stimuli and category-irrelevant stimulus features remained important for explicit task goals. These results may inform our understanding of bias in general and suggest that bias may emerge when category information is present even when one's explicit focus is on individuals.


Assuntos
Encéfalo/fisiologia , Conectoma , Memória , Adolescente , Adulto , Sinais (Psicologia) , Feminino , Objetivos , Humanos , Imageamento por Ressonância Magnética , Masculino
7.
Eur J Nucl Med Mol Imaging ; 48(8): 2351-2362, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33420915

RESUMO

PURPOSE: The aim of this work was to demonstrate the suitability of AAZTA conjugated to PSMA inhibitor (B28110) labeled with scandium-44 as a new PET tracer for diagnostic imaging of prostate cancer. BACKGROUND: Nowadays, scandium-44 has received significant attention as a potential radionuclide with favorable characteristics for PET applications. A polyaminopolycarboxylate heptadentate ligand based on a 1,4-diazepine scaffold (AAZTA) has been thoroughly studied as chelator for Gd3+ ions for MRI applications. The excellent results of the equilibrium, kinetic, and labeling studies led to a preliminary assessment of the in vitro and in vivo behavior of [44Sc][Sc-(AAZTA)]- and two derivatives, i.e., [44Sc][Sc (CNAAZTA-BSA)] and [44Sc][Sc (CNAAZTA-cRGDfK)]. RESULTS: B28110 was synthesized by hybrid approach, combining solid-phase peptide synthesis (SPPS) and solution chemistry to obtain high purity (97%) product with an overall yield of 9%. Subsequently, the radioactive labeling was performed with scandium-44 produced from natural calcium target in cyclotron, in good radiochemical yields (RCY) under mild condition (pH 4, 298 K). Stability study in human plasma showed good RCP% of [44Sc]Sc-B28110 up to 24 h (94.32%). In vivo PET/MRI imaging on LNCaP tumor-bearing mice showed high tracer accumulation in the tumor regions as early as 20 min post-injection. Ex vivo biodistribution studies confirmed that the accumulation of 44Sc-PSMA-617 was two-fold lower than that of the radiolabeled B28110 probes. CONCLUSIONS: This work demonstrated the suitability of B28110 for the complexation with scandium-44 at room temperature and the high performance of the resulting new tracer based on AAZTA chelator for the diagnosis of prostate cancer using PET.


Assuntos
Tomografia por Emissão de Pósitrons , Neoplasias da Próstata , Animais , Linhagem Celular Tumoral , Glutamato Carboxipeptidase II/metabolismo , Humanos , Masculino , Camundongos , Neoplasias da Próstata/diagnóstico por imagem , Radioquímica , Compostos Radiofarmacêuticos , Distribuição Tecidual
8.
Psychon Bull Rev ; 27(4): 791-800, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32472329

RESUMO

The current study investigated category learning across two experiments using face-blend stimuli that formed face families controlled for within- and between-category similarity. Experiment 1 was a traditional feedback-based category-learning task, with three family names serving as category labels. In Experiment 2, the shared family name was encountered in the context of a face-full name paired-associate learning task, with a unique first name for each face. A subsequent test that required participants to categorize new faces from each family showed successful generalization in both experiments. Furthermore, perceived similarity ratings for pairs of faces were collected before and after learning, prior to generalization test. In Experiment 1, similarity ratings increased for faces within a family and decreased for faces that were physically similar but belonged to different families. In Experiment 2, overall similarity ratings decreased after learning, driven primarily by decreases for physically similar faces from different families. The post-learning category bias in similarity ratings was predictive of subsequent generalization success in both experiments. The results indicate that individuals formed generalizable category knowledge prior to an explicit demand to generalize and did so both when attention was directed towards category-relevant features (Experiment 1) and when attention was directed towards individuating faces within a family (Experiment 2). The results tie together research on category learning and categorical perception and extend them beyond a traditional category-learning task.


Assuntos
Generalização Psicológica , Aprendizagem por Associação de Pares , Percepção Visual , Adolescente , Adulto , Face , Feminino , Humanos , Masculino , Nomes , Adulto Jovem
9.
Mater Sci Eng C Mater Biol Appl ; 104: 109897, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500019

RESUMO

Bisphosphonates are a class of drugs widely used in the clinical treatment of disorders of bone metabolism, such as osteoporosis, fibrous dysplasia, myeloma and bone metastases. Because of the negative side effects caused by oral administration of bisphosphonates, various silica mesoporous materials have been investigated for a confined and controlled release of these drugs. Here, we propose biosilica from diatoms as suitable substrate for alendronate local activation of bone cells. Following a novel strategy, sodium alendronate can be in vivo incorporated into biosilica shells of cultured Thalassiosira weissflogii diatoms, by feeding the algae with an aqueous solution of the drug. After acid/oxidative treatments for removing organic matter, the resulting bisphosphonate-functionalized mesoporous biosilica was characterized and tested as osteoinductive support. Effects on osteoblast growth and anti-osteoclast activity have been examined by evaluating SaOS-2, BMSC, J774 cell viability on the alendronate-"doped" biosilica. The loading percentage of sodium alendronate into biosilica, estimated as 1.45% w/w via TGA, was able to decrease metabolic activity of J774 osteoclasts-like cells till 5% over glass control. We demonstrated a good osteoconductive ability and activation of a tissue regeneration model together with osteoclasts inhibition of the functionalized biosilica, opening the way to interesting applications for diatom microalgae as a bioinspired mesoporous material for tissue engineering.


Assuntos
Alendronato/farmacologia , Osso e Ossos/efeitos dos fármacos , Diatomáceas/química , Dióxido de Silício/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Termogravimetria , Água/química
10.
Data Brief ; 24: 103831, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30997370

RESUMO

Diatoms are unicellular photosynthetic microalgae that produce a sophisticated mesoporous biosilica shell called frustule. Easy to achieve and extract, diatom frustules represent a low-cost source of mesoporous biocompatible biosilica. In this paper, the possibility to in vivo functionalize the diatom biosilica with bisphosphonates (BPs) was investigated. In particular, two BPs were tested: the amino-containing sodium alendronate (ALE) and the amino-lacking sodium etidronate (ETI). According to first SEM-EDX analysis, the presence of the amino-moiety in ALE structure allowed a better incorporation of this BP into living diatom biosilica, compared to ETI. Then, diatom growth was deeply investigated in presence of ALE. After extraction of functionalized frustules, ALE-biosilica was further characterized by XPS and microscopy, and ALE release was evaluated by ferrochelation assay. Moreover, the bone regeneration performances of ALE-functionalized frustules were preliminarily investigated on bone osteoblast-like cells, via Comassie staining. Data are related to the research article "In vivo functionalization of diatom biosilica with sodium alendronate as osteoactive material".

11.
JAMA Psychiatry ; 75(12): 1252-1260, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30285056

RESUMO

Importance: The extent of cognitive deterioration after schizophrenia (SZ) onset is poorly understood because prior longitudinal studies used small samples of older individuals with established illness. Objective: To examine the association of age at onset and subsequent longitudinal course of prefrontal activity during the first 2 years of illness in youths with SZ and healthy control participants (HCs). Design, Setting, and Participants: This naturalistic, longitudinal, functional magnetic resonance imaging (fMRI) study included patients with recent-onset SZ and HCs aged 12 to 25 years enrolled in an ongoing study of cognition in recent-onset psychosis in the Sacramento, California, area from October 13, 2004, through June 25, 2013. Participants completed clinical assessments and an established measure of cognitive control, the AX Continuous Performance Task (AX-CPT), during fMRI at baseline and at 6-, 12-, and 24-month follow-up. Whole-brain, voxelwise, and an a priori dorsolateral prefrontal cortex (DLPFC) region of interest analyses were performed. Group differences in developmental trajectories were examined by focusing on behavioral performance (d'-context) and cognitive control-associated brain activity. The association of antipsychotic medication and clinical factors were also examined. Data were analyzed from April 15, 2015, through August 29, 2017. Main Outcomes and Measures: Primary outcomes included group differences (HC vs SZ) in behavioral performance (d'-context from AX-CPT) and brain activity for cue B-A trials of the AX-CPT in an a priori DLPFC region of interest at baseline and across the age span. Secondary analysis examined the influence of antipsychotics on behavioral performance and DLPFC activity. Results: Among the sample of 180 participants (66.1% male; mean [SD] age at baseline, 19.2 [3.2] years), 87 patients with SZ (mean [SD] age, 19.6 [3.0] years) showed impaired performance compared with 93 HCs (mean [SD] age, 18.8 [3.4] years) across the age span (estimated difference [SE], -0.571 [0.12], d'-context; P < .001). Patients with SZ showed reduced activation in the DLPFC and parietal cortex (false discovery rate cluster corrected to P < .05) compared with HCs under conditions of high cognitive control at baseline. Region-of-interest analysis showed reduced activation in the DLPFC bilaterally for patients with SZ, with a trajectory that paralleled that of HCs across the age span (left DLPFC ß [SE] estimates, 0.409 [0.165] for the HC group and -0.285 [0.130] for the SZ group [main effect of group, P = .03]; right DLPFC ß [SE] estimates, 0.350 [0.103] for the HC group and -0.469 [0.157] for the SZ group [P = .003]). Antipsychotic medication, clinical symptoms, and global functioning were associated with SZ performance. Conclusions and Relevance: During the initial 1 to 2 years after illness onset, young individuals with SZ showed deficits in DLPFC activation and cognitive control, with developmental trajectories comparable to those of HCs. Younger age at onset was not associated with reduced cognition or activation. For individuals contributing to longitudinal analysis, results suggest that young patients do not show deterioration or disruption of ongoing brain development in the initial years after illness onset.


Assuntos
Disfunção Cognitiva/etiologia , Progressão da Doença , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/complicações , Adolescente , Adulto , Idade de Início , Estudos de Casos e Controles , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia , Adulto Jovem
12.
Adv Mater ; 30(19): e1704289, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29178521

RESUMO

Diatoms are unicellular photosynthetic microalgae, ubiquitously diffused in both marine and freshwater environments, which exist worldwide with more than 100 000 species, each with different morphologies and dimensions, but typically ranging from 10 to 200 µm. A special feature of diatoms is their production of siliceous micro- to nanoporous cell walls, the frustules, whose hierarchical organization of silica layers produces extraordinarily intricate pore patterns. Due to the high surface area, mechanical resistance, unique optical features, and biocompatibility, a number of applications of diatom frustules have been investigated in photonics, sensing, optoelectronics, biomedicine, and energy conversion and storage. Current progress in diatom-based nanotechnology relies primarily on the availability of various strategies to isolate frustules, retaining their morphological features, and modify their chemical composition for applications that are not restricted to those of the bare biosilica produced by diatoms. Chemical or biological methods that decorate, integrate, convert, or mimic diatoms' biosilica shells while preserving their structural features represent powerful tools in developing scalable, low-cost routes to a wide variety of nanostructured smart materials. Here, the different approaches to chemical modification as the basis for the description of applications relating to the different materials thus obtained are presented.

13.
Sensors (Basel) ; 16(11)2016 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-27869726

RESUMO

Early diagnosis of plant virus infections before the disease symptoms appearance may represent a significant benefit in limiting disease spread by a prompt application of appropriate containment steps. We propose a label-free procedure applied on a device structure where the electrical signal transduction is evaluated via impedance spectroscopy techniques. The device consists of a droplet suspension embedding two representative purified plant viruses i.e., Tomato mosaic virus and Turnip yellow mosaic virus, put in contact with a highly hydrophobic plasma textured silicon surface. Results show a high sensitivity of the system towards the virus particles with an interestingly low detection limit, from tens to hundreds of attomolar corresponding to pg/mL of sap, which refers, in the infection time-scale, to a concentration of virus particles in still-symptomless plants. Such a threshold limit, together with an envisaged engineering of an easily manageable device, compared to more sophisticated apparatuses, may contribute in simplifying the in-field plant virus diagnostics.


Assuntos
Impedância Elétrica , Vírus de Plantas/metabolismo , Silício/química , Interações Hidrofóbicas e Hidrofílicas , Tobamovirus/metabolismo
14.
Data Brief ; 8: 312-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27331108

RESUMO

Diatoms microalgae produce biosilica nanoporous rigid outershells called frustules that exhibit an intricate nanostructured pore pattern. In this paper two specific Thalassiosira weissflogii culture conditions and size control procedures during the diatoms growth are described. Data from white field and fluorescence microscopy, evaluation of cell densities and cell parameters (k value and R value) according to cell culture conditions are listed. Different cleaning procedures for obtaining bare frustules are described. In addition, FTIR and spectrofluorimetric analyses of cleaned biosilica are shown. The data are related to the research article "Chemically Modified Diatoms Biosilica for Bone Cell Growth with Combined Drug-Delivery and Antioxidant Properties" [1].

15.
Chempluschem ; 80(7): 1062, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31973270

RESUMO

This month's cover is dedicated to the joint project coordinated by Prof. Gianluca M. Farinola involving the Università degli Studi di Bari Aldo Moro, CNR ICCOM and IMIP in Bari, Università Politecnica delle Marche, and Jaber Innovation. The cover picture shows an SEM image of nanostructured biosilica produced by- Thalassiosira weissflogii- diatoms covalently functionalized with the radical scavenger TEMPO (green disks) and loaded with the antibiotic Ciprofloxacin (red/white capsules), which is used to combat infections related to orthopedic implants. Read the full text of the article at 10.1002/cplu.201402398.

16.
Chempluschem ; 80(7): 1104-1112, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31973278

RESUMO

Nanostructured biosilica produced by Thalassiosira weissflogii diatoms is covalently functionalized with the cyclic nitroxide 2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), an efficient scavenger of reactive oxygen species (ROS) in biological systems. Drug delivery properties of the TEMPO-functionalized biosilica are studied for Ciprofloxacin, an antimicrobial thoroughly employed in orthopedic or dental implant related infections. The resulting TEMPO-biosilica, combining Ciprofloxacin drug delivery with anti-oxidant properties, is demonstrated to be a suitable material for fibroblasts and osteoblast-like cells growth.

17.
Cogn Neurosci ; 5(3-4): 177-85, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24967816

RESUMO

It has been proposed that imagining the future depends on the ability to retrieve episodic details from past experiences in order to recombine them into novel possible experiences; consequently, the processes of remembering and imagining rely on similar neural substrates, including the hippocampus. We used fMRI and both univariate and multivariate analysis techniques to test this prediction. Unbiased univariate analysis did not reveal differences in the hippocampus between remembering and imagining; however, multivariate analyses revealed evidence that patterns of activity within the hippocampus distinguish between remembering and imagining. Thus, while the hippocampus seems to be involved in both remembering the past and imagining the future, the pattern of activity within the hippocampus distinguishes between these two different tasks.


Assuntos
Hipocampo/fisiologia , Imaginação/fisiologia , Rememoração Mental/fisiologia , Adolescente , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Análise Multivariada , Adulto Jovem
19.
J Neurosci ; 28(41): 10422-33, 2008 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-18842902

RESUMO

Recent studies suggest that subtype-selective activators of M(1)/M(4) muscarinic acetylcholine receptors (mAChRs) may offer a novel approach for the treatment of psychotic symptoms associated with schizophrenia and Alzheimer's disease. Previously developed muscarinic agonists have provided clinical data in support of this hypothesis, but failed in clinical development because of a lack of true subtype specificity and adverse effects associated with activation of other mAChR subtypes. We now report characterization of a novel highly selective agonist for the M(1) receptor with no agonist activity at any of the other mAChR subtypes, termed TBPB [1-(1'-2-methylbenzyl)-1,4'-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one]. Mutagenesis and molecular pharmacology studies revealed that TBPB activates M(1) through an allosteric site rather than the orthosteric acetylcholine binding site, which is likely critical for its unprecedented selectivity. Whole-cell patch-clamp recordings demonstrated that activation of M(1) by TBPB potentiates NMDA receptor currents in hippocampal pyramidal cells but does not alter excitatory or inhibitory synaptic transmission, responses thought to be mediated by M(2) and M(4). TBPB was efficacious in models predictive of antipsychotic-like activity in rats at doses that did not produce catalepsy or peripheral adverse effects of other mAChR agonists. Finally, TBPB had effects on the processing of the amyloid precursor protein toward the non-amyloidogenic pathway and decreased Abeta production in vitro. Together, these data suggest that selective activation of M(1) may provide a novel approach for the treatment of symptoms associated with schizophrenia and Alzheimer's disease.


Assuntos
Sítio Alostérico/fisiologia , Amiloide/metabolismo , Antipsicóticos/farmacologia , Benzimidazóis/farmacologia , Piperidinas/farmacologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Receptor Muscarínico M1/química , Receptor Muscarínico M1/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Benzimidazóis/administração & dosagem , Benzimidazóis/metabolismo , Células CHO , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Condutividade Elétrica , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Técnicas In Vitro , Masculino , Técnicas de Patch-Clamp , Piperidinas/administração & dosagem , Piperidinas/metabolismo , Células Piramidais/efeitos dos fármacos , Células Piramidais/fisiologia , Ratos , Ratos Sprague-Dawley , Receptor Muscarínico M1/agonistas , Receptor Muscarínico M1/efeitos dos fármacos , Receptores de Dopamina D2/metabolismo , Receptores de N-Metil-D-Aspartato/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Transfecção
20.
Chem Commun (Camb) ; (36): 3756-8, 2007 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-17851618

RESUMO

A novel cyclization process of 2,3-bis(trimethylsilyl)buta-1,3-diene with various acyl chlorides in the presence of aluminium trichloride affords 2,5-disubstituted or 2,3,5-trisubstituted furans in short reaction time; a subsequent acylation process of the furan ring occurs if the reaction time is prolonged.

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