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Intranasal delivery of nanostructured lipid carriers,solid lipid nanoparticles and nanoemulsions:A current overview of in vivo studies

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Acta Pharmaceutica Sinica B 2021年第4期11卷 925-940页

作者： Cláudia Pina Costa Joao Nuno Moreira JoséManuel Sousa Lobo Ana catarina silva UCIBIO/REQUIMTE MedtechLaboratory of Pharmaceutical TechnologyDepartment of Drug SciencesFaculty of PharmacyUniversity of PortoPorto 4050-313Portugal CNC-Center for Neuroscience and Cell Biology Center for Innovative Biomedicine and Biotechnology(CIBB)University of CoimbraFaculty of Medicine(Pólo I)Coimbra 3004-504Portugal UC-University of Coimbra CIBBFaculty of PharmacyPólo Das Ciências da SaúdeCoimbra 3000-548Portugal FP-ENAS(UFP Energy Environment and Health Research Unit)CEBIMED(Biomedical Research Centre)Faculty of Health SciencesUniversity Fernando PessoaPorto 4249-004Portugal

The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the *** the various strategies that have been studied to circumvent this challenge,the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising *** addition,the encapsulation of the drugs in lipid-based nanocarriers,such as solid lipid nanoparticles(SLNs),nanostructured lipid carriers(NLCs)or nanoemulsions(NEs),can improve nose-to-brain transport by increasing the bioavailability and site-specifc *** review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers(SLNs,NLCs and NEs)for nose-to-brain *** on the literature available from the past two years,we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal *** results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried *** the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear,it appears that the intranasal route together with the use of NLCs,SLNs or NEs is advantageous for targeting drugs to the *** systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs,so they are expected to be approved by regulatory authorities in the coming years.

关键词： Nose-to-brain delivery Intranasal administration Nanostructured lipid carriers NLC Solid lipid nanoparticles SLN Nanoemulsions In vivo studies Pharmacokinetic Pharmacodynamics

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Diversity of the Formicidae (Hymenoptera) carrion communities in Lisbon (Portugal): preliminary approach as seasonal and geographic indicators

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Forensic Sciences Research 2018年第1期3卷 65-73页

作者： António Neto-silva Ricardo Jorge Dinis-Oliveira catarina Prado e Castro Department of Public Health Forensic Sciences and Medical EducationFaculty of MedicineUniversity of PortoPortoPortugal Department of Sciences IINFACTS-Institute of Research and Advanced Training in Health Sciences and TechnologiesUniversity Institute of Health Sciences(IUCS)CESPUCRLGandraPortugal UCIBIO REQUIMTE-Laboratory of ToxicologyDepartment of Biological SciencesFaculty of PharmacyUniversity of PortoPortoPortugal Department of Life Sciences Centre for Functional EcologyUniversity of CoimbraCoimbraPortugal

The value of the Formicidae (Insecta,Hymenoptera) community in forensic investigations is poorly studied in *** order to better understand the structure and dynamics of this group of insects in cadavers and their putative value in forensic investigations,studies were carried out in Lisbon area during one *** carcasses were used as a model of human *** entomofauna attracted to the carcasses was collected over a period of about 2 months in each season of the *** collection of ants was performed at regular intervals,daily in the first 23 days and then with intervals of 2,3 or 5 days until the end of the *** stages of cadaveric decomposition were recognized with the ants being present in all of *** hundred and nine specimens were captured: 7 in autumn,6 in winter,90 in spring and 206 in *** specimens belong to three subfamilies and seven different *** of them had never been mentioned before as being associated to cadavers in this geographical *** and summer had the greater diversity of species and a larger number of *** luteus was the dominant species in spring and Tapinoma nigerrimum in *** the information of other similar studies carried out in the Iberian Peninsula,the sarcosaprophagous Formicidae community found in Lisbon is unique and different from other studied locations,which supports the need to perform regional *** results shown that ants do not present a definite pattern of succession,but some species have the potential to be seasonal or geographic indicators.

关键词： Forensic science forensic entomology Formicidae sarcosaprophagous community decomposition process postmortem interval seasonal study

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Epigenetic regulation of TP53 is involved in prostate cancer radioresistance and DNA damage response signaling

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5404-5416页

作者： catarina maced.-silva Vera Miranda-Gonçalves Nuno Tiago Tavares Daniela Barros-silva Joana Lencart João Lobo Ângelo Oliveira Margareta PCorreia Lucia Altucci Carmen Jerónimo Cancer Biology&Epigenetics Group Research Center of IPO Porto(CI-IPOP)/CI-IPOP@RISE(Health Research Network)Portuguese Oncology Institute of Porto(IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca(Porto.CCC)R.Dr.António Bernardino de Almeida4200-072PortoPortugal Department of Precision Medicine University of Campania“Luigi Vanvitelli”80138NaplesItaly Department of Pathology and Molecular Immunology ICBAS-School of Medicine&Biomedical SciencesUniversity of PortoR.Jorge de Viterbo Ferreira 2284050-313PortoPortugal Medical Physics Radiobiology and Radiation Protection Group-Research Center of IPO Porto(CI-IPOP)/CI-IPOP@RISE(Health Research Network)Portuguese Oncology Institute of Porto(IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca(Porto.CCC)R.Dr.António Bernardino de Almeida4200-072PortoPortugal Department of Medical Physics Portuguese Oncology Institute of Porto4200-072PortoPortugal Department of Pathology Portuguese Oncology Institute of PortoPortoPortugal Department of Radiation Oncology Portuguese Oncology Institute of PortoPortoPortugal BIOGEM Molecular Biology and Genetics Research Institute83100AvellinoItaly IEOS Institute of Endocrinology and Oncology80100NaplesItaly

External beam radiotherapy(RT)is a leading first-line therapy for prostate cancer(PCa),and,in recent years,significant advances have been ***,RT resistance can arise and result in long-term recurrence or disease progression in the worst-case ***,making crucial the discovery of new targets for PCa ***,we generated a radioresistant PCa cell line,and found p53 to be highly expressed in radioresistant PCa cells,as well as in PCa patients with recurrent/disease progression submitted to *** dissection revealed that RT could promote p53 expression via epigenetic ***,a decrease of H3K27me3 occupancy at TP53 gene promoter,due to increased KDM6B activity,was observed in radioresistant PCa ***,p53 is essential for efficient DNA damage signaling response and cell recovery upon stress induction by prolonged fractionated ***,KDM6B inhibition by GSK-J4 significantly decreased p53 expression,consequently attenuating the radioresistant phenotype of PCa cells and hampering in vivo 3D tumor ***,this work contributes to improve the understanding of p53 as a mediator of signaling transduction in DNA damage repair,as well as the impact of epigenetic targeting for PCa radiosensitization.

关键词： TP53 damage cancer

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Posterior corneal astigmatism modifications after cataract surgery and its role on total corneal astigmatism

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Annals of Eye Science 2018年第1期3卷 267-275页

作者： Diana silva Mafalda Mota catarina Pedrosa Peter Pêgo Sara Pinto Cristina Vendrell Isabel Prieto Ophthalmology Department Hospital Prof.Dr.Fernando Fonseca E.P.E.AmadoraPortugal

Background:In recent years posterior corneal astigmatism and its effect on total corneal astigmatism has been studied,with research showing that this can impact total *** study aims to ascertain if there is significant change in the posterior corneal astigmatism after cataract surgery and its impact on the total ***:Analysis of 76 eyes that underwent cataract surgery with monofocal intraocular lens *** topography was performed with Pentacam(OCULUS®)pre-and *** corneal astigmatism was calculated with the algorithm of vergence *** compared preoperative and postoperative changes in the magnitude and axis differences of anterior corneal curvature astigmatism,posterior corneal curvature astigmatism and the calculated total corneal *** calculated the correlation between the total preoperative astigmatism and the difference between total corneal astigmatism and anterior corneal ***:The mean preoperative and postoperative posterior astigmatism was 0.31±0.02 D,showing no significant differences before and after surgery(P=0.989).Statistically significant differences between the calculated total corneal astigmatism and anterior corneal astigmatism were registered preoperatively and postoperatively in the with-the-rule anterior(WTR)corneal astigmatism(P=0.004,P<0.0001);against-the-rule(ATR)anterior corneal astigmatism(P<0.0001,P<0.0001)and in the oblique(P=0.026,P=0.019)*** posterior corneal astigmatism and the total corneal astigmatism correlated positively with the differences between the total corneal and anterior corneal astigmatism(R=0.378,P=0.001).Conclusions:There were statistically significant differences between the magnitude of the total astigmatism and anterior corneal astigmatism,underlining the impact of posterior corneal astigmatism.A positive correlation between the preoperative posterior astigmatism and the difference between the total corneal and the ant

关键词： Astigmatism cataract surgery intraocular lens posterior corneal curvature total corneal astigmatism

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Alpha-1 antitrypsin deficiency and Pi^(*)Z allele as important co-factors in the development of liver fibrosis

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World Journal of Hepatology 2024年第8期16卷 1099-1110页

作者： Ana Isabel Ferreira catarina Guimarães Vitor maced. silva Sofia Xavier Joana Magalhães JoséCotter Department of Gastroenterology Hospital da Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal Life and Health Sciences Research Institute School of MedicineUniversity of MinhoBraga 4710-057Portugal Life and Health Sciences Research Institute/3B’s PT Government Associate LaboratoryBraga 4710-057Portugal Department of Pulmonology Hospital Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal

BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant *** To evaluate the impact of clinical parameters and AATD phenotypes,particularly the Pi*Z allele,in liver *** Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology *** Included 69 patients,49.3%had Pi*MZ phenotype and 10.1%Pi**** age≥55 years,age at diagnosis≥41 years and AAT at diagnosis<77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,P<0.001;AUC=0.836,P<0.001;AUC=0.681,P=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,P<0.001;AUC=0.795,P<0.001).Patients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033).Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kPa(P=0.040).CONCLUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosis<77 mg/*** created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.

关键词： Alpha-1 antitrypsin deficiency Liver fibrosis Nonalcoholic fatty liver disease fibrosis score Fibrosis-4 index Liver stiffness measurement

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Targeting of Pollen Tubes to Ovules Is Dependent on Nitric Oxide （NO） Signaling

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Molecular Plant 2008年第4期1卷 703-714页

作者： Ana Margarida Prado Renato Colaco Nuno Moreno Ana catarina silva Jose A. Feijo Instituto Gulbenkian de Ciencla Centro de Blologia do Desenvolvimento PT-2780-156 Oeiras Portugal Universidade de Lisboa Faculdade de Clencias Dept Biologia Vegetal Campo Grande Ed.C2. PT-1749-016 Lisboa Portugal

The guidance signals that drive pollen tube navigation inside the pistil and micropyle targeting are still, to a great extent, unknown. Previous studies in vitro showed that nitric oxide （NO） works as a negative chemotropic cue for pollen tube growth in lily （Lilium Iongiflorum）. Furthermore, Arabidopsis thaliana Atnosl mutant plants, which show de- fective NO production, have reduced fertility. Here, we focus in the role of NO in the process of pollen-pistil communication, using Arabidopsis in-vivo and lily semi-vivo assays. Cross-pollination between wild-type and Atnosl plants shows that the mutation affects the pistil tissues in a way that is compatible with abnormal pollen tube guidance. Moreover, DAF- 2DA staining for NO in kanadi floral mutants showed the presence of NO in an asymmetric restricted area around the micropyle. The pollen-pistil interaction transcriptome indicates a time-course-specific modulation of transcripts of AtNOS1 and two Nitrate Reductases （nrl and nr2）, which collectively are thought to trigger a putative NO signaling pathway. Semivivo assays with isolated ovules and lily pollen further showed that NO is necessary for micropyle targeting to occur. This evidence is supported by CPTIO treatment with subsequent formation of balloon tips in pollen tubes facing ovules. Activation of calcium influx in pollen tubes partially rescued normal pollen tube morphology, suggesting that this pathway is also dependent on Ca^2＋ signaling. A role of NO in modulating Ca^2＋ signaling was further substantiated by direct imaging the cytosolic free Ca^2＋ concentration during NO-induced re-orientation, where two peaks of Ca^2＋ occur--one during the slowdown/stop response, the second during re-orientation and growth resumption. Taken together, these results provide evidence for the participation of NO signaling events during pollen-pistil interaction. Of special relevance, NO seems to directly affect the targeting of pollen tubes to the ovule＇s micropyle by modu

关键词： pollen tubes NO fertilization guidance calcium signaling

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Plug-In Vehicle Acceptance and Probable Utilization Behaviour

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Journal of Transportation Technologies 2012年第1期2卷 67-74页

作者： Patrícia Baptista catarina Rolim Carla silva 不详

This paper presents a study undertaken to understand the plug-in vehicle acceptance and probable utilization behaviour in terms of charging habits and utility factor (probability of driving in electrical mode). A survey was designed to be answered via World Wide Web, throughout 3 months and only accessible to Portuguese inhabitants. The survey was composed by biographical and car ownership info, mobility patterns, awareness toward plug-in vehicle technologies, price premium and, finally, potential buyer’s attitudes regarding charging vehicles with electricity from the grid. An explanation of how each vehicle technology works in the case of a regular hybrid (HEV), a plug-in hybrid (PHEV) and a pure electric vehicle (EV) was provided. A total sample of 809 volunteers answered the survey, aged above 18 years old, 50% male and 50% female. The results allowed the estimation of the typical daily driving distance, the Utility Factor curve for plug-in hybrid future users, the charging preferences for future users of pure electric or plug-in hybrid vehicles and the necessary feebates to promote the market penetration of such technologies. Other correlations were also analyzed between driving patterns, type of owned car, price premium and the willingness to buy pure electric and plug-in hybrid vehicles. The main policy implications are that an increase of awareness campaigns is necessary if the government intends to support the plug-in electric vehicle technology widespread and a minimum of 5000 € investment per ton of avoided CO2 will be necessary in a year.

关键词： Pure Electric Vehicles Plug-In Hybrid Vehicles Utility Factor Frequency Period of Recharging

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An Exploratory Behavioral Study in Children of Four Years of Age on the Hypothesis of a Two Streams System in Touch Perception and Language Development

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Psychology Research 2018年第11期8卷 567-571页

作者： David Catela catarina silva Joana Reis Ana Paula Seabra Polytechnic Institute of Santarém SantarémPortugal

A two streams system seems to exist for tactile *** asked kindergarten children to identify(semantic)and describe the function of grasped unseen instruments of their daily life(fork,knife,spoon,brush,toothbrush,pencil,and scissor),and then,to simulate its use(pragmatic).The capacity to describe the function of the set of instruments was significantly superior to that of identifying them by name,although there was a significant direct association between identification and description of the function in the responses to the set of *** simulation of the instrument function was of two types:(i)use―the child simulated how the instrument is grasped and used;and(ii)incorporation―the child simulated the function of the instrument with her/his own *** results support the hypothesis of a two streams tactile system(semantic and pragmatic),and that kindergarten children have the ability to incorporate functional properties of instruments of their daily life,probably as a support for language development.

关键词： children language development tactile perception tool two streams system

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Antifungal activity and antidiarrheal activity via antimotility mechanisms of (-)-fenchone in experimental models

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World Journal of Gastroenterology 2020年第43期26卷 6795-6809页

作者： Michelle Liz de Souza Pessoa Leiliane Macena Oliveira silva Maria Elaine Cristina Araruna catarina Alves de Lima Serafim Edvaldo Balbino Alves Junior Alessa Oliveira silva Matheus Marley Bezerra Pessoa Hermes Diniz Neto Edeltrudes de Oliveira Lima Leonia Maria Batista Department of Pharmaceutical Sciences IPeFarMFederal University of ParaibaJoao Pessoa 58051-970ParaibaBrazil Health Sciences Center Federal University of ParaibaJoaoPessoa 58051-970ParaibaBrazil Postgraduate Program in Natural and Synthetic Bioactive Products Universidade Federal da ParaibaJoão Pessoa 58051-900Brazil

BACKGROUND(-)-Fenchone is a bicyclic monoterpene present in essential oils of plant species,such as Foeniculum vulgare and Peumus boldus,used to treatment of gastrointestinal *** studies report its anti-inflammatory,antioxidant,and antinociceptive *** To investigate antidiarrheal activity related to gastrointestinal motility,intestinal secretion and antimicrobial *** A castor oil-induced diarrhea model was used to evaluate antidiarrheal *** transit and gastric emptying protocols were used to assess a possible antimotility *** receptors,presynaptic α2-adrenergic and tissue adrenergic receptors,KATP channels,nitric oxide were investigated to uncover antimotility mechanisms of action and castor oil-induced enteropooling to elucidate antisecretory *** antimicrobial activity was evaluated in the minimum inhibitory concentration model,the fractional inhibitory concentration index using the(-)-fenchone association method with standard antifungal ***(-)-Fenchone(75,150 and 300 mg/kg)showed antidiarrheal activity,with a significant decrease in the evacuation *** activity is possibly related to a percentage of reduced intestinal transit(75,150 and 300 mg/kg).The antimotility effect of(-)-fenchone decreased in the presence of pilocarpine,yohimbine,propranolol,L-NG-nitroarginine methyl ester or *** the enteropooling model,no reduction in intestinal fluid weight was observed.(-)-Fenchone did not show antibacterial activity;on the other hand,inhibits the growth of strains of fungi with a minimum fungicide concentration of 32μg/***,when it was associated with amphotericin B,no synergism was *** The antidiarrheal effect of(-)-fenchone in this study involves antimotility effect and not involve antisecretory mechanisms.(-)-Fenchone presents antifungal activity;however,it did not show antibacterial activity.

关键词： (-)-Fenchone Monoterpenes Diarrhea Motility Antifungal

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Drug Therapeutic in the Subacute and Chronic Phase of Chikungunya Virus Infection

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Open Journal of Rheumatology and Autoimmune Diseases 2021年第2期11卷 36-47页

作者： Mariana do Socorro Quaresma silva Rita catarina Medeiros Sousa Cezar Augusto Muniz Caldas Universidade Federal do Pará Belém Pará Brasil Universidade Tropical Medicine Nucleus Belém Pará Brasil

Background: Chikungunya fever is an infectious disease that can evolve to a subacute or chronic condition, with changes in the daily activities of patients. Drugs that aim to reduce these symptoms are used, such as corticoids (acute phase) and disease-modifying anti-rheumatic drugs (chronic phase). Objective: To evaluate the clinical response to drug therapy in the subacute and chronic phase of infection by the Chikungunya virus. Methodology: A prospective and a retrospective study with patients with subacute and chronic Chikungunya infection, out at the infection and autoimmunity outpatient clinic at the Nucleus of Tropical Medicine, from January 2016 to December 2019, in the morning of Thursdays. The patient was observed in the Baseline, first and second return, and drugs were introduced according to the stage of the disease with subsequent reassessment. The Visual Analogue Scale (VAS) was applied to all evaluation moments. Results: 101 patients were evaluated, and arthralgia was the predominant symptom in the three evaluated moments. According to the VAS, moderate baseline pain was observed in 58.1% and 58.6% of subacute and chronic cases, respectively. On the first return, moderate pain still predominated in 46.2% in subacute cases and 43% in chronic cases. In the second visit, all patients were in the chronic phase of the disease, 43.8% had VAS with no pain. Regarding the number of compromised joints in the Baseline, polyarticular involvement predominated in both subacute (79%) and chronic (74.1%) cases, in the first return, oligoarticular involvement predominated in 53.8% of subacute cases and 54.7% in chronic cases and, the second return, 40.6% of the patients had oligoarticular involvement and 43.8% had no joint involvement. As for the use of medications in the Baseline, 33.4% of subacute cases used antiinflammatory drugs,

关键词： Chikungunya Fever Post-Infectious Inflammatory Disease Alphavirus

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