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1.
J Colloid Interface Sci ; 672: 552-563, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38852356

RESUMO

The solubilization of sodium diclofenac (Na-DFC) in a glycerol monooleate-based emulsion triggers series of structural changes. Incorporation of Na-DFC, leads to formation of a reverse hexagonal mesophase between 2 and 5 wt% Na-DFC. Between 6 and 9 wt% Na-DFC, the hexagonal symmetry gradually transitions to a disordered lamellar mesophase. These structural shifts impact the system's storage modulus, structuring enthalpy, and structural diffusivity. Despite these transitions, the driving force for Na-DFC release remains consistent, leading to hypothesize that the interfacial structure remains unchanged during Na-DFC release. The nano-structural modifications imposed by the Na-DFC load and release were assessed by small-angle X-ray diffraction (SAXD), spin-probe electron paramagnetic resonance (EPR), and nuclear quadrupole resonance (NQR). The selective solubilization of Na-DFC was demonstrated by SAXD peak fittings, revealing an increase of hexagonally oriented rods at the expense of non-oriented micelles, rather than gradual micellar elongation. Computation of the EPR spectra also showcased the selective solubilization of Na-DFC at an enhanced free energy interface (γ), evidenced by step-wise variations in polarity, microviscosity, and order parameters. Additionally, NQR analysis highlighted a higher anisotropy for sodium compared to deuterium, linking the selective solubilization of Na-DFC to heterogeneous structural transformations. These findings underscore the heterogeneous nature of solubilization-release processes, driven by locally increased micellar free energy. Consequently, the loaded Na-DFC interfaces maintain a constant γ, ensuring a consistent release driving force despite the structural transitions affecting the matrix. The ability to selectively solubilize guest molecules may herald a new era in the utilization of selective molecular interfacial loading.

2.
Clin Ter ; 175(3): 193-202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38767078

RESUMO

Objective: Artificial intelligence (AI) is the ability of a computer machine to display human capabilities such as reasoning, learning, planning, and creativity. Such processing technology receives the data (already prepared or collected), processes them, using models and algorithms, and answers questions about forecasting and decision-making. AI systems are also able to adapt their behavior by analyzing the effects of previous actions and working then autonomously. Artificial intelligence is already present in our lives, even if it often goes unnoticed (shopping networked, home automation, vehicles). Even in the medical field, artificial intelligence can be used to analyze large amounts of medical data and discover matches and patterns to improve diagnosis and prevention. In forensic medicine, the applications of AI are numerous and are becoming more and more valuable. Method: A systematic review was conducted, selecting the articles in one of the most widely used electronic databases (PubMed). The research was conducted using the keywords "AI forensic" and "machine learning forensic". The research process included about 2000 Articles published from 1990 to the present. Results: We have focused on the most common fields of use and have been then 6 macro-topics were identified and analyzed. Specifically, articles were analyzed concerning the application of AI in forensic pathology (main area), toxicology, radiology, Personal identification, forensic anthropology, and forensic psychiatry. Conclusion: The aim of the study is to evaluate the current applications of AI in forensic medicine for each field of use, trying to grasp future and more usable applications and underline their limitations.


Assuntos
Inteligência Artificial , Medicina Legal , Humanos , Medicina Legal/métodos , Aprendizado de Máquina , Previsões
3.
Clin Ter ; 175(3): 96-97, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38767066

RESUMO

Abstract: Recent events have brought the debate on end-of-life issues to the forefront, particularly regarding the principle of self-determination for depressed patients. Belgian legislation, in fact, allows for requesting euthanasia when patients, capable of expressing their own will consciously, suffer in an unbearable manner and find no meaning in continuing their existence, even in the absence of incurable and/or severely debilitating conditions. The state of the art is an increasing number of people who die from euthanasia. An open question is when a situation can be defined as unbearable. Moreover, does such an assessment necessarily lead to death, or are there other solutions? In our opinion, such a practice should be limited to prevent inappropriate applications that could lead to infringing depressed patients' rights.


Assuntos
Depressão , Humanos , Depressão/psicologia , Depressão/etiologia , Assistência Terminal/psicologia , Autonomia Pessoal , Eutanásia/legislação & jurisprudência , Bélgica , Direitos do Paciente
4.
Clin Ter ; 175(2): 110-111, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38571467

RESUMO

Abstract: The Cospito case has highlighted a widely debated bioethical issue regarding the need to choose between safeguarding the life of a detainee and their right to self-determination through the practice of a hunger strike. Recently, the Italian National Bioethics Committee has been called upon to give an opinion on this matter. On the other hand, the media resonance of this case has shed light on the need to pose an ethical and social question regarding such situations: does the physician have an obligation to protect the detainee's health at the expense of their free choice? To be able to answer, it is necessary to understand whether law no. 219/17 is applicable to this context.


Assuntos
Bioética , Médicos , Humanos , Jejum , Temas Bioéticos , Itália
6.
Clin Ter ; 175(1): 57-67, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38358478

RESUMO

Introduction: Historical mistreatment and violence directed toward women's bodies extend to the field of medicine, and obstetric and gynecological practices are not immune to such misconduct. Obstetric violence (OV) refers to actions involving disrespectful, abusive, or coercive treatment directed at pregnant and birthing women. This includes institutional and personal attitudes that lead to the violation of women's autonomy, human rights, and sexual and reproductive health. Despite various international legislative initiatives and recommendations from the World Health Organization (WHO) addressing disrespectful and abusive treatment, OV is still poorly known to Italian public opinion. This study aims to investigate whether the concept of OV has been conversely assimilated in judicial decisions. Materials and methods: A retrospective analysis was conducted to scrutinize judgments in Italy until June 2023 related to OV. The Italian legal database 'De Jure Giuffrè', which collects sentences by various Courts, and the terms 'obstetric' and 'violence' as keywords were used for the research. Results: The full-text revision of the results (n. 41 sentences) al-lowed the selection of 5 eligible contributions covering the following issues: Informed Consent, Kristeller maneuver, Vaginal Birth After Cesarean (VBAC), Acceleration of childbirth without indication, and Episiotomy. The analysis of individual judgments was complemented by an examination of the key issues involved. Conclusions: The reviewed judgments frequently seemed to be grounded in technical aspects and inclined towards a predominant evaluation of childbirth outcomes. However, some encouraging aspects emerged, particularly in terms of attention to the female body, acknowledgment of consequences within the intimate-relational dimension, and a commitment to the principle of self-determination through the provision of free and informed consent. Ensuring the psychophysical well-being of women and unborn children, fostering positive interactions between pregnant women and medical staff, and actively working to reduce the grounds for litigation are among actual emerging priorities in healthcare. In this sense, fundamental elements include the implementation of continuous staff training and education as well as a focus on promoting the self-determination of women, leveraging new technologies for this purpose, and ensuring legal protection of their rights.


Assuntos
Julgamento , Violência , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Itália
7.
Clin Ter ; 174(5): 451-468, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37750379

RESUMO

Background: Z-Drugs are a category of non-benzodiazepine sedative-hypnotic drugs that include Zolpidem, Zopiclone and Zaleplon. They are all rapidly adsorbed and have a very short half- life, features that make them first-line treatment of insomnia and, in the meantime, first-choice drugs in cases of poisoning for criminal purposes. Z-drugs are frequently use in Drug Facilitated Crime cases (DFC) and Drug Facilitated Sexual Assault (DFSA), namely crimes, robberies, extortion and sexual violence committed after administration of incapacitating substances able to induce sedative-hypnotic effects. In these circumstances, the psychoactive substance is considered as a weapon and constitutes an aggravating circumstance in the criminal act: accordingly, judicial authority legitimates the analytical determination of these substances. Currently, few tests able to detect such drugs are available in daily clinical practice. Aim: The aim of this work is to evaluate the effective utilization of Z-Drugs. Methods: We have analyzed the literature, focusing on cases in which the criminal use of such incapacitating substances has been demonstrated. Relevant scientific articles were identified from PubMed, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE up to December 2022 using the following keywords: "z-drugs", "drug facilitated crime", "forensic toxicology". The resulting references were screened to exclude duplicates. In addition, non-English papers were excluded. This evaluation left 10 articles (8 case reports and 2 original studies) divided as follows: 1 case report of a DFC (robbery), 6 cases of confirmed DFSA, 3 cases of suspected DFSA, 2 original studies about DFC. Results: The totality of the selected cases showed positive toxicological tests for a single intake of z-drugs. Conclusions: This work has shown the limitations of screening tests currently in use in the emergency rooms. Forensic toxicology tests should be introduced in daily clinical practice.


Assuntos
Vítimas de Crime , Delitos Sexuais , Humanos , Crime , Hipnóticos e Sedativos , Preparações Farmacêuticas , Relatos de Casos como Assunto
8.
Phys Chem Chem Phys ; 24(10): 6011-6025, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35199803

RESUMO

Despite the array of applications for cationic polythiophenes (CPTs), there is still a need for structure-function guidelines and mechanistic understanding of their solution- and solid-state properties. This work presents a solution- and solid-state investigation of the effect of O-alkylation proximity on the hydrogen bonding (H-bonding) capabilities of alkoxy-CPTs, based on comparing an imidazolium alkoxy CPT with strong cation-pi, pi+ and positive charge-assisted hydrogen bonding (+CAHB) capabilities (PIMa), with two isothiouronium alkoxy CPTs with two-point +CAHB capabilities (PT1 & PT2), which have short and long alkoxy side chains, respectively. Our results show that a closer proximity of O-alkylation strengthens the +CAHB capabilities of PT1: in aqueous solutions, PT2 aggregates have a stronger interaction with cationic EPR spin probes than aggregates of PIMa and PT1, which in turn show a similar extent of repulsion towards the cationic spin probes. In solid-state, atomic force microscopy (AFM) shows that PIMa generates dendritic structures onto mica, with features of diffusion-limited aggregation (DLA), indicating strong interactions with the anionic substrate due to a high configurational entropy during spreading, regardless of being drop-casted from water or 1,4-dioxane-water (W-DI), despite the latter disturbing H-bonding due to selective solvation. PT1 is also capable of generating dendritic structures resembling ballistic aggregation (BA). However, this occurs only when casting from water, since W-DI generates island-like aggregates resembling attachment limited aggregation (ALA), which is the morphology generated by PT2 regardless of the solvent. Finally, spin-coated films of PIMa and PT1 show similar dispersivity of the surface free energy (SFE), which in turn is larger than that in PT2 films, which are also more affected when casted from W-DI, presenting much larger decreases of dispersivity. These results constitute a novel empirical structure-function guideline that could be useful for optimal design and/or processing of alkoxy CPTs. For example, dendritic patterns have recently gained attention since the colloidal droplet drying is related to engineering applications including inkjet printing, biosensing, and functional material design, while the SFE is relevant for opto- and bio-electronic applications of conjugated polyelectrolytes (CPEs). This information could also be useful when analyzing previous results obtained from alkoxy CPTs with different side chain lengths.

9.
Langmuir ; 36(9): 2278-2290, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32027512

RESUMO

Cationic imidazolium-functionalized polythiophenes with single- or double-methylation of the imidazolium ring were used to study the impact of imidazolium-methylation on (i) the solution concentration-driven aggregation in the presence of paramagnetic probes with different ionic and hydrophobic constituents and (ii) their surface free energy (SFE) as spin-coated films deposited on plasma-activated glass. Electron paramagnetic resonance spectroscopy shows that the differences in film structuration between the polymers with different methylations originate from the early stages of aggregation. In the solid state, higher degree of imidazolium-methylation generates smaller values of total SFE, γS, (by around 2 mN/m), which could be relevant in optoelectronic applications. Methylation also causes a decrease in the polar contribution of γS (γSp), suggesting that methylation decreases the polar nature of the imidazolium ring, probably due to the blocking of its H-bonding capabilities. The values of γS obtained in the present work are similar to the values obtained for doped films of neutral conjugated polymers, such as polyaniline, poly(3-hexylthiophene), and polypyrrole. However, imidazolium-polythiophenes generate films with a larger predominance of the dispersive component of γS (γSd), probably due to the motion restriction in the ionic functionalities in a conjugated polyelectrolyte, in comparison to regular dopants. The presence of 1,4-dioxane increases γSp, especially, in the polymer with larger imidazolium-methylation (and therefore unable to interact through H-bonding), probably by a decrease of the imidazolium-glass interactions. Singly-methylated imidazolium polythiophenes have been applied as electrode selective ("buffer") interlayers in conventional and inverted organic solar cells, improving their performance. However, clear structure-function guidelines are still needed for designing high-performance polythiophene-based interlayer materials. Therefore, the information reported in this work could be useful for such applications.

10.
J Eur Acad Dermatol Venereol ; 34(8): 1803-1814, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31999869

RESUMO

BACKGROUND: Acne, a disease of the sebaceous gland with multifactorial pathogenesis, affects more than 85% of adolescents. A better deepening of the mechanisms underlying the disease is needed to define effective and mechanism-targeted treatments. OBJECTIVE: To understand whether the sebocyte differentiation process could be involved in the pathogenesis of the disease. METHODS: Protein expressions were evaluated by Western blot analysis and ELISA; mRNA levels by real-time RT-PCR, lipid analysis and lipid peroxidation were performed by gas chromatography, mass spectrometry and spectrophotometric assay. RESULTS: In vitro, low differentiated SZ95 sebocyte expressed an up-modulation of genes involved in sebogenesis and a higher level of insulin receptor respect to differentiated cells, resulting in an increased response to insulin and in the production of acne-like sebum. The induction of SZ95 sebocyte differentiation by the peroxisome proliferator-activated receptor γ (PPARγ) modulator NAC-GED0507 reduced the response to insulin normalizing the sebum production and decreasing the release of proinflammatory mediators. In vivo treatment of acne patients with NAC-GED0507 1% gel ameliorated clinical manifestations and induced in sebum the expression of PPARγ, associated with the decrease in mammalian target of rapamycin activation and levels of inflammatory molecules, confirming the results obtained in vitro. CONCLUSIONS: The study provides relevant insight into acne pathogenesis, identifying an alteration of sebocyte differentiation as pathogenetic basis of the disease and the induction of the differentiation process as a therapeutic target in acne therapy interfering with all pathogenic mechanisms.


Assuntos
Acne Vulgar , Acne Vulgar/tratamento farmacológico , Adolescente , Diferenciação Celular , Células Epiteliais , Humanos , Glândulas Sebáceas , Sebo
11.
ACS Macro Lett ; 8(4): 473-478, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-31289694

RESUMO

The synthesis of functional poly(2-alkyl-2-oxazoline) (PAOx) copolymers with complex nanoarchitectures using a graft-through ring-opening metathesis polymerization (ROMP) approach is described. First, well-defined norbornene-terminated poly(2-ethyl-2-oxazoline) (PEtOx) macromonomers (MM) were prepared by cationic ringopening polymerization. ROMP of these MMs produced bottlebrush copolymers with PEtOx side chains. In addition, PEtOx-based branched MMs bearing a terminal alkyne group were prepared and conjugated to an azide-containing bis-spirocyclohexyl nitroxide via Cu-catalyzed azide-alkyne cycloaddition (CuAAC). ROMP of this branched MM, followed by in situ cross-linking, provided PEtOx-based brush-arm star polymers (BASPs) with nitroxide radicals localized at the core-shell interface. These PEtOx-based nitroxide-containing BASPs displayed relaxivity values on par with state-of-the-art polyethylene glycol (PEG)-based nitroxide materials, making them promising as organic radical contrast agents for metal-free magnetic resonance imaging (MRI).

12.
ACS Macro Lett ; 7(4): 472-476, 2018 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30271675

RESUMO

The polymerization of functional monomers provides direct access to functional polymers without need for postpolymerization modification; however, monomer synthesis can become a bottleneck of this approach. New methods that enable rapid installation of functionality into monomers for living polymerization are valuable. Here, we report the three-step convergent synthesis (two-step longest linear sequence) of a divalent exo-norbornene imide capable of efficient coupling with various nucleophiles and azides to produce diversely functionalized branched macromonomers optimized for ring-opening metathesis polymerization (ROMP). In addition, we describe an efficient iterative procedure for the synthesis of tri-and tetra-valent branched macromonomers. We demonstrate the use of these branched macromonomers for the synthesis of Janus bottlebrush block copolymers as well as for the generation of bottlebrush polymers with up to three conjugated small molecules per repeat unit. This work significantly expands the scalability and diversity of nanostructured macromolecules accessible via ROMP.

13.
Langmuir ; 34(32): 9424-9434, 2018 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-30032619

RESUMO

Drug delivery is considered a mature scientific and technological platform for producing innovative medicines with nanosystems composed of intelligent bio-materials that carry active pharmaceutical ingredients forming advanced drug delivery nanosystems (aDDnSs). Shikonin and its enantiomer alkannin are natural products that have been extensively studied in vitro and in vivo for, among others, their antitumor activity, and various efforts have been made to prepare shikonin-loaded drug delivery systems. This study is focused on chimeric aDDnSs and specifically on liposomal formulations combining three lipids (egg-phosphatidylcholine; dipalmitoyl phosphatidylcholine; and distearoyl phosphatidylcholine) and a hyperbranched polymer (PFH-64-OH). Furthermore, PEGylated liposomal formulations of all samples were also prepared. Calorimetric techniques and electron paramagnetic resonance were used to explore and evaluate the interactions and stability of the liposomal formulations, showing that the presence of hyperbranched polymers promote the overall stability of the chimeric aDDnSs based on the drug release profile enhancement. Furthermore, results showed that polyethylene glycol enhances drug stabilization inside the liposomes, forming a stable and promising carrier for shikonin with improved characteristics.


Assuntos
Antineoplásicos/química , Portadores de Fármacos/química , Naftoquinonas/química , 1,2-Dipalmitoilfosfatidilcolina/química , Calorimetria/métodos , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Lipossomos/química , Tamanho da Partícula , Fosfatidilcolinas/química , Polietilenoglicóis/química , Eletricidade Estática
14.
Langmuir ; 34(25): 7364-7378, 2018 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-29783844

RESUMO

Aggregation of cationic isothiouronium polythiophenes with alkoxy-spacers of different lengths at the 3-position of the thiophene ring was studied in solvents of different polarities. Hydrogen-bonding capacity was assessed by steady-state absorption and fluorescence spectroscopy, whereas the aggregation in aqueous solutions was studied by electron paramagnetic resonance spectroscopy, using paramagnetic probes of different polarities. The two polymers displayed similar features in respect to conformation, effect of cosolvents on aggregation, unstructured absorption-fluorescence spectra, Stokes shifts when aggregated, solvatochromic effect, and self-quenching concentration. However, these polymers also showed different specific interactions with water, Stokes shifts in water, effect of the solvent on the extent of dominant state of the S1 level, and also different inner cavities and hydrophobic-hydrophilic surface area in aqueous solution aggregates. Water maximized the difference between the polymers concerning the effect of specific increases in concentration, whereas the presence of 1,4-dioxane generated almost identical effects on both polymers.

15.
J Inorg Biochem ; 177: 211-218, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29031179

RESUMO

A series of new organometallic carbosilane dendrimers functionalized with Copper(II) complex on the surface were synthesized and characterized as potential anticancer agents. These metallodendrimers were synthesized through the reaction of dendritic ligands containing N,N- and N,O- donor atoms able to act as chelating agents with CuCl2 as metallic ion precursor. The structural characterization of these complexes was addressed through the use of different analytical and spectroscopical techniques. Particularly, an electron paramagnetic resonance study was performed to corroborate the coordination properties of these dendritic ligands. A preliminary study was carried out to establish the cytotoxicity of the new synthesized compounds in human prostate (PC3) and human cervical (HeLa) cancer cell lines in order to evaluate their potential as anticancer agents and compare their activity with other copper or analogous ruthenium metallodendrimers.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Cobre/química , Dendrímeros/farmacologia , Silanos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Dendrímeros/síntese química , Dendrímeros/química , Espectroscopia de Ressonância de Spin Eletrônica , Humanos , Ligantes , Silanos/síntese química , Silanos/química
16.
ACS Cent Sci ; 3(7): 800-811, 2017 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-28776023

RESUMO

Metal-free magnetic resonance imaging (MRI) agents could overcome the established toxicity associated with metal-based agents in some patient populations and enable new modes of functional MRI in vivo. Herein, we report nitroxide-functionalized brush-arm star polymer organic radical contrast agents (BASP-ORCAs) that overcome the low contrast and poor in vivo stability associated with nitroxide-based MRI contrast agents. As a consequence of their unique nanoarchitectures, BASP-ORCAs possess per-nitroxide transverse relaxivities up to ∼44-fold greater than common nitroxides, exceptional stability in highly reducing environments, and low toxicity. These features combine to provide for accumulation of a sufficient concentration of BASP-ORCA in murine subcutaneous tumors up to 20 h following systemic administration such that MRI contrast on par with metal-based agents is observed. BASP-ORCAs are, to our knowledge, the first nitroxide MRI contrast agents capable of tumor imaging over long time periods using clinical high-field 1H MRI techniques.

17.
Biochem Pharmacol ; 138: 96-106, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28461124

RESUMO

The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) controls the expression of genes involved in the regulation of lipid and glucose metabolism, cell proliferation/differentiation as well as inflammatory pathways. Pivotal studies in human sebocytes and isolated sebaceous glands have raised the interesting possibility that compounds acting on PPARγ can modulate sebaceous lipids and inflammation and, as such, may be useful in the treatment of acne. To investigate the role of this receptor in the regulation of lipid synthesis, proliferation and inflammation, we used the SZ95 sebaceous gland cell line stimulated with insulin. In sebocytes, insulin signaling activated the phosphatidylinositide 3-kinase-Akt (PI3K/Akt) and mammalian target of rapamycin (mTOR) pathways, which, in turn, induced high protein/lipid synthesis, increased cell growth and proliferation as well as inflammation. As regards lipogenesis, insulin initially stimulated the formation of unsaturated lipids and then the neosynthesis of lipids. The results showed, that the modulation of PPARγ, counteracted the insulin-induced altered lipogenesis, evident through a decrease in gene expression of key enzymes responsible for the synthesis of fatty acids, and through a reduction of lipid species synthesis analyzed by Oil/Nile Red staining and GC-MS. PPARγ modulation also regulated the insulin-induced proliferation, inhibiting the cell cycle progression and p21WAF1/CIP1 (p21) protein reduction. Moreover, the expression of inflammatory cytokines, induced by insulin or lipopolysaccharide (LPS), was down-modulated. In PPARγ-deficient cells or in the presence of GW9662 antagonist, all these observed effects were abolished, indicating that PPARγ activation plays a role in regulating alteration of lipogenesis, cell proliferation and inflammatory signaling. We demonstrated that selective modulation of PPARγ activity is likely to represent a therapeutic strategy for the treatment of acne.


Assuntos
Regulação da Expressão Gênica , Lipogênese , PPAR gama/metabolismo , Glândulas Sebáceas/metabolismo , Sebo/metabolismo , Transdução de Sinais , Acetanilidas/efeitos adversos , Acetanilidas/farmacologia , Anilidas/efeitos adversos , Anilidas/farmacologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/agonistas , Citocinas/metabolismo , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipoglicemiantes/antagonistas & inibidores , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Antagonistas da Insulina/efeitos adversos , Antagonistas da Insulina/farmacologia , Lipogênese/efeitos dos fármacos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/toxicidade , PPAR gama/agonistas , PPAR gama/antagonistas & inibidores , PPAR gama/genética , Fenilpropionatos/efeitos adversos , Fenilpropionatos/farmacologia , Interferência de RNA , Glândulas Sebáceas/citologia , Glândulas Sebáceas/efeitos dos fármacos , Glândulas Sebáceas/imunologia , Sebo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
18.
Clin Ter ; 168(1): e28-e32, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28240759

RESUMO

OBJECTIVES: We compared the outcome of elective laparoscopic cholecystectomy (LC) in a teaching hospital and a private communityhospital to assess the impact of the involvement of residents. MATERIALS AND METHODS: The following parameters were studied prospectively in patients who underwent elective LC during the period from September 2014 to February 2016 in a teaching university hospital (group A) and in a private community hospital (group B): age, sex, body mass index (BMI), comorbidities, American Society of Anaesthesiologists (ASA) score, length of surgery from skin incision to skin closure, use of drain, 30-day perioperative morbidity and mortality, and length of postoperative hospital stay. RESULTS: The group A consisted of 93 elective LC and the group B of 167 elective LC. Operative time was significantly longer in group A. Intraoperative complications were similar and no conversion was necessary in both groups. An increased rate of postoperative complications was observed in group A. All postoperative complications were managed with conservative therapy. No mortality occurred. At logistic regression analysis, the only factor favouring the occurrence of complications was the hospital type. CONCLUSIONS: Our study shows that elective LC can be performed in a teaching hospital with comparable intraoperative morbidity and increased postoperative complications. The greater rate of morbidity found in the teaching hospital may be due to an increased vigilance linked to the presence of residents and not to the lack of expertise.


Assuntos
Colecistectomia Laparoscópica/métodos , Procedimentos Cirúrgicos Eletivos/métodos , Complicações Intraoperatórias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Feminino , Hospitais Comunitários , Hospitais de Ensino , Humanos , Itália , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Médicos/organização & administração , Estudos Prospectivos , Resultado do Tratamento
19.
J Phys Chem B ; 121(6): 1169-1175, 2017 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-28099013

RESUMO

Dynamic nuclear polarization is an emerging technique for sensitizing solid-state NMR experiments by transferring polarization from electrons to nuclei. Stable biradicals, the polarization source for the cross effect mechanism, are typically codissolved at millimolar concentrations with proteins of interest. Here we describe the high-affinity biradical tag TMP-T, created by covalently linking trimethoprim, a nanomolar affinity ligand of dihydrofolate reductase (DHFR), to the biradical polarizing agent TOTAPOL. With TMP-T bound to DHFR, large enhancements of the protein spectrum are observed, comparable to when TOTAPOL is codissolved with the protein. In contrast to TOTAPOL, the tight binding TMP-T can be added stoichiometrically at radical concentrations orders of magnitude lower than in previously described preparations. Benefits of the reduced radical concentration include reduced spectral bleaching, reduced chemical perturbation of the sample, and the ability to selectively enhance signals for the protein of interest.


Assuntos
Tetra-Hidrofolato Desidrogenase/química , Trimetoprima/química , Ligantes , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Tetra-Hidrofolato Desidrogenase/metabolismo
20.
J Colloid Interface Sci ; 483: 374-384, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27571688

RESUMO

Omega fatty acids, mainly the triglyceride of docosahexaenoic acid (TG-DHA), are considered important nutraceuticals. These compounds are water-insoluble and their transport across membranes depends on their carriers. Dendrimers are known as drug carriers across cell membranes and also as permeation enhancers. The solubilization of TG-DHA and dendrimer into a microemulsion (ME) system serving as a carrier could be used for a targeted delivery in the future. The interactions between TG-DHA and second generation poly(propyleneimine) dendrimers (PPI-G2) and their effect on structural transitions of ME were explored along the water dilution line using electron paramagnetic resonance and pulsed-gradient spin-echo NMR along with other analytical techniques. The microviscosity, order parameter, and micropolarity of all studied systems decrease upon water dilution. Incorporation of TG-DHA reduces the microviscosity, order, and micropolarity, whereas PPI-G2 leads to an increase in these parameters. The effect of PPI-G2 is more pronounced at relative high contents (1 and 5wt%) where PPI-G2 interacts with the hydrophilic headgroups of the surfactants. In the macroscale, the effects of TG-DHA and PPI-G2 differ mostly in the bicontinuous region, where macroviscosity increases upon TG-DHA incorporation and decreases upon solubilization of 5wt% PPI-G2. From DSC measurements it was concluded that in the presence of TG-DHA the PPI-G2 is intercalated easily at the interface.


Assuntos
Dendrímeros/química , Ácidos Docosa-Hexaenoicos/química , Polipropilenos/química , Tensoativos/química , Triglicerídeos/química , Água/química , Portadores de Fármacos , Emulsões , Interações Hidrofóbicas e Hidrofílicas , Solubilidade , Propriedades de Superfície , Viscosidade
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