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1.
Chem Biol Drug Des ; 100(5): 699-721, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36002440

RESUMO

Application of materials capable of energy harvesting to increase the efficiency and environmental adaptability is sometimes reflected in the ability of discovery of some traces in an environment-either experimentally or computationally-to enlarge practical application window. The emergence of computational methods, particularly computer-aided drug discovery (CADD), provides ample opportunities for the rapid discovery and development of unprecedented drugs. The expensive and time-consuming process of traditional drug discovery is no longer feasible, for nowadays the identification of potential drug candidates is much easier for therapeutic targets through elaborate in silico approaches, allowing the prediction of the toxicity of drugs, such as drug repositioning (DR) and chemical genomics (chemogenomics). Coronaviruses (CoVs) are cross-species viruses that are able to spread expeditiously from the into new host species, which in turn cause epidemic diseases. In this sense, this review furnishes an outline of computational strategies and their applications in drug discovery. A special focus is placed on chemogenomics and DR as unique and emerging system-based disciplines on CoV drug and target discovery to model protein networks against a library of compounds. Furthermore, to demonstrate the special advantages of CADD methods in rapidly finding a drug for this deadly virus, numerous examples of the recent achievements grounded on molecular docking, chemogenomics, and DR are reported, analyzed, and interpreted in detail. It is believed that the outcome of this review assists developers of energy harvesting materials and systems for detection of future unexpected kinds of CoVs or other variants.


Assuntos
Tratamento Farmacológico da COVID-19 , Reposicionamento de Medicamentos , Computadores , Desenho de Fármacos , Descoberta de Drogas/métodos , Humanos , Simulação de Acoplamento Molecular
2.
J Hazard Mater ; 436: 129259, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35739778

RESUMO

Is it possible to accelerate cell internalization by hybridization of nanomaterials? Herein we support the realization of using metal-organic frameworks (MOFs) with the assistance of rigid porphyrin structure (H2TMP) aimed at drug loading, drug release, relative cell viability, and targeted in vitro drug delivery. There are several MOFs, i.e., UiO-66-NH2 (125 ± 12.5 nm), UiO-66-NH2 @H2TMP (160 ± 14 nm), UiO-66-NH2 @H2TMP@DOX, and UiO-66-NH2 @H2TMP@DOX@RO were synthesized and characterized applying HEK-293, HT-29, MCF-7, and MCF-10A cell lines. MTT investigations proved a significantly higher relative cell viability for H2TMP-aided leaf-extract-coated nanocarriers (above 62 % relative cell viability). Furthermore, the rigid H2TMP structure improved drug loading capacity by 24 % through an enhanced hydrogen bond, van der Waals, and π-π interactions. The in vitro targeted drug delivery experiments were conducted on HT-29 and MCF-7 cell lines. First, nanocarriers were treated with HT-29 cells, where UiO-66-NH2 @H2TMP@DOX@RO appeared as the best nanocarrier. Then, the selected nanocarrier was extracted from the HT-29 cell line and treated with the MCF-7 cell line. For the first time, the DOX remained inside the UiO-66-NH2 @H2TMP@DOX@RO after successful delivery to the HT-29 cell lines was observed on the MCF-7 cell line, and the second targeted drug delivery was performed. The results of this survey can enlighten the future ahead of cell internalization in MOF-based hybrid nanostructures.


Assuntos
Estruturas Metalorgânicas , Compostos Organometálicos , Porfirinas , Células HEK293 , Humanos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Compostos Organometálicos/farmacologia , Ácidos Ftálicos , Porfirinas/farmacologia
3.
RSC Adv ; 12(10): 5769-5771, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35424562

RESUMO

The study mentioned in the title of this comment paper contains some calculations/results that disagree with some basic chemistry concepts. These misleading calculations include (i) both kinetic and isotherm modelling through linear equations, and (ii) calculating the thermodynamic parameters for the adsorption processes. Thus, we run through the correct way to make these calculations. In our opinion, it is very confusing to continue to disseminate erroneous methods as applied in the original paper.

4.
Chemosphere ; 299: 134359, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35318020

RESUMO

Metal-organic frameworks (MOFs) biocompatible systems can host enzymes/bacteria/viruses. Herein we synthesized a series of fatty acid amide hydrolase (FAAH)-decorated UiO-66-NH2 based on Citrus tangerine leaf extract for drug delivery and biosensor applications. Five chemically manipulated FAAH-like benzamides were localized on the UiO-66-NH2 surface with physical interactions. Comprehensive cellular and molecular analyses were conducted on HEK-293, HeLa, HepG2, PC12, MCF-7, and HT-29 cell lines (cytotoxicity assessment after 24 and 48 h). MTT results proved above 95 and 50% relative cell viability in the absence and presence of the drug, respectively. A complete targeted drug-releasing capability of nanocarriers was demonstrated after capping with leaf extract from Citrus tangerine, with a stimuli-responsive effect in acidic media. Targeted delivery was complete to the nucleus and cytoplasm of HT-29 cell, but merely to the cytoplasm of HeLa cell lines. Nanocarrier could be targeted for drug delivery to the cytoplasm of the HeLa cell line and to both the nucleus and cytoplasm of HT-29 cell lines. MOF-based nanocarriers proved authentic in vivo towards kidney and liver tissues with targeted cancerous cells efficiently. Besides, FAAH-like molecules revealed optical biosensor potential with high selectivity (even ˂5 nM LOD) towards ssDNA, sgRNA, and Anti-cas9 proteins.


Assuntos
Benzamidas , Extratos Vegetais , Células HEK293 , Células HeLa , Humanos , Estruturas Metalorgânicas , Ácidos Ftálicos
5.
Chemosphere ; 287(Pt 4): 132453, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34610372

RESUMO

Tetracycline (TC) is one of the antibiotics that is found in wastewaters. TC is toxic, carcinogenic, and teratogenic. In this study, the tetracycline was removed from water by adsorption using dioxide silicon nanoparticles (SiO2 NPs) biosynthesized from the extract of Nerium oleander leaves. These nanoparticles were characterized using SEM-EDX, BET-BJH, FTIR-ATR, TEM, and XRD. The influences of various factors such as pH solution, SiO2 NPs dose, adsorption process time, initial TC concentration, and ionic strength on adsorption behaviour of TC onto SiO2 NPs were investigated. TC adsorption on SiO2 NPs could be well described in the pseudo-second-order kinetic model and followed the Langmuir isotherm model with a maximum adsorption capacity was 552.48 mg/g. At optimal conditions, the experimental adsorption results indicated that the SiO2 NPs adsorbed 98.62% of TC. The removal of TC using SiO2 NPs was 99.56% at conditions (SiO2 NPs dose = 0.25 g/L, C0 = 25 mg/L, and t = 40 min) based on Box-Behnken design (BBD) combined with response surface methodology (RSM) modelling. Electrostatic interaction governs the adsorption mechanism is attributed. The reusability of SiO2 NPs was tested, and the performance adsorption was 85.36% after the five cycles. The synthesized SiO2 NPs as promising adsorbent has a potential application for antibiotics removal from wastewaters.


Assuntos
Nanopartículas , Nerium , Poluentes Químicos da Água , Adsorção , Antibacterianos , Concentração de Íons de Hidrogênio , Cinética , Extratos Vegetais , Folhas de Planta/química , Dióxido de Silício , Tetraciclina , Poluentes Químicos da Água/análise
6.
J Hazard Mater ; 423(Pt B): 127130, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34530276

RESUMO

Green biomaterials play a crucial role in the diagnosis and treatment of diseases as well as health-related problem-solving. Typically, biocompatibility, biodegradability, and mechanical strength are requirements centered on biomaterial engineering. However, in-hospital therapeutics require an elaborated synthesis of hybrid and complex nanomaterials capable of mimicking cellular behavior. Accumulation of hazardous cations like K+ in the inner and middle ear may permanently damage the ear system. We synthesized nanoplatforms based on Allium noeanum to take the first steps in developing biological porous nanomembranes for hazardous cation detection in biological media. The 1,1,1-tris[[(2'-benzyl-amino-formyl)phenoxy]methyl]ethane (A), 4-amino-benzo-hydrazide (B), and 4-(2-(4-(3-carboxy-propan-amido)benzoyl)hydrazineyl)-4-oxobutanoic acid (B1) were synthesized to obtain green ligands based on 4-X-N-(…(Y(hydrazine-1-carbonyl)phenyl)benzamide, with X denoting fluoro (B2), methoxy (B3), nitro (B4), and phenyl-sulfonyl (B5) substitutes. The chemical structure of ligand-decorated adenosine triphosphate (ATP) molecules (S-ATP) was characterized by FTIR, XRD, AFM, FESEM, and TEM techniques. The cytotoxicity of the porous membrane was patterned by applying different cell lines, including HEK-293, PC12, MCF-7, HeLa, HepG2, and HT-29, to disclose their biological behavior. The morphology of cultured cells was monitored by confocal laser scanning microscopy. The sensitivity of S-ATP to different cations of Na+, Mg2+, K+, Ba2+, Zn2+, and Cd2+ was evaluated by inductively coupled plasma atomic emission spectroscopy (ICP-AES) in terms of extraction efficiency (η). For pH of 5.5, the η of A-based S-ATP followed the order Na+ (63.3%) > Mg2+ (62.1%) > Ba2+ (7.6%) > Ca2+ (5.5%); while for pH of 7.4, Na+ (37.0%) > Ca2+ (33.1%) > K+ (25.7%). The heat map of MTT and dose-dependent evaluations unveiled acceptable cell viability of more than 90%. The proposed green porous nanomembranes would pave the way to use multifunctional green porous nanomembranes in biological membranes.


Assuntos
Benzamidas , Sódio , Cátions , Células HEK293 , Humanos , Porosidade
7.
J Pharm Biomed Anal ; 206: 114387, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34583125

RESUMO

Chronic hyperglycemia and hyperlipidemia are associated with excessive formation of reactive oxygen species and advanced glycation end-products. The present study aimed to evaluate the potential in vitro antidiabetic properties of Kielmeyera coriacea inner bark. The main phytochemical compounds were identified by UHPLC-ESI/MSn and the ethanol extract and its fractions were used to evaluate their antioxidant and anti-glycation capacities, as well as their inhibitory potential against glycoside and lipid hydrolases activities. The polar fractions, especially the n-butanol fraction, had free radical scavenging and quenching properties (ORAC and FRAP values>1800 and 1000 µmol trolox eq/g, respectively, and DPPH IC50<4 µg/mL), and inhibited ROS production (p < 0.01), lipid peroxidation (p < 0.001), glycation (IC50 ~ 10 µg/mL in the BSA-fructose assay; IC50 ~ 200 µg/mL in the BSA-methylglyoxal and arginine-methylglyoxal assays), α-amylase (IC50<0.1 µg/mL) and lipase (IC50<5 µg/mL), with no cytotoxicity. Biomolecules well-known as potent antioxidants were identified for the first time in the inner bark of K. coriacea, such as protocatechuic acid, epicatechin and procyanidins A, B and C. Together, our results support the antioxidant, anti-glycation and glycoside and lipid hydrolases inhibitory properties of the inner bark of K. coriacea, a species found in the Brazilian savanna, which makes it especially useful to combat oxidative stress and hyperglycemia and hyperlipidemia.


Assuntos
Antioxidantes , alfa-Amilases , Antioxidantes/farmacologia , Produtos Finais de Glicação Avançada , Hipoglicemiantes/farmacologia , Lipase , Extratos Vegetais/farmacologia
8.
Eur J Med Res ; 26(1): 86, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348796

RESUMO

As one of the leading causes of elderly patients' hospitalisation, proximal femur fractures (PFFs) will present an increasing socioeconomic problem in the near future. This is a result of the demographic change that is expressed by the increasing proportion of elderly people in society. Peri-operative management must be handled attentively to avoid complications and decrease mortality rates. To deal with the exceptional needs of the elderly, the development of orthogeriatric centres to support orthogeriatric co-management is mandatory. Adequate pain medication, balanced fluid management, delirium prevention and the operative treatment choice based on comorbidities, individual demands and biological rather than chronological age, all deserve particular attention to improve patients' outcomes. The operative management of intertrochanteric and subtrochanteric fractures favours intramedullary nailing. For femoral neck fractures, the Garden classification is used to differentiate between non-displaced and displaced fractures. Osteosynthesis is suitable for biologically young patients with non-dislocated fractures, whereas total hip arthroplasty and hemiarthroplasty are the main options for biologically old patients and displaced fractures. In bedridden patients, osteosynthesis might be an option to establish transferability from bed to chair and the restroom. Postoperatively, the patients benefit from early mobilisation and early geriatric care. During the COVID-19 pandemic, prolonged time until surgery and thus an increased rate of complications took a toll on frail patients with PFFs. This review aims to offer surgical guidelines for the treatment of PFFs in the elderly with a focus on pitfalls and challenges particularly relevant to frail patients.


Assuntos
Fraturas do Fêmur/cirurgia , Idoso , COVID-19/epidemiologia , Delírio/prevenção & controle , Fraturas do Colo Femoral/classificação , Fraturas do Colo Femoral/cirurgia , Colo do Fêmur/anatomia & histologia , Fraturas do Quadril/cirurgia , Humanos , Complicações Pós-Operatórias/prevenção & controle , SARS-CoV-2
9.
BMC Cancer ; 21(1): 575, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011306

RESUMO

BACKGROUND: No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin. METHODS: We performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥ 2 increased serum creatinine). The most differentially expressed miRNAs between the two groups were selected for quantification at baseline and D5 in a larger cohort of patients. The association between miRNAs and nephrotoxicity was evaluated by calculating the odds ratio (OR) from univariate logistic regression. Receiver operating characteristic curves (ROC) were used to estimate the area under the curve (AUC), sensitivity, and specificity. RESULTS: MiR-3168 (p = 1.98 × 10- 8), miR-4718 (p = 4.24 × 10- 5), and miR-6125 (p = 6.60 × 10- 5) were the most differentially expressed miRNAs and were further quantified in 43, 48, and 53 patients, respectively. The baseline expression of miR-3168 (p = 0.0456, OR = 1.03, 95% CI: 1.00-1.06) and miR-4718 (p = 0.0388, OR = 1.56, 95% CI: 1.03-2.46) were associated with an increased risk of nephrotoxicity, whereas miR-6125 showed a trend (p = 0.0618, OR = 1.73, 95% CI: 0.98-3.29). MiR-4718 showed the highest AUC (0.77, 95% CI: 0.61-0.93) with sensitivity of 66.76 and specificity of 79.49. CONCLUSIONS: We have provided evidence of baseline plasmatic expression of miR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity.


Assuntos
Injúria Renal Aguda/epidemiologia , Biomarcadores Tumorais/metabolismo , Cisplatino/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , MicroRNAs/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Idoso , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Creatinina/sangue , Feminino , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/genética , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Curva ROC , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Análise de Sequência de RNA , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
10.
Orthopade ; 50(11): 937-945, 2021 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-33666674

RESUMO

BACKGROUND: Obtaining informed consent is a challenging task and is part of the educational objectives in the German NKLM. Teaching formats are inconsistent and time-consuming, with little emphasis on legal aspects, although they have moved into the focus of attention since the implementation of patient rights laws and play an important role in legal proceedings. OBJECTIVES: The aim of this study was the evaluation of medical students' knowledge about the legal aspects of obtaining informed consent. A legal analysis was performed, and the patient rights laws were reviewed with reference to implications for undergraduate medical education. MATERIALS AND METHODS: After the analysis of laws and jurisdiction, multiple-choice questions regarding the legal aspects of obtaining informed consent were created and placed in the Progress Test Medicine (PTM). A statistical analysis of the results of Berlin medical students was performed descriptively. RESULTS: The answers of 2625 (winter semester 2018/19) and 2409 (summer semester 2019) medical students in Berlin were analyzed. The rate of students who answered the questions about the procedures requiring informed consent and adequate time for consideration increased over time but did not reach comparable values to all PTM questions. Questions about required content were answered correctly by 30 to 60% of the students, regardless of their level of training; we did not see an increase along with the time of study. CONCLUSION: In our study, we were able to show that medical students of all educational levels show tentativeness when it comes to the legal aspects of obtaining informed consent. Yet, the legal framework offers room for new teaching formats like "Co-Action", introduced in this paper for the first time, where students acquire informed consent while being supervised by the medical doctor in charge.


Assuntos
Estudantes de Medicina , Berlim , Humanos , Consentimento Livre e Esclarecido , Direitos do Paciente , Incerteza
11.
J Hazard Mater ; 398: 122903, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-32512448

RESUMO

The present research describes the synthesis of new nanomagnetic activated carbon material with high magnetization, and high surface area prepared in a single pyrolysis step that is used for the carbonization, activation, and magnetization of the produced material. The pyrolysis step of tucumã seed was carried out in a conventional tubular oven at 600 °C under N2-flow. It was prepared three magnetic carbons MT-1.5, MT-2.0, MT-2.5, that corresponds to the proportion of biomass: ZnCl2 always 1:1 and varying the proportion of NiCl2 of 1.5, 2.0, and 2.5, respectively. These magnetic nanocomposites were characterized by Vibrating Sample Magnetometer (VSM), X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, hydrophobic/hydrophilic balance, CHN/O elemental analysis, modified Boehm titration, N2 adsorption-desorption isotherms; and pHpzc. All the materials obtained presented Ni particles with an average crystallite size of less than 33 nm. The MT-2.0 was employed for the removal of nicotinamide and propranolol from aqueous solutions. Based on Liu isotherm, the Qmax was 199.3 and 335.4 mg g-1 for nicotinamide and propranolol, respectively. MT-2.0 was used to treat simulated pharmaceutical industry effluents attaining removal of all organic compounds attaining up to 99.1 % of removal.


Assuntos
Carvão Vegetal , Poluentes Químicos da Água , Adsorção , Cloretos , Fenômenos Magnéticos , Niacinamida , Níquel , Propranolol , Pirólise , Poluentes Químicos da Água/análise , Zinco
12.
J Hazard Mater ; 396: 122699, 2020 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-32344362

RESUMO

The anti-cancer drug Flutamide (FLUT) is widely used and is of great environmental concern. The solar photo-Fenton (SPF) process can be an effective treatment for the removal of this type of micropollutant. The use of a single addition of 5 mg L-1 of Fe2+ and 50 mg L-1 of H2O2 achieved 20% primary degradation and only 3.05% mineralization. By using three additions of 5 mg L-1 Fe2+, with an initial H2O2 concentration of 150 mg L-1, 58% primary degradation was achieved, together with 12.07% mineralization. Consequently, thirteen transformation products (TPs) were formed. The SPF process was further combined with adsorption onto avocado seed activated carbon (ASAC) as an environmentally friendly approach for the removal of remained FLUT and the TPs. Doehlert design was used to assess the behavior of 13 TPs by optimizing the contact time and the adsorbent mass load. The optimal conditions for removal of FLUT and the TPs were 14 mg of ASAC and a contact time of 40 min. Remained FLUT and the TPs were totally removed using the adsorption process. The mechanisms of adsorption of FLUT and the TPs were strongly influenced by their polarity and π-π interactions of the TPs onto ASAC.


Assuntos
Antineoplásicos , Poluentes Químicos da Água , Adsorção , Flutamida , Hospitais , Peróxido de Hidrogênio , Oxirredução , Águas Residuárias , Poluentes Químicos da Água/análise
13.
Environ Res ; 183: 109223, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32045729

RESUMO

Flutamide (FLUT) is a non-steroidal drug mainly used in the treatment of prostate cancer and has been detected in the aquatic environment at ng L-1 levels. The environmental fate and effects of FLUT have not yet been studied. Conventional treatment technologies fail to completely remove pharmaceuticals, so the solar photo-Fenton process (SPF) has been proposed as an alternative. In this study, the degradation of FLUT, at two different initial concentrations in ultra-pure water, was carried out by SPF. The initial SPF conditions were pH0 5, [Fe2+]0 = 5 mg L-1, and [H2O2]0 = 50 mg L-1. Preliminary elimination rates of 53.4% and 73.4%. The kinetics of FLUT degradation could be fitted by a pseudo-first order model and the kobs were 6.57 × 10-3 and 9.13 × 10-3 min-1 t30W and the half-life times were 95.62 and 73.10 min t30W were achieved for [FLUT]0 of 5 mg L-1 and 500 µg L-1, respectively. Analysis using LC-QTOF MS identified thirteen transformation products (TPs) during the FLUT degradation process. The main degradation pathways proposed were hydroxylation, hydrogen abstraction, demethylation, NO2 elimination, cleavage, and aromatic ring opening. Different in silico (quantitative) structure-activity relationship ((Q)SAR) freeware models were used to predict the toxicities and environmental fates of FLUT and the TPs. The in silico predictions indicated that these substances were not biodegradable, while some TPs were classified near the threshold point to be considered as PBT compounds. The in silico (Q)SAR predictions gave positive alerts concerning the mutagenicity and carcinogenicity endpoints. Additionally, the (Q)SAR toolbox software provided structural alerts corresponding to the positive alerts obtained with the different mutagenicity and carcinogenicity models, supporting the positive alerts with more proactive information.


Assuntos
Antineoplásicos , Flutamida , Poluentes Químicos da Água , Flutamida/química , Peróxido de Hidrogênio , Concentração de Íons de Hidrogênio , Medição de Risco
14.
Sci Rep ; 9(1): 9312, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31249357

RESUMO

Cisplatin (CDDP) combined with radiotherapy (RT) is employed in head and neck squamous cell carcinoma (HNSCC) with variable toxicities and clinical response. Glutathione S-transferases (GSTs) participate in CDDP excretion from cells, and genes encoding GSTs, GSTM1, GSTT1and GSTP1, are polymorphic in humans. This prospective study aimed to evaluate the roles of GSTM1, GSTT1, and GSTP1 Ile105Val polymorphisms in outcomes of HNSCC patients treated with CDDP chemoradiation. Ninety patients were genotyped by multiplex PCR. Urinary CDDP measurements were performed by HPLC. Treatment side effects and response were analysed by conventional criteria. Patients with GSTT1 genes showed 7.23- and 5.37-fold higher likelihood of presenting vomiting and ototoxicity, lower glomerular filtration rate (GFR), and lower elimination of CDDP in urine relative to patients with deleted genes. Patients harbouring the GSTP1 IleVal or ValVal genotypes showed 4.28-fold higher likelihood of presenting grade 2 or 3 vomiting and lower GFR with treatment than those harbouring the IleIle genotype. In multivariate Cox analysis, patients with the GSTP1 105ValVal genotype had 3.87 more chance of presenting disease progression than those with the IleIle or IleVal genotype (p < 0.01). Our findings provide preliminary evidence that inherited abnormalities in CDDP metabolism, related to GSTT1 and GSTP1 Ile105Val polymorphisms, alter outcomes of HNSCC patients treated with CDDP and RT.


Assuntos
Quimiorradioterapia , Cisplatino/farmacologia , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Cisplatino/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Análise de Sobrevida , Resultado do Tratamento
15.
PLoS One ; 12(5): e0177086, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28481921

RESUMO

This study investigated the influence of sodium restriction and antihypertensive drugs on atherogenesis utilizing hypertensive (H) low-density lipoprotein-receptor knockout mice treated or not with losartan (Los) or hydralazine (Hyd) and fed low-sodium (LS) or normal-sodium (NS) chow. Despite reducing the blood pressure (BP) of H-LS mice, the LS diet caused arterial lipid infiltration due to increased plasma total cholesterol (TC) and triglycerides (TG). Los and Hyd reduced the BP of H-LS mice, and Los effectively prevented arterial injury, likely by reducing plasma TG and nonesterified fatty acids. Aortic lipid infiltration was lower in Los-treated H-LS mice (H-LS+Los) than in normotensive (N)-LS and H-LS mice. Aortic angiotensin II type 1 (AT1) receptor content was greater in H-NS than H-LS mice and in H-LS+Hyd than H-LS+Los mice. Carboxymethyl-lysine (CML) and receptor for advanced glycation end products (RAGE) immunostaining was greater in H-LS than H-NS mice. CML and RAGE levels were lower in LS animals treated with antihypertensive drugs, and Hyd enhanced the AT1 receptor level. Hyd also increased the gene expression of F4/80 but not tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-10, intercellular adhesion molecule-1 or cluster of differentiation 66. The novelty of the current study is that in a murine model of simultaneous hypertension and hyperlipidemia, the pleiotropic effect of chronic, severe sodium restriction elicited aortic damage even with reduced BP. These negative effects on the arterial wall were reduced by AT1 receptor antagonism, demonstrating the influence of angiotensin II in atherogenesis induced by a severely LS diet.


Assuntos
Aterosclerose/etiologia , Pressão Sanguínea , Dieta Hipossódica , Hiperlipidemias/complicações , Hipertensão/prevenção & controle , Animais , Hipertensão/complicações , Camundongos , Camundongos Knockout , Receptores de LDL/genética
16.
Protoplasma ; 254(2): 817-837, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27352314

RESUMO

Sargassum cymosum was exposed to cadmium (Cd) to determine any physiological and ultrastructural effects. To accomplish this, S. cymosum samples were cultivated under photosynthetic active radiation (PAR) and Cd (0, 0.1, 0.2, 0.4 and 0.8 mg L-1) during 7 and 14 days in laboratory-controlled conditions (0 mg L-1 Cd at both exposure times as control). Seaweeds had high retention capacity (over 90 %) for both exposure times. Growth rates showed significant increases by 14 days, especially for 0.1 and 0.4 mg L-1 Cd. Photosynthetic parameters were unaffected by Cd treatments. Chlorophyll contents were present in higher concentrations for all Cd treatments compared to respective control. Carotenoid profile showed significant differences in total composition and proportion of fucoxanthin and ß-carotene, and no lutein was detected at 14 days. Phenolic and flavonoid compounds showed major accumulation at 14 days. Transmission electron microscopy (TEM) analyses presented major alterations in Cd-treated samples, when compared with respective control, in particular disorganization of cell wall fibrils. When compared to respective control samples, multivariate analyses showed disparate and complex interactions among metabolites in Cd-exposed seaweeds, giving evidence of physiological defence response. Thus, it can be concluded that Cd is a stressor for S. cymosum, resulting in physiological and structural alterations related to defence mechanisms against oxidative stress and toxicological effects resulting from long-term metal exposure. However, in the present paper, some observed changes also appear to result from acclimation mechanisms under lower concentration of Cd relative to the tolerance of S. cymosum to experimental conditions.


Assuntos
Cádmio/toxicidade , Sargassum/citologia , Sargassum/metabolismo , Alga Marinha/citologia , Alga Marinha/metabolismo , Análise de Variância , Antioxidantes/metabolismo , Cádmio/análise , Carboidratos/análise , Sobrevivência Celular/efeitos dos fármacos , Clorofila/metabolismo , Clorofila A , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Fluorescência , Análise Multivariada , Fenóis/análise , Fotossíntese/efeitos dos fármacos , Análise de Componente Principal , Sargassum/efeitos dos fármacos , Sargassum/ultraestrutura , Água do Mar/química , Alga Marinha/efeitos dos fármacos , Alga Marinha/ultraestrutura , Solubilidade
17.
Mar Environ Res ; 115: 89-97, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26724873

RESUMO

Seasonal changes in the biochemistry and photophysiology of the brown macroalga Cystoseira tamariscifolia was analyzed in southern Spain. Total carbon and nitrogen contents, phenolic compounds, antioxidant and photosynthetic activities were seasonally determined over two years. Carbon, nitrogen and photoprotective phenolic contents were higher in winter and spring than in summer and autumn. Antioxidant levels were highest in spring and we found a positive correlation between phenolic content and antioxidant activity (EC50). Photosynthetic capacity (ETRmax) and photosynthetic efficiency (αETR) were also highest in spring, and there was a positive correlation between ETRmax and the amount of phenols present. Increased irradiance in spring enhanced algal productivity, antioxidant activity and the production of photoprotective compounds but in summer nutrient depletion due to thermal stratification of coastal waters reduced photosynthetic activity and the photoprotective capacity of C. tamariscifolia. Electron microscopy showed that phenols occurred in the cytoplasm of cortical cells inside physodes. Spring would be the best period to harvest C. tamariscifolia to extract photoprotectors and antioxidants for potential commercial uses, although the environmental impacts would need to be carefully assessed.


Assuntos
Phaeophyceae/fisiologia , Antioxidantes/análise , Carbono/análise , Nitrogênio/análise , Phaeophyceae/química , Phaeophyceae/efeitos da radiação , Phaeophyceae/ultraestrutura , Fenóis/análise , Fotossíntese/fisiologia , Estações do Ano , Luz Solar
19.
J Microsc Ultrastruct ; 4(2): 85-94, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-30023214

RESUMO

Studies have clearly demonstrated the damaging effects of UV-B exposure on macroalgae, but few have reported the impact of UV-B on spore germination and development at juvenile stages. Therefore, this work aimed to analyze the effects of UV-B radiation on germlings of Nemalion helminthoides at the tetrasporophytic phase. To accomplish this, germlings of N. helminthoides were cultivated in the laboratory and separated into two groups. The control group was exposed onlyto photosynthetic radiation, while the treatment group was exposed to photosynthetic radiation + UV-B for 2 hours during a period of 12 days. Control germlings showed increasing cellular proliferation and accumulation of reserve substances, as well as intense ramification in the last observed stages between 9 days and 12 days of development. Moreover, the chloroplasts presented a typical globular pyrenoid, profusely traversed by thylakoid membranes. Treated germlings, by contrast, showed intracellular damage, such as cell wall thickness, loss of chloroplast organization, changes in mitochondrial cristae, and increasing atrophy of the Golgi bodies. Additionally, changes in developmental patterns were observed, including loss of polarity in the first divisions of carpospores and abnormal stem ramification. The quantification of autofluorescence data coincided with the ultrastructural changes observed in the chloroplasts of cells exposed to UV-B. It can be concluded that exposure to radiation changed the developmental pattern and morphology of the germlings of N. helminthoides.

20.
Protoplasma ; 252(5): 1347-59, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25666304

RESUMO

By evaluating carotenoid content, photosynthetic pigments and changes in cellular morphology, growth rates, and photosynthetic performance, this study aimed to determine the effect of cadmium (Cd) on the development of young gametophytes of Gelidium floridanum. Plants were exposed to 7.5 and 15 µM of Cd for 7 days. Control plants showed increased formation of new filamentous thallus, increased growth rates, presence of starch grains in the cortical and subcortical cells, protein content distributed regularly throughout the cell periphery, and intense autofluorescence of chloroplasts. On the other hand, plants treated with Cd at concentrations of 7.5 and 15 µM showed few formations of new thallus with totally depigmented regions, resulting in decreased growth rates. Plants exposed to 7.5 µM Cd demonstrated alterations in the cell wall and an increase in starch grains in the cortical and subcortical cells, while plants exposed to 15 µM Cd showed changes in medullary cells with no organized distribution of protein content. The autofluorescence and structure of chloroplasts decreased, forming a thin layer on the periphery of cells. Cadmium also affected plant metabolism, as visualized by a decrease in photosynthetic pigments, in particular, phycoerythrin and phycocyanin contents, and an increase in carotenoids. This result agrees with decreased photosynthetic performance and chronic photoinhibition observed after treatment with Cd, as measured by the decrease in electron transport rate. Based on these results, it was concluded that exposure to Cd affects cell metabolism and results in significant toxicity to young gametophytes of G. floridanum.


Assuntos
Cádmio/toxicidade , Células Germinativas Vegetais/efeitos dos fármacos , Rodófitas/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Carotenoides/metabolismo , Clorofila/metabolismo , Cloroplastos/metabolismo , Transporte de Elétrons , Células Germinativas Vegetais/fisiologia , Células Germinativas Vegetais/ultraestrutura , Fotossíntese , Rodófitas/citologia , Rodófitas/fisiologia
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