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1.
J Sleep Res ; 30(3): e13135, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32618040

RESUMO

Disturbed sleep during gestation may lead to adverse outcomes for both mother and child. Animal research plays an important role in providing insights into this research field by enabling ethical and methodological requirements that are not possible in humans. Here, we present an overview and discuss the main research findings related to the effects of prenatal sleep deprivation in animal models. Using systematic review approaches, we retrieved 42 articles dealing with some type of sleep alteration. The most frequent research topics in this context were maternal sleep deprivation, maternal behaviour, offspring behaviour, development of sleep-wake cycles in the offspring, hippocampal neurodevelopment, pregnancy viability, renal physiology, hypertension and metabolism. This overview indicates that the number of basic studies in this field is growing, and provides biological plausibility to suggest that sleep disturbances might be detrimental to both mother and offspring by promoting increased risk at the behavioural, hormonal, electrophysiological, metabolic and epigenetic levels. More studies on the effects of maternal sleep deprivation are needed, in light of their major translational perspective.


Assuntos
Transtornos do Sono-Vigília/fisiopatologia , Animais , Pesquisa Biomédica , Modelos Animais de Doenças , Feminino , Humanos , Gravidez
2.
J Sleep Res ; 27(2): 197-205, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28560797

RESUMO

Sleep deprivation during pregnancy is an emerging concern, as it can adversely affect the development of the offspring brain. This study was conducted to evaluate the effects of deprivation of rapid eye movement (REM) sleep during the third term of pregnancy on the sleep-wake profiles of neonates in the Wistar rat model. Sleep-wake patterns were assessed through electrophysiological measures and behavioural observations during postnatal days 1-21 on pups born to REM sleep-deprived dams and control rats. Pups of REM sleep-deprived dams had active sleep that was not only markedly higher in percentage during all the days studied, but also had reduced latency during later postnatal days 15-21. Quiet sleep and wake periods were lower. These factors, along with less frequent but longer sleep-wake cycles, indicated maturational delay in the sleep-wake neural networks. The disruption of time-bound growth of sleep-wake neural networks was substantiated further by the decreased slope of survival plots in the sleep bouts. Examination of altered sleep-wake patterns during early development may provide crucial information concerning deranged neural development in the offspring. This is the first report, to our knowledge, to show that maternal sleep deprivation during pregnancy can delay and impair the development of sleep-wake profile in the offspring.


Assuntos
Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Privação do Sono/fisiopatologia , Sono REM/fisiologia , Animais , Animais Recém-Nascidos , Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Eletromiografia/métodos , Feminino , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Ratos , Ratos Wistar , Sono/fisiologia , Privação do Sono/complicações , Privação do Sono/diagnóstico , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/fisiopatologia
3.
Psychogeriatrics ; 18(3): 155-165, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29878472

RESUMO

In contrast to newborns, who spend 16-20 h in sleep each day, adults need only about sleep daily. However, many elderly may struggle to obtain those 8 h in one block. In addition to changes in sleep duration, sleep patterns change as age progresses. Like the physical changes that occur during old age, an alteration in sleep pattern is also a part of the normal ageing process. As people age, they tend to have a harder time falling asleep and more trouble staying asleep. Older people spend more time in the lighter stages of sleep than in deep sleep. As the circadian mechanism in older people becomes less efficient, their sleep schedule is shifted forward. Even when they manage to obtain 7 or 8 h sleep, they wake up early, as they have gone to sleep quite early. The prevalence of sleep disorders is higher among older adults. Loud snoring, which is more common in the elderly, can be a symptom of obstructive sleep apnoea, which puts a person at risk for cardiovascular diseases, headaches, memory loss, and depression. Restless legs syndrome and periodic limb movement disorder that disrupt sleep are more prevalent in older persons. Other common medical problems of old age such as hypertension diabetes mellitus, renal failure, respiratory diseases such as asthma, immune disorders, gastroesophageal reflux disease, physical disability, dementia, pain, depression, and anxiety are all associated with sleep disturbances.


Assuntos
Envelhecimento/fisiologia , Síndrome das Pernas Inquietas/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Sono/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Índia/epidemiologia , Masculino , Prevalência , Síndrome das Pernas Inquietas/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Transtornos do Sono-Vigília/diagnóstico , Ronco/epidemiologia
4.
Cancer ; 121(4): 570-9, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25312684

RESUMO

BACKGROUND: Aldoxorubicin, a prodrug of doxorubicin, covalently binds to serum albumin, allowing for the administration of much higher doses of doxorubicin in a previous clinical study. The current phase 1B/2 study evaluated the safety of aldoxorubicin, including preliminary efficacy and safety of its maximum tolerated dose (MTD). METHODS: Patients aged 18 to 70 years with recurrent/refractory malignant solid tumors received aldoxorubicin at a dose of 230 mg/m(2) , 350 mg/m(2) , or 450 mg/m(2) (170 mg/m(2) , 260 mg/m(2) , or 335 mg/m(2) doxorubicin equivalents, respectively) by intravenous infusion once every 21 days for up to 8 consecutive cycles. RESULTS: A total of 25 patients were enrolled, including 17 patients (68%) with advanced soft tissue sarcoma (STS). The MTD of aldoxorubicin was 350 mg/m(2) ; dose-limiting toxicities included grade 4 neutropenia and grade 3 febrile neutropenia (NCI CTCAE v4.0). Drug-related adverse events included myelosuppression, nausea, fatigue, alopecia, stomatitis, vomiting, and oropharyngeal pain. No clinically significant cardiac toxicities were reported. Seven patients (28%) had elevated serum troponin levels while taking part in the study, but these elevations were not clinically significant or associated with cardiac findings. A partial response was achieved in 20% of patients, and stable disease was reported in 40% of patients. The median progression-free survival was 4.80 months, and the median overall survival was 11.25 months. Among patients with STS who were treated at the MTD (13 patients), a partial response was achieved in 38% and stable disease in 46%; the median progression-free survival was 11.25 months and the median overall survival was 21.71 months. CONCLUSIONS: Aldoxorubicin at a dose of 350 mg/m(2) administered once every 21 days for up to 8 cycles was found to be acceptably safe and demonstrated preliminary efficacy in patients with advanced solid tumors, including STS. Further investigation of aldoxorubicin is ongoing.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Sarcoma/tratamento farmacológico , Adulto , Idoso , Alopecia/induzido quimicamente , Medula Óssea/efeitos dos fármacos , Esquema de Medicação , Neutropenia Febril/induzido quimicamente , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Pró-Fármacos , Sarcoma/patologia , Índice de Gravidade de Doença , Estomatite/induzido quimicamente , Resultado do Tratamento , Vômito/induzido quimicamente
5.
Langmuir ; 31(1): 432-41, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25552289

RESUMO

Using porous hollow fiber membranes, this study illustrates a novel technique to continuously synthesize polymer-coated drug crystals by antisolvent crystallization. The synthesized polymer-coated drug crystals involve crystals of the drug Griseofulvin (GF) coated by a thin layer of the polymer Eudragit RL100. The process feed, an acetone solution of the drug GF containing the dissolved polymer, was passed through the shell side of a membrane module containing many porous hollow fibers of Nylon-6. Through the lumen of the hollow fibers, the antisolvent water was passed at a higher pressure to inject water jets through every pore in the fiber wall into the shell-side acetone feed solution, creating an extremely high level of supersaturation and immediate crystallization. It appears that the GF crystals are formed first and serve as nuclei for the precipitation of the polymer Eudragit, which forms a thin coating around the GF crystals. The polymer-coated drug crystals were collected by a filtration device at the shell-side outlet of the membrane module, and the surface morphology, particle size distribution, and the polymer coating thickness were then characterized by scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM), laser diffraction spectroscopy (LDS), and thermogravimetric analysis (TGA). To study the properties of the coated drug crystals, X-ray diffraction (XRD), Raman spectroscopy, and dissolution tests were implemented. These results indicate that a polymer-coated, free-flowing product was successfully developed under appropriate conditions in this novel porous hollow fiber antisolvent crystallization (PHFAC) method. The coated drug particles can be potentially used for controlled release. The molecular and the crystal structures of GF were not affected by the PHFAC method, which may be easily scaled up.


Assuntos
Resinas Acrílicas/química , Portadores de Fármacos/química , Griseofulvina/química , Membranas Artificiais , Solventes/química , Acetona/química , Cristalização , Tamanho da Partícula , Porosidade
7.
Langmuir ; 30(26): 7804-10, 2014 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-24903705

RESUMO

Continuous polymer coating of nanoparticles is of interest in many industries such as pharmaceuticals, cosmetics, food, and electronics. Here we introduce a polymer coating/precipitation technique to achieve a uniform and controllable nanosize polymer coating on nanoparticles in a continuous manner. The utility of this technique is demonstrated by coating Aerosil silica nanoparticles (SNPs) of diameter 12 nm with the polymer Eudragit RL 100. Both hydrophilic and hydrophobic SNPs were successfully coated. After determining the cloud point of an acetone solution of the polymer containing a controlled amount of the nonsolvent water, the solid hollow fiber cooling crystallization (SHFCC) technique was employed to continuously coat SNPs with the polymer. A suspension of the SNPs in an acetone-water solution of the polymer containing a surfactant was pumped through the lumen of solid polypropylene hollow fibers in a SHFCC device; cold liquid was circulated on the shell side. Because of rapid cooling-induced supersaturation and heterogeneous nucleation, precipitated polymers will coat the nanoparticles. The thickness and morphology of the nanocoating and the particle size distribution of the coated SNPs were analyzed by scanning transmission electron microscopy (STEM) with electron energy loss spectroscopy (EELS), thermogravimetric analysis (TGA), and dynamic light scattering (DLS). Results indicate that uniformly polymer-coated SNPs can be obtained from the SHFCC device after suitable post-treatments. The technique is also easily scalable by increasing the number of hollow fibers in the SHFCC device.


Assuntos
Nanopartículas/química , Polímeros/química , Dióxido de Silício/química , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Termogravimetria
8.
Environ Sci Pollut Res Int ; 31(39): 51401-51414, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39107645

RESUMO

Waste printed circuit boards (WPCBs) encompass abundant metals (gold, silver, and copper), along with other harmful materials including brominated epoxy resins, plastics, and heavy metals (lead, mercury, and cadmium). Direct burning and landfilling of WPCBs may cause severe health issues and impair the environment. Therefore, sustainable treatment of WPCBs is necessary to recover valuable metals and remove hazardous materials before disposal. The present work investigates the separation of copper-rich metallic fractions from the WPCBs by the combination of hammer milling and ultrasonic irradiation. Initially, discarded mobile phone PCBs are pre-processed and shortened into 1 × 1 cm2. Downscaled WPCBs are fed into the hammer mill to obtain the fine ground powder. The Powdered WPCBs are further processed through ultrasonic treatment to acquire metal-rich fraction. XRD, SEM-EDS, and ICP/AAS analysis revealed that the current technique can efficiently separate the metal-rich fraction without using toxic solvents. Results show the enhancement of copper fraction from 42.73 to 87 wt. % after ultrasonic treatment of WPCBs ground powder. Further, nitric acid leaching has been implemented to metal-rich fractions, and the parameters have been optimized for copper leaching with the assistance of response surface methodology (RSM) of the design of experiments (DOE). Quantitative dissolution (98.96%) of copper occurred using 3.5 M nitric acid within 3 h at 30 °C with 50 GPL pulp density and 500 rpm agitation speed. Finally, the kinetics of the leaching process were studied to conform the kinetics model. Moreover, the activation energy for diffusion (19.075 kJ/mole) and reaction kinetics model (13.29 kJ/mole) has also been calculated. The low energy consumption due to room temperature pre-treatment and effective leaching ensures the industrial feasibility of the proposed process.


Assuntos
Cobre , Cobre/química , Cinética , Resíduo Eletrônico , Ultrassom , Metais Pesados
9.
Clin Cancer Res ; 30(2): 323-333, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38047868

RESUMO

PURPOSE: Chordomas are ultrarare tumors of the axial spine and skull-base without approved systemic therapy. Most chordomas have negative expression of thymidylate synthase (TS), suggesting a potential for responding to the antifolate agent pemetrexed, which inhibits TS and other enzymes involved in nucleotide biosynthesis. We evaluated the therapeutic activity and safety of high-dose pemetrexed in progressive chordoma. PATIENTS AND METHODS: Adult patients with previously treated, progressive chordoma participated in an open-label, single-institution, single-arm, pilot clinical trial of intravenous pemetrexed 900 mg/m2 every 3 weeks and supportive medications of folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate according to RECIST v1.1. Secondary endpoints included adverse events, progression-free survival (PFS), tumor molecular profiles, and alterations in tissue and blood-based biomarkers. RESULTS: Fifteen patients were enrolled and the median number of doses administered was 15 (range, 4-31). One patient discontinued treatment due to psychosocial issues after four cycles and one contracted COVID-19 after 13 cycles. Of the 14 response-evaluable patients, 2 (14%) achieved a partial response and 10 (71%) demonstrated stable disease. Median PFS was 10.5 months (95% confidence interval: 9 months-undetermined) and 6-month PFS was 67%. Adverse events were expected and relatively mild, with one grade 3 creatinine increased, and one each of grade 3 and 4 lymphopenia. No grade 5 adverse events, unexpected toxicities, or dose-limiting toxicities were observed. Several patients reported clinical improvement in disease-related symptoms. CONCLUSIONS: High-dose pemetrexed appears tolerable and shows objective antitumor activity in patients with chordoma. Phase II studies of high-dose pemetrexed are warranted.


Assuntos
Cordoma , Neoplasias Pulmonares , Adulto , Humanos , Pemetrexede/efeitos adversos , Cordoma/patologia , Projetos Piloto , Glutamatos/efeitos adversos , Guanina/uso terapêutico , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Neoplasias Pulmonares/tratamento farmacológico
10.
Sleep Med Clin ; 18(4): 463-471, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38501518

RESUMO

Yoga Nidra is a promising technique through which body is consciously simulated into a profound relaxation state similar to attained during naturally occurring deep sleep. It is aimed to attain complete emotional, physical, and mental relaxation of body and mind. In postmenopausal phase of life, regular practice of Yoga Nidra at home preferably in morning, can help in reduction in anxiety and pain associated with early morning awakenings. This nonpharmacological technique has a therapeutic potential to improve sleep quality and quantity, and overall well-being.


Assuntos
Meditação , Distúrbios do Início e da Manutenção do Sono , Yoga , Humanos , Feminino , Yoga/psicologia , Distúrbios do Início e da Manutenção do Sono/terapia , Pós-Menopausa , Meditação/psicologia , Nível de Saúde
11.
Waste Manag ; 171: 621-627, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37837909

RESUMO

Informal recycling activities of waste printed circuit boards, such as pyrolysis and landfilling, cause severe environmental harm to society. Pyrolysis of resin and polymer fraction leads to the generation of toxic effluents, and landfilling causes the leaching of heavy metals into the groundwater. A sustainable and eco-friendly way to recover base and precious elements will be an economically attractive option. Current research studied the cradle-to-gate environmental impacts of the sequential recovery of copper and gold through delamination, leaching, solvent extraction, electrowinning and cementation from waste printed circuit boards with the help of life cycle assessment.GaBi software was utilized to assess environmental impacts such as global warming, abiotic depletion (fossil), acidification potential and human toxicity potential during the process. Inventory data was collected by conducting several experiments and from optimizing parameters for recycling and separating 4.53 g of copper and 2.25 mg of gold from 16 g of component-free waste printed circuit boards. Results indicate that the chemical pre-treatment or delamination process for separating metal clads from the non-metallic fraction is primarily involved in the impact category. The higher impact during delamination is due to electricity consumption. The proposed study also corroborates the industrial viability of recycling valuable metals from waste printed circuit boards to minimize the environmental impacts. The outcomes of this work could be beneficial in creating the environmental guiding principle for WPCBs recycling plants.

12.
Mol Neurobiol ; 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37987958

RESUMO

Therapeutic options to contain seizures, a transitional stage of many neuropathologies, are limited due to the blood-brain barrier (BBB). Herbal nanoparticle formulations can be employed to enhance seizure prognosis. Bacoside A (BM3) and bacopaside I (BM4) were isolated from Bacopa monnieri and synthesized as nanoparticles (BM3NP and BM4NP, respectively) for an effective delivery system to alleviate seizures and associated conditions. After physicochemical characterization, cell viability was assessed on mouse neuronal stem cells (mNSC) and neuroblastoma cells (N2a). Thereafter, anti-seizure effects, mitochondrial membrane potential (MMP), apoptosis, immunostaining and epileptic marker mRNA expression were determined in vitro. The seizure-induced changes in the cortical electroencephalogram (EEG), electromyography (EMG), Non-Rapid Eye Movement (NREM) and Rapid Eye Movement (REM) sleep were monitored in vivo in a kainic acid (KA)-induced rat seizure model. The sizes of BM3NPs and BM4NPs were 165.5 nm and 689.6 nm, respectively. They were biocompatible and also aided in neuroplasticity in mNSC. BM3NPs and BM4NPs depicted more than 50% cell viability in N2a cells, with IC50 values of 1609 and 2962 µg/mL, respectively. Similarly, these nanoparticles reduced the cytotoxicity of N2a cells upon KA treatment. Nanoparticles decreased the expression of epileptic markers like fractalkine, HMGB1, FOXO3a and pro-inflammatory cytokines (P < 0.05). They protected neurons from apoptosis and restored MMP. After administration of BM3NPs and BM4NPs, KA-treated rats attained a significant reduction in the epileptic spikes, sleep latency and an increase in NREM sleep duration. Results indicate the potential of BM3NPs and BM4NPs in neutralizing the KA-induced excitotoxic seizures in neurons.

13.
J Mater Chem B ; 11(21): 4715-4724, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37171084

RESUMO

Alzheimer's disease (AD) is a progressive complex neurodegenerative disorder affecting millions of individuals worldwide. Currently, there is no effective treatment for AD. AD is characterized by the deposition of amyloid plaques/fibrils. One major strategy for managing this disease is by slowing the progression of AD using different drugs which could potentially limit free-radical formation, oxidative stress and lipid peroxidation and promote the survival of neurons exposed to ß-amyloid. Inhibition of amyloid fibrillization and clearance of amyloid plaques/fibrils are essential for the prevention and treatment of AD. The thiophilic interaction between the side chain of an aromatic residue in a polypeptide and a sulphur atom of the compound can effectively inhibit amyloid fibril formation. In this work, we have synthesized cysteine-capped gold nanoclusters (Cy-AuNCs) which exhibit inherent red emission and can disintegrate amyloid fibrils through the aforementioned thiophilic interactions. Herein, we also used molecular docking to study the thiophilic interactions between the sulphur atom of Cy-AuNCs and the aromatic rings of the protein. Finally, the gold cluster was functionalized with a brain targeting molecule, Levodopa (AuCs-LD), to specifically target the brain and to facilitate passage through the blood brain barrier (BBB). Both Cy-AuNCs and AuCs-LD showed good biocompatibility and the inherent fluorescence properties of nanoclusters enabled real time imaging. The efficacy of the nanoclusters to disintegrate amyloid fibrils and their ability to cross the BBB were demonstrated both in vitro and in vivo in the BBB model and the AD animal model respectively. Our results imply that nanoparticle-based artificial molecular chaperones may offer a promising therapeutic approach for AD.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Animais , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Cisteína , Amiloide/química , Placa Amiloide , Ouro/química , Simulação de Acoplamento Molecular , Enxofre/uso terapêutico
14.
Biochemistry ; 51(36): 7064-77, 2012 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-22873692

RESUMO

The steroid hydroxylases CYP17A1 (P450c17, 17-hydroxylase/17,20-lyase) and CYP21A2 (P450c21, 21-hydroxylase) catalyze progesterone hydroxylation at one or more sites within a 2 Å radius. We probed their hydrogen atom abstraction mechanisms and regiochemical plasticity with deuterium-labeled substrates: 17-[(2)H]-pregnenolone; 17-[(2)H]-, 16α-[(2)H]-, 21,21,21-[(2)H(3)]-, and 21-[(2)H]-progesterone; and 21,21,21-[(2)H(3)]-17-hydroxyprogesterone. Product distribution and formation rates with recombinant human P450-oxidoreductase and wild-type human CYP17A1 or mutation A105L (reduced progesterone 16α-hydroxylation) and wild-type human CYP21A2 or mutation V359A (substantial progesterone 16α-hydroxylation) were used to calculate intramolecular and intermolecular kinetic isotope effects (KIEs). The intramolecular KIEs for CYP17A1 and mutation A105L were 4.1 and 3.8, respectively, at H-17 and 2.9 and 5.1, respectively, at H-16α. Mutation A105L 21-hydroxylates progesterone (5% of products), and wild-type CYP17A1 also catalyzes a trace of 21-hydroxylation, which increases with 16α-[(2)H]- and 17-[(2)H]-progesterone. The intramolecular KIEs with CYP21A2 mutation V359A and progesterone were 6.2 and 3.8 at H-21 and H-16α, respectively. Wild-type CYP21A2 also forms a trace of 16α-hydroxyprogesterone, which increased with 21,21,21-[(2)H(3)]-progesterone substrate. Competitive intermolecular KIEs paralleled the intramolecular KIE values, with (D)V values of 1.4-5.1 and (D)V/K values of 1.8-5.1 for these reactions. CYP17A1 and CYP21A2 mutation V359A both 16α-hydroxylate 16α-[(2)H]-progesterone with 33-44% deuterium retention, indicating stereochemical inversion. We conclude that human CYP17A1 has progesterone 21-hydroxylase activity and human CYP21A2 has progesterone 16α-hydroxylase activity, both of which are enhanced with deuterated substrates. The transition states for C-H bond cleavage in these hydroxylation reactions are either significantly nonlinear and/or asymmetric, and C-H bond breakage is partially rate-limiting for all reactions.


Assuntos
Deutério/química , Esteroide 17-alfa-Hidroxilase/química , Esteroide 17-alfa-Hidroxilase/metabolismo , Esteroide 21-Hidroxilase/química , Esteroide 21-Hidroxilase/metabolismo , Humanos , Cinética , Ligação Proteica , Esteroides/síntese química , Esteroides/química , Esteroides/metabolismo
15.
Proc Natl Acad Sci U S A ; 106(23): 9138-43, 2009 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-19497877

RESUMO

Nematode parasitism is a worldwide health problem resulting in malnutrition and morbidity in over 1 billion people. The molecular mechanisms governing infection are poorly understood. Here, we report that an evolutionarily conserved nuclear hormone receptor signaling pathway governs development of the stage 3 infective larvae (iL3) in several nematode parasites, including Strongyloides stercoralis, Ancylostoma spp., and Necator americanus. As in the free-living Caenorhabditis elegans, steroid hormone-like dafachronic acids induced recovery of the dauer-like iL3 in parasitic nematodes by activating orthologs of the nuclear receptor DAF-12. Moreover, administration of dafachronic acid markedly reduced the pathogenic iL3 population in S. stercoralis, indicating the potential use of DAF-12 ligands to treat disseminated strongyloidiasis. To understand the pharmacology of targeting DAF-12, we solved the 3-dimensional structure of the S. stercoralis DAF-12 ligand-binding domain cocrystallized with dafachronic acids. These results reveal the molecular basis for DAF-12 ligand binding and identify nuclear receptors as unique therapeutic targets in parasitic nematodes.


Assuntos
Ancylostoma/metabolismo , Necator americanus/metabolismo , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/metabolismo , Infecções por Strongylida/parasitologia , Strongyloides stercoralis/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/metabolismo , Linhagem Celular , Colestenos/metabolismo , Cristalografia por Raios X , Humanos , Larva , Modelos Moleculares , Estrutura Terciária de Proteína , Receptores Citoplasmáticos e Nucleares/química , Esteroides/metabolismo , Infecções por Strongylida/tratamento farmacológico
16.
Membranes (Basel) ; 12(7)2022 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-35877859

RESUMO

In the past 30 years, plasma polymerization has emerged as a versatile technique for depositing ultrathin nanocoating on a variety of substrates for applications that range from providing lubricity to the substrate, protection from harsh environments, promoting adhesion, surface modification to applications of coating in ultrafiltration and gas separation membranes. Applications in the field of volatile organic compound (VOC) recovery and membrane distillation have also gained importance in recent years. Most of these applications use silicone and fluorosilicone-based plasma polymers that provide versatility, good separation characteristics, and long-term stability to the membrane. However, plasma polymers are known to age with time. The current study focuses on the aging behavior of silicone and fluorosilicone plasma polymers in different environments that include air, ionized air, heat, aqueous solutions of inorganic chemicals, as well as harsh solvents such as hexane, dichloromethane (DCM), and toluene. Membrane gas permeance and gas selectivity were used to quantitatively measure the aging behavior of the coatings on gas separation membranes, while water and VOC flux were used to measure the effect of aging for membranes designed for membrane distillation and VOC separation. It was found that while all plasma polymers of this study showed changes in membrane gas permeance on exposure to air, they fundamentally retained their membrane separation characteristics in all the studied environments. Significant changes in gas permeability characteristics were observed on exposure of the membranes to organic solvents like dichloromethane, 2-propanol, hexane, and toluene, which are attributed to dimensional changes in the hollow fiber substrate rather than changes in plasma polymer characteristics. Ionized air was also found to have a significant effect on the gas permeability characteristic of the membranes, reducing the gas permeance by as much as 50% in some cases. This is attributed to accelerated oxidation and crosslinking of the polymer in ionized air. XPS studies showed an increase in the oxygen content of the polymer on aging. Differences were found in the aging behavior of polymer coatings made from different monomers with long-chain monomers such as hexamethyltrisiloxane offering more stable coatings. The cross-link density of the polymer also influenced the aging behavior, with the more cross-linked polymer showing a lesser influence on aging in a chemical environment. No significant effect of aging was found on applications of these polymer coatings in the field of membrane distillation, pervaporation, and VOC removal, and a stable performance was observed over a long period of time. It was also noted that the selection of co-monomers played a significant role in membrane distillation, with polymers forming fluoro co-monomers giving better results. The current study also demonstrated the usefulness of plasma polymers in controlling the pore size of microporous membranes that can find useful applications in bio-filtration and VOC recovery.

17.
Sleep Vigil ; 6(1): 229-233, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34786533

RESUMO

Purpose: Post-menopausal life is fairly long period of life that is marked by poor health and sleep. Fatigue amidst extraordinary pandemic stress had taken a toll on the sleep quality and overall wellbeing. Yogic sleep can be instrumental in relaxing the brain and help in achieving self-control of mind and body in the post-menopausal life. This can be a non-pharmacological intervention to improve the wellbeing of women. Methods: Effect of 24 weeks of yoga-nidra practice and exercise module was tested in a post-menopausal subject after taking baseline of 4 weeks on parameters like sleep latency, total sleep time, mood on waking and during day, BMI, and activity rhythm of body using 24 h actigraphy and sleep diary. Results: After administering the dual protocol, there was remarkable elevation in mood both on waking up and entire day from 5th week onwards. Mood shifted toward a happier state. Latency to sleep decreased after 4 weeks, while total sleep time improved only after 16 weeks of dual management strategy. The BMI was also reduced to 28.4 from initial value of 30.3. Morning awakening patterns did not change, but it was not accompanied by pain or headache. Conclusion: The results indicated the therapeutic potential of yoga-nidra and exercise package in this actigraphy-based longitudinal pilot study. Yoga-nidra can be easily practiced at home, and thus, it is a promising non-pharmacological strategy for aging population in improving their wellbeing.

18.
Bioresour Technol ; 344(Pt B): 126418, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34838962

RESUMO

This short communication investigated biodiesel production from Euglena Sanguineamicroalgaeand custard appleusing nano CaO as a heterogeneous catalyst. Different solvents were used to extract the oil at a fixed speed, time, and temperature for the samples to estimate the optimized oil yield%. The catalyst was synthesized by sol gel method in nano-scale. It was further characterized by FTIR spectroscopy, SEM, and XRD. The algal oil was pre-treated and trans-esterified with a catalyst to produce alkyl esters. The optimized process variables were determined using response surface methodology by varying parameters such as methanol to oil ratio and catalyst weight% for algal bio-oil and MeOH to oil ratio, time, and catalyst weight% for seed oil. The GC-MS was done to characterize the presence of biodiesel. Kinetic studies were done for the optimized condition for the algal oil and seed oil and it follows the pseudo-first order reaction.


Assuntos
Annona , Euglena , Biocombustíveis , Catálise , Esterificação , Cinética , Óleos de Plantas
19.
Int Med Case Rep J ; 15: 7-14, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35079224

RESUMO

PURPOSE: To report a case of combined central retinal vein and artery occlusion that evolved into ischemic optic neuropathy following the Pfizer COVID-19 vaccination. METHODS: Patient was followed with optical coherence tomography (OCT), fluorescein angiography, and Humphrey visual field. RESULTS: Patient was able to recover vision from count fingers to 20/30 on a combination of aflibercept, steroidal and non-steroidal anti-inflammatories, a diuretic (acetazolamide), antiplatelet agents (aspirin and pentoxifylline), and an anticoagulant (apixaban). CONCLUSION: COVID-19 vaccination may be associated with a myriad of sight-threatening ocular thrombotic conditions, which may respond to a combination of anti-inflammatory and anticoagulant therapies.

20.
ACS Appl Mater Interfaces ; 14(27): 31321-31331, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35771504

RESUMO

Garments protective against chemical warfare agents (CWAs) or accidently released toxic chemicals must block the transport of toxic gases/vapors for a substantial time and allow moisture transport for breathability. These demands are challenging: either the barriers block CWAs effectively but have poor breathability or barriers have excellent breathability but cannot block CWAs well. Existing protective garments employ large amounts of active carbon, making them quite heavy. Metal-organic framework (MOF)-based adsorbents are being investigated as sorbents for CWAs. Breathable laminate of graphene oxide (GO) flakes supported on a porous membrane reduces permeation rates of CWA simulants substantially. We developed a multilayered membrane-based flexible barrier: GO laminate-based membrane over a MOF nanocrystal-filled expanded polytetrafluorethylene (ePTFE) membrane having submicrometer pores. The GO laminate-based layer developed a steady breakthrough concentration level almost 2 orders of magnitude below the usual breakthrough level. This highly reduced level of CWA was blocked by the MOF nanocrystal-filled membrane substrate layer over a highly extended period. We demonstrated the blocking of CWAs, mustard (HD), soman (GD), a sarin simulant [dimethyl methyl phosphonate (DMMP)], and ammonia for an extended period while the moisture transmission rate was substantial. The times for complete blockage of ammonia, HD, GD, and DMMP were 2750 min, 1075 min, 176 min, and 7 days, respectively. This remarkable performance resulted from a very low steady-state penetrant permeation through GO-laminate membrane and substantial penetrant sorption by MOF nanocrystals; furthermore, both layers show high moisture vapor transmission.

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