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1.
Environ Pollut ; 334: 122116, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37394053

ABSTRACT

Tire tread particles (TTP) are environmentally prevalent microplastics and generate toxic aqueous leachate. We determined the total carbon and nitrogen leachate concentrations and chemical profiles from micron (∼32 µm) and centimeter (∼1 cm) TTP leachate over 12 days. Dissolved organic carbon (DOC) and total dissolved nitrogen (TDN) were used to measure the concentration of leached compounds. Nontargeted chemical analysis by comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOF-MS) was used to compare the chemical profiles of leachates. After leaching for 12 days, DOC was 4.0 times higher in the micron TTP leachate than in the centimeter TTP leachate, and TDN was 2.6 times higher. The total GC×GC/TOF-MS chromatographic feature peak area was 2.9 times greater in the micron TTP leachate than the centimeter TTP leachate, and similarly, the total relative abundance of 54 tentatively identified compounds was 3.3 times greater. We identified frequently measured tire-related chemicals, such as 6PPD, N-cyclohexyl-N'-phenylurea (CPU), and hexa(methoxymethyl)melamine (HMMM), but nearly 50% of detected chemicals were not previously reported in tire literature or lacked toxicity information. Overall, the results demonstrate that smaller TTP have a greater potential to leach chemicals into aquatic systems, but a significant portion of these chemicals are not well-studied and require further risk assessment.


Subject(s)
Dissolved Organic Matter , Phenylenediamines , Plastics , Water Pollutants, Chemical , Dissolved Organic Matter/analysis , Dissolved Organic Matter/chemistry , Dissolved Organic Matter/classification , Gas Chromatography-Mass Spectrometry , Plastics/analysis , Plastics/chemistry , Plastics/classification , Particle Size , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/classification , Phenylenediamines/analysis , Phenylenediamines/chemistry , Phenylenediamines/classification , Risk Assessment
2.
Anticancer Agents Med Chem ; 21(9): 1191-1199, 2021.
Article in English | MEDLINE | ID: mdl-32842946

ABSTRACT

BACKGROUND: It takes a lot more studies to evaluate the molecular interaction of nanoparticles with the drug, their drug delivery potential and release kinetics. Thus, we have taken in silico and in vitro approaches into account for the evaluation of the drug delivery ability of the chitosan nanoparticles. OBJECTIVE: The present work was aimed to study the interaction of chitosan nanoparticles with appropriate aromatase inhibitors using in silico tools. Further, synthesis and characterization of chitosan nanoparticles having optimal binding energy and affinity between drug and polymer in terms of size, encapsulation efficiency were carried out. METHODS: In the current study, molecular docking was used to map the molecular interactions and estimation of binding energy involved between the nanoparticles and the drug molecules in silico. Letrozole is used as a model cytotoxic agent currently being used clinically; hence Letrozole loaded chitosan nanoparticles were formulated and characterized using photomicroscope, particle size analyzer, scanning electron microscope and fourier transform infra-red spectroscopy. RESULTS: Letrozole had the second-highest binding affinity within the core of chitosan with MolDock (-102.470) and Re-rank (-81.084) scores. Further, it was investigated that formulated nanoparticles were having superior drug loading capacity and high encapsulation efficiency. In vitro drug release study exhibited prolonged release of the drug from chitosan nanoparticles. CONCLUSION: Results obtained from the in silico and in vitro studies suggest that Letrozole loaded nanoparticles are ideal for breast cancer treatment.


Subject(s)
Antineoplastic Agents/pharmacology , Aromatase Inhibitors/pharmacology , Breast Neoplasms/drug therapy , Letrozole/pharmacology , Molecular Docking Simulation , Nanoparticles/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Aromatase Inhibitors/chemical synthesis , Aromatase Inhibitors/chemistry , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Chitosan/chemistry , Chitosan/pharmacology , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Humans , Letrozole/chemical synthesis , Letrozole/chemistry , Molecular Structure , Polymers/chemistry , Polymers/pharmacology , Structure-Activity Relationship
3.
Cureus ; 12(2): e6983, 2020 Feb 13.
Article in English | MEDLINE | ID: mdl-32206455

ABSTRACT

Guillian-Barre Syndrome (GBS) typically presents as symmetrical ascending flaccid muscle weakness with areflexia, and with or without sensory symptoms. However, some patients may present atypically, and accordingly, different variants of GBS have been reported in the literature. Pharyngeal-cervical-brachial variant is one of the rare variants and is characterized by muscle weakness extending from the oropharyngeal and neck area to the proximal upper extremities. Many physicians and neurologists are unfamiliar about pharyngeal-cervical-brachial variant, which is often misdiagnosed as brainstem stroke, myasthenia gravis or botulism. Herein, we report a case of pharyngeal-cervical-brachial variant of GBS. To the best of our knowledge, this is the first reported case of pharyngeal-cervical-brachial variant of GBS in children from Nepal. A 14-year-old Asian male presented with weakness of bilateral upper limb, dysphagia, and nasal intonation of voice. A diagnosis of pharyngeal-cervical-brachial variant of GBS was made after excluding all other possible differentials and based on cerebrospinal fluid analysis and nerve conduction study. The patient improved following conservative management. Pharyngeal-cervical-brachial variant of GBS should always be considered in any patient presenting with symmetrical upper limb weakness and bulbar palsy. This is to ensure early diagnosis, treatment, and follow-up of the potential complications.

4.
Data Brief ; 24: 103904, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31193225

ABSTRACT

Litho- and biostratigraphic data are provided of 5 stratigraphic sections in Romania covering the "Badenian" marine flooding that occurred in the Central Paratethys during the middle Miocene (Langhian). The dataset includes stratigraphic logs and descriptions of the profiles, and biostratigraphic analyses on calcareous nannofossils and foraminifera. In addition, characteristic stratigraphic features and representative fossils, including tiny Streptochilus foraminifera in the Campinita section in the SE Carpathian Foredeep, are presented in photographs. The data show that the flooding is characterized by the sudden abundance of Langhian calcareous nannofossils and foraminifera with a strong Mediterranean affinity.

5.
Steroids ; 95: 96-103, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25582615

ABSTRACT

Steroidal 5α-reductase, a key enzyme involved in the transformation of testosterone to dihydrotestosterone, is unstable during the purification leading to loss of the activity. Therefore, due to unstable nature, the crystal structure of the 5α-reductase is unknown. In the present study, we have generated a comparative pharmacophoric model for both isoforms of steroidal 5α-reductase using 6-azasteroids. The steric and electrostatic maps generated for both isoforms provides structure framework for designing of new inhibitors. Further, 3D-maps are also helpful in understanding variability in the activity of the compounds. Statistical measures generated for both enzymes showed good internal and external prediction. Overall, the analyses of models provides structural requirement of dual and selective steroidal 5α-reductase inhibitors in an interactive fashion.


Subject(s)
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism , 5-alpha Reductase Inhibitors/chemistry , 5-alpha Reductase Inhibitors/pharmacology , Azasteroids/chemistry , Azasteroids/pharmacology , Models, Molecular , Quantitative Structure-Activity Relationship , Molecular Conformation , Static Electricity
6.
Neuropharmacology ; 21(10): 981-4, 1982 Oct.
Article in English | MEDLINE | ID: mdl-7145036

ABSTRACT

Administration of bicuculline (3.5 mg/kg i.p.) or pentylenetetrazol (30 mg/kg i.p.) 3 min before each of a series of 5 electroconvulsive shocks (ECS), given over 10 days (1, 3, 5, 8 and 10), prevented the enhanced behavioural responses to the dopamine agonist apomorphine and the 5-hydroxytryptamine agonist quipazine 24 hr after the last application of ECS. Pretreatment with these antagonists of gamma-aminobutyric acid (GABA) also abolished the rise in the concentration of GABA in the corpus striatum, normally seen after repeated ECS. Taken with data showing that the change in GABA concentration occurred at times when enhanced monoamine-mediated behavioural responses were seen, these results suggest that the enhanced behavioural responses following repeated ECS might be associated with changes in GABA function. Daily injection for 8 days with pentylenetetrazol (30 mg/kg) resulted in enhanced apomorphine-mediated behaviour. However, there was no change in the concentration of striatal GABA at this time.


Subject(s)
Behavior, Animal/drug effects , Brain Chemistry , Electroshock , gamma-Aminobutyric Acid/analysis , Animals , Apomorphine/pharmacology , GABA Antagonists , Male , Pentylenetetrazole/pharmacology , Quipazine/pharmacology , Rats , Rats, Inbred Strains
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