pH-responsive chitosan/acrylamide/gold/nanocomposite supported with silver nanoparticles for controlled release of anticancer drug.

In this study, we prepared a pH-responsive nanocomposite hydrogel based on chitosan grafted with acrylamide monomer and gold nanoparticles using gamma irradiation method (Cs-g-PAAm/AuNPs). The nanocomposite was enhanced with a layer coating of silver nanoparticles to improve the controlled release of the anticancer drug fluorouracil while increasing antimicrobial activity and decreasing the cytotoxicity of silver nanoparticles in nanocomposite hydrogel by combining with gold nanoparticles to enhance the ability to kill a high number of liver cancer cells. The structure of the nanocomposite materials was studied using FTIR spectroscopy and XRD patterns, which demonstrated the entrapment of gold and silver nanoparticles within the prepared polymer matrix. Dynamic light scattering data revealed the presence of gold and silver in the nanoscale with the polydispersity indexes in the mid-range values, indicating that distribution systems work best. Swelling experiments at various pH levels revealed that the prepared Cs-g-PAAm/Au-Ag-NPs nanocomposite hydrogels were highly responsive to pH changes. Bimetallic pH-responsive Cs-g-PAAm/Au-Ag-NPs nanocomposites exhibit strong antimicrobial activity. The presence of AuNPs reduced the cytotoxicity of AgNPs while increasing their ability to kill a high number of liver cancer cells.Cs-g-PAAm/Au-Ag-NPs has a high amount of fluorouracil drug loaded at pH 7.4 reaching 95 mg/g with a maximum drug release of 97% within 300 min. Cs-g-PAAm/Au-Ag-NPs have been recommended to use as oral delivery of anticancer drugs because they secure the encapsulated drug in the acidic medium of the stomach and release it in the intestinal pH.

Design of pH-responsive polymeric nanocarrier for targeted delivery of pyrogallol with enhanced antitumor potential in colon cancer.

PURPOSE: To synthesize a polymeric pH-sensitive nanocarrier for the delivery of pyrogallol and investigate the anti-tumor activity of pyrogallol-loaded polymeric nanogel against colon cancer in rats. METHODS: Poly(ethylene glycol)/polyacrylic acid (PEG/PAAc) nanogel was performed using gamma irradiation technique at irradiation doses; 30,40, and 50 kGy. The particle size distribution and diameter were investigated under the influence of various parameters by using dynamic light scattering analysis (DLS). The particle size was diminished by increasing AAc content and irradiation dose. Characterization of the performed nanogel was performed by (FT-IR) and (TEM). In vitro drug release behavior of the nanogel towards pyrogallol drug was assessed. Furthermore, the anti-cancer therapeutic efficiency of pyrogallol loaded PEG/PAAc nanogel was evaluated in a chemically induced colon cancer model in rats. RESULTS: Pyrogallol/PEG/PAAc significantly reduced tumor incidence and volume as compared to DMH group. Also, it activated apoptotic pathway via up-regulating Bax, cytochrome C, cleaved caspase-3, p53, and down-regulating Bcl-2 expression. Furthermore, it attenuated cell cycle progression via reducing Cyclin A, Cyclin D1, and Cyclin E expression. It exhibited anti-proliferative activity through inhibiting PI3K/AKT signaling and downregulating the phosphorylation of AKT. It reduced pro-inflammatory cytokines TNF-α and IL-6. Results were confirmed by histopathological examination of colonic tissue. Interestingly, pyrogallol/PEG/PAAc demonstrated anti-tumor potential more efficiently than free pyrogallol, revealing localized drug delivery. CONCLUSION: This formulation could be considered as a promising agent in the treatment of colon cancer.

Engineered Superabsorbent Nanocomposite Reinforced with Cellulose Nanocrystals for Remediation of Basic Dyes: Isotherm, Kinetic, and Thermodynamic Studies.

In this study, cellulose nanocrystals (CNCs) were produced from pea peels by acid hydrolysis to be used with pectin and acrylic acid (AAc) to form Pectin-PAAc/CNC nanocomposite by γ-irradiation. The structure, morphology, and properties of the nanocomposite were investigated using Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM) techniques. The nanocomposite hydrogel was used for the removal of methylene blue dye (MB) from wastewater. The results revealed that the presence of CNCs in the polymeric matrix enhances the swelling and adsorption properties of Pectin-PAAc/CNC. The optimum adsorbate concentration is 70 mg/L. The kinetic experimental data were fit by pseudo-first-order (PFO), pseudo-second-order (PSO), and Avrami (Avr) kinetic models. It was found that the kinetic models fit the adsorption of MB well where the correlation coefficients of all kinetic models are higher than 0.97. The Avr kinetic model has the lowest ∆qe (normalized standard deviation) value, making it the most suitable one for describing the adsorption kinetics. The adsorption isotherm of MB by Pectin-PAAc follows the Brouers-Sotolongo model while that by Pectin-PAAc/CNC follows the Langmuir isotherm model. The negative values of ∆G confirmed the spontaneous nature of adsorption, and the positive value of ∆H indicated the endothermic nature of the adsorption.

Urtica dioica extracts abolish scopolamine-induced neuropathies in rats.

Alzheimer's disease (AD) is characterized by alterations in monoamines, oxidative stress, and metabolic dysfunctions. We aim to assess the therapeutic impacts of roots or leaf extract from Urtica dioica (UD; stinging nettle) against scopolamine (SCOP)-induced memory dysfunction, amnesia, and oxidative stress in rats. Spatial memory was assessed by Y maze test. Tissue analyses of norepinephrine (NE), dopamine (DA), serotonin (5-HT), malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH, GSSG), AMP, ADP, and ATP were assessed by HPLC. mRNA levels of Tau and Hsp70 were estimated by PCR. UD extracts particularly nettle root (NR) significantly normalized the SCOP-induced memory deficits even more potent than sermion (SR) and donepezil (DON). Similarly, NR had potent therapeutic impacts on the levels of cortical and hippocampal monoamines e.g. DA, NE, and 5-HT. SCOP induced a dramatic oxidative stress as measured by MDA, NO, and GSSG levels; however, UD extracts showed significant anti-oxidative stress impacts. Additionally, UD extracts restored ATP levels and reduced the levels of AMP and ADP compared to SCOP-treated rats. Furthermore, cortical Tau and hippocampal Hsp70 were modulated by UD extracts particularly NR compared to the SCOP group. In conclusion, UD extracts particularly roots have potential therapeutic impacts against SCOP-induced neuroinflammatory and/or Alzheimer-like phenotype in rats.

Over-the-counter analgesic powder use in patients presenting with intracerebral hemorrhage: A case series.

INTRODUCTION: Over-the-counter (OTC) analgesics including aspirin-containing powder formulations (BC Powder, Goody's Powder) (ACPFs) are commonly utilized in the United States. While the ACPFs have been associated with upper gastrointestinal bleeding, we describe a case series of patients presenting with intracerebral hemorrhage (ICH) within 24 hours of ingestion. METHODS: We reviewed all ICH patients presenting to a comprehensive stroke center from September 1, 2014 through June 30, 2016 to identify patients who reported taking BC Powder or Goody's Powder within 7 days of their stroke. Baseline characteristics, medication use, stroke risk factors, clinical imaging, and laboratory testing were reviewed retrospectively. RESULTS: Of 334 patients admitted with ICH during the study period, 6 (2%) reported use of OTC analgesic powders within 1 week of their index stroke. All had consumed at least 1 packet within 24 hours of their ICH. All patients were African American and all except 1 patient were females. Three patients had no identified traditional stroke risk factors and 3 other patients had evidence of mild hypertension history. CONCLUSIONS: Over-the-counter analgesic powders containing high doses of aspirin including BC Powder and Goody's Powder may contribute to ICH in patients with no or minimal risk factors. Providers should inquire about the use of these powders in ICH patients particularly among African Americans.

Radiation preparation of L-arginine/acrylic acid hydrogel matrix patch for transdermal delivery of propranolol HCl in hypertensive rats.

In the present study, L-arginine/acrylic acid (Arg/AAc) batch hydrogel was successfully prepared by gamma irradiation for transdermal delivery of propranolol HCl in hypertensive rats. The resulted system has been characterized by FTIR to confirm the hydrogel formation. The swelling behavior of the prepared hydrogels was investigated as a function of time and pH. The kinetics of swelling has been investigated. In vivo pharmacokinetics evaluation, skin irritation test, and histopathological studies were investigated. Furthermore, the antihypertensive efficacy of transdermal propranolol-loaded Arg/AAc hydrogel on methyl prednisolone acetate-induced hypertensive rats was evaluated. It was found that the prepared patches exhibited a sustained release of the drug into systemic circulation over oral route which is subjected to hepatic first-pass metabolism, coupled with a short plasma half-life. Transdermal administration displayed a prolonged antihypertensive effect in spontaneously hypertensive rats. Moreover, the skin irritation test and histopathological examination indicated that the prepared patches are not irritant and can be safely applied on the skin. These results indicated that the hydrogel system composed of Arg and AAc has potential as a transdermal delivery system.

Early Echocardiography Has a Low Yield in Patients with Transient Ischemic Attack.

STUDY OBJECTIVE: Current guidelines recommend patients presenting with transient ischemic attack (TIA) undergo echocardiography to evaluate for a cardiac source. However, echocardiography is not available daily at many centers. We assessed the yield from early transthoracic echocardiography (TTE) in consecutive patients with TIA evaluated in an emergency department observation unit (EDOU) protocol. METHODS: This observational cohort study took place in an academic medical center from January 1, 2011 to July 31, 2013. Patients seen in the emergency department, assigned to the EDOU for a TIA accelerated diagnostic protocol and discharged with a diagnosis of TIA were included. We retrospectively collected baseline patient characteristics, ABCD2 score, neuroimaging, telemetry, TTE, and 3-month clinical outcomes. RESULTS: Of 236 subjects (mean age 62 ± 15 years, 68% female, 57% African American, 17% with history of stroke, 27% with history of cardiac disease, mean ABCD2 score 3.8 ± 1.5, mean EDOU length of stay 18.6 ± 6.2 hours), abnormal bedside cardiac examination was identified in 19 (8%) patients, abnormal electrocardiogram (ECG)/telemetry in 41 (17%), and abnormal TTE in 64 (27%), 41 of which suggested a patent foramen ovale. Among 136 (58%) patients with no previous cardiac disease or stroke, a normal bedside cardiac examination, and normal ECG/telemetry, TTE identified no high-risk cardiac causes. CONCLUSION: In patients with TIA presenting to an EDOU with no previous cardiac disease or stroke, normal cardiac examination, and normal ECG/telemetry, early TTE had a low yield for identifying high-risk cardiac causes. In EDOUs where TTE is not available daily, outpatient TTE for this patient subgroup may be considered to limit prolonged lengths of stay.

A comparison of physiological and transcriptome responses to water deprivation and salt loading in the rat supraoptic nucleus.

Salt loading (SL) and water deprivation (WD) are experimental challenges that are often used to study the osmotic circuitry of the brain. Central to this circuit is the supraoptic nucleus (SON) of the hypothalamus, which is responsible for the biosynthesis of the hormones, arginine vasopressin (AVP) and oxytocin (OXT), and their transport to terminals that reside in the posterior lobe of the pituitary. On osmotic challenge evoked by a change in blood volume or osmolality, the SON undergoes a function-related plasticity that creates an environment that allows for an appropriate hormone response. Here, we have described the impact of SL and WD compared with euhydrated (EU) controls in terms of drinking and eating behavior, body weight, and recorded physiological data including circulating hormone data and plasma and urine osmolality. We have also used microarrays to profile the transcriptome of the SON following SL and remined data from the SON that describes the transcriptome response to WD. From a list of 2,783 commonly regulated transcripts, we selected 20 genes for validation by qPCR. All of the 9 genes that have already been described as expressed or regulated in the SON by osmotic stimuli were confirmed in our models. Of the 11 novel genes, 5 were successfully validated while 6 were false discoveries.

Adsorption and desorption of phosphate and nitrate ions using quaternary (polypropylene-g-N,N-dimethylamino ethylmethacrylate) graft copolymer.

Study has been made on the preparation of functionalized copolymer by grafting N,N-(dimethylaminoethyl) methacrylate (DMAEMA) onto polypropylene (PP) films using gamma-irradiation technique. The effect of monomer concentration and irradiation dose on the grafting yield was studied. It was found that grafting yield increases with increasing the monomer concentration and irradiation dose. Subsequent quaternization of the amine group of PDMAEMA graft chain using different reagents, 1-bromo octadecane, methyl iodide and benzyl chloride, to improve their ionic character was carried out. The grafted PP films were characterized by IR spectroscopy, and mechanical and thermal properties. During the adsorption of phosphate (PO(4)(3-)) and nitrate (NO(3)(-)) ions, the rate of adsorption, pH effect, desorbability and initial feed concentration effect were investigated. It was found that the adsorption of PO(4)(3-) and NO(3)(-) ions increases with increasing the adsorption time up to 10h and decreases with increasing the pH of medium. The desorbability is ranging from 18 to 30%, and it is relatively difficult to desorb PO(4)(3-) and NO(3)(-) ions from the functionalized grafted copolymers. Results showed good possibility for the use of such functionalized grafted film in the field of removal of some anions such as PO(4)(3-) and NO(3)(-) from their media.