Investigation of the Effects of Dioctyl Sulfosuccinate on the Photodegradation of Benzo[a]Pyrene in Aqueous Solutions under Various Wavelength Regimes.

Due to the relatively high concentrations of polycyclic aromatic hydrocarbons (PAHs) in oil samples, oil spills in aquatic ecosystems release significant amounts of PAHs. Although remediation efforts often take place during or immediately after an oil spill incident, a portion of the released PAHs remains in the body of water. A natural phenomenon resulting from the direct exposure of PAHs to sunlight is photodegradation. This article investigates the effect of dioctyl sulfosuccinate (DOSS) on the photodegradation of benzo[a]pyrene (BaP), the most toxic PAH in the priority pollutants list of the US Environmental Protection Agency (EPA). DOSS is a surfactant typically used in the remediation of oil spills. Three lamps with maximum emission wavelengths at 350 nm, 419 nm, and 575 nm were individually and simultaneously used to irradiate aqueous solutions of BaP in the absence and the presence of DOSS. When irradiated with the 419 nm lamp or the 575 lamp, BaP showed no photodegradation. Upon irradiation with the 350 nm lamp and with the simultaneous use of the three lamps, the photodegradation of BaP followed first-order kinetics. Independent of the irradiation wavelength, the presence of DOSS increased the half-life of BaP in the aqueous solution. In the case of the 350 nm lamp, the rate constant of photodegradation in the absence and the presence of DOSS varied from (3.79 ± 0.97) × 10-3 min-1 to (1.10 ± 0.13) × 10-3 min-1, respectively. Under simultaneous irradiation with the lamps, the rate constant of photodegradation varied from (1.12 ± 0.35) × 10-3 min (no DOSS) to (3.30 ± 0.87) × 10-4 (with DOSS). Since the largest rate constants of photodegradation were observed in the absence of DOSS, the longer half-lives of BaP in the presence of surfactant were attributed to the incorporation of PAH molecules into the DOSS micelles.

Costimulatory Molecules OX40 and OX40L Upregulation in Oral Squamous Cell Carcinoma: A Blood-Based Study.

OBJECTIVES: This research aimed to determine OX40 and OX40L mRNA expression in blood samples of naive oral squamous cell carcinoma (OSCC) patients in different histological grades and clinical stages. The in silico analysis was performed using the STRING database for functional association and a better understanding of the interactions of OX40 and its ligand with other proteins. MATERIALS AND METHODS: In this study, we recruited 141 newly diagnosed patients of OSCC. Levels of OX40 and OX40L mRNA expression were explored using real-time quantitative polymerase chain reaction. An in silico tool was also utilized to evaluate the OX40/OX40L interactome. RESULTS: The results showed higher OX40 expressional levels in the late stage (23-fold) compared with the early stage (8.5-fold) (p = < 0.001). A similar trend was seen in OX40L mRNA expression, revealing a fold change of 5.8 in the early stage in comparison to 9.9-fold change in the late stage (p = < 0.001). Overexpression of OX40 and OX40L was found in different histological grades (p = 0.005 and p = < 0.001, respectively). Overexpression of OX40 and OX40L was detected in habits such as smoking and paan intake, whereas statistically significant upregulation was observed in the cheek, lip, and alveolus tumors. However, there was no substantial difference in OX40 and OX40L expression based on age or gender. The functional interactions, that is, interactomes of OX40 and OX40L with other proteins have been determined by in silico analysis. CONCLUSION: Based on current study findings, despite OX40 and OX40L upregulation in newly diagnosed OSCC patients, it is speculated that the physiological function of these molecules is altered due to immune system exhaustion.

Enhanced Antidepressant Activity of Nanostructured Lipid Carriers Containing Levosulpiride in Behavioral Despair Tests in Mice.

The potential of levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for enhanced antidepressant and anxiolytic effects was evaluated in the current study. A forced swim test (FST) and tail suspension test (TST) were carried out to determine the antidepressant effect whereas anxiolytic activity was investigated using light-dark box and open field tests. Behavioral changes were evaluated in lipopolysaccharide-induced depressed animals. The access of LSP to the brain to produce therapeutic effects was estimated qualitatively by using fluorescently labeled LSP-NLCs. The distribution of LSP-NLCs was analyzed using ex vivo imaging of major organs after oral and intraperitoneal administration. Acute toxicity studies were carried out to assess the safety of LSP-NLCs in vivo. An improved antidepressant effect of LSP-NLCs on LPS-induced depression showed an increase in swimming time (237 ± 51 s) and struggling time (226 ± 15 s) with a reduction in floating (123 ± 51 s) and immobility time (134 ± 15 s) in FST and TST. The anxiolytic activity in the light-dark box and open field tests exhibited superiority over LSP dispersion. Near-infrared images of fluorescently labeled LSP-NLCs demonstrated the presence of coumarin dye in the brain after 1 h of administration. An acute toxicity study revealed no significant changes in organ-to-body weight ratio, serum biochemistry or tissue histology of major organs. It can be concluded that nanostructured lipid carriers can efficiently deliver LSP to the brain for improved therapeutic efficacy.

Augmented Oral Bioavailability and Prokinetic Activity of Levosulpiride Delivered in Nanostructured Lipid Carriers.

The present study is aimed to develop and optimize levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for improving oral bioavailability and prokinetic activity of LSP. LSP-NLCs were optimized with D-optimal mixture design using solid lipid, liquid lipid and surfactant concentrations as independent variables. The prepared LSP-NLCs were evaluated for physicochemical properties and solid-state characterization. The in vivo oral pharmacokinetics and prokinetic activity of LSP-NLCs were evaluated in rats. LSP-NLCs formulation was optimized at Precirol® ATO 5/Labrasol (80.55/19.45%, w/w) and Tween 80/Span 80 concentration of 5% (w/w) as a surfactant mixture. LSP-NLCs showed a spherical shape with a particle size of 152 nm, a polydispersity index of 0.230 and an entrapment efficiency of 88%. The DSC and PXRD analysis revealed conversion of crystalline LSP to amorphous state after loading into the lipid matrix. LSP-NLCs displayed a 3.42- and 4.38-flods increase in AUC and Cmax after oral administration compared to LSP dispersion. In addition, LSP-NLCs showed enhanced gastric emptying (61.4%), intestinal transit (63.0%), and fecal count (68.8) compared to LSP dispersion (39.7%, 38.0% and 51.0, respectively). Taken together, these results show improved oral bioavailability and prokinetic activity of LSP-NLCs and presents a promising strategy to improve therapeutic activity of LSP for efficient treatment of gastric diseases.

Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability.

Poor aqueous solubility of eplerenone (EPL) is a major obstacle to achieve sufficient bioavailability after oral administration. In this study, we aimed to develop and evaluate eplerenone nanocrystals (EPL-NCs) for solubility and dissolution enhancement. D-optimal combined mixture process using Design-Expert software was employed to generate different combinations for optimization. EPL-NCs were prepared by a bottom-up, controlled crystallization technique during freeze-drying. The optimized EPL-NCs were evaluated for their size, morphology, thermal behavior, crystalline structure, saturation solubility, dissolution profile, in vivo pharmacokinetics, and acute toxicity. The optimized EPL-NCs showed mean particle size of 46.8 nm. Scanning electron microscopy revealed the formation of elongated parallelepiped shaped NCs. DSC and PXRD analysis confirmed the crystalline structure and the absence of any polymorphic transition in EPL-NCs. Furthermore, EPL-NCs demonstrated a 17-fold prompt increase in the saturation solubility of EPL (8.96 vs. 155.85 µg/mL). The dissolution rate was also significantly higher as indicated by ∼95% dissolution from EPL-NCs in 10 min compared to only 29% from EPL powder. EPL-NCs improved the oral bioavailability as indicated by higher AUC, Cmax, and lower Tmax than EPL powder. Acute oral toxicity study showed that EPL-NCs do not pose any toxicity concern to the blood and vital organs. Consequently, NCs prepared by controlled crystallization technique present a promising strategy to improve solubility profile, dissolution velocity and bioavailability of poorly water-soluble drugs.

Colouterine fistula with a foreign body.

Foreign bodies in vagina are known to have been inserted by the patient herself or by some other person; as an aid to masturbation, sexual intercourse or sexual assault. The two most common items retained in adult females are tampons and burst condoms. Since long, vaginal deliveries and Obstetric and Gynaecological interventions have been associated with vesicovaginal and rectovaginal fistulae. We present a case of a 24 years old Pakistani woman with a colouterine fistula. Although vesicouterine fistulae have rarely been reported previously, world-literature has only a few documented cases of colouterine fistula.

Low-temperature time-resolved phosphorescence excitation emission matrices for the analysis of phenanthro-thiophenes in chromatographic fractions of complex environmental extracts.

The present study investigates the analytical potential of low-temperature photoluminescence spectroscopy for the analysis of seven phenanthrothiophenes with molecular mass 234 g mol-1. The studied PASHs include Phenanthro [1,2-b]thiophene, Phenanthro [2,1-b]thiophene, Phenanthro [2,3-b]thiophene, Phenanthro [3,2-b]thiophene, Phenanthro [3,4-b]thiophene, Phenanthro [4,3-b]thiophene and Phenanthro [9,10-b]thiophene. Excitation and emission spectra recorded from n-alkane solutions at room temperature, 77 K and 4.2 K show phosphorescence emission from all the studied isomers at cryogenic temperatures. The analytical figures of merit obtained under steady state (fluorescence) and time-resolved (phosphorescence) conditions provide limits of detection at the parts-per-billion (ng mL-1) concentration levels. Processing 77 K and 4.2 K phosphorescence data with parallel factor analysis showed to be a robust approach to the determination of phenanthro-thiophenes in complex fluorophore mixtures.

Potential and Applications of Nanocarriers for Efficient Delivery of Biopharmaceuticals.

During the past two decades, the clinical use of biopharmaceutical products has markedly increased because of their obvious advantages over conventional small-molecule drug products. These advantages include better specificity, potency, targeting abilities, and reduced side effects. Despite the substantial clinical and commercial success, the macromolecular structure and intrinsic instability of biopharmaceuticals make their formulation and administration challenging and render parenteral delivery as the only viable option in most cases. The use of nanocarriers for efficient delivery of biopharmaceuticals is essential due to their practical benefits such as protecting from degradation in a hostile physiological environment, enhancing plasma half-life and retention time, facilitating absorption through the epithelium, providing site-specific delivery, and improving access to intracellular targets. In the current review, we highlight the clinical and commercial success of biopharmaceuticals and the overall applications and potential of nanocarriers in biopharmaceuticals delivery. Effective applications of nanocarriers for biopharmaceuticals delivery via invasive and noninvasive routes (oral, pulmonary, nasal, and skin) are presented here. The presented data undoubtedly demonstrate the great potential of combining nanocarriers with biopharmaceuticals to improve healthcare products in the future clinical landscape. In conclusion, nanocarriers are promising delivery tool for the hormones, cytokines, nucleic acids, vaccines, antibodies, enzymes, and gene- and cell-based therapeutics for the treatment of multiple pathological conditions.

Synthesis of 9-Aminoacridine Derivatives as Anti-Alzheimer Agents.

In the present study, some 9-aminoacridine derivatives have been synthesized by condensation of 9-aminoacridine with substituted phenacyl, benzoyl, and benzyl halides (RM1-RM6). Compounds were investigated for acetylcholinesterase and butyrylcholinesterase inhibition potential, considering these enzymes playing a key role in Alzheimer's disease. All derivatives showed better inhibition of enzymes than the standard galantamine, whereas except RM4, all exhibit better results than tacrine, a well-known acridine derivative used for the treatment of Alzheimer's disease.