Novel 5-oxo-hexahydroquinoline derivatives: design, synthesis, in vitro P-glycoprotein-mediated multidrug resistance reversal profile and molecular dynamics simulation study

Overexpression of the efflux pump P-glycoprotein (P-gp) is one of the important mechanisms of multidrug resistance (MDR) in many tumor cells. In this study, 26 novel 5-oxo-hexahydroquinoline derivatives containing different nitrophenyl moieties at C-4 and various carboxamide substituents at C-3 were designed, synthesized and evaluated for their ability to inhibit P-gp by measuring the amount of rhodamine 123 (Rh123) accumulation in uterine sarcoma cells that overexpress P-gp (MES-SA/Dx5) using flow cytometry. The effect of compounds with highest MDR reversal activities was further evaluated by measuring the alterations of MES-SA/Dx5 cells' sensitivity to doxorubicin (DXR) using MTT assay. The results of both biological assays indicated that compounds bearing 2-nitrophenyl at C-4 position and compounds with 4-chlorophenyl carboxamide at C-3 demonstrated the highest activities in resistant cells, while they were devoid of any effect in parental nonresistant MES-SA cells. One of the active derivatives, 5c, significantly increased intracellular Rh123 at 100 mu M, and it also significantly reduced the IC50 of DXR by 70.1% and 88.7% at 10 and 25 mu M, respectively, in MES-SA/Dx5 cells. The toxicity of synthesized compounds against HEK293 as a noncancer cell line was also investigated. All tested derivatives except for 2c compound showed no cytotoxicity. A molecular dynamics simulation study was also performed to investigate the possible binding site of 5c in complex with human P-gp, which showed that this compound formed 11 average H-bonds with Ser909, Thr911, Arg547, Arg543 and Ser474 residues of P-gp. A good agreement was found between the results of the computational and experimental studies. The findings of this study show that some 5-oxo-hexahydroquinoline derivatives could serve as promising candidates for the discovery of new agents for P-gp-mediated MDR reversal

Laboratory Tests and Field Surveys to Explore the Optimum Frequency for GPR Surveys in Detecting Qanats

In this paper, we discuss the results of laboratory tests and field surveys using ground penetrating radar (GPR) method to detect qanats at the main campus of Shahid Bahonar University of Kerman (SBUK), Iran. The main purpose of laboratory experiments was to explore the optimum frequency of GPR surveys to detect qanats for the subsoil in the study site. We performed a variety of laboratory tests with a 3 GHz antenna to detect qanats (simulated using dielectric empty targets) hosted by sand with volumetric water content (VWC) values in the range 1.5-8%. The depth to each target was progressively increased until either approaching the edges of the sandbox or modelling a qanat depth for which GPR data could not detect the target anymore. The scaling factors were calculated for each test to estimate the maximum depth of detecting qanats as a function of the scaled GPR frequency. The results showed that in areas where the subsoil is dominated by sand, medium-frequency GPR antennas can penetrate to depths of a few tens of meters, but the penetration depth considerably decreases when the soil moisture and/or clay content of the medium increase. Based on the results of laboratory simulations, qanats are detectable at a maximum normalized depth of about 15-17 times of the wavelengths in very dry sands with VWC less than 5% while the detectable range rapidly drops down to less than 3 or 4 times of the wavelengths in more humid sands with VWC of about 8%. We also discuss the results of a few field GPR surveys that were measured using antennas with the 50 MHz and the 250 MHz frequencies in the northwestern part of the study area. The processed GPR images could detect a qanat in the position compatible with the results of previous remote sensing studies performed in the area. The depth to the detected qanat is 13.5 m, which is a little bit beyond the maximum limit predicted by the laboratory tests

Short-term Results of Using Injectable Bone Cement Technique in the Treatment of Unstable Distal Radius Fractures

Abstract: Background & Aims: Treatment of osteoporotic distal radius fracture with metaphyseal defect is often complicated by secondary displacement, because of posterior cortex comminution. The aim of this study was to investigate functional outcomes and advantages of injection of bone cement in stabilizing and maintaining this fracture reduction. Methods: This prospective study was performed on 20 patients aged fifty years and older. After primary reduction and bone cement injection into metaphyseal void through minimal dorsal distal forearm incision, a short arm cast was applied for 3 weeks. Then the cast was removed and free use of the wrist was begun. Patients were assessed after 6 weeks, 3 months and 6 months in regard to active wrist range of motion, pain score, grip strength, DASH score, modified Mayo wrist score and standard radiographic parameters. Results: The patients included 3 men and 17 women with the mean age of 67 years old. According to the AO classification, there were seventeen type-A3 and three type-C2 distal radius fractures. At final follow up, the active range of motion of the injured side relative to uninjured side averaged 91% of flexion, 93% of extension, 91% of radial deviation, 93% of ulnar deviation, 98% of pronation and 99% of supination. Mean DASH score was 4.4. Grip strength was 90% of the uninjured side. According to the modified Mayo wrist score, there were fourteen excellent and six good results. Mean final radiographic parameters were 10° of volar angle, 24° of radial inclination, 10 mm of radial length, 1 mm of ulnar variance, and 0.3 mm of intraarticular gap. Each of median nerve hyposthesia due to compression before reduction, loss of reduction, soft tissue cement deposit and reflex sympathetic dystrophy, occurred in one patient. None of the patients had further complications. Conclusion: According to the results, injection of bone cement in osteoporotic unstable distal radius fracture can be considered a safe and effective treatment method; it causes clinical functional improvement and rapid rehabilitation with little complications. Keywords: Radius fractures, Osteoporosis, Bone cement

Paradox of Modern Pregnancy: A Phenomenological Study of Women's Lived Experiences from Assisted Pregnancy

The purpose of our study was describing the meaning of pregnancy through Assisted Reproductive Technologies (ARTs). A qualitative design with hermeneutic phenomenology approach was selected to carry out the research. Semistructured in-depth interviews were conducted with 12 women who experienced assisted pregnancy. Three themes emerged from women's experience including finding peace in life, paradoxical feelings, and struggling to realize a dream. We concluded that pregnancy is the beginning of a new and hard struggle for women with fertility problems. The findings of our study resulted in helpful implications for the health care professionals managing assisted pregnancies. Copyright © 2015 Fahimeh Ranjbar et al

Point source generation of chiral fields:measures of near- and far-field optical helicity

To consider the relationship between different measures of chirality in an optical field, the simplest case is considered: direct spontaneous emission of circularly polarized light by a point source. In the electromagnetic fields radiated from a suitably chiral source, such as a low-symmetry chiral molecule undergoing radiative decay, optical helicity is exhibited in the extent of a difference in left- and right-handed circular polarization components. There are several practical measures for quantifying the emergence of ensuing optical helicity, exhibiting different forms of dependence on the properties of the emitter and the positioning of a detector. By casting each measure in terms of an irreducible helicity density, connections and distinctions can be drawn between results expressible in either classical or quantum form

Rapid and Green Synthesis of some Benzothiazole-, Benzimidazole-and Benzoxazole-2-thiol Derivatives Using Copper Sulfate in Aqueous Media

In this study an easy, green, efficient and simple approach is reported for the synthesis of some benzothiazole-, benzimidazole-and benzoxazole-2-thiol derivatives. The proposed approach employs the reaction of corresponding aromatic amine with potassium isopropyl xanthate (Z11) in the presence of copper sulfate (CuSO 4 ) as a catalyst under conventional heating and ultrasonic irradiation. The advantages of this protocol are: using water and glycerol as green solvents, commercially available precursors, simple work-up, an inexpensive catalyst, high yield and short reaction time

A combined hydrogen storage system of Mg(BH4)(2)-LiNH2 with favorable dehydrogenation

The decomposition properties of Mg(BH4)2−LiNH2 mixtures were investigated. Apparent NH3 release appeared from 50 to 300 °C for the Mg(BH4)2−LiNH2 mixtures with mole ratios of 1:1.5, 1:2, and 1:3, while only hydrogen release was detected for the mixture with a mole ratio of 1:1. In the case of the Mg(BH4)2−LiNH2 (1:1) sample, the onset of the first-step dehydrogenation starts at 160 °C, with a weight loss of 7.2 wt % at 300 °C, which is improved significantly compared to the pure Mg(BH4)2 alone. From Kissinger’s method, the activation energy, Ea, for the first and second step dehydrogenation in Mg(BH4)2−LiNH2 (1:1) was estimated to be about 121.7 and 236.6 kJ mol−1, respectively. The improved dehydrogenation in the combined system may be ascribed to a combination reaction between [BH4] and [NH2], resulting in the formation of Li−Mg alloy and amorphous B−N compound