The direct actions of cannabidiol and 2-arachidonoyl glycerol at GABAA receptors.

Cannabidiol (CBD) is a major non-intoxicating component of cannabis and possesses anti-epileptic, anxiolytic and anti-hyperalgesic properties. The mechanism of action of CBD in producing such effects remains unclear. Despite evidence that some endogenous and synthetic cannabinoids interact with GABAA receptors, no-one has yet investigated the effects of CBD. Here we used two-electrode voltage clamp electrophysiology to compare the actions of CBD with those of the major central endocannabinoid, 2-arachidonoyl glycerol (2-AG) on human recombinant GABAA receptors (synaptic α1-6ßγ2 and extrasynaptic α4ß2δ) expressed on Xenopus oocytes. CBD and 2-AG were positive allosteric modulators at α1-6ßγ2 receptors, with low micromolar potencies. The maximal level of enhancement seen with either CBD or 2-AG were on α2-containing GABAA receptor subtypes, with approximately a 4-fold enhancement of the GABA EC5 evoked current, more than twice the potentiation seen with other α-subunit receptor combinations. Further we observed ß-subunit selectivity, whereby modulatory activity was higher at ß2/ß3 over ß1 subunits. The ß1-subunit homologous mutant ß2(V436T) substantially diminished the efficacy of both drugs to a third of that obtained with wild-type ß2 subunit combinations, but without changing potency. The potency of CBD increased and efficacy preserved in binary α1/α2ß2 receptors indicating that their effects do not involve the classic benzodiazepine site. Exploration of extrasynaptic α4ß2δ receptors revealed that both compounds enhanced GABA EC5 evoked currents at concentrations ranging from 0.01-1µM. Taken together these results reveal a mode of action of CBD on specifically configured GABAA receptors that may be relevant to the anticonvulsant and anxiolytic effects of the compound.

Direct NMR evidence of phase solitons in the spin ground state of overdoped manganites.

Charge ordering phenomena in overdoped La1-xCaxMnO3 (LCMO) manganites with x>or=0.5 are generally believed to be associated with the formation of charge stripes composed of alternating Mn3+ and Mn4+ charges. However, a number of recent experiments indicate that instead of stripes the charge in these systems is spatially organized in a uniform charge density wave. At the same time theory predicts that the ground state is modulated by an incommensurate (IC) orbital and charge soliton lattice. Here, by using nuclear magnetic resonance we provide the first direct evidence that the spin ground state in overdoped LCMO manganites is IC modulated with phase solitons. At higher temperatures the solitonic superstructure is replaced by a uniform spin-density wave, subjected to coherent slow fluctuations, showing a striking similarity with slow fluctuations in the striped phase of high T{c} cuprates and nickelates.

Ciprofloxacin conjugated to diphenyltin(IV): a novel formulation with enhanced antimicrobial activity.

The metalloantibiotic of formula Ph2Sn(CIP)2 (CIPTIN) (HCIP = ciprofloxacin) was synthesized by reacting ciprofloxacin hydrochloride (HCIP·HCl) (an antibiotic in clinical use) with diphenyltin dichloride (Ph2SnCl2DPTD). The complex was characterized in the solid state by melting point, FT-IR, X-ray Powder Diffraction (XRPD) analysis, 119Sn Mössbauer spectroscopy, X-ray Fluorescence (XRF) spectroscopy, and Thermogravimetry/Differential Thermal Analysis (TG-DTA) and in solution by UV-Vis, 1H NMR spectroscopic techniques and Electrospray Ionisation Mass Spectrometry (ESI-MS). The crystal structure of CIPTIN and its processor HCIP was also determined by X-ray crystallography. The antibacterial activity of CIPTIN, HCIP·HCl, HCIP and DPTD was evaluated against the bacterial species Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis), by the means of Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Inhibition Zones (IZs). CIPTIN shows lower MIC values than those of HCIP·HCl (up to 4.2-fold), HCIP (up to 2.7-fold) or DPTD (>135-fold), towards the tested microbes. CIPTIN is classified into bactericidal agents according to MBC/MIC values. The developing IZs are 40.8 ± 1.5, 34.0 ± 0.8, 36.0 ± 1.1 and 42.7 ± 0.8 mm, respectively which classify the microbes P. aeruginosa, E. coli, S. aureus and S. epidermidis to susceptible ones to CIPTIN. These IZs are greater than the corresponding ones of HCIP·HCl by 1.1 to 1.5-fold against both the tested Gram negative and Gram positive bacteria. CIPTIN eradicates the biofilm of P. aeruginosa and S. aureus more efficiently than HCIP·HCl and HCIP. The in vitro toxicity and genotoxicity of CIPTIN were tested against human skin keratinocyte cells (HaCaT) (IC50 = 2.33 µM). CIPTIN exhibits 2 to 9-fold lower MIC values than its IC50 against HaCaT, while its genotoxic effect determined by micronucleus assay is equivalent to the corresponding ones of HCIP·HCl or HCIP.

Interaction of Et2SnCl2 with 5'-IMP and 5'-GMP.

The interactions of Et2SnCl2 with 5'-IMP and 5'-GMP have been studied in aqueous solutions by 1H- and 31P-NMR spectroscopy as a function of pH. At low pH values (< 4.0) Sn(IV) interacts with the pyrophosphate oxygens of these nucleotides. At intermediate pH values (4-9.5) no interaction of the metal with the nucleotides take place, while at pH > 9.5 the sugar O'2 and O'3 atoms are the preferred coordination sites. In addition, the solid adducts obtained from aqueous solutions at pH = 3-4 of the above interactions correspond to formulae; (Et2Sn)2(5'-IMP)2(H2O) and (Et2Sn)3(5'-GMP)2(OH)2(H2O)2 as their elemental analysis show. IR spectra and solid state 13C, 31P-NMR spectra 119Sn Mössbauer and solution 119Sn-NMR spectra once more confirm the pyrophosphate involvement in bonding with Sn(IV) in oligomeric or polymeric structures and trigonal bipyramidal or octahedral geometries.

Caregiving tasks among family caregivers of patients with lung cancer.

PURPOSE/OBJECTIVES: To describe family caregivers' perceptions of time spent and difficulty experienced with performing specific caregiving tasks for patients with lung cancer. To compare adult child and spousal caregivers in relation to time and difficulty of tasks. DESIGN: A secondary analysis of data from a study using a cross-sectional, descriptive, comparison design. SETTING: A university outpatient oncology center, two veterans administration outpatient clinics, and a private outpatient oncology practice. SAMPLE: 78 family caregivers of patients with lung cancer (62 spouses and 16 adult children). METHODS: Data that previously had been collected using a structured interview guide were analyzed using descriptive statistics, comparison of item means, and multivariate analysis of variance. MAIN RESEARCH VARIABLES: Time and difficulty with caregiving tasks. FINDINGS: The most time-consuming tasks for adult children and spouses were providing emotional support, transportation, and monitoring symptoms. The most difficult duties were emotional support, behavioral management, monitoring symptoms, and household tasks. Time and difficulty of tasks did not differ significantly between adult child and spousal caregivers. CONCLUSIONS: Some caregivers may require guidance in providing transportation, emotional support, behavioral management, and symptom management. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can make a significant impact in assisting family members in providing care by addressing the provision of transportation, emotional support, behavioral management, and symptom management.

Structural, static and dynamic magnetic properties of dextran coated γ-Fe(2)O(3) nanoparticles studied by (57)Fe NMR, Mössbauer, TEM and magnetization measurements.

The structural and magnetic properties and spin dynamics of dextran coated and uncoated γ-Fe(2)O(3) (maghemite) nanoparticles have been investigated using high resolution transmission electron microscopy (HRTEM), (57)Fe nuclear magnetic resonance (NMR), Mössbauer spectroscopy and dc magnetization measurements. The HRTEM observations indicated a well-crystallized system of ellipsoid-shaped nanoparticles, with an average size of 10 nm. The combined Mössbauer and magnetic study suggested the existence of significant interparticle interactions not only in the uncoated but also in the dextran coated nanoparticle assemblies. The zero-field NMR spectra of the nanoparticles at low temperatures are very similar to those of the bulk material, indicating the same hyperfine field values at saturation in accord with the performed Mössbauer measurements. The T(2) NMR spin-spin relaxation time of the nanoparticles has also been measured as a function of temperature and found to be two orders of magnitude shorter than that of the bulk material. It is shown that the thermal fluctuations in the longitudinal magnetization of the nanoparticles in the low temperature limit may account for the shortening and the temperature dependence of the T(2) relaxation time. Thus, the low temperature NMR results are in accord with the mechanism of collective magnetic excitations, due to the precession of the magnetization around the easy direction of the magnetization at an energy minimum, a mechanism originally proposed to interpret Mössbauer experiments in magnetic nanoparticles. The effect of the surface spins on the NMR relaxation mechanisms is also discussed.

Synthesis, structural characterization and in vitro inhibitory studies against human breast cancer of the bis-(2,6-di-tert-butylphenol)tin(IV) dichloride and its complexes.

Four new organotin(IV) complexes of bis-(2,6-di-tert-butylphenol)tin(IV) dichloride [(tert-Bu-)(2)(HO-Ph)](2)SnCl(2) (1) with the heterocyclic thioamides 2-mercapto-pyrimidine (PMTH), 2-mercapto-4-methyl-pyrimidine (MPMTH), 2-mercapto-pyridine (PYTH) and 2-mercapto-benzothiazole (MBZTH), of formulae {[(tert-Bu-)(2)(HO-Ph)](2)Sn(PMT)(2)} (2), {[(tert-Bu-)(2)(HO-Ph)](2)Sn(MPMT)(2)} (3), {[(tert-Bu-)(2)(HO-Ph)](2)SnCl(PYT)} (4) and {[(tert-Bu-)(2)(HO-Ph)](2)SnCl(MBZT)} (5), have been synthesized and characterized by elemental analysis, (1)H-, (13)C-, (119)Sn-NMR, EPR, FT-IR, Raman and Mössbauer spectroscopic techniques. The crystal and molecular structures of compounds 1­5 have been determined by X-ray diffraction. The geometries around the metal center adopted in complexes 1­5 varied between tetrahedral in 1, trigonal bipyramidal in 3, 4, 5 and distorted octahedral in 2. Two carbon atoms from aryl groups and two chlorine atoms form a distorted tetrahedron in the case of 1. Two carbon, two sulfur and two nitrogen atoms from thione ligands form a distorted octahedral geometry around tin(IV) with trans-C(2), cis-N(2), cis-S(2)-configurations in 2. However, in the case of 4 and 5 complexes two carbon, one sulfur, one nitrogen and one chloride atom form a distorted trigonal bipyramidal arrangement. Finally, in the case of 3 the trigonal bipyramidal geometry is achieved by two carbon, two sulfur and one nitrogen atom in a unique coordination mode of thioamides toward the tin(IV) cation. Compounds 1­5 were tested for their in vitro cytotoxicity against the human breast adenocarcinoma (MCF-7) cell line. Compound 3 exhibits strong cytotoxic activity against MCF-7 cells (IC(50) = 0.58 ± 0.1 µM).

Poststroke depression and treatment effects on functional outcomes.

BACKGROUND: Poststroke depression (PSD) is common after stroke; however, the relationship to poststroke function is inconclusive. Our objectives were to 1) determine the relationship between PSD at baseline (1 month poststroke) and function (12 weeks later) and 2) assess the impact of depression improvement on 12-week function among those with depression at baseline. METHODS: We completed a secondary analysis of data from a cohort study of participants with and without PSD. We used logistic regression to identify factors associated with 12-week functional dependence for 1) all 367 participants and 2) the 174 participants with PSD. RESULTS: In the PSD cohort, 3 characteristics were found to be independently associated with 12-week dependence: increased medical comorbidity (odds ratio [OR] 1.10, 95%confidence interval [CI] 1.02-1.22), increased stroke severity (OR 1.42, 95% CI 1.19-1.69), and increased baseline depression severity (OR 1.13, 95% CI 1.03-1.23). Depression severity was significantly different between those considered dependent and independent at 12 weeks (entire cohort, PHQ-9 7.31 vs 5.18, p = 0.008; depressed cohort, PHQ-9 9.94 vs 7.27, p = 0.019). CONCLUSION: Among study participants with PSD, the severity of depression symptoms at baseline was associated with dependence; however, our results are inconclusive as to whether improvement of depression is independently associated with functional recovery at 12 weeks. Even if the treatment and improvement of PSD does not directly influence functional recovery poststroke, it is essential for PSD to be identified and treated due to its high symptom burden and association with other negative health and social outcomes.

Synthesis, structural characterization and biological studies of the triphenyltin(IV) complex with 2-thiobarbituric acid.

The reaction between 2-thiobarbituric acid (H(2)TBA), which was treated with an equimolar amount of potassium hydroxide, in a water with triphenytin chloride in methanol, results in the formation of the {[Ph(3)Sn(O-HTBA)]}(n) (1) complex. Crystals of the hydrated 1 with formula {[Ph(3)Sn(O-HTBA)]·0.7(H(2)O)}(n) were growth from methanol/acetonitrile solution, of the white precipitation, filtered off, from the reaction. The crystal structure of complex 1 has been determined by X-ray diffraction at 120 K. Complex 1 is polymeric. The geometry around the tin(IV) ions is trigonal bi-pyramidal with coordination to three C atoms from phenyl groups and one O atom from a de-protonated HTBA ligand. Complex 1 and the already known [(n-Bu)(3)Sn(O-HTBA)·H(2)O] (2) were evaluated for their in vitro cytotoxic activity (cell viability) against human cancer cell lines: HeLa (cervical), OAW-42 (ovarian), MCF-7 (breast, ER positive), MDA-MB-231 (breast, ER negative), A549 (lung), Caki-1 (renal) and additionally, the normal human lung cell line MRC-5 (normal human fetal lung fibroblast cells) and normal immortalized human mammary gland epithelial cell line MTSV17 with a Trypan Blue assay. Moreover complex 1 was evaluated for its in vitro cell growth proliferation activity against leiomyosarcoma cells (LMS), MCF-7 and MRC-5 cells with a Thiazolyl Blue Tetrazolium Bromide (MTT) assay. The type of cell death caused by complexes 1 and 2 was also evaluated by use of flow cytometry assay. The results showed that these compounds mediate a strong cytotoxic response to normal and cancer cell lines tested through apoptosis and induce cell cycle arrest in S phase of the cell cycle, suggesting DNA intercalation (direct or indirect) with the complexes. Finally, the influence of these complexes 1 and 2 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied.

Development and psychometric testing of the Bakas Caregiving Outcomes Scale.

BACKGROUND: Family caregivers of stroke survivors experience more depression, emotional problems, social inactivity, and general ill-health than noncaregiving individuals. While a number of instruments measure these variables in family caregivers, they are often too global, indicating the need for a situation-specific instrument measuring life changes resulting from providing care. OBJECTIVES: To develop and psychometrically test the Bakas Caregiving Outcomes Scale (BCOS) measuring changes in family caregiving outcomes in the stroke population. METHOD: 48 items were developed, with 27 being judged as content valid by a panel of five experts. Psychometric testing with two convenience samples of family caregivers of stroke survivors (ns = 92, 104) was conducted using item analysis, Cronbach's alpha, factor analysis, and hierarchical multiple regression. RESULTS: Item analysis in sample no. 1 resulted in a 12-item scale with alpha = .90. The scale was further shortened to a 10-item scale in sample no. 2 with alpha = .77. Unidimensionality was supported by factor analysis in both samples. Using hierarchical multiple regression, 63% of the variance of the 12-item BCOS in sample no. 1, and 45% of the variance of the 10-item BCOS in sample no. 2 was accounted for by the constructs in the conceptual model. Criterion-related validity was supported in both samples by significant correlations with the LIFE-3 and a criterion variable with the same response format as the BCOS. Significant BCOS correlations with the SF-36 Health Survey subscales in sample no. 2 provided further evidence of criterion-related validity. CONCLUSION: The 10-item BCOS is a brief, easy to administer instrument that has evidence of reliability and validity in family caregivers of stroke survivors. The 10-item BCOS could serve as a valuable measure in research, as well as an assessment tool to identify family caregivers in need of intervention.

Effective caregiving approaches for patients with Alzheimer's disease.

To address the need for nonpharmacologic approaches to managing difficult behaviors in patients with dementia, a repeated measures design was used to test the effectiveness of educational and behavioral intervention on behavioral and functional outcomes in home-dwelling patients with dementia and their caregivers' knowledge of dementia. Baseline and 6-month postintervention data were collected for 108 subjects (54 caregiver/patient pairs) following random assignment to an intervention or comparison group. Findings included increases in caregiver knowledge in two treatment groups and patient self-care ability in one treatment group and ratings of the most effective behavioral interventions by caregivers.

Varied pore organization in mesostructured semiconductors based on the [SnSe4](4-) anion.

Open framework metal chalcogenide solids, with pore sizes in the nano- and mesoscale, are of potentially broad technological and fundamental interest in research areas ranging from optoelectronics to the physics of quantum confinement. Although there have been significant advances in the design and synthesis of mesostructured silicas, the construction of their non-oxidic analogues still remains a challenge. Here we describe a synthetic strategy that allows the preparation of a large class of mesoporous materials based on supramolecular assembly of tetrahedral Zintl anions [SnSe4]4- with transition metals in the presence of cetylpyridinium (CP) surfactant molecules. These mesostructured semiconducting selenide materials are of the general formulae (CP)4-2xMxSnSe4 (where 1.0 < x < 1.3; M=Mn, Fe, Co, Zn, Cd, Hg). The resulting materials are open framework chalcogenides and form mesophases with uniform pore size (with spacings between 35 and 40 A). The pore arrangement depends on the synthetic conditions and metal used, and include disordered wormhole, hexagonal and even cubic phases. All compounds are medium bandgap semiconductors (varying between 1.4 and 2.5 eV). We expect that such semiconducting porous networks could be used for optoelectronic, photosynthetic and photocatalytic applications.