Left ventricular ejection fraction, myocardial blood flow and hemodynamic variables in adenosine and regadenoson vasodilator 82-Rubidium PET.

AIMS: In most Rubidium-(Rb)-positron emission tomography (PET) studies, dipyridamole was used as vasodilator. The aim was to evaluate vasodilator PET left ventricular ejection fraction (LVEF), myocardial blood flow (MBF), hemodynamics, and the influence of adenosine and regadenoson on these variables. METHODS AND RESULTS: Consecutive patients (N = 2299) with prior coronary artery disease (CAD) or no prior CAD undergoing adenosine/regadenoson 82Rb-PET were studied and compared according to CAD status and normal/abnormal PET (summed stress score 0-3 vs. ≥4). Rest and stress LVEF differed significantly depending on CAD status and scan results. In patients with no prior CAD, rest/stress LVEF were 68% and 72%, in patients with prior CAD 60% and 63%. LVEF during stress increased 5 ± 6% in normal compared to 1 ± 8% in abnormal PET (P<0.001). Global rest myocardial blood flow(rMBF), stress MBF(sMBF) and myocardial flow reserve (sMBF/rMBF) were significantly higher in no prior CAD patients compared to prior CAD patients(1.3 ± 0.5, 3.3 ± 0.9, 2.6 ± 0.8 and 1.2 ± 0.4, 2.6 ± 0.8, 2.4 ± 0.8 ml/g/min, respectively, P<0.001) and in normal versus abnormal scans, irrespective of CAD status(no prior CAD: 1.4 ± 0.5, 3.5 ± 0.8, 2.8 ± 0.8 and 1.2 ± 0.8, 2.5 ± 0.8, 2.2 ± 0.7; prior CAD: 1.3 ± 0.4, 3.1 ± 0.8, 2.7 ± 0.8 and 1.1 ± 0.4, 2.3 ± 0.7, 2.2 ± 0.7 ml/g/min, respectively, P<0.001). LVEF and hemodynamic values were similar for adenosine and regadenoson stress. Stress LVEF ≥70% excluded relevant ischemia (≥10%) with a negative predictive value (NPV) of 94% (CI 92-95%). CONCLUSIONS: Rest/stress LVEF, LVEF reserve and MBF values are lower in abnormal compared to normal scans. Adenosine and regadenoson seem to have similar effect on stress LVEF, MBF and hemodynamics. A stress LVEF ≥70% has a high NPV to exclude relevant ischemia.

Inward rectifier potassium currents in mammalian skeletal muscle fibres.

Inward rectifying potassium (Kir) channels play a central role in maintaining the resting membrane potential of skeletal muscle fibres. Nevertheless their role has been poorly studied in mammalian muscles. Immunohistochemical and transgenic expression were used to assess the molecular identity and subcellular localization of Kir channel isoforms. We found that Kir2.1 and Kir2.2 channels were targeted to both the surface and the transverse tubular system membrane (TTS) compartments and that both isoforms can be overexpressed up to 3-fold 2 weeks after transfection. Inward rectifying currents (IKir) had the canonical features of quasi-instantaneous activation, strong inward rectification, depended on the external [K(+)], and could be blocked by Ba(2+) or Rb(+). In addition, IKir records show notable decays during large 100 ms hyperpolarizing pulses. Most of these properties were recapitulated by model simulations of the electrical properties of the muscle fibre as long as Kir channels were assumed to be present in the TTS. The model also simultaneously predicted the characteristics of membrane potential changes of the TTS, as reported optically by a fluorescent potentiometric dye. The activation of IKir by large hyperpolarizations resulted in significant attenuation of the optical signals with respect to the expectation for equal magnitude depolarizations; blocking IKir with Ba(2+) (or Rb(+)) eliminated this attenuation. The experimental data, including the kinetic properties of IKir and TTS voltage records, and the voltage dependence of peak IKir, while measured at widely dissimilar bulk [K(+)] (96 and 24 mm), were closely predicted by assuming Kir permeability (PKir) values of ∼5.5 × 10(-6 ) cm s(-1) and equal distribution of Kir channels at the surface and TTS membranes. The decay of IKir records and the simultaneous increase in TTS voltage changes were mostly explained by K(+) depletion from the TTS lumen. Most importantly, aside from allowing an accurate estimation of most of the properties of IKir in skeletal muscle fibres, the model demonstrates that a substantial proportion of IKir (>70%) arises from the TTS. Overall, our work emphasizes that measured intrinsic properties (inward rectification and external [K] dependence) and localization of Kir channels in the TTS membranes are ideally suited for re-capturing potassium ions from the TTS lumen during, and immediately after, repetitive stimulation under physiological conditions.

Alternative cycling modes of the Na(+)/K(+)-ATPase in the presence of either Na(+) or Rb(+).

A comprehensive study of the interaction between Na(+) and K(+) with the Na(+)/K(+)-ATPase requires dissecting the incidence of alternative cycling modes on activity measurements in which one or both of these cations are absent. With this aim, we used membrane fragments containing pig-kidney Na(+)/K(+)-ATPase to perform measurements, at 25°C and pH=7.4, of ATPase activity and steady-state levels of (i) intermediates containing occluded Rb(+) at different [Rb(+)] in media lacking Na(+), and (ii) phosphorylated intermediates at different [Na(+)] in media lacking Rb(+). Most relevant results are: (1) Rb(+) can be occluded through an ATPasic cycling mode that takes place in the absence of Na(+) ions, (2) the kinetic behavior of the phosphoenzyme formed by ATP in the absence of Na(+) is different from the one that is formed with Na(+), and (3) binding of Na(+) to transport sites during catalysis is not at random unless rapid equilibrium holds.

E2→E1 transition and Rb(+) release induced by Na(+) in the Na(+)/K(+)-ATPase. Vanadate as a tool to investigate the interaction between Rb(+) and E2.

This work presents a detailed kinetic study that shows the coupling between the E2→E1 transition and Rb(+) deocclusion stimulated by Na(+) in pig-kidney purified Na,K-ATPase. Using rapid mixing techniques, we measured in parallel experiments the decrease in concentration of occluded Rb(+) and the increase in eosin fluorescence (the formation of E1) as a function of time. The E2→E1 transition and Rb(+) deocclusion are described by the sum of two exponential functions with equal amplitudes, whose rate coefficients decreased with increasing [Rb(+)]. The rate coefficient values of the E2→E1 transition were very similar to those of Rb(+)-deocclusion, indicating that both processes are simultaneous. Our results suggest that, when ATP is absent, the mechanism of Na(+)-stimulated Rb(+) deocclusion would require the release of at least one Rb(+) ion through the extracellular access prior to the E2→E1 transition. Using vanadate to stabilize E2, we measured occluded Rb(+) in equilibrium conditions. Results show that, while Mg(2+) decreases the affinity for Rb(+), addition of vanadate offsets this effect, increasing the affinity for Rb(+). In transient experiments, we investigated the exchange of Rb(+) between the E2-vanadate complex and the medium. Results show that, in the absence of ATP, vanadate prevents the E2→E1 transition caused by Na(+) without significantly affecting the rate of Rb(+) deocclusion. On the other hand, we found the first evidence of a very low rate of Rb(+) occlusion in the enzyme-vanadate complex, suggesting that this complex would require a change to an open conformation in order to bind and occlude Rb(+).

Regadenoson pharmacologic rubidium-82 PET: a comparison of quantitative perfusion and function to dipyridamole.

BACKGROUND: Dipyridamole is used for stress (82)rubidium chloride ((82)RbCl) PET because of its long hyperemic duration. Regadenoson has advantages of a fixed dose and favorable symptom profile, but its mean maximal hyperemia is only 2.3 minutes. To determine its suitability for (82)RbCl PET, we imaged subjects using a regadenoson protocol based on its hyperemic response and compared the images in the same subjects having dipyridamole PET. METHODS: In 32 subjects (23 M), we assessed visually by blinded interpretation and quantitatively compared summed stress and difference scores, total perfusion deficit (TPD), LVEF, LV volumes, and change in stress-rest function. Linear correlation and Bland-Altman analysis of the paired measurements were applied for evaluation of differences. Paired t test and Pearson's correlation were applied for testing of significance. RESULTS: The images were interpreted the same by visual assessment. Twenty-six (26) subjects had reversible defects; by quantitation the SSS was 12.9 ± 7.0 and 14.1 ± 6.4 (P = .23) and SDS was 7.0 ± 6.8 versus 7.6 ± 6.2 (P = .40) for dipyridamole and regadenoson, respectively. Six (6) subjects had <5% likelihood of CAD and were normal by both. All paired measurements showed a high positive correlation between regadenoson and dipyridamole; stress segmental perfusion Reg = 0.93Dip + 4.4, r = 0.88; TPD Reg = 0.94Dip + 0.41, r = 0.93; LVEF Reg = 0.92Dip + 4.7, r = 0.95; stress minus rest LVEF Reg = 0.87Dip - 0.99, r = 0.82. CONCLUSION: Regadenoson stress (82)RbCl PET perfusion defect and cardiac function measurements are visually and quantitatively equivalent to dipyridamole studies and can be obtained with the clinical advantages of regadenoson.

Antidepressant, psychostimulant, and nootropic effects of major and trace element composition.

The antidepressant, psychostimulant, and nootropic effects of a composition of major and trace elements including KCl, RbNO3, magnesium sulfate, and zinc sulfate were studied on the models of behavioural despair (Porsolt test) and conditioned passive avoidance test. The preparation was found to shorten the immobilization time in the Porsolt test and promote retention of the conditioned passive avoidance. The most pronounced psychostimulant effect of the substance was observed at a dose of 4.68 mg/kg and the most pronounced antidepressant effect was found at a dose of 18.72 mg/kg. Maximum nootropic activity of the preparation was found at a dose of 93.6 mg/kg.

Mechanistic examination of thallium and potassium interactions in Daphnia magna.

The trace element thallium (Tl) exerts its toxic effects, at least in part, through its mimicry of potassium (K+) and subsequent impairment of K+ homeostasis. However, the specific nature of this effect remains poorly understood, especially in aquatic biota that are threatened by elevated concentrations of Tl associated with mining and refining effluents. In this study experiments were conducted to mechanistically examine the relationship between Tl and K+ in terms of uptake and toxicity in the regulatory model species Daphnia magna. In one set of experiments the effects of K+, the K+ analog rubidium (Rb+), and generalized K+ channel blocker cesium (Cs+) on Tl-induced acute toxicity were examined. The presence of increasing concentrations of K+ and Rb+ in exposure water reduced waterborne Tl toxicity, indicating that the actions of Tl were mediated at least in part through interactions with K+. However, in the presence of elevated water Cs+, the toxicity of Tl paradoxically increased. Pharmaceuticals with putative blocking actions on K+ channels failed to alter whole-body K+ of control organisms, but in the case of clozapine and chlorpropamide, whole-body K+ status was significantly elevated relative to exposures with Tl alone, which tended to reduce this metric. These data identify inwardly rectifying and voltage gated K+ channels as potential loci of Tl toxicity. Experiments using rubidium (Rb+) as a tracer of K+, showed that waterborne Tl affects the uptake of K+, but the magnitude of inhibition by Tl was not sufficient to explain the effect on whole-body K+. While these data indicate interactions between Tl and K occur at K+ transporters in D magna, they also indicate that environmental levels of K+ are likely to ameliorate toxicity in most natural waters.

Investigation of the Effects and Mechanisms of Anticancer Action of a Ru(II)-Arene Iminophosphorane Compound in Triple Negative Breast Cancer Cells.

Triple negative breast cancer (TNBC) is one of the breast cancers with poorer prognosis and survival rates. TNBC has a disproportionally high incidence and mortality in women of African descent. We report on the evaluation of Ru-IM (1), a water-soluble organometallic ruthenium compound, in TNBC cell lines derived from patients of European (MDA-MB-231) and African (HCC-1806) ancestry (including IC50 values, cellular and organelle uptake, cell death pathways, cell cycle, effects on migration, invasion, and angiogenesis, a preliminary proteomic analysis, and an NCI 60 cell-line panel screen). 1 was previously found highly efficacious in MDA-MB-231 cells and xenografts, with little systemic toxicity and preferential accumulation in the tumor. We observe a similar profile for this compound in the two cell lines studied, which includes high cytotoxicity, apoptotic behavior and potential antimetastatic and antiangiogenic properties. Cytokine M-CSF, involved in the PI3/AKT pathway, shows protein expression inhibition with exposure to 1. We also demonstrate a p53 independent mechanism of action.

Developmental and functional studies of the SLC12 gene family members from Drosophila melanogaster.

The electroneutral cation-chloride cotransporter gene family, SLC12, contains nine members in vertebrates. These include seven sodium and/or potassium-coupled chloride transporters and two membrane proteins of unknown function. Although SLC12 family members have been identified in a number of lower species, the functional properties of these proteins are unknown. There are five SLC12 homologues in Drosophila melanogaster, including at least one member on each of the four main branches of the vertebrate phylogenetic tree. We have employed in situ hybridization to study the expression patterns of the Drosophila SLC12 proteins during embryonic development. Our studies indicate that all five members of this family are expressed during early embryogenesis (stages 1-6), but that spatial and temporal expression patterns become more refined as development proceeds. Expression during late embryogenesis was seen predominantly in the ventral nerve cord, salivary gland, gut, and anal pad. In parallel studies, we have carried out transport assays on each of the five Drosophila homologues, expressed as recombinant proteins in the cultured insect cell line High Five. Under our experimental conditions, we found that only one of these proteins, CG4357, transported the potassium congener (86)Rb. Additional experiments established that rubidium transport via CG4357 was saturable (K(m) = 0.29 +/- 0.05 mM), sodium-dependent (half-saturation constant = 53 +/- 11 mM), chloride-dependent (half-saturation constant = 48 +/- 5 mM), and potently inhibited by bumetanide (inhibitor constant = 1.17 +/- 0.08 muM), a specific inhibitor of Na(+)-K(+)-2Cl(-) cotransporters. Taken together, our results provide strong evidence that CG4357 is an insect ortholog of the vertebrate Na(+)-K(+)-2Cl(-) cotransporters.

Synthesis, crystal structure and leishmanicidal activity of new trimethoprim Ru(III), Cu(II) and Pt(II) metal complexes.

Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania, which has very limited treatment options and affects poor and underdeveloped populations. The current treatment is plagued by many complications, such as high toxicity, high cost and resistance to parasites; therefore, novel therapeutic agents are urgently needed. Herein, the synthesis, characterization and in vitro leishmanicidal potential of new complexes with the general formula [RuCl3(TMP)(dppb)] (1), [PtCl(TMP)(PPh3)2]PF6 (2) and [Cu(CH3COO)2(TMP)2]·DMF (3) (dppb = 1,4-bis(diphenylphosphino)butane, PPH3 = triphenylphosphine and TMP = trimethoprim) were evaluated. The complexes were characterized by infrared, UV-vis, cyclic voltammetry, molar conductance measurements, elemental analysis and NMR experiments. Also, the geometry of (2) and (3) were determined by single crystal X-ray diffraction. Despite being less potent against promastigote L. amazonensis proliferation than amphotericin B reference drug (IC50 = 0.09 ± 0.02 µM), complex (2) (IC50 = 3.6 ± 1.5 µM) was several times less cytotoxic (CC50 = 17.8 µM, SI = 4.9) in comparison with amphotericin B (CC50 = 3.3 µM, SI = 36.6) and gentian violet control (CC50 = 0.8 µM). Additionally, complex (2) inhibited J774 macrophage infection and amastigote number by macrophages (IC50 = 6.6 and SI = 2.7). Outstandingly, complex (2) was shown to be a promising candidate for a new leishmanicidal therapeutic agent, considering its biological power combined with low toxicity.

Thermally induced structural metamorphosis of ZnO:Rb nanostructures for antibacterial impacts.

In this work, we report on the synthesis of pure and Rb doped ZnO (ZnO:Rb) nanoparticles by a simple combustion technique followed by thermal treatment in an open-air atmosphere. The prepared samples were characterized using UV-vis spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), photoluminescence, Raman spectroscopy and scanning electron microscopy. The wurtzite hexagonal phase structure of ZnO and a secondary phase of Rb2ZnO2 was observed after doping ZnO with Rb. FTIR and DSC confirmed the functional groups and the thermal stability of the ZnO samples. Field emission scanning electron microscope showed an irregular shaped agglomerated morphology for the ZnO:Rb samples. The chemical states of the undoped and Rb doped samples were identified using X-ray photoelectron spectroscopy for both pure and ZnO:Rb samples. In addition, ZnO:Rb samples exhibit good antimicrobial activities against Bacillus subtilis with a change in antibacterial behaviour as compared to pure ZnO structures indicating their multifunctional applications.

FtsZ filament dynamics at steady state: subunit exchange with and without nucleotide hydrolysis.

We have measured three aspects of FtsZ filament dynamics at steady state: rates of GTP hydrolysis, subunit exchange between protofilaments, and disassembly induced by dilution or excess GDP. All three reactions were slowed with an increase in the potassium concentration from 100 to 500 mM, via replacement of potassium with rubidium, or with an increase in the magnesium concentration from 5 to 20 mM. Electron microscopy showed that the polymers assembled under the conditions of fastest assembly were predominantly short, one-stranded protofilaments, whereas under conditions of slower dynamics, the protofilaments tended to associate into long, thin bundles. We suggest that exchange of subunits between protofilaments at steady state involves two separate mechanisms: (1) fragmentation or dissociation of subunits from protofilament ends following GTP hydrolysis and (2) reversible association and dissociation of subunits from protofilament ends independent of hydrolysis. Exchange of nucleotides on these recycling subunits could give the appearance of exchange directly into the polymer. Several of our observations suggest that exchange of nucleotide can take place on these recycling subunits, but not directly into the FtsZ polymer. Annealing of protofilaments was demonstrated for the L68W mutant in EDTA buffer but not in Mg buffer, where rapid cycling of subunits may obscure the effect of annealing. We also reinvestigated the nucleotide composition of FtsZ polymers at steady state. We found that the GDP:GTP ratio was 50:50 for concentrations of GTP >100 microM, significantly higher than the 20:80 ratio previously reported at 20 microM GTP.

Brain norepinephrine: enhanced turnover after rubidium treatment.

After biosynthesis of norepinephrine was inhibited, treatment of rats for 10 days with rubidium chloride (0.6 milliequivalent per kilogram of body weight) caused an increase in the rate of disappearance of norepinephrine in the brainstem but not in the telencephalon. Also the utilization of intracisternally injected tritiated norepinephrine was increased and was accompanied by a shift in the pattern of norepinephrine metabolism to normetanephrine. These data suggest that greater amounts of neuronally stored norepinephrine were released to central adrenergic receptors.

Rubidium and lithium: opposite effects on amine-mediated excitement.

In mice the activation caused by morphine was antagonized by previous treatment with lithium and was potentiated by previous treatment with rubidium. Other antimanic drugs antagonized the morphine activation as well. The effect of rubidium was similar to that of the antidepressant drugs imipramine and pargyline. Rubidium may merit clinical evaluation as an antidepressant agent in man.

Shark pit organs: response to chemicals.

Nerve fibers from pit organs and canal neuromasts are distinguished by the nature of their electrophysiological response to mechanical and chemical stimulation. Pit organs respond to touch but have a relatively high threshold compared with canal neuromasts. They respond readily to sodium and potassium chloride solutions, the rate of discharge increasing with the concentration of the solution. Order of effectiveness with 1 molar solutions of monovalent cations is as follows: potassium, rubidium > sodium, ammonium > cesium, lithium. Anions are ineffective. Divalent cations such as calcium and magnesium are inhibitory. Responses to acid, sugar, and quinine are either very slight or inhibitory.

Intracellular Imaging of Glutathione with MnO2 Nanosheet@Ru(bpy)32+-UiO-66 Nanocomposites.

Fluorescent detection of glutathione (GSH) in the living system has attracted much attention, but current fluorescent probes are usually exposed to the exterior environment, leading to photobleaching and premature leakage and subsequently limiting the sensitivity and photostability. Herein, luminescent metal-organic frameworks [Ru(bpy)32+ encapsulated in UiO-66] coated with manganese dioxide nanosheets [MnO2 NS@Ru(bpy)32+-UiO-66] were prepared by an in situ growth method and further explored to construct a GSH-switched fluorescent sensing platform. Because of the splendid fluorescence quenching ability, special probe leakage blocking role and distinguished recognition of the MnO2 NS, and the improved fluorescence of Ru(bpy)32+ by UiO-66, a low background, highly sensitive and selective detection of GSH with a low limit of detection as 0.28 µM was realized. At the same time, the preparation of MnO2 NS@Ru(bpy)32+-UiO-66 nanocomposites is simple and less toxic, and there was no notable loss of cell survivability after being exposed to MnO2 NS@Ru(bpy)32+-UiO-66 below the concentrations of 120 µg mL-1 for 24 h. Consequently, the results coming from this effort suggest that the new sensing platform will have a great potential in the detection of GSH in living cells.

Application of 82 Sr/82 Rb generator in neurooncology.

INTRODUCTION: The applicability of "Rubidium Chloride, 82 Rb from Generator" radiopharmaceutical for brain tumors (BT) diagnostics is demonstrated on the basis of the application experience of the radiopharmaceutical in neurooncology. EXPERIMENTAL: A total of 21 patients with various brain tumors and nonneoplastic abnormal brain masses were investigated. RESULTS AND DISCUSSIONS: The results of the imaging and differential diagnostics of malignant and benign tumors, nonneoplastic abnormal brain masses and lesions revealed the prevalence of high uptake of the radiopharmaceutical in the malignant tumors in comparison with benign glioma and arteriovenous malformations in which 82 Rb-chloride accumulates in the vascular phase but does not linger further. The ultra-short half-life of radionuclide 82 Rb (76 s) along with a low absorbed radiation dose with 82 Rb-chloride by intravenous administration create a new possibility of successive use of two or more radiopharmaceuticals for the examination of the same patient. For instance, PET examination with 18 F-FDG, 11 C-methionine, 11 C-choline, or any other radiopharmaceutical can be carried out in just 7-15 min. after 82 Rb-chloride injection. CONCLUSION: Research demonstrated an effectiveness of 82 Rb-chloride application as a diagnostic agent in neurooncology. A method of dosing and administration of the generator-produced radiopharmaceutical has been worked out. It is possible to do up to 600 PET sessions using one Russian 82 Rb generator GR-01. The generator is proved to be reliable and easy to use. The interest in 82 Rb-chloride as a tumor-seeking radiopharmaceutical rose due to the active application of the modern devices PET/CT in the routine clinical practice.

Rubidium-doped titanium surfaces with modulatory effects on MC3T3-E1 cell response and antibacterial capacity against Staphylococcus aureus.

To simultaneously impart excellent biological activity and antibacterial function to titanium-based metal materials, rubidium-doped titanium surfaces were prepared via alkali heat treatment, subsequent hydrothermal treatment and final heat treatment. The alkali heat treatment was employed to fabricate an amorphous sodium titanate hydrogel layer on titanium substrates. Thereafter, rubidium was introduced through the hydrothermal process. After final heat treatment, crystallized rubidium titanate and sodium titanate were obtained on titanium surfaces. The viability of MC3T3-E1 cells was inhibited on rubidium-doped titanium surfaces for short-term (day 1). With prolonged duration, the viability and alkali phosphatase (ALP) activity were comparable for various surfaces with different amounts of rubidium (day 5). With further increased culture duration, the collagen synthesis (day 10) and in vitro mineralization of osteoblasts were found to be significantly enhanced on rubidium-doped titanium surfaces. The Rb-doped Ti surfaces showed antibacterial capacity against Staphylococcus aureus at both 12 and 24 h. The results indicate that doping rubidium into titanium surfaces could simultaneously endow materials with favorable osteogenic and antibacterial capacity.

Nitric oxide and glutamate are contributors of anti-seizure activity of rubidium chloride: A comparison with lithium.

The neuro-protective effects of rubidium and lithium as alkali metals have been reported for different central nervous system dysfunctions including mania and depression. The aim of this study was evaluating as well as comparing the effects of rubidium chloride (RbCl) and lithium chloride (LiCl) on different seizures paradigms in mice and determining the involvement of NMDA receptors and nitrergic pathway. To assess the seizures threshold, animals received intravenous pentylenetetrazole (PTZ, 0.5%; 1 mL/min). Male NMRI mice (6-8 weeks) received intraperitoneal (i.p.) injections of different doses of RbCl and LiCl. Doses greater than 10 mg/kg of RbCl showed a significant anticonvulsant activity 60 min after administration; the anticonvulsant effects of LiCl was observed at the doses more than 5 mg/kg and after 30 min in PTZ-induced seizure threshold. But, RbCl (10, 20 mg/kg, i.p) or LiCl (5, 10 mg/kg, i.p) injection did not induce protection against maximal electroshock (MES) or intraperitoneal injection of PTZ lethal dose (80 mg/kg)-induced seizure models. Pre-treatment with L-NAME (non-selective nitric oxide synthase (NOS) inhibitor, 10 mg/kg; i.p.) and 7-nitroindazole (selective neuronal NOS inhibitor, 30 mg/kg; i.p.) enhanced the anticonvulsive effects of both RbCl (5 mg/kg, i.p.) and LiCl (1 mg/kg, i.p.) in PTZ-induced seizure threshold model. Injection of MK-801 (NMDA receptor antagonist, 0.05 mg/kg; i.p.) before RbCl (5 mg/kg, i.p.; P < 0.001) and LiCl (1 mg/kg, i.p.; P < 0.001) administration increased the anti-seizure activity. But, treatment with L-arginine (precursor of nitric oxide, 100 mg/kg; i.p.) decreased the seizure threshold of both RbCl (20 mg/kg, i.p.; P < 0.001) and LiCl (10 mg/kg, i.p.; P < 0.001). Measurement of nitrite levels in hippocampus of animals revealed a remarkable reduction after treatment with RbCl (20 mg/kg, i.p; P < 0.05) and LiCl (10 mg/kg, i.p; P < 0.01). To conclude, rubidium may protect central nervous system against seizures in PTZ-induced seizures threshold model through NMDA/nitrergic pathways with a similarity to lithium effects in mice.

Rubidium-containing mesoporous bioactive glass scaffolds support angiogenesis, osteogenesis and antibacterial activity.

In this study, rubidium-containing mesoporous bioglass (Rb-MBG) scaffolds were formed with the investigation of the influence of Rb addition on angiogenic and osteogenic differentiation abilities of hBMSC. The phase composition, microstructure, pore size distribution, ion release, biological activity, drug loading rate, and release rate of Rb-MBG were characterized. The proliferation and differentiation of hBMSC, the markers of bone formation (ALP, COL-1) and angiogenesis (VEGF, HIF-1α), and wnt/ß-catenin related-signaling pathway gene were studied by cell culture. Rb-MBG loaded with antibacterial agents enoxacin (ENX), coliforms and Staphylococcus aureus were cultured together to study the antibacterial effects. The results indicate that the samples have a 350-550 µm large pore structure and 4.5-5.5 nm mesoporous size. Adding Rb can increase the activity of ALP, the secretion of VEGF and COLI, and the expression of HIF-1α of hBMSCs. Rb containing MBG is likely to enhance the proliferation and differentiation of hBMSCs through the influence of Wnt/ß-catenin signal path. Rb-MBG scaffold can load effectively and release Rb ions and ENX continuously to damage the bacterial cell membrane with the synergistic effect, and therefore achieve antibacterial results. In conclusion, adding Rb to MBG supports angiogenesis and osteogenesis of hBMSCs, as well as antibacterial activity.