In vivo distribution of liposome-encapsulated hemoglobin determined by positron emission tomography.

Positron emission tomography (PET) is a noninvasive imaging technology that enables the determination of biodistribution of positron emitter-labeled compounds. Lipidic nanoparticles are useful for drug delivery system (DDS), including the artificial oxygen carriers. However, there has been no appropriate method to label preformulated DDS drugs by positron emitters.

Functional brain areas associated with manipulation of a prehensile tool: a PET study.

Using PET, brain areas representing the use of a well-learned tool (chopsticks) were investigated in 10 normal common users. The experimental task was to hold the tool in their right hand and use it to pick up and transport a small pin from a table. Data for the same task performed using only the fingers were also obtained as a control.

Hemodynamic influences of azelnidipine, a novel calcium channel blocker, on cerebral circulation in hypertensive patients with ischemic white matter lesions.

Calcium channel blockers have been widely used for the treatment of hypertension because several clinical trials have demonstrated their strong action on lowering blood pressure and their role in preventing cardiovascular events such as stroke and coronary heart disease. However, there have been few reports on the effects on cerebral hemodynamics when blood pressure is lowered with this class of drug. In this study, we used positron emission tomography and acetazolamide challenge tests to measure cerebral blood flow and cerebrovascular reserve before and after administration of a novel calcium channel blocker, azelnidipine, in nine hypertensive patients (mean age, 66.

Abnormal Ca2+ mobilization in hippocampal slices of epileptic animals fed a zinc-deficient diet.

On the basis of the evidence of the enhanced susceptibility to kainate-induced seizures in zinc-deficient mice and rats, the mechanism of the enhanced susceptibility was examined focused on neuronal Ca(2+) mobilization. Brain slices were prepared from rats fed a zinc-deficient diet for 4 weeks. Intracellular fura-2 signals in the hippocampal CA3, in which the basal fura-2 signals were higher in zinc deficiency, were significantly more increased 4s after delivery of kainate (1 mM/1 microl, 1 s) to the dentate granule cell layer.

Positive modulation of long-term potentiation at hippocampal CA1 synapses by low micromolar concentrations of zinc.

The role of zinc, an endogenous N-methyl-d-aspartate (NMDA) receptor antagonist, in long-term potentiation (LTP) at hippocampal CA1 synapses is poorly understood. In the present study, the effect of exogenous zinc and zinc chelators on CA1 LTP was examined by using hippocampal slices from rats. CA1 LTP after tetanic stimulation (100 Hz, 1 s) was potentiated in the presence of 5 microM ZnCl(2), but not in the presence of 30 microM.

[Antineovascular gene therapy by Ago2 knockdown].

Small interfering RNA (siRNA), which induces sequence-dependent gene silencing, has been widely studied. We previously developed polycation liposomes (PCL) as carriers of plasmid DNA and succeeded in showing their potent gene expression efficiency. In the present study, we optimized PCL for siRNA transfection and used it to determine the role of Argonaute2 (Ago2), a main constitution protein of RNA-induced silencing complex (RISC), on angiogenesis.

Statistical parametric analysis of cerebral blood flow in vascular dementia with small-vessel disease using Tc-HMPAO SPECT.

Background: Subcortical ischemic vascular dementia (SVD) caused by small-artery disease is a major cause of dementia. It still remains unclear, however, whether SVD may present with localized regional cerebral blood flow (rCBF) changes. We aimed to clarify the local rCBF changes associated with dementia in patients with early-stage SVD.

Phototoxicity of coproporphyrin as a novel photodynamic therapy was enhanced by liposomalization.

This study attempted the liposomalization of coproporphyrin I (CPI) with hydrophobic properties. Liposomalization of CPI was not successful at any pH when using lactate buffer. In contrast, when using 9% sucrose/10mM phosphate buffer (pH 7.

Attenuation of abnormal glutamate release in zinc deficiency by zinc and Yokukansan.

The mechanism of the abnormal increase in extracellular glutamate concentration in the hippocampus induced with 100mM KCl in zinc deficiency is unknown. In the present study, the changes in glutamate release (exocytosis) and GLT-1, a glial glutamate transporter, expression were studied in young rats fed a zinc-deficient diet for 4 weeks. Exocytosis at mossy fiber boutons was enhanced as reported previously and GLT-1 protein was increased in the hippocampus.

Chronic middle cerebral artery occlusion: a hemodynamic and metabolic study with positron-emission tomography.

Background And Purpose: Chronic middle cerebral artery (MCA) occlusion is more common than generally thought. It is important to assess the cerebral hemodynamic status in patients with this chronic condition. We investigated the cerebral hemodynamic and metabolic disturbances in these patients in relation to the development of the collateral vasculature.

Particle size-dependent triggering of accelerated blood clearance phenomenon.

A repeat-injection of polyethylene glycol-modified liposomes (PEGylated liposomes) causes a rapid clearance of them from the blood circulation in certain cases that is referred to as the accelerated blood clearance (ABC) phenomenon. In the present study, we examined whether polymeric micelles trigger ABC phenomenon or not. As a preconditioning treatment, polymeric micelles (9.

Effective delivery of an angiogenesis inhibitor by neovessel-targeted liposomes.

Angiogenesis is critical for tumor growth and metastasis, and several angiogenesis inhibitors have been developed for the treatment of cancer. Previously, we identified angiogenic vessel-homing peptide, Ala-Pro-Arg-Pro-Gly (APRPG), by use of a phage-displayed peptide library. APRPG peptide-modified liposomes have been revealed to be useful for the delivery of encapsulated drugs to angiogenic vasculature in tumor-bearing animals.

Antiangiogenic cancer therapy using tumor vasculature-targeted liposomes encapsulating 3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one, SU5416.

Previously, we identified angiogenic vessel-homing peptide Ala-Pro-Arg-Pro-Gly (APRPG), and showed that APRPG-modified liposomes could selectively target to tumor neovasculature. Here, we designed an APRPG-modified liposome encapsulating SU5416, an angiogenesis inhibitor, to overcome the solubility problem, and to enhance the antiangiogenic activity of SU5416. Liposomal SU5416 appeared to have the appropriate characteristics, such as particle size and stability in serum.

Cerebral hemodynamics and oxygen metabolism in patients with moyamoya syndrome associated with atherosclerotic steno-occlusive arterial lesions.

Background: Patients with major cerebral artery steno-occlusion and the formation of the moyamoya-like vessels associated with some other disorders have been distinguished from moyamoya disease and classified as moyamoya syndrome. The hemodynamic and metabolic backgrounds of the moyamoya syndrome associated with atherosclerosis have not yet been investigated. We aimed to elucidate the hemodynamic and metabolic characteristics associated with the development of basal moyamoya-like vessels in moyamoya syndrome with atherosclerosis.

Suppressive effect of Yokukansan on excessive release of glutamate and aspartate in the hippocampus of zinc-deficient rats.

Yokukansan (TJ-54), a herbal medicine, has been used as a cure for insomnia and irritability in children. Yokukansan also improves behavioral and psychological symptoms such as agitation, aggression and irritability in patients with dementia including Alzheimer's disease, in which the glutamatergic neurotransmitter system is perturbed. However, the action of Yokukansan in synaptic neurotransmission is unknown.

Attenuation of hippocampal mossy fiber long-term potentiation by low micromolar concentrations of zinc.

The role of zinc in long-term potentiation (LTP) at hippocampal mossy fiber synapses is controversial because of the contrary results obtained when using zinc chelators. On the basis of the postulation that exogenous zinc enhances the action of zinc released from mossy fibers, mossy fiber LTP after tetanic stimulation (100 Hz, 1 sec) was checked in the presence of exogenous zinc at low micromolar concentrations. Mossy fiber LTP was significantly attenuated in the presence of 5-30 microM ZnCl(2), and the amplitude of field excitatory postsynaptic potentials 60 min after tetanic stimulation was decreased to almost the basal level.

Ariakemicins A and B, novel polyketide-peptide antibiotics from a marine gliding bacterium of the genus Rapidithrix.

Ariakemicins A (1) and B (2), unusual linear hybrid polyketide-nonribosomal peptide antibiotics, were discovered from the fermentation extract of the marine gliding bacterium Rapidithrix sp. These metabolites were positional isomers with regard to a double bond and chromatographically inseparable, rendering the structure study on a mixture basis. The ariakemicins were composed of threonine, two omega-amino-(omega-3)-methyl carboxylic acids with diene or triene units, and delta-isovanilloylbutyric acid.

Enhanced experimental tumor metastasis with age in senescence-accelerated mouse.

Tumor metastasis is affected by the host immune surveillance system. Since aging may attenuate the host immune potential, the experimental tumor metastasis may be enhanced with age. In the present study, we investigated this alteration of experimental tumor metastasis with age.

Enhancement of social isolation-induced aggressive behavior of young mice by zinc deficiency.

Neuropsychological behavior via activation of the hypothalamic-pituitary-adrenal (HPA) axis was analyzed using young mice fed a zinc-deficient diet for 2 weeks. Serum corticosterone concentration was significantly increased after 2-week zinc deprivation, whereas zinc concentration in the brain was not decreased. In the resident-intruder test, the rate of mice that exhibited aggressive behavior to the total mice was significantly higher in isolated zinc-deficient mice than in isolated control mice.

Enhancement of hippocampal mossy fiber activity in zinc deficiency and its influence on behavior.

The extracellular concentration of glutamate in the hippocampus is increased by hippocampal perfusion with CaEDTA, a membrane-impermeable zinc chelator, suggesting that the activity of glutamatergic neurons in the hippocampus are influenced by the extracellular concentrations of zinc. In the present study, the relationship between the extracellular concentrations of zinc and mossy fiber activity in the hippocampus was examined in mice and rats fed a zinc-deficient diet for 4 weeks. Timm's stain, by which histochemically reactive zinc in the presynaptic vesicles is detected, was attenuated in the hippocampus in zinc deficiency.

In vivo quantitative autoradiographic analysis of brain muscarinic receptor occupancy by antimuscarinic agents for overactive bladder treatment.

We evaluated the effects of five clinically used antimuscarinic agents for overactive bladder (OAB) treatment on in vivo muscarinic receptor binding in rat brain by quantitative autoradiography. There was a dose-related decrease in in vivo specific +N-[11C]methyl-3-piperidyl benzilate ([11C](+)3-MPB) binding in each brain region of rats 10 min after i.v.

Chemoprevention of tumor metastasis by liposomal beta-sitosterol intake.

To investigate chemopreventive effect of liposomal beta-sitosterol on tumor metastasis, we prepared liposomal beta-sitosterol composed of egg yolk phosphatidylcholine for oral delivery. Although orally administered beta-sitosterol (4 micromol as beta-sitosterol/mouse) was not absorbed into plasma, the amount of immune response cytokines such as IL-12 and IL-18 was increased in the small intestine after the liposome intake. Moreover, after daily oral administration of the liposome for 7 d, natural killer (NK) cell activity in the mice was increased, suggesting that the immune surveillance activity of mice was enhanced by the liposomal beta-sitosterol intake.

Unnarmicins A and C, new antibacterial depsipeptides produced by marine bacterium Photobacterium sp. MBIC06485.

Two new antibiotic depsipeptides, unnarmicins C (1) and A (2), were isolated from the fermentation broth of a marine bacterium, Photobacterium sp. strain MBIC06485. The structure of 1 was established by spectroscopic studies and chiral analyses of its chemical degradation/conversion products, and that of 2 by comparing its NMR, MS, and CD data with those of 1.

Antineovascular therapy with angiogenic vessel-targeted polyethyleneglycol-shielded liposomal DPP-CNDAC.

Causing damage to angiogenic vessels is a promising approach for cancer chemotherapy. The present study is a codification of a designed liposomal drug delivery system (DDS) for antineovascular therapy (ANET) with 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine (CNDAC). The authors have previously reported that liposomalized 5'-O-dipalmitoylphosphatidyl CNDAC (DPP-CNDAC), a phospholipid derivative of the novel antitumor nucleoside CNDAC, is quite useful for ANET.

MRI-based correction for partial-volume effect improves detectability of intractable epileptogenic foci on 123I-iomazenil brain SPECT images.

Unlabelled: (123)I-Iomazenil brain SPECT has been used for the detection of epileptogenic foci, especially when surgical intervention is considered. Although epileptogenic foci exhibit a decrease in (123)I-iomazenil accumulation, normal cerebral cortices often exhibit similar findings because of thin cortical ribbons, gray matter atrophy, or pathologic brain structures. In the present study, we created (123)I-iomazenil SPECT images corrected for gray matter volume using MRI and tested whether the detectability of the epileptogenic foci improved.