Synthesis of VIP-lipopeptide using a new linker to modify liposomes: towards the development of a drug delivery system for active targeting.

A new component for the solid phase peptide synthesis of lipopeptide, 2-[(4R,5R)-5-({[(9H-fluoren-9-yl)methoxy]carbonylaminomethyl}-2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]acetic acid (2), was designed and synthesized from (-)-2,3-O-isopropylidene-D-threitol (3) in 4 steps. The key step was the selective alkylation of 3 with benzyl bromoacetate in the presence of Cs2CO3. Vasoactive intestinal peptide (VIP)-lipopeptide (1) incorporating this linker was synthesized by solid phase peptide synthesis.

Arthritic joint-targeting small interfering RNA-encapsulated liposome: implication for treatment strategy for rheumatoid arthritis.

RNA interference, mediated by small interfering RNA (siRNA), is effective in silencing genes with a high degree of specificity. To explore the therapeutic potential of systemically administered siRNA for rheumatoid arthritis (RA), we tested the complex of siRNA and the recently developed wrapsome (siRNA/WS) containing siRNA-encapsulated liposome in mice with collagen-induced arthritis (CIA). Mice with CIA received an intravenous injection of Cy5-labeled siRNA/WS. Fluorescence stereoscopic microscopy and flow cytometry were used to assess the siRNA/WS tissue distribution. The efficacy of siRNA-targeting tumor necrosis factor (TNF)-α/WS in CIA was evaluated by arthritis score. TNF-α mRNA levels in the joints were measured by real-time reverse transcriptase-polymerase chain reaction. The intensity of Cy5 fluorescence was higher in arthritic joints than in nonarthritic sites in Cy5-siRNA/WS-treated mice and remained higher up to 48 h after injection, compared with that in naked Cy5-siRNA-treated mice. Cy5 fluorescence intensity was higher in synovial cells than in splenocytes, bone marrow cells, and peripheral blood leukocytes. The majority of Cy5-positive synovial cells were CD11b⁺ with only a few CD3⁺ cells. Treatment with TNF-α siRNA/WS resulted in significant decreases in severity of arthritis and TNF-α mRNA level in the joints compared with control siRNA/WS. In conclusion, the use of our WS allowed efficient and targeted delivery of siRNAs to arthritic joints. The siRNA/WS was mainly incorporated into CD11b⁺ cells, including macrophages and neutrophils, in the inflamed synovium, suggesting its potential therapeutic effects in RA by silencing the expression of inflammatory molecules produced by these cells.

Hypointensity of draining veins on susceptibility-weighted magnetic resonance images might indicate normal venous flow and a lower risk of intracerebral hemorrhage in patients with intracranial arteriovenous shunt(s).

Patients with intracranial arteriovenous shunt(s) have a risk of intracerebral hemorrhage (ICH). We investigated the signal intensity of draining veins on susceptibility-weighted imaging (SWI) and the status of venous drainage shown by digital subtraction angiography (DSA). We then evaluated whether the signal intensity of draining veins on SWI is related to normal venous flow (NVF) and/or ICH. We analyzed SWI and DSA in 10 consecutive patients with intracranial arteriovenous shunt(s). Opacification of draining veins in the normal venous phase by DSA was judged as NVF. We evaluated the relationship between the intensity of draining veins on SWI and the presence of NVF before and after treatment. The relationship between the intensity of draining veins on SWI and the presence of ICH surrounding the draining veins was also evaluated. Of 10 patients with untreated arteriovenous shunt(s), two had arteriovenous malformation and eight had a dural arteriovenous fistula with cortical venous reflux. We analyzed 26 draining veins before treatment. In preoperative analysis, draining veins with hypointensity were significantly more likely to show NVF than were draining veins with isointensity or hyperintensity (45.5% vs. 0.0%, P = 0.007). While 69.2% of the areas surrounding draining veins with isointensity or hyperintensity showed ICH, no veins with hypointensity showed ICH (P = 0.011, odds ratio 0.036; 95% confidence interval 0.0017-0.80). In conclusion, draining veins with hypointensity on SWI may contain NVF, despite arteriovenous shunting. The areas surrounding these veins might have a lower risk of ICH because of less venous hypertension.

Rare Case of Floating Intimal Flap Associated with Atheromatous Carotid Plaque.

BACKGROUND: A mobile carotid plaque can be detected by duplex ultrasonography and is a high-risk factor for embolic stroke. CASE DESCRIPTION: We herein present a case involving an 80-year-old man with an asymptomatic carotid floating flap diagnosed by duplex ultrasonography and treated with carotid endarterectomy. Intraoperatively, an ulceration was found immediately proximal to the neck of the floating flap, and the shape and size of the ulceration were quite similar to those of the floating flap. In a histopathologic examination of the specimen resected by carotid endarterectomy, the plaque lacked the internal elastic lamina (IEL) at the ulceration, calcification was observed in the plaque and medial layer at the ulceration, and the floating flap consisted of the IEL accompanied by calcification, fibrin, and foamy cells. CONCLUSIONS: Progression of the atheroma and Mönckeberg sclerosis might have affected disruption of the IEL, causing the IEL to finally peel off. A floating intimal flap accompanied by an atheroma without intraplaque hemorrhage is a rare cause of mobile plaque formation. This type of mobile plaque might not be dissolved by medical treatment alone. In such cases, surgical treatment is a suitable therapeutic choice to prevent stroke.

Simplifying the Chemical Structure of Cationic Lipids for siRNA-Lipid Nanoparticles.

We report a potent cationic lipid, SST-02 ((3-hydroxylpropyl)dilinoleylamine), which possesses a simple chemical structure and is synthesized just in one step. Cationic lipids are key components of siRNA-lipid nanoparticles (LNP), which may serve as potential therapeutic agents for various diseases. For a decade, chemists have given enhanced potency and new functions to cationic lipids along with structural complexity. In this study, we conducted a medicinal chemistry campaign pursuing chemical simplicity and found that even dilinoleylmethylamine (SST-01) and methylpalmitoleylamine could be used for the in vitro and in vivo siRNA delivery. Further optimization revealed that a hydroxyl group boosted potency, and SST-02 showed an ID50 of 0.02 mg/kg in the factor VII (FVII) model. Rats administered with 3 mg/kg of SST-02 LNP did not show changes in body weight, blood chemistry, or hematological parameters, while the AST level decreased at a dose of 5 mg/kg. The use of SST-02 avoids a lengthy synthetic route and may thus decrease the future cost of nucleic acid therapeutics.

Pharmacokinetic evaluation of liposomal nanoparticle-encapsulated nucleic acid drug: A combined study of dynamic PET imaging and LC/MS/MS analysis.

In vivo biodistribution analyses, especially in tumors, of nucleic acids delivered with nanoparticles are important to develop drug delivery technologies for medical use. We previously developed wrapsome® (WS), an ~100 nm liposomal nanoparticle that can encapsulate siRNA, and reported that WS accumulates in tumors in vivo and inhibits their growth by an enhanced permeability and retention effect. In the present study, we evaluated the pharmacokinetics of nucleic acid-containing nanoparticles by combining dynamic positron emission tomography (PET) imaging and liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis. An 18-mer phosphorothioate oligodeoxynucleotide (ODN), trabedersen, was used as a model drug and was encapsulated in WS. Dynamic PET imaging and time-activity curve analysis of WS-encapsulated 64Cu-labeled ODNs administered to mice with MIA PaCa-2 subcutaneous xenograft tumors showed tumor accumulation (~3% injected dose per gram (%ID/g)) and liver accumulation (~30 %ID/g) at 24 h. Under these conditions, LC/MS/MS analysis showed that the level of intact ODNs was 1.62 %ID/g in the tumor and 1.70 %ID/g in the liver. From these pharmacokinetic data, the intact/accumulated ODN ratios were calculated using the following equation: intact/accumulated ODN ratio (%) = %ID/g LC/MS/MS, tissue, mean/%ID/g PET, tissue, mean × 100. Interestingly, the ratios for the tumor and kidney were maintained at 20-50% over 48 h after administration of the WS-encapsulated form. In contrast, the ratio for the liver rapidly decreased at 24 h, showing the same pattern as that for naked ODN. These different patterns indicate that WS effectively protected the ODN in the tumor and kidney, but protected it less efficiently in the liver. A combined approach of dynamic PET imaging and LC/MS/MS analysis will assist the development of nanoparticle-encapsulated nucleic acid drugs, such as those using WSs, to determine their detailed pharmacokinetics.

[Case of reversible ischemic neurological deficit presented as hemiballism].

Ballism is characterized by continuous, coarse, flinging involuntary movements involving the limbs. Although persistent involuntary movements caused by cerebrovascular diseases mostly in middle-aged patients are well known, transient involuntary movements are an unusual manifestation of cerebrovascular diseases. We describe a rare case of reversible ischemic neurologic deficit (RIND) presented as hemiballism. A 71-year-old man was admitted to our hospital for hemiballism in the right limbs. On magnetic resonance (MR) imagings, there was no evidence of acute ischemic stroke, but MR angiography revealed severe stenosis of left middle cerebral artery. Electroencephalogram showed no epileptic discharge. For hemiballism, chlorpromazine and haloperidol were administered in addition to antiplatelet management for ischemic attack, and the patient completely recovered on the 5 days of hospitalization. Transient ischemic attacks (TIA) or RIND typically present with neurological deficits such as loss of muscle power, reduced sensation, or visual loss. Involuntary movements are not generally regarded to be TIA or RIND. Involuntary movements such as hemiballism, however, can occur as a symptom of TIA or RIND, which should be recognized and differentiated from conditions like partial seizures. Moreover, they may be an indicator of severe carotid stenotic or occlusive diseases, and patients may be at high risk of ischemic events. Early diagnosis and timely treatment are required to prevent ischemic events.

A Case of Rapid Malignant Brain Swelling Subacutely After Reperfusion Therapy for Internal Carotid Artery Occlusion.

BACKGROUND: Severe complications after reperfusion therapy for acute major vessel occlusion are not well described. We present an extremely rare case of a patient with rapid malignant brain swelling subacutely after acute ischemic stroke. CASE DESCRIPTION: An 84-year-old man underwent reperfusion therapy for acute left internal carotid artery occlusion; complete reperfusion was achieved. Although magnetic resonance imaging on postoperative day 1 revealed a small hemorrhagic infarction and subarachnoid hemorrhage unrelated to a left middle cerebral artery aneurysm in the left frontal lobe, neurologic deficits resolved completely. On postoperative day 5, the patient developed a fever and sudden disorder of consciousness with right hemiparesis. Urosepsis was diagnosed, and computed tomography revealed massive hemorrhagic infarction in the left frontal lobe and diffuse subarachnoid hemorrhage. Emergent hematoma evacuation and clipping were performed. Although the aneurysm was unruptured, brain swelling was severe despite a patent middle cerebral artery. Computed tomography performed immediately postoperatively (within 6 hours after preoperative computed tomography) showed severe left brain swelling with midline shift. The patient died on postoperative day 15. CONCLUSIONS: This case has similarities to both second-impact syndrome after head trauma and perfusion breakthrough phenomenon. Initial ischemic damage following reperfusion therapy and damage secondary to sepsis and subarachnoid hemorrhage may have led to rapid malignant brain swelling in this patient. Careful management is important for patients receiving reperfusion therapy.

Iatrogenic Removal of the Intima in the Middle Cerebral Artery by a Stent Retriever: A Report of Two Cases.

BACKGROUND: Mechanical thrombectomy improves functional outcomes in patients with acute ischemic stroke. However, stent retrievers have the risk of vascular damage. CASE DESCRIPTION: We present 2 cases of patients with acute internal carotid artery occlusion who experienced removal of the intima by a stent retriever. In both patients, a 6 × 30-mm Solitaire stent was fully deployed from the M2 portion and slowly withdrawn. White membranes were retrieved outside the strut in both patients. Histopathologic examination showed that one membrane consisted of thickened intima and internal elastic lamina and the other consisted of calcified intima and internal elastic lamina. One patient who suffered embolic stroke experienced recurrent infarction within 24 hours after operation, and the damaged vessel was occluded on magnetic resonance angiography 21 days after stroke. In another patient with carotid artery dissection, the damaged vessel showed asymptomatic stenosis on magnetic resonance angiography 90 days after stroke. Arteries with both atherosclerosis and vessel dissection may be vulnerable to high radial expansion force. CONCLUSIONS: Full deployment of a relatively large-sized stent into a vulnerable vessel may cause vessel dissection after removal of the intima. Appropriate material selection and treatment strategy while considering stroke etiology and the occlusion site are important to prevent vessel damage.

Papillary tumor of the pineal region.

A 48-year-old female presented with an extremely rare primary tumor of the pineal region with papillary features manifesting as morning headaches persisting for 1 month. Magnetic resonance imaging showed a well-defined mass, with some cystic components, in the region of the pineal gland. The tumor was completely removed through an occipital transtentorial approach in the prone position. Histological examination found a distinctive papillary growth pattern in which the vessels were covered by multiple layers of tumor cells. The histological diagnosis was papillary tumor of the pineal region (PTPR), which has recently been described as a distinct clinicopathological entity requiring careful follow up because the prognosis is not well understood. Postoperatively, the patient has continued to do well, with no recurrence at the 8-month follow-up examination. PTPR should be considered in the differential diagnosis of pineal tumors. PTPR may have been frequently misinterpreted in the past as either ependymoma or choroid plexus papilloma due to the similar morphology.

X-ray absorption fine structure combined with x-ray fluorescence spectrometry. Part 15. Monitoring of vanadium site transformations on titania and in mesoporous titania by selective detection of the vanadium K alpha1 fluorescence.

X-ray absorption fine structure combined with X-ray fluorescence spectrometry was applied to various V+TiO2 hybrid samples. Emitted V K alpha1 fluorescence from the sample was selectively counted by using a high-energy-resolution (0.4 eV) spectrometer equipped with a Ge(331) crystal. Two advantages of this method, extremely high signal/background ratio and the compatibility of measurements in the atmosphere of reaction gas (in situ study in relation to heterogeneous catalysis), were effective at the V K-edge. Structure transformation of the V sites was spectroscopically followed for the V/TiO2 catalyst. The monooxo tetrahedral vanadate site was demonstrated to exist at 473 K. It transformed into dispersed species of 5-fold coordination in ambient air and further into polymeric VO(x) species in 0.85 kPa of water at 290 K. In the presence of 3.2 kPa of 2-propanol, dissociative adsorption of 2-propanol on the dispersed V species was strongly suggested at 290-473 K. In situ structure changes of V sites on TiO2 were reported by means of XAFS for the first time. The V(V) sites for the V/TiO2 catalysts were essentially identical with those for V supported on mesoporous (high-surface-area) TiO2 and V-TiO2 sample prepared by the sol-gel method. However, predominant V(IV) sites were found for mesoporous V-TiO2. The V(IV) sites substituted on the Ti sites of TiO2. When the molar ratio of V/Ti increased from 1/100 to 1/5.0, major octahedral V sites in the TiO2 matrix looked to transform into tetrahedral ones.

Retrospective analysis of neurological outcome after intra-arterial thrombolysis in basilar artery occlusion.

BACKGROUND: Basilar artery occlusion usually has a very poor outcome and is associated with a high mortality rate. Local intra-arterial thrombolysis may improve the clinical outcome and reduce mortality in the treatment of acute basilar artery occlusion. We evaluated the possible variables affecting recanalization and clinical outcome in patients with basilar artery occlusions undergoing thrombolytic therapy. METHODS: We analyzed retrospectively the clinical course and outcome of a series of 26 patients between 1998 and 2001. All patients who were examined within 24 hours after onset of symptoms underwent emergency cerebral angiography and subsequent intra-arterial thrombolysis. Three patients additionally received percutaneous transluminal angioplasty of underlying stenosis at the site of thrombosis. RESULTS: Outcome was good in 9 patients (34.6%) and poor in 17 (65.4%). Recanalization could be achieved in 24 patients (92.3%) and was not affected by age, sex, site of occlusion, etiology, thrombolytic drugs, or time interval. Good outcome was associated with younger age, good initial clinical condition, and no evidence of brain stem infarction. There was no association between the interval (greater or less than 6 hours) from the onset of symptoms until the end of thrombolysis and survival. CONCLUSIONS: We confirm that intra-arterial thrombolysis reduces mortality in basilar artery occlusion. Young patients (<75 years) without any infarct in brain stem before the start of treatment seem to be the ideal candidates for thrombolysis. Basilar artery thrombosis could and should be reopened, even late (after 6 hours) after symptom onset.

[Liposome modified with VIP-lipopeptide as a new drug delivery system].

We have designed a novel lipid analog (lipopeptide) that mimics the structural features of modified phospholipids. This lipopeptide is easily synthesized using a peptide synthesizer and has been shown to be useful for the modification of liposomes, which are used as an active targeted drug delivery system (DDS). Vasoactive intestinal peptide (VIP) has high homology with pituitary adenylate cyclase activating peptide (PACAP). There are three major PACAP receptors: PAC1R, VPAC1R, and VPAC2R. PAC1R has affinity only for PACAP, whereas VPAC1R and VPAC2R have the same affinity for both VIP and PACAP. In the present study, we synthesized several lipopeptides conjugated with VIP through different linkers and found that liposomes modified with these lipopeptides (VIP-Lips) selectively recognized the PACAP/VIP receptors. The anti-cancer activity of these VIP-Lips was evaluated by encapsulation of an antitumor drug, doxorubicin (DOX), into the modified liposomes (VIP-Lips-DOX) against the human osteosarcoma cell line, Saos-2, which highly expresses the VIP receptor. cAMP production was then measured to determine how well the VIP-Lips were able to recognize VPAC2R. The results clearly indicate that the proposed lipopeptide methodology holds promise as a DDS for cancer therapy.

Saturated fatty acid and TLR signaling link ß cell dysfunction and islet inflammation.

Consumption of foods high in saturated fatty acids (FAs) as well as elevated levels of circulating free FAs are known to be associated with T2D. Though previous studies showed inflammation is crucially involved in the development of insulin resistance, how inflammation contributes to ß cell dysfunction has remained unclear. We report here the saturated FA palmitate induces ß cell dysfunction in vivo by activating inflammatory processes within islets. Through a combination of in vivo and in vitro studies, we show ß cells respond to palmitate via the TLR4/MyD88 pathway and produce chemokines that recruit CD11b(+)Ly-6C(+) M1-type proinflammatory monocytes/macrophages to the islets. Depletion of M1-type cells protected mice from palmitate-induced ß cell dysfunction. Islet inflammation also plays an essential role in ß cell dysfunction in T2D mouse models. Collectively, these results demonstrate a clear mechanistic link between ß cell dysfunction and inflammation mediated at least in part via the FFA-TLR4/MyD88 pathway.

Preparation of liposomes modified with lipopeptides using a supercritical carbon dioxide reverse-phase evaporation method.

Although liposomes are considered to be one of the most promising carriers for drug delivery systems (DDS), they have drawbacks such as insufficient drug-entrapment efficiency and long-term stability. The objectives of this study are to improve the trapping efficiency by addition of lipopeptides (LPs), and using a supercritical CO(2) reverse-phase evaporation (SCRPE) process, along with incorporation of PEG-modified phospholipids to improve long-term stability. In this study, bovine serum albumin (BSA) was used as a model drug substance for entrapment by liposomes. Improvements in the entrapment efficiency and stability of liposomes were achieved by modification with LPs and use of a SCRPE preparation process. The BSA-entrapment efficiency of liposomes modified with cationic LPs with arginine residues, as a result of their ionic interactions, was six times that of liposomes prepared by the Bangham method. Use of a SCRPE method along with LP modification further enhanced entrapment and enabled spontaneous formation of unilamellar liposomes with long-term stability. Liposomes consisting of DPPC/Chol/C(16)-Arg2/DSPE-PEG2000 (60/30/5/5), with up to 70% entrapment efficiency for BSA and a stability level of 90% for over 40 h, were obtained. DSC and SAXS analyses indicated that certain amounts of LP in the DPPC induced phase-transitional and structural changes in the lamellar membrane, and these changes improved the DDS carrier properties.The SCRPE method provides organic-solvent-free liposomes, and the LPs for the liposome modification are derivatives of amino acids and fatty acids, which are sustainable and biocompatible materials. This study therefore suggests that there are opportunities for the development of novel DDS carriers with excellent performance and which address environmental concerns.

Reversible clinical and magnetic resonance imaging of central pontine myelinolysis following surgery for craniopharyngioma: serial magnetic resonance imaging studies.

An 18-year-old girl presented with central pontine myelinolysis (CPM) following surgery for craniopharyngioma. Postoperatively, the patient developed diabetes insipidus with remarkable fluctuation of serum sodium level, suffered a seizure, and developed mental state changes and quadriparesis. Magnetic resonance (MR) imaging obtained soon after the development of the symptoms showed no significant abnormalities. MR imaging obtained 2 months later demonstrated typical trident or bat-like signal abnormalities in the center of the pons, compatible with CPM. Serial MR imaging obtained at 7 and 10 months showed the lesion had decreased in size or almost completely resolved and the patient almost completely recovered. CPM is well known, but neurosurgeons should consider the possibility following surgery for craniopharyngioma.

A nanoparticle system specifically designed to deliver short interfering RNA inhibits tumor growth in vivo.

Use of short interfering RNA (siRNA) is a promising new approach thought to have a strong potential to lead to rapid development of gene-oriented therapies. Here, we describe a newly developed, systemically injectable siRNA vehicle, the "wrapsome" (WS), which contains siRNA and a cationic lipofection complex in a core that is fully enveloped by a neutral lipid bilayer and hydrophilic polymers. WS protected siRNA from enzymatic digestion, providing a long half-life in the systemic circulation. Moreover, siRNA/WS leaked from blood vessels within tumors into the tumor tissue, where it accumulated and was subsequently transfected into the tumor cells. Because the transcription factor KLF5 is known to play a role in tumor angiogenesis, we designed KLF5-siRNA to test the antitumor activity of siRNA/WS. KLF5-siRNA/WS exhibited significant antitumor activity, although neither WS containing control scrambled-siRNA nor saline containing KLF5-siRNA affected tumor growth. KLF5-siRNA/WS inhibited Klf5 expression within tumors at both mRNA and protein levels, significantly reducing angiogenesis, and we detected no significant acute or long-term toxicity. Our findings support the idea that siRNA/WS can be used to knock down specific genes within tumors and thereby exert therapeutic effects against cancers.

Synthesis and evaluation of a novel lipid-peptide conjugate for functionalized liposome.

A novel lipid analog based on amino acids for liposome modification was developed. It consisted of three different kinds of amino acid derivatives and two fatty acids, and can react directly with the peptide synthesized first on resin by Fmoc solid-phase synthesis. In this study, lipid analog conjugated with HIV-TAT peptide (domain of human immunodeficiency virus TAT protein) was synthesized and successfully incorporated into liposome. The liposome containing the lipopeptide bearing HIV-TAT exhibited efficient cellular uptake.

High-resolution and high-intensity powder diffractometer at BL15XU in SPring-8.

A new ultra-high-resolution powder diffractometer for synchrotron radiation has been constructed at beamline BL15XU, SPring-8. The two-axis diffractometer is optimized for high-flux and high-coherent X-ray beams, which are provided by combining a planar undulator and a large offset rotated-inclined Si(111) double-crystal monochromator. The optics design of the diffractometer is based on transmission geometry, which employs a capillary specimen and reflection geometries using a flat-plate specimen. The intensity data are collected using a 2theta step-scan technique in both geometries. The diffractometer can be arranged in a variety of optical configurations, e.g. simple receiving slits, flat crystal analyzer of Ge(111) or Si(111), and in-vacuum-type long horizontal parallel slits. A minimum full width at half-maximum against 2theta was 0.00572 degrees at lambda = 0.63582 A for the (200) reflections from Si powder in the transmission geometry employing the Ge(111) crystal analyzer. A wide temperature range (32-900 K), which is controlled by a He/N(2) gas stream system, is available. 288 structure parameters of a zeolite ZSM-5 sample have been demonstrated to successfully refine with a R(wp) value of 6.96% by a Rietveld analysis of the high-resolution powder diffraction data from a 1 mm-diameter capillary specimen.

Non-existence of positive glitches in spectra using the YB(66) double-crystal monochromator of BL15XU at Spring-8.

YB(66) is suitable for dispersing synchrotron radiation in the 1-2 keV energy range with a 2d lattice spacing of 1.17 nm. When used with an undulator there are no positive glitches at 1385.6 and 1438 eV in spectra dispersed by a YB(66) 400 double-crystal monochromator as observed using bending-magnet or wiggler beamlines. The transmission function of a YB(66) double-crystal monochromator has been measured by means of a Si PIN photodetector, and X-ray absorption near-edge structure (XANES) of Mg, Al and Si were measured at high resolution. From all of these experiments it has been clarified that a YB(66) double-crystal monochromator is well suited for soft X-ray beamlines on third-generation light sources.