Effects of aliskiren-based therapy on ambulatory blood pressure profile, central hemodynamics, and arterial stiffness in nondiabetic mild to moderate hypertensive patients

J Clin Hypertens (Greenwich). 2012;00:000–000. ©2012 Wiley Periodicals, Inc. Aliskiren is a direct renin inhibitor that exerts its effect at the rate‐limiting step of the renin‐angiotensin system. This study was performed to examine the beneficial effects of aliskiren‐based antihypertensive therapy on the ambulatory blood pressure (BP) profile, central hemodybamics, and arterial stiffness in untreated Japanese patients with mild to moderate hypertension. Twenty‐one Japanese nondiabetic patients with untreated mild to moderate essential hypertension were initially given aliskiren once daily at 150 mg, and the dose was titrated up to 300 mg as needed. After 12 weeks of aliskiren‐based therapy, the clinic, ambulatory, and central BP values as well as brachial‐ankle pulse wave velocity (baPWV) were all significantly decreased compared with baseline (clinic systolic BP, 151±11 mm Hg vs 132±11 mm Hg; clinic diastolic BP, 91±13 mm Hg vs 82±9 mm Hg; 24‐hour systolic BP, 144±12 mm Hg vs 133±11 mm Hg; 24‐hour diastolic BP, 88±8 mm Hg vs 81±9 mm Hg; central BP, 162±16 mm Hg vs 148±14 mm Hg; baPWV, 1625±245 cm/s vs 1495±199 cm/s; P<.05). These results show that aliskiren, as a first‐line regimen, improves the ambulatory BP profile and may have protective vascular effects in Japanese nondiabetic patients with untreated mild to moderate essential hypertension.     

A case of multiple metastatic malignant melanoma with the largest lesion in the ileum and no skin lesion

We report the case of a 72-year-old woman with malignant melanoma and multiple metastases; the largest tumor was in the ileum. The patient experienced general fatigue and bloody feces for 1 month before consulting a nearby clinic. Blood tests revealed anemia, and fecal occult blood was positive, but no abnormalities were detected using gastrointestinal endoscopy and colonoscopy or the skin of the entire body. Computed tomography images of the chest, abdomen, and pelvic region, and positron emission tomography–computed tomography images of the entire body revealed multiple nodules in the ileum, left mammary gland, left thyroid, right inguinal lymph node, and on the fascia of the right thoracic area and right buttocks. The tumor in the left mammary gland was excised and immunohistochemical analysis revealed that the excised tissue was positive for HMB45, melan-A, and MITF, but negative for S-100 protein. Diagnosed with melanoma with multiple metastases, the patient underwent four cycles of dacarbazine, nimustine hydrochloride, and vincristine (DAV) plus interferon beta chemotherapy and one cycle of dacarbazine, nimustine hydrochloride, cisplatin, and tamoxifen (DAC-Tam) chemotherapy. Two series of embolizations of the artery feeding the ileum tumors, as well as a series of plasma and red blood cell transfusions, were performed for ileum tumor hemorrhage. The patient was hospitalized eight times, for a total of 204 days during the 1-year survival period before her death from respiratory failure.     

Successful endoscopic dilatation of a severe stricture of the cervical esophagus after definitive combined chemotherapy plus radiotherapy for esophageal cancer

We describe an improved endoscopic technique for antegrade dilatation of a cervical esophageal stricture performed with the use of using a guide wire, an endoscopic retrograde cholangiopancreatic-duct (ERCP) catheter, and a balloon dilator. The patient was a 55-year-old woman who had a cervical esophageal stricture associated with definitive chemoradiotherapy for advanced esophageal squamous cell carcinoma. Endoscopy showed the stricture was located at the esophageal orifice. The membranous stricture was punctured with an ERCP catheter, and balloon dilators were passed through the stricture under C-arm fluoroscopy. This technique is considered useful for managing severe strictures of the cervical esophagus after combined chemotherapy plus radiotherapy for esophageal cancer.     

Synthesis of Pd–Ru solid-solution nanoparticles by pulsed plasma in liquid method

We have synthesized solid-solution nanoparticles (Pd : Ru = 1 : 3, 1 : 1 and 3 : 1) in an immiscible Pd–Ru system by the pulsed plasma in liquid method using Pd–Ru mixture bulk electrodes. The particle sizes of the floated and sedimented samples were measured to be <10 and <20 nm, respectively, via high-resolution transmission electron microscopy (HR-TEM). The lattice parameters of nanoparticles followed the Vegard''s law, and the energy-dispersive X-ray spectroscopy (EDX) results almost coincided with those obtained for the starting bulk mixtures. The solid-solution structures and local structure were confirmed via HR-TEM, X-ray photoelectron spectroscopy (XPS) and X-ray absorption fine structure spectroscopy (XAFS).

We have synthesized solid-solution nanoparticles (Pd : Ru = 1 : 3, 1 : 1 and 3 : 1) in an immiscible Pd–Ru system by the pulsed plasma in liquid method using Pd–Ru mixture bulk electrodes.     

Histidine-conjugated DNA as a biomolecular depot for metal ions

Histidine is a versatile amino acid residue that plays a critical role in the active sites of many metalloenzymes. DNA is an attractive biomolecular scaffold owing to its chemical and thermal stability and easy accessibility. Herein, we report histidine-conjugated DNA oligonucleotides, which were synthesized by combining DNA alphabets and natural metal-binding amino acids, as novel biohybrid materials and demonstrate their use as molecular depots for various metal ions. Moreover, histidine-conjugated DNA oligonucleotides could be successfully used in asymmetric catalysis (up to 90% conversion and 95% ee) as DNA metalloenzymes and in 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) oxidation reactions as horseradish-peroxidase (HRP)-mimicking DNAzymes with suitable metal cofactors. Nature-inspired histidine-DNA hybrids will become an attractive strategy to construct fine-tuned coordination environments as an alternative to bioremediation and the development of multimetal enzymes.

Histidine is a versatile amino acid residue that plays a critical role in the active sites of many metalloenzymes.     

Detailed magnetic analysis and successful deep-neural-network-based conformational prediction for [VO(dmso)5][BPh4]2

Pentakis(dimethylsulfoxide-κO)oxidovanadium(iv) bis(tetraphenylborate), [VO(dmso)₅][BPh₄]₂ (dmso: dimethylsulfoxide), was synthesized, and its pseudo-C₄ VO₆ coordination geometry was revealed by a single-crystal X-ray method. A novel equation set was obtained for magnetic susceptibility and magnetization of the d¹ complexes, considering the axial distortion and the spin–orbit coupling for the ²D free-ion term. The equation set enabled magnetic simulation for significantly symmetry-lowered d¹ complexes to obtain the anisotropic g-values and also the excitation energies. In addition, conformational prediction was conducted, using the enumeration results on the basis of the group theory. The dominant conformers were predicted on the basis of the density functional theory (DFT) method, and especially, the conformer in the crystal was successfully predicted by a deep neural network method.

The conformer in the crystal was successfully predicted by a deep neural network method.     

Continuous syntheses of carbon-supported Pd and Pd@Pt core–shell nanoparticles using a flow-type single-mode microwave reactor

Continuous syntheses of carbon-supported Pd@Pt core–shell nanoparticles were performed using microwave-assisted flow reaction in polyol to synthesize carbon-supported core Pd with subsequent direct coating of a Pt shell. By optimizing the amount of NaOH, almost all Pt precursors contributed to shell formation without specific chemicals.

Continuous syntheses of carbon-supported Pd@Pt core–shell nanoparticles were performed using flow processes including microwave-assisted Pd core–nanoparticle formation.

Continuous flow syntheses have attracted attention as a powerful method for organic, nanomaterial, and pharmaceutical syntheses because of various features that produce benefits in terms of efficiency, safety, and reduction of environmental burdens.^1–7 Advances of homogeneous heating and mixing techniques in continuous flow reactors have engendered further developments for precise reaction control, which is expected to create innovative materials through combination with multiple-step flow syntheses.Microwave (MW) dielectric heating has been recognized as a promising methodology for continuous flow syntheses because rapid or selective heating raises the reaction rate and product yield.^8–18 For the last two decades, most MW apparatus has been batch-type equipped with a stirring mechanism in a multi-mode cavity. Therefore, conventionally used MW-assisted flow reactors have been mainly of the modified batch-type. Results show that the electromagnetic field distribution can be spatially disordered, causing inhomogeneous heating of the reactor.^19–25 Improvements of reactors suitable for flow-type work have been studied actively in recent years to improve their energy efficiency and to make irradiation of MW more homogeneous.^26–37We originally designed a MW flow reactor system that forms a homogeneous heating zone through generation of a uniform electromagnetic field in a cylindrical single-mode MW cavity.^26,30 The temperatures of flowing liquids in the reactor were controlled precisely via the resonance frequency auto-tracking function. Continuous flow syntheses of metal nanoparticle, metal-oxide, and binary metal core–shell systems with uniform particle size have been achieved using our MW reactor system.^26,38,39 Furthermore, large-scale production necessary for industrial applications can be achieved through integration of multiple MW reactors.³⁰Carbon-supported metal catalysts are widely used in various chemical transformations and fine organic syntheses. Particularly, binary metal systems such as Pd@Pt core–shell nanoparticles have attracted considerable interest for electro-catalysis in polymer electrolyte membrane fuel cells (PEMFC) because of their enhanced oxygen reduction activity compared to a single-use Pt catalyst. Binary metal systems also contribute to minimization of the usage of valuable Pt.^40–51 Earlier studies of carbon-supported Pd@Pt syntheses involved multiple steps of batch procedures such as separation, washing and pre-treatment of core metal nanoparticles, coating procedures of metal shells, and dispersion onto carbon supports. Flow-through processes generally present advantages over batch processes in terms of simplicity and high efficiency in continuous material production.We present here a continuous synthesis of carbon-supported Pd and Pd@Pt core–shell nanoparticles as a synthesis example of a carbon-supported metal catalyst using our MW flow reactor. This system incorporates the direct transfer of a core metal dispersion into a shell formation reaction without isolation. Nanoparticle desorption is prevented by nanoparticle synthesis directly on a carbon support. The presence of protective agents that are commonly used in nanoparticle syntheses, such as poly(N-vinylpyrrolidone), can limit the chemical activity of the catalyst. Nevertheless, this system requires no protective agent. Moreover, this system is a simple polyol synthesis that uses no strong reducing agent. It therefore imposes little or no environmental burden. For this study, the particle size and distribution of metals in Pd and Pd@Pt core–shell nanoparticles were characterized using TEM, HAADF-STEM observations, and EDS elemental mapping. From electrochemical measurements, the catalytic performance of Pd@Pt core–shell nanoparticles was evaluated.A schematic view of the process for the continuous synthesis of carbon-supported Pd@Pt core–shell nanoparticles is presented in Fig. 1. Details of single-mode MW flow reactor are described in ESI.^† We attempted to conduct a series of reactions coherently in a flow reaction system, i.e., MW-assisted flow reaction for the synthesis of carbon supported core Pd nanoparticles with subsequent deposition of the Pt shell. Typically, a mixture containing Na₂[PdCl₄] (1–4 mM) in ethylene glycol (EG), carbon support (Vulcan XC72, 0.1 wt%), and an aqueous NaOH solution were prepared. This mixture was introduced continuously into the PTFE tube reactor placed in the center of the MW cavity. Here, EG works as the reaction solvent as well as the reducing agent that converts Pd(ii) into Pd(0) nanoparticles. The MW heating temperature was set to 100 °C with the flow rate of 80 ml h^−l, which corresponds to residence time of 4 s. The carbon-supported Pd nanoparticles were transferred directly to the Pt shell formation process without particle isolation. The dispersed solution was introduced into a T-type mixer and was mixed with a EG solution of H₂[PtCl₆]·6H₂O (10 mM). The molar ratio of Pd : Pt was fixed to 1 : 1. Subsequently, after additional aqueous NaOH solution was mixed at the second T-mixer, the reaction mixture was taken out of the mixer and was let to stand at room temperature (1–72 h) for Pt shell growth.Open in a separate windowFig. 1Schematic showing continuous synthesis of carbon-supported Pd and Pd@Pt core–shell nanoparticles. The Pd nanoparticles were dispersed on the carbon support by MW heating of the EG solution. The solution was then transferred directly to Pt shell formation.Rapid formation of Pd nanoparticles with average size of 3.0 nm took place at the carbon-support surface during MW heating in the tubular reactor (Fig. 2a). Most of the Pd(ii) precursor was converted instantaneously to Pd(0) nanoparticles and was well dispersed over the carbon surface. Fig. 2b shows the time profile of the outlet temperature and applied MW power during continuous synthesis of carbon-supported Pd nanoparticles. The solution temperature rose instantaneously, reaching the setting temperature in a few seconds. This temperature was maintained with high precision (±2 °C) by the continuous supply of ca. 18 W microwave power. No appreciable deposition of metal was observed inside of the PTFE tube. It is noteworthy that Pd of 98% or more was supported on carbon by heating for 4 s at 100 °C from ICP-OES measurement. Our earlier report described continuous polyol (EG) synthesis of Pd nanoparticles as nearly completed with 6 s at 200 °C.³⁹ The reaction temperature in polyol synthesis containing the carbon was considerably low, suggesting that selective reduction reaction occurs on the carbon surface, which is a high electron donating property.Open in a separate windowFig. 2(a) TEM image of carbon-supported Pd nanoparticles synthesized using the MW flow reactor. The average particle size was 3.0 nm. (b) The time profile of the temperature at the reactor outlet and applied microwave power during continuous synthesis of carbon-supported Pd nanoparticles. Na₂[PdCl₄] = 2 mM, NaOH = 10 mM.The concentrations of Na₂[PdCl₄] precursor and NaOH affect the Pd nanoparticle size. Results show that the Pd particle size increased as the initial concentration of Na₂[PdCl₄] increased (Fig. S1a and b^†). Change of NaOH concentration exerted a stronger influence on the particle size. Nanoparticles of 12.3 nm were observed without addition of NaOH, whereas 2.6 nm size particles were deposited at the concentration of 20 mM (Fig. S1c and d^†). The higher NaOH concentration led to instantaneous nucleation and rapid completion of reduction. The Pd nanoparticle surface is equilibrated with Pd–O⁻ and Pd–OH depending on the NaOH concentration. The surface is more negative at high concentrations of NaOH because of the increase of the number of Pd–O⁻, which inhibits the mutual aggregation and further particle growth. Furthermore, to control the Pd nanoparticle morphology, we conducted synthesis by adding NaBr, which has been reported as effective for cubic Pd nanoparticle synthesis.⁵² However, because reduction of the Pd precursor derives from electron donation from both the polyol and the carbon support, morphological control was not achieved (Fig. S2^†). That finding suggests that morphological control is difficult to achieve by adding surfactant agents to the polyol.For Pt shell formation, carbon supported Pd nanoparticles (3.0 nm average particle size) were mixed with H₂[PtCl₆]·6H₂O solution with the molar ratio of Pd : Pt = 1 : 1. Then additional NaOH solution was mixed. As described in earlier reports,³⁹ alkaline conditions under which base hydrolysis and reduction of [PtCl₆]²⁻ to [Pt(OH)₄]²⁻ takes place are necessary for effective Pt shell formation. It is noteworthy that the added Pt precursor was almost entirely supported on carbon within 24 h in cases where an appropriate amount of additional NaOH (5 mM) was mixed by the second T-mixer (Fig. 3a). However, for 10 mM, nucleation and growth of single Pt nanoparticles were enhanced in place of core–shell formation. Consequently, a mixture of Pd@Pt and single Pt nanoparticles was formed on the carbon support (Fig. 3b). Very fine Pt nanoparticles were observed in the supernatant solution.Open in a separate windowFig. 3(a) Time profiles of residual ratio of Pt in the mixed solutions. Horizontal axis was left standing time. Carbon-support in the mixed solution after added the Pt precursor was precipitated by centrifugation. The supernatant solution was measured by ICP-OES. Concentrations of additional NaOH were 0, 5, and 10 mM. (b) TEM image of carbon-supported Pd@Pt core–shell nanoparticles. The synthesis conditions of Pd nanoparticles were Na₂[PdCl₄] (2 mM) and NaOH (10 mM). The molar ratio of Na₂[PdCl₄] : H₂[PtCl₆]·6H₂O was 1 : 1, and additional NaOH concentration was 10 mM. After left standing for 72 h, the mixture of Pd@Pt and single Pt nanoparticles (1–2 nm) was formed on carbon-support. Fig. 4a portrays a TEM image of carbon supported Pd@Pt core–shell nanoparticles. The average particle size of Pd@Pt core–shell nanoparticles was 3.6 nm after being left to stand for 24 h: larger than the initial Pd nanoparticles (3.0 nm). Fig. 4b shows the HAADF-STEM image of Pd@Pt core–shell nanoparticles supported on carbon. The core–shell structure of the particles can be ascertained from the contrast of the image. The Z-contrast image shows the presence of brighter shells over darker cores. Actually, the contrast is strongly dependent on the atomic number (Z) of the element.⁵³ The Z values of Pt (Z = 78) and Pd (Z = 46) differ considerably. Therefore, the image shows the formation of Pd@Pt core–shell structure with the uniform elemental distribution. Elemental mapping images by STEM-EDS show that both Pd and Pt metals were present in all the observed nanoparticles (Fig. 4c). Based on the atomic ratio (Pd : Pt = 49 : 51), they show good agreement with the designed values. The Pt shell thickness was estimated as about 0.6 nm, which corresponds to 2–3 atomic layer thickness of Pt encapsulating the Pd core metal, indicating good agreement with Fig. 4b image. For an earlier study, uniform Pt shells were formed by dropwise injection of the Pt precursor solution because the Pt shell growth rate differs depending on the crystal plane of the Pd nanoparticle.⁴⁶ For more precise control of shell thickness in our system, the Pt precursor solution should be mixed in multiple steps.Open in a separate windowFig. 4(a) TEM image and (b) HAADF-STEM image of carbon-supported Pd@Pt core–shell nanoparticles and the line profile of contrast. (c) Elemental mapping image of carbon-supported Pd@Pt core–shell nanoparticles, where Pd and Pt elements are displayed respectively as red and green. The EDS atomic ratio of Pd : Pt was 49 : 51. The synthesis conditions of Pd nanoparticles were Na₂[PdCl₄] (2 mM) and NaOH (10 mM). The molar ratio of Na₂[PdCl₄] : H₂[PtCl₆]·6H₂O was 1 : 1. The concentration of additional NaOH were 5 mM. It was left standing for 24 h.A comparison of the catalytic performance of the carbon-supported Pd@Pt core–shell and Pt nanoparticles is shown in Fig. S3.^† For this experiment, carbon-supported Pt nanoparticles with Pt 2 mM were prepared as a reference catalyst using a similar synthetic method. The initial Pt mass activities of the carbon-supported Pd@Pt and Pt nanoparticles were, respectively, 0.39 and 0.24 A mg_Pt⁻¹, improving by the core–shell structure. In addition, durability tests for carbon-supported Pd@Pt nanoparticles show that the reduction rate of Pt mass activity after 5000 cycles was only 2%. The catalytic activities of carbon-supported Pd@Pt nanoparticles were superior in terms of durability, suggesting that the Pt shell was firmly formed.     

Can decompression surgery relieve low back pain in patients with lumbar spinal stenosis combined with degenerative lumbar scoliosis?

Introduction

Decompression with fusion is usually recommended in patients with lumbar spinal stenosis (LSS) combined with degenerative lumbar scoliosis (DLS). However, elderly patients with LSS and DLS often have other comorbidities, and surgical treatment must be both safe and effective. The aim of this study was to investigate whether decompression surgery alone alleviates low back pain (LBP) in patients with LSS and DLS, and to identify the predictors of postoperative residual LBP.

Materials and methods

A total of 75 patients (33 males and 42 females) with a mean age of 71.8 years (range 53–86 years) who underwent decompression surgery for LSS with DLS (Cobb angle ≥ 10°) and had a minimum follow-up period of 1 year, were retrospectively reviewed using the Japanese Orthopaedic Association scoring system for the assessment of lumbar spinal diseases (JOA score). Radiographic measurements included coronal and sagittal Cobb angles, apical vertebral rotation (Nash-Moe method), and anteroposterior and lateral spondylolisthesis. Logistic regression analysis was performed to investigate the predictors of residual LBP after surgery.

Results

Forty-nine patients had preoperative LBP, of which 29 (59.1 %) experienced postoperative relief of LBP. Logistic regression analysis demonstrated that the degree of apical vertebral rotation on preoperative radiography was significantly associated with postoperative residual LBP (odds ratio, 8.16, 95 % confidence interval, 1.55–83.81, p = 0.011).

Conclusion

A higher degree of apical vertebral rotation may therefore be an indicator of mechanical LBP in patients with LSS and DLS. Decompression with fusion should be recommended in these patients.