Impaired Processing of Prohormones in Secretogranin III-Null Mice Causes Maladaptation to an Inadequate Diet and Stress.

Secretogranin III (SgIII), a member of the granin family, binds both to another granin, chromogranin A (CgA), and to a cholesterol-rich membrane that is destined for secretory granules (SGs). The knockdown of SgIII in adrenocorticotropic hormone (ACTH)-producing AtT-20 cells largely impairs the regulated secretion of CgA and ACTH. To clarify the physiological roles of SgIII in vivo, we analyzed hormone secretion and SG biogenesis in newly established SgIII-knockout (KO) mice.

Calcium phosphate-based organic-inorganic hybrid nanocarriers with pH-responsive on/off switch for photodynamic therapy.

Photodynamic therapy (PDT) is a promising treatment modality for malignant tumors in a light-selective manner. To improve the PDT efficacy, numerous kinds of nanocarriers have been developed to deliver photosensitizers (PSs) selectively into the tumor through leaky tumor-associated vasculature. However, the corresponding prolonged retention of the nanocarrier in the bloodstream may lead to unfavorable photochemical damage to normal tissues such as skin.

siRNA-Loaded Polyion Complex Micelle Decorated with Charge-Conversional Polymer Tuned to Undergo Stepwise Response to Intra-Tumoral and Intra-Endosomal pHs for Exerting Enhanced RNAi Efficacy.

Small interfering RNA (siRNA) needs an efficient delivery vehicle to reach the cytoplasm of target cells for successful RNA interference (RNAi) therapy. This study aimed to develop an siRNA-loaded polyion complex (PIC) micelle equipped with a smart polymeric shell featuring tumor targetability and endosome escapability for enhanced RNAi activity in cancer cells. To this end, an acidic pH-responsive polypeptide was designed to exert a stepwise change in its charged state from negative to modestly positive and highly positive in response to slightly acidic environment of tumor (pH ∼6.

Expression of Secretogranin III in Chicken Endocrine Cells: Its Relevance to the Secretory Granule Properties of Peptide Prohormone Processing and Bioactive Amine Content.

The expression of secretogranin III (SgIII) in chicken endocrine cells has not been investigated. There is limited data available for the immunohistochemical localization of SgIII in the brain, pituitary, and pancreatic islets of humans and rodents. In the present study, we used immunoblotting to reveal the similarities between the expression patterns of SgIII in the common endocrine glands of chickens and rats.

Precise engineering of siRNA delivery vehicles to tumors using polyion complexes and gold nanoparticles.

For systemic delivery of siRNA to solid tumors, a size-regulated and reversibly stabilized nanoarchitecture was constructed by using a 20 kDa siRNA-loaded unimer polyion complex (uPIC) and 20 nm gold nanoparticle (AuNP). The uPIC was selectively prepared by charge-matched polyionic complexation of a poly(ethylene glycol)-b-poly(L-lysine) (PEG-PLL) copolymer bearing ∼40 positive charges (and thiol group at the ω-end) with a single siRNA bearing 40 negative charges. The thiol group at the ω-end of PEG-PLL further enabled successful conjugation of the uPICs onto the single AuNP through coordinate bonding, generating a nanoarchitecture (uPIC-AuNP) with a size of 38 nm and a narrow size distribution.

Fine-tuning of charge-conversion polymer structure for efficient endosomal escape of siRNA-loaded calcium phosphate hybrid micelles.

For efficient delivery of siRNA into the cytoplasm, a smart block copolymer of poly(ethylene glycol) and charge-conversion polymer (PEG-CCP) is developed by introducing 2-propionic-3-methylmaleic (PMM) amide as an anionic protective group into side chains of an endosome-disrupting cationic polyaspartamide derivative. The PMM amide moiety is highly susceptible to acid hydrolysis, generating the parent cationic polyaspartamide derivative at endosomal acidic pH 5.5 more rapidly than a previously synthesized cis-aconitic (ACO) amide control.

Systemic siRNA delivery to a spontaneous pancreatic tumor model in transgenic mice by PEGylated calcium phosphate hybrid micelles.

Efficient systems for delivery of small interfering RNA (siRNA) are required for clinical application of RNA interference (RNAi) in cancer therapy. Herein, we developed a safe and efficient nanocarrier comprising poly(ethylene glycol)-block-charge-conversional polymer (PEG-CCP)/calcium phosphate (CaP) hybrid micelles for systemic delivery of siRNA and studied their efficacy in spontaneous bioluminescent pancreatic tumors from transgenic mice. PEG-CCP was engineered to provide the siRNA-loaded hybrid micelles with enhanced colloidal stability and biocompatibility due to the PEG capsule and with endosome-disrupting functionality due to the acidic pH-responsive CCP segment where the polyanionic structure could be converted to polycationic structure at acidic pH through cis-aconitic amide cleavage.

[Epidural anesthesia for femoral head replacement in a spinocerebellar ataxia patient: a case report].

Perioperative management of a spinocerebellar ataxia patient by epidural anesthesia is reported. A 67-year-old woman with left femur neck fracture underwent femoral head replacement. An epidural catheter was placed without difficulty at the L3-4 interspace using the loss of resistance technique.

[Continuous infusion of low-dose remifentanil for palliation of pain with epidural catheterization].

Background: To prospectively determine the safety and effectiveness of continuous infusion of low-dose remifentanil for the reduction of pain in patients for epidural catheterization.

Methods: This study was approved by the institutional review board. Written informed consent was obtained.

[Comparison of the clotting factor activity and thawing time in different thawing procedures of the fresh frozen plasma].

Background: Fresh frozen plasma (FFP) should be thawed in a water bath at 30-37 degrees C. Suitable temperature, the prevention for bacterial contamination, and the efficiency of the process are necessary for a thawing procedure. In this study, we compared the clotting factor activity and thawing time in different thawing procedures; a water bath, the thermostatic thawing chamber (FP-40, Hokuyo ; Kawasumi, Japan), and the microwave system (Transfusio-therm 2000 AMCO; Zeipel, Germany).

Dual environment-responsive polyplex carriers for enhanced intracellular delivery of plasmid DNA.

In this study, we describe a multifunctional, nontoxic delivery vehicle with dual-environment sensitivity to deliver plasmid DNA (pDNA) into the cytoplasm of cells. This delivery vehicle was designed to be destabilized by reduction of disulfide cross-links in the intracellular environment and also to contain pH-sensitive membrane-destabilizing activity in acidic late endosomal/lysosomal compartments to allow escape of pDNA into the cell cytoplasm. Polyion complex formation was used to form ternary polyplexes using ionic polymers containing specific chemistries to achieve functional demands.

Pancreatic cancer therapy by systemic administration of VEGF siRNA contained in calcium phosphate/charge-conversional polymer hybrid nanoparticles.

Development of an efficient in vivo delivery vehicle of small interfering RNA (siRNA) is the key challenge for successful siRNA-based therapies. In this study, toward systemic delivery of siRNA to solid tumors, a smart polymer/calcium phosphate (CaP)/siRNA hybrid nanoparticle was prepared to feature biocompatibility, reversible stability and endosomal escape functionality using a pH sensitive block copolymer of poly(ethylene glycol) and charge-conversional polymer (PEG-CCP), of which anionic functional groups could be converted to cationic groups in an endosomal acidic condition for facilitated endosomal escape. Nanoparticles were confirmed to be approximately 100nm in size, narrowly dispersed and spherical.

Rapid transformation from spherical nanoparticles, nanorods, cubes, or bipyramids to triangular prisms of silver with PVP, citrate, and H2O2.

Rapid sphere-to-prism (STP) transformation of silver was studied in aqueous AgNO(3)/NaBH(4)/polyvinylpyrrolidone (PVP)/trisodium citrate (Na(3)CA)/H(2)O(2) solutions by monitoring time-dependent surface plasmon resonance (SPR) bands in the UV-vis region, by examining transmission electron microscopic (TEM) images, and by analyzing emitted gases during fast reaction. Roles of PVP, Na(3)CA, and H(2)O(2) were studied without addition of a reagent, with different timing of each reagent's addition, and with addition of H(2)O(2) to mixtures of spheres and prisms. Results show that prisms can be prepared without addition of PVP, although it is useful to synthesize smaller monodispersed prisms.

[Difficulty in left-sided double-lumen tube placement in patients undergoing surgical graft replacement of the descending aorta is predicted from tracheobronchial compression].

Background: In surgical graft replacement of the descending aorta graft, one-lung ventilation (OLV) is required to provide adequate surgical view and to allow removal of blood from the left lung. It is best to use a double-lumen tube (DLT) to assure OLV but it is sometimes difficult to place the left-sided DLT due to thoracic aneurysm or the dissection lumen. We retrospectively investigated tracheobronchial anatomy by chest X-ray and chest computed tomography (CT) in 29 cases of descending aorta replacement to determine how best to manage difficult placement of the left-sided DLT.

Sivelestat relaxes vascular smooth muscle contraction in human gastric arteries.

Sivelestat sodium hydrate (sivelestat) is a novel synthetic drug and specific inhibitor of neutrophil elastase that has been approved in Japan as a treatment for acute lung injury associated with systemic inflammatory response syndrome. It is important to determine how sivelestat affects hemodynamics and the regulatory mechanisms of vascular smooth muscle (VSM). We recently found that sivelestat relaxes porcine coronary artery VSM via selective inhibition of Ca(2+) sensitization induced by a receptor agonist without affecting the normal Ca(2+)-induced contraction.

Sivelestat relaxes porcine coronary artery via inhibition of Ca2+ sensitization induced by a receptor agonist.

Sivelestat sodium hydrate (sivelestat) is a novel synthetic drug and specific inhibitor of neutrophil elastase that has been approved in Japan as a treatment for acute lung injury associated with systemic inflammatory response syndrome. There are no reports on the effects of sivelestat on the contractile regulation of vascular smooth muscle. The purpose of the present study was to assess the effects of sivelestat on porcine coronary artery.

Survival case of Vibrio vulnificus infection with multiple endocrine neoplasia type I.

A 35-year-old female with malabsorption syndrome who underwent a pancreatoduodenectomy for multiple endocrine adenomatosis 13 years prior was admitted to our hospital with diarrhea, general fatigue, high fever, and eruption in the lower legs. The patient had consumed raw shrimp a few days before onset and presented systemic inflammatory response syndrome at the time of hospitalization. Vibrio vulnificus was isolated from a blood culture performed before admission to the intensive care unit.

[Anesthetic management of combined lung volume reduction surgery and off-pump coronary artery bypass grafting].

A 54-year-old man with severe emphysema and stenosis of coronary artery was scheduled for combined surgery of lung volume reduction and an off-pump coronary artery bypass grafting. His FEV1.0 was 600 ml and %FEV1.