Correlation between particle size/domain structure and magnetic properties of highly crystalline Fe3O4 nanoparticles

Highly crystalline single-domain magnetite Fe3O4 nanoparticles (NPs) are important, not only for fundamental understanding of magnetic behaviour, but also for their considerable potential applications in biomedicine and industry. Fe3O4 NPs with sizes of 10–300 nm were systematically investigated to reveal the fundamental relationship between the crystal domain structure and the magnetic properties. The examined Fe3O4 NPs were prepared under well-controlled crystal growth conditions using a large-scale liquid precipitation method. The crystallite size of cube-like NPs estimated from X-ray diffraction pattern increased linearly as the particle size (estimated by transmission electron microscopy) increased from 10 to 64.7 nm, which indicates that the NPs have a single-domain structure. This was further confirmed by the uniform lattice fringes. The critical size of approximately 76 nm was obtained by correlating particle size with both crystallite size and magnetic coercivity; this was reported for the first time in this study. The coercivity of cube-like Fe3O4 NPs increased to a maximum of 190 Oe at the critical size, which suggests strong exchange interactions during spin alignment. Compared with cube-like NPs, sphere-like NPs have lower magnetic coercivity and remanence values, which is caused by the different orientations of their polycrystalline structure.This work was supported by JSPS KAKENHI Grant Number 26709061 and 16K13642. This work was partly supported by the Center for Functional Nano Oxide at Hiroshima University. The authors also gratefully acknowledge the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan for providing scholarships (C. W. K.)

Carrier-mediated active transport of the glucuronide and sulfate of 6- hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040) into rat liver: quantitative comparison of permeability in isolated hepatocytes, perfused liver and liver i

ABSTRACT The hepatic uptake of glucuronic acid and sulfate conjugates of 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040), a dual inhibitor of 5-lipoxygenase and thromboxane A 2 synthetase, was investigated in rats. The biliary excretion clearance values for the glucuronide and the sulfate, obtained after i.v. administration of E3040, were similar and corresponded to approximately 30% of the hepatic blood flow rate. The influx clearance values of E3040 conjugates in the presence of 3% bovine serum albumin, measured by a multiple indicator dilution method in the perfused liver, were 1.20 ml/min/g liver for the glucuronide and 0.74 ml/min/g liver for the sulfate, which were twice and equal to the normal hepatic plasma flow rate, respectively, which suggests the presence of an efficient transport system(s). The uptake of E3040 conjugates into the isolated hepatocytes is mediated by Na ϩ -independent active transport system(s), which is inhibited by dibromosulfophthalein and bile acids. The uptake for the sulfate had high-affinity and high-capacity transport activity (K m ϭ 25 M; V max ϭ 7.8 nmol/min/10 6 cells) compared with that for the glucuronide (K m ϭ 59 M; V max ϭ 2.2 nmol/min/10 6 cells). The uptakes of E3040 conjugates (glucuronide, sulfate) exhibited a mutual competitive inhibition. It is suggested that both conjugates share a multispecific organic anion transporter located on the sinusoidal membrane. Conjugative metabolism, such as glucuronidation and sulfation, is an important pathway for the inactivation or detoxification of xenobiotics. On the other hand, conjugative metabolites of certain drugs with pharmacologically active (such as the 6-glucuronide of morphine; In previous studies, we reported the disposition of glucuronide and sulfate of E3040, a novel dual inhibitor of 5-lipoxygenase and thromboxane A 2 synthetase, after administration Received for publication May 24, 1996. ABBREVIATIONS: E3040, 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole; [ C]E3040, [2- 14 C]6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole dihydrochloride; SD rats, Sprague-Dawley rats; DBSP, dibromosulfophthalein; HEPES, N-2-hydroxyethylpiperazine-NЈ-2-ethanesulfonic acid; MID method, multiple indicator dilution method; HPLC, high-performance liquid chromatography; BSA, bovine serum albumin; TLC, thin-layer chromatography; AUC ϱ , the area under the plasma concentration-time profiles from zero to infinity; CL bile , the biliary excretion clearance; CL renal , the urinary excretion clearance; CL u,renal , the unbound urinary excretion clearance; X bile , the amount excreted into the bile; X urine , the amount excreted into the urine; CL tot , the total body clearance; PS inf , the influx clearance; PS u,inf , the unbound influx clearance; K inf , the influx rate constant; K eff , the efflux rate constant; K seq , the sequestration rate constant; K m , Michaelis constant; V max , maximal uptake rate; P dif , the nonspecific uptake clearance; LUR, the first-pass liver uptake ratio; UWL, the unstirred water layer; PCMBS, p-chloromercuriphenylsulfonic acid; DIDS, 4,4Ј-diisothiocyanatostilbene-2,2Ј-disulfonic acid; FCCP, carbonyl cyanide-p-(trifluoromethoxy)-phenylhydrazone; C/M, cell-to-medium concentration

Randomized Controlled Trial on the Necessity of Chemical Cleaning as Preoperative Preparation for Colorectal Cancer Surgery

The use of preoperative oral antibiotics for the preparation of elective colorectal surgery remains controversial. We examined the necessity of chemical preparation using oral antibiotics compared with mechanical preparation, to achieve the further reduction of infection rates in colorectal resection. Consecutive 91 patients were included in this prospective clinical trial of colon preparation. 45 patients received mechanical preparation alone with the polyethylene glycol lavage solution (group A), while 46 patients received mechanical preparation and chemical bowel preparation with 1.5g Kanamycin for 3 days orally before surgery (group B). Cefotiam hydrochloride was administered for 3 consecutive days after surgery in both groups. Specimens for culture were obtained pre-, intra- and post-operatively. In the specimens of intraoperative colonic mucosal swabs, Escherichia coli (E. coli) was significantly less cultured in group B than in group A. Postoperative diarrhea was observed in 7 patients of group A (15.5%) and in 20 patients of group B (43.5%) (p<0.05). The surgical site infection (SSI) rate was 20.0% in group A and 36.9% in group B (p=0.1041). Although there was no significant difference, SSI rate tended to be higher in group B than in group A. In conclusion, chemical preparation with oral intake of 1,500mg Kanamycin for 3 days before surgery did not add any advantages to mechanical preparation and is considered unnecessary to perform colorectal surgery

MicroRNA-133 regulates the expression of GLUT4 by targeting KLF15 and is involved in metabolic control in cardiac myocytes

GLUT4 shows decreased levels in failing human adult hearts. We speculated that GLUT4 expression in cardiac muscle may be fine-tuned by microRNAs. Forced expression of miR-133 decreased GLUT4 expression and reduced insulin-mediated glucose uptake in cardiomyocytes. A computational miRNA target prediction algorithm showed that KLF15 is one of the targets of miR-133. It was confirmed that over-expression of miR-133 reduced the protein level of KLF15, which reduced the level of the downstream target GLUT4. Cardiac myocytes infected with lenti-decoy, in which the 3′UTR with tandem sequences complementary to miR-133 was linked to the luciferase reporter gene, had decreased miR-133 levels and increased levels of GLUT4. The expression levels of KLF15 and GLUT4 were decreased at the left ventricular hypertrophy and congestive heart failure stage in a rat model. The present results indicated that miR-133 regulates the expression of GLUT4 by targeting KLF15 and is involved in metabolic control in cardiomyocytes

Skin Autofluorescence and Atherosclerosis

Advanced glycation end-products (AGEs) are thought to play a major role in the pathogenesis of diabetic vascular complications. Skin autofluorescence (AF) was recently reported to represent tissue AGEs accumulation with a non-invasive method. The aim of the present study was to evaluate association between AF value and diabetic vascular complications, such as retinopathy, nephropathy and cervical atherosclerosis using the carotid intima-media thickness (IMT), an established marker of cardiovascular disease in patients with type 2 diabetes. A total of 68 patients with type 2 diabetes were enrolled in a cross-sectional manner. AGEs accumulation was measured with AF reader. Clinical parameters were collected at the time of AF and IMT measurement. Max-IMT was correlated with age and AF (r=0.407, p=0.001), but not with HbA1c, GA, and pentosidine. Also, AF was not correlated with HbA1c, GA and pentosidine, but was correlated with age (r=0.560, p<0.001), duration of diabetes (r=0.256, p<0.05). Multivariate regression analysis revealed that AF, but not age, was an independent determinant of max-IMT. In conclusion, AF might be a beneficial surrogate marker for evaluating carotid atherosclerosis in patients with type 2 diabetes non-invasively

Skin Autofluorescence and Atherosclerosis

Advanced glycation end-products (AGEs) are thought to play a major role in the pathogenesis of diabetic vascular complications. Skin autofluorescence (AF) was recently reported to represent tissue AGEs accumulation with a non-invasive method. The aim of the present study was to evaluate association between AF value and diabetic vascular complications, such as retinopathy, nephropathy and cervical atherosclerosis using the carotid intima-media thickness (IMT), an established marker of cardiovascular disease in patients with type 2 diabetes. A total of 68 patients with type 2 diabetes were enrolled in a cross-sectional manner. AGEs accumulation was measured with AF reader. Clinical parameters were collected at the time of AF and IMT measurement. Max-IMT was correlated with age and AF (r=0.407, p=0.001), but not with HbA1c, GA, and pentosidine. Also, AF was not correlated with HbA1c, GA and pentosidine, but was correlated with age (r=0.560, p<0.001), duration of diabetes (r=0.256, p<0.05). Multivariate regression analysis revealed that AF, but not age, was an independent determinant of max-IMT. In conclusion, AF might be a beneficial surrogate marker for evaluating carotid atherosclerosis in patients with type 2 diabetes non-invasively

Analysis of different complexes of type IIa sodium-dependent phosphate transporter in rat renal cortex using blue-native polyacrylamide gel electrophoresis

Type IIa sodium-dependent phosphate transporter (NaPi-IIa) can be localized in the apical plasma membrane of renal proximal tubule to carry out a rate-limiting step of phosphate reabsorption. For the apical localization, NaPi-IIa is required to form a macromolecular complex with some adaptor proteins such as Na+/H+ exchanger regulatory factor 1 (NHERF-1) and ezrin. However, the detail of macromolecular complex containing NaPi-IIa in the apical membrane of the renal proximal tubular cells has not been clarified. In this study, we identified at least four different complexes (220, 480, 920, 1,100 kDa) containing NaPi-IIa by using blue-native polyacrylamide gel electrophoresis. Interestingly, LC-MS/MS analysis and immunoprecipitation analysis reveal that megalin is a component of larger complexs (920 and 1,100 kDa). In addition, NaPi-IIa can be heterogeneously co-localized with ezrin and megalin on the apical membrane of renal proximal tubuler cells by fluorescence microscopy analysis. These results suggest that NaPi-IIa can form some different complexes on the apical plasma membrane of renal proximal tubular cells

Association of IFNGR2 gene polymorphisms with pulmonary tuberculosis among the Vietnamese

Interferon-γ (IFN-γ) is a key molecule of T helper 1 (Th1)-immune response against tuberculosis (TB), and rare genetic defects of IFN-γ receptors cause disseminated mycobacterial infection. The aim of the present study was to investigate whether genetic polymorphisms found in the Th1-immune response genes play a role in TB. In our study, DNA samples were collected from two series of cases including 832 patients with new smear-positive TB and 506 unrelated individuals with no history of TB in the general population of Hanoi, Vietnam. Alleles of eight microsatellite markers located around Th1-immune response-related genes and single nucleotide polymorphisms near the promising microsatellites were genotyped. A set of polymorphisms within the interferon gamma receptor 2 gene (IFNGR2) showed a significant association with protection against TB (P = 0.00054). Resistant alleles tend to be less frequently found in younger age at diagnosis (P = 0.011). Luciferase assays revealed high transcriptional activity of the promoter segment in linkage disequilibrium with resistant alleles. We conclude that the polymorphisms of IFNGR2 may confer resistance to the TB development of newly infected individuals. Contribution of the genetic factors to TB appeared to be different depending on age at diagnosis

Inhibition of Casein Kinase 2 Modulates XBP1-GRP78 Arm of Unfolded Protein Responses in Cultured Glial Cells

Stress signals cause abnormal proteins to accumulate in the endoplasmic reticulum (ER). Such stress is known as ER stress, which has been suggested to be involved in neurodegenerative diseases, diabetes, obesity and cancer. ER stress activates the unfolded protein response (UPR) to reduce levels of abnormal proteins by inducing the production of chaperon proteins such as GRP78, and to attenuate translation through the phosphorylation of eIF2α. However, excessive stress leads to apoptosis by generating transcription factors such as CHOP. Casein kinase 2 (CK2) is a serine/threonine kinase involved in regulating neoplasia, cell survival and viral infections. In the present study, we investigated a possible linkage between CK2 and ER stress using mouse primary cultured glial cells. 4,5,6,7-tetrabromobenzotriazole (TBB), a CK2-specific inhibitor, attenuated ER stress-induced XBP-1 splicing and subsequent induction of GRP78 expression, but was ineffective against ER stress-induced eIF2α phosphorylation and CHOP expression. Similar results were obtained when endogenous CK2 expression was knocked-down by siRNA. Immunohistochemical analysis suggested that CK2 was present at the ER. These results indicate CK2 to be linked with UPR and to resist ER stress by activating the XBP-1-GRP78 arm of UPR