[Cephalic artery peak velocity variation during passive leg raising can predict fluid responsiveness in mechanically ventilated severe sepsis patients with spontaneous breathing].

Objective: To explore whether cephalic artery peak velocity variation during passive leg raising (ΔVpeak(CA)-PLR) could effectively predict fluid responsiveness in mechanically ventilated severe sepsis patients with spontaneous breathing. Methods: Total of 38 patients on mechanical ventilation with spontaneous breathing admitted to the Fourth Departments of Intensive Care Unit (ICU) of Fujian Provincial Hospital from January to December in 2017 were enrolled.The patients were diagnosed with severe sepsis or sepsis shock.The peak velocity in cephalic artery (Vpeak(CA)) during PLR was measured by bedside portable ultrasonic, and then ΔVpeak(CA)-PLR was calculated.All patients received volume expansion (VE) test and the changes of stroke volume during VE test (ΔSV-VE) were measured.Patients were classified as responsive group or non-responsive group according to the ΔSV-VE increased ≥15% or not after VE test.Furthermore, the sensitivity and specificity of ΔVpeak(CA)-PLR for predicting fluid responsiveness were evaluated by receiver operating characteristic (ROC) curve.The comparisons between groups were performed with Student's unpaired two-tailed t test, and Pearson's test was used for the correlation analysis. Results: Among the patients, 22 cases responded to VE test and the rest 16 cases did not.There were no significantly differences in age, gender, body mass index, infection site, sepsis-related organ failure assessment score, acute physiology and chronic health evaluation Ⅱ score, ventilator parameters and dose of vasoactive agent between the two groups.The ΔVpeak(CA)-PLR in responsive group was markedly higher than that in non-responsive group (15.7%±4.2% vs 6.9%±4.3%, t=6.240, P<0.05), and the ΔVpeak(CA)-PLR in the responsive group was positively related to the ΔSV-VE (r=0.723, P<0.05). Furthermore, the area of ΔVpeak(CA)-PLR under ROC curve was 0.912.The sensitivity and specificity of ΔVpeak(CA)-PLR≥12.2% to predict fluid responsiveness in the patients with sepsis were 81.8% and 87.5%, respectively. Conclusion: ΔVpeak(CA)-PLR measured by bedside portable ultrasonic can predict the fluid responsiveness in mechanically ventilated severe sepsis patients with spontaneous breathing, and it can be used to guide further fluid resuscitation.

[The effect of microRNA-21 on myocardial fibrosis in mice with chronic viral myocarditis].

Objective: To explore the effect of microRNA-21 (miR-21) on myocardial fibrosis in mice with chronic viral myocarditis (CVMC) and related mechanisms. Methods: Forty 4-week-old Balb/c male mice were randomly divided into 4 groups (n=10 each): phosphate buffer saline (PBS) group, CVMC group, CVMC+miR-21 inhibitor group, CVMC+isotype control group. The first injection of Coxsackie virus B3 (CVB3) or PBS was performed on day 0, and the total study time was 42 days. Each mouse in CVMC group, CVMC+miR-21 inhibitor group and CVMC+isotype control group was intraperitoneally (i.p) injected with 100TCID50 CVB3 0.1, 0.15, and 0.2 ml on day 0, 14, and 28, respectively. The mice in PBS group were i.p injected with the same dose of PBS at the same time point. After the initial infection, each mouse in CVMC+miR-21 inhibitor group and CVMC+isotype control group was intravenously injected with 0.1 ml miR-21 inhibitor or 0.1 ml isotype control, on day 14 and 28. Cardiac function was measured on surviving mice of 4 groups by echocardiography on day 42. Then, the hearts were removed aseptically to observe the expressions of green fluorescence protein (GFP). The myocardial pathological changes were examined with HE, Masson staining and the myocardial pathological scores (PS), the collagen volume fraction (CVF) were calculated respectively. The levels of miR-21, collagen typeⅠ-A1 (COL1-A1) and collagen type Ⅲ-A1 (COL3-A1) mRNA in heart were detected by quantitative real-time polymerase chain reaction (RT-qPCR). Furthermore, the expressions of transforming growth factor-ß1 (TGF-ß1) and mothers against decapentaplegic homolog 7(Smad7) in heart were determined with Western blot assay. Results: (1) Cardiac function in 4 groups: Compared with PBS group, left ventricular end systolic diameter (LVESD) and left ventricular end diastolic diameter (LVEDD) were markedly increased in CVMC group and CVMC+isotype control group (all P<0.05), whereas the left ventricular ejection fraction (LVEF) was decreased (P<0.05). LVESD and LVEDD were significantly decreased, and LVEF was increased in CVMC+miR-21 inhibitor group compared with those in CVMC group and CVMC+isotype control group (all P<0.05). (2) Myocardial pathological changes: The expressions of GFP in CVMC+miR-21 inhibitor group and CVMC+isotype control group were visible in heart tissues frozen sections. The hearts in CVMC group and CVMC+isotype control group were enlarged and stiff, inflammatory cells were visible and significantly increased myocardial fibrosis was evidenced in mice of these two groups. Higher PS and CVF were evidenced in CVMC group (PS: 1.14±0.69 vs. 0, CVF: (17.86±2.61)% vs. (5.70±1.42)%, all P<0.05) and CVMC+isotype control group(PS: 1.00±0.63 vs. 0, CVF: (16.78±2.58)% vs. (5.70±1.42)%, all P<0.05) compared to PBS group. Compared with CVMC group and CVMC+isotype control group, degree of cardiac fibrosis was reduced in mice of CVMC+miR-21 inhibitor group (CVF: (11.01±2.55)% vs. (17.86±2.61)%, (11.01±2.55)% vs. (16.78±2.58)%, all P<0.05), whereas PS were similar between them (PS: 0.89±0.60 vs. 1.14±0.69, 0.89±0.60 vs. 1.00±0.63, all P>0.05). (3) Cardiac expressions of miR-21, COL1-A1 and COL3-A1 mRNA: The cardiac expressions of miR-21, COL1-A1 mRNA, COL3-A1mRNA in CVMC group and CVMC+isotype control group were markedly higher than those in PBS group (all P<0.05), which were significantly downregulated in CVMC+miR-21 inhibitor group (all P<0.05 vs. CVMC group and CVMC+isotype control group). (4) The cardiac expressions of TGF-ß1 and Smad7 protein: The cardiac expressions of TGF-ß1 protein in CVMC group and CVMC+isotype control group were markedly higher, whereas the cardiac Smad7 protein expressions were significantly lower (all P<0.05) than those in PBS group (all P<0.05), these changes could be reversed in CVMC+miR-21 inhibitor group (P<0.05 vs. CVMC group and CVMC+isotype control group). Conclusions: Our results suggest that miR-21 contributes to the myocardial fibrosis in CVMC mice through modulating TGF-ß1/Smad7 signaling pathway.

In situ forming oxidised hyaluronic acid/adipic acid dihydrazide hydrogel for prevention of epidural fibrosis after laminectomy.

Post-operative epidural fibrosis is a biological response after laminectomy that may lead to clinical symptoms, such as radicular pain. An ideal material for prevention of epidural fibrosis should be able to inhibit fibroblast adhesions and reduce formation of scar tissue. An injectable hydrogel would be the material of choice for this purpose, since it could fill an irregular surgical defect completely, gelate in situ and be delivered in a minimally-invasive manner. The objective of this study was to evaluate, in vitro and in vivo, the cytocompatibility and anti-adhesive effect of an oxidised hyaluronic acid/adipic acid dihydrazide (oxi-HA/ADH) hydrogel. Different cell types present in the spine were used to test the cytocompatibility of the hydrogel. The hydrogel extraction medium had no deleterious effects on neural cells (PC-12), but reduced fibroblasts viability (NIH/3T3). Although the hydrogel did not change the release of lactate dehydrogenase from myoblasts (C2C12) and Schwann cells (RSC96), the extraction medium concentration slightly affected the mitochondrial activity of these two cell types. qPCR showed that the hydrogel down-regulated S100a and P4hb expression in NIH/3T3 cells, supporting the hypothesis that the hydrogel might inhibit fibroblast activity. The animal study showed a reduction of scar tissue formation as well as severity of adhesion between scar tissue and the dura mater in a rat laminectomy model. Superficially, the peel-off test showed significantly decreased tenacity. In conclusion, the oxi-HA/ADH hydrogel is a promising injectable and thermosensitive material for prevention of post-operative epidural fibrosis.

Cognitive impairment and hippocampal atrophy in chronic kidney disease.

BACKGROUND: Cognition impairment is well known in patients with chronic kidney disease (CKD). The relationship between brain structure and cognitive performance in CKD patients is still under investigation. The study aimed to quantitatively assess the relationship between brain structure and cognitive performance in patients with CKD. METHODS: We recruited 39 patients with CKD and 39 age- and sex-matched control participants from a tertiary medical center. All participants underwent 3-T MRI scan neuropsychological assessments, and renal function tests. FreeSurfer software was used for imaging processing and analysis, including measurement of cortical thickness and gray matter (GM) and white matter volumes. RESULTS: Compared with control subjects (73.1±7.5 years old), patients with CKD (76.4±8.4 years old) had significantly lower scores on the Mini-Mental State Examination, and forward digit span test (P<.01). Patients with CKD had smaller cerebral GM volume, hippocampus, and decreased cortical thickness (P<.01) relative to the control group. Estimated glomerular filtration rate (eGFR) was correlated with cognitive performance, cortical thickness, GM volume, and hippocampal volume (P<.001). Linear regression analysis revealed that eGFR and GM volume were independently negatively associated with cognitive performance (P<.001), while eGFR and age were negatively associated with cortical thinning and GM volume after controlling for confounding factors. CONCLUSIONS: This study demonstrated that impaired kidney function is associated not only with poor cognitive performance, but also with small cerebral GM volume and reduced cortical thickness.

Hippocampal Atrophy Is Associated with Altered Hippocampus-Posterior Cingulate Cortex Connectivity in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

BACKGROUND AND PURPOSE: Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. MATERIALS AND METHODS: Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively. RESULTS: Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized ß = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized ß = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity (F2,12 = 0.284, P = .757, R2 = 0.045). CONCLUSIONS: In left mesial temporal lobe epilepsy with hippocampal sclerosis, the left inferior cingulum bundle undergoes degeneration in tandem with the left hippocampal volume, whereas intrinsic functional connectivity seems to react by compensating the loss of connectivity. Such insight might be helpful in understanding the development of the epileptic network in left mesial temporal lobe epilepsy with hippocampal sclerosis.

Association between sleep disorders and hypertension in Taiwan: a nationwide population-based retrospective cohort study.

There is insufficient evidence to assess the risk for hypertension in patients with sleep disorders (SDs) in a large population-based cohort study. The aim of this study was to examine the risk of hypertension in groups both with and without SDs. Taiwan's National Health Insurance Research Database (NHIRD) data from 2005 to 2010 were used in a retrospective cohort study. A Cox proportional hazard regression analysis was used to evaluate the effects of SDs on hypertension risk. The overall incidence of hypertension was 120.7 per 1000 person-years for patients with SDs, which was significantly higher than that of the non-SD comparison cohort (76.4 per 1000 person-years). Overall, patients with SDs had a higher risk of hypertension compared with comparison cohort (adjusted hazard ratio (HR)=1.58, 95% confidence interval (CI)=1.26-1.79). Among patients aged <40 years, patients with SDs had a higher risk for hypertension than the comparison cohort (adjusted HR, 2.90 (95% CI, 2.46-3.14)). Compared with the cohort without insomnia, patients with insomnia had a 21% higher risk for hypertension (adjusted HR, 1.21 (95% CI, 1.01-1.76)). Compared with non-SD comparison cohort, patients with SDs had a higher risk for developing hypertension, particularly pronounced among those who were younger adults (age ⩽40 years) and who had insomnia. We suggest that possible persisting exposure to sleep problems was correlated with a greater risk of hypertension.

Gonorrhea infection increases the risk of prostate cancer in Asian population: a nationwide population-based cohort study.

This nationwide population-based retrospective cohort study evaluated the risk of developing prostate cancer among patients with gonorrhea. We identified cases of newly diagnosed gonorrhea in men between 2000 and 2010 from the Taiwan National Health Insurance Research Database. Each patient with gonorrhea was matched to four controls, based on age and index year. All subjects were followed up from the index date to December 31, 2010. The Cox proportional hazards regression model was used to assess the risk of prostate cancer. A total of 355 men were included in the study group, and 1,420 age-matched subjects without gonorrhea were included in the control group. After adjusting for age, comorbidities, urbanization level, hospital level, and monthly income, gonorrhea was significantly associated with an increased risk of prostate cancer (adjusted hazard ratio = 5.66, 95% confidence interval = 1.36-23.52). Men aged 45-70 years and those with lower monthly income were more strongly associated with prostate cancer in the study group than the control group. The higher risk for developing prostate cancer were also found in those without syphilis, without genital warts, without diabetes mellitus, without chronic obstructive pulmonary disease, without benign prostatic hypertrophy, without chronic prostatitis, and without alcoholism. The Kaplan-Meier analysis showed the risk of prostate cancer was significantly higher in the study group than in the control group. Gonorrhea may be involved in the development of prostate cancer. More intensive screening and prevention interventions for prostate cancer should be recommended in men with gonorrhea.

Evaluation of adhesion force and binding affinity of phytohemagglutinin erythroagglutinating to EGF receptor on human lung cancer cells.

PHA-E is a natural product extracted from red kidney beans, and it has been reported to induce cell apoptosis by blocking EGFR in lung cancer cells. Because EGF is the major in vivo competitor to PHA-E in clinical application, PHA-E must be proved that has better affinity to EGFR than EGF. This study would focus on how PHA-E tightly bind to EGFR and the results would compare with EGF. The adhesion force, measured by AFM, between EGFR and PHA-E was 207.14±74.42 pN that was higher than EGF (183.65±86.93 pN). The equilibrium dissociation constant of PHA-E and EGF to EGFR was 2.4 10(-9)±1.4 10(-9) and 7.3 10(-8)±2.7 10(-8), respectively, that could evaluate binding affinity. The result showed that binding affinity of PHA-E to EGFR was one order higher than EGF to EGFR. In the results of flow cytometer and confocal microscope, we found binding efficiency of EGF to EGFR was decrease as the concentration of PHA-E increased. In the analysis of Western blot, treatment of A-549 cells with PHA-E resulted in a dose-dependent decrease in EGFR phosphorylation. In conclusion, we found that PHA-E had better adhesion force and binding affinity to EGFR than that of the EGF. The interaction between PHA-E and EGFR could block EGF binding and then inhibit EGFR phosphorylation. PHA-E could be developed into a new target molecule for lung cancer treatment that could be immobilized on the drug carrier to guide therapeutic particles to the tumor site.

Inhibition of intracellular dipeptidyl peptidases 8 and 9 enhances parthenolide's anti-leukemic activity.

Parthenolide is selectively toxic to leukemia cells; however, it also activates cell protective responses that may limit its clinical application. Therefore, we sought to identify agents that synergistically enhance parthenolide's cytotoxicity. Using a high-throughput combination drug screen, we identified the anti-hyperglycemic, vildagliptin, which synergized with parthenolide to induce death of the leukemia stem cell line, TEX (combination index (CI)=0.36 and 0.16, at effective concentration (EC) 50 and 80, respectively; where CI <1 denotes statistical synergy). The combination of parthenolide and vildagliptin reduced the viability and clonogenic growth of cells from acute myeloid leukemia patients and had limited effects on the viability of normal human peripheral blood stem cells. The basis for synergy was independent of vildagliptin's primary action as an inhibitor of dipeptidyl peptidase (DPP) IV. Rather, using chemical and genetic approaches we demonstrated that the synergy was due to inhibition of the related enzymes DPP8 and DPP9. In summary, these results highlight DPP8 and DPP9 inhibition as a novel chemosensitizing strategy in leukemia cells. Moreover, these results suggest that the combination of vildagliptin and parthenolide could be useful for the treatment of leukemia.

The development of iron-free partially stabilized cement for use as dental root-end filling material.

AIM: To determine the effect of increasing the proportion of zinc on partially stabilized cement (PSC) produced using a one-step sol gel process. METHODOLOGY: A one-step sol-gel process of Portland cement-based PSC with Zn was synthesized by replacing iron nitrate. The crystalline phases of the PSC-Zn powder were analysed by using X-ray diffraction (XRD). The experimental groups [i.e., MTA, PSC-Fe (control), PSC with 1% Zn, PSC with 3% Zn, and PSC with 5% Zn] were immersed in simulated body fluid for 3 h, 1 and 3 days to evaluate the hydration product formation. The microstructure and surface morphology were analysed using scanning electron microscopy (SEM). Initial and final setting times of the materials were determined using an ASTM Vicat needle testing machine. To evaluate the cytotoxicity of PSC-Zn system, primary osteoblasts cell lines were used. RESULTS: The addition of increased weight percentages of Zn, resulted in a more unstable phase which favoured the formation of a monoclinic structure of C3 S with an increased hydration reaction of PSC and reduced setting time. The cytotoxicity testing of PSC with Zn revealed that the material was not toxic. CONCLUSIONS: The newly synthesized PSC-Zn material had short setting time and was biocompatible.

The trend of hypertension and its relationship to the weight status among Taiwanese young adolescents.

This study evaluates prevalence of hypertension in 1996 and 2006, and examines the relationship between hypertension and weight of Taiwanese young adolescents. Two cross-sectional surveys, administered in 1996 and 2006, to junior-high school in Taipei were included. Anthropometric and blood pressure were measured using standard methods, and structured questionnaire was used to collect personal history and lifestyle characteristics. Overweight and obesity are defined based on Taiwan's Department of Health criteria and bases pre-hypertension and hypertension on the 90th and 95th percentile distribution of blood pressure of the population of both surveys. The prevalence of pre-hypertension in Taiwan between 1996 and 2006 increased from 12.0 to 14.4% for boys and decreased from 9.5 to 9.4% for girls. Hypertension increased from 22.8-29.7% and 12.5-20.7% for both boys and girls, respectively. In 1996, compared with normal young adolescents, the risk of hypertension for overweight was 1.8 times higher for boys and 3.4 times for girls. However, the risk of hypertension for overweight in 2006 was 1.7 times higher for boys and 1.5 times higher for girls compared with normal. Every unit increment of body mass index and waist circumference was associated with 17-27% and 6-11% risk of hypertension in both genders in 1996, and was associated with 9-13% and 4% risk of hypertension among young adolescents in 2006, respectively. The prevalence of hypertension has increased significantly in young adolescents, especially for overweight. It is necessary to enrol young adolescents in weight management programs to prevent hypertension-related co-morbidities.

Early-life exposure to lipopolysaccharide reduces the severity of experimental autoimmune encephalomyelitis in adulthood and correlated with increased urine corticosterone and apoptotic CD4+ T cells.

Early-life exposure to bacterial endotoxins, such as lipopolysaccharides (LPS), can provide neuroprotection against experimental autoimmune encephalomyelitis (EAE) during adulthood, possibly through altering the responsiveness of the immune system. Here, we show that exposure of LPS to neonatal rats resulted in a sustained elevation of corticosterone level in urine when compared with saline-treated rats, and that the high level of urine corticosterone was maintained during the progression of EAE (P<0.05). This high level of production of corticosterone plays an important role in altering the predisposition to EAE-induced neuroinflammation, as a positive correlation occurred between the concentration of urine corticosterone and the increased apoptotic CD4(+) T cells from the peripheral blood. LPS-treated rats also showed a reduced number of CD3(+) T cells in the spinal cord. The splenic antigen-presenting cells showed a reduced expression of MHC II during EAE development in LPS-exposed rats when compared with rats exposed to the saline-treated control. Together, these findings suggest that treating neonatal rats with LPS evokes a sustained elevation of glucocorticoid, which may suppress immune response during EAE by increasing apoptosis of CD4(+) T cells and reducing the expression of MHC II on antigen-presenting cells. Therefore, exposing neonates to bacterial endotoxin may further be developed as an immunization strategy to prevent human multiple sclerosis and other inflammatory brain diseases.

Combined effect of C-reactive protein gene SNP +2147 A/G and interleukin-6 receptor gene SNP rs2229238 C/T on anthropometric characteristics among school children in Taiwan.

OBJECTIVE: The purpose of this study was to explore the combined effect of the C-reactive protein (CRP) +2147 A/G (rs1205) and interleukin (IL)-6R rs2229238 C/T single-nucleotide polymorphisms (SNPs) on the anthropometric variables of school children in Taiwan. SUBJECTS AND DESIGN: Cross-sectional analyses were performed using the data from the Taipei Children Heart Study-II. After multi-stage sampling, we selected 430 boys and 463 girls with an average age of 13.1 years. We genotyped these individuals for the CRP +2147 A/G and IL-6R rs2229238 C/T SNPs using a TaqMan 5' nuclease assay. Anthropometric characteristics, which included body height, body weight (BW), body mass index (BMI), waist circumference (WC), hip circumference (HC), body fat percentage (BF), and waist circumference to height ratio (WHtR), were measured/calculated. RESULTS: When considering the CRP +2147 A/G polymorphism, GG genotype boys were heavier and had larger BMI, WC, HC, BF and WHtR than A allele carriers. The odds ratio (OR) of larger WHtR in GG genotype boys was 2.14 (95% CI: 1.09-4.21). For the IL-6R rs2229238 C/T polymorphism, T allele carrier girls had larger WC and WHtR than those carrying the CC genotype. The OR of a larger HC for T allele carrier boys was 2.33 (95% CI: 1.16-4.68). Boys with the GG genotype of CRP +2147 A/G and the CC genotype of IL-6R rs2229238 C/T had higher OR for BW, BMI, WC, HC, BF and WHtR than boys who were carriers of the A allele of CRP +2147 A/G and had the CC genotype of IL-6R rs2229238 C/T (OR range=3.86-8.04, all P<0.05). CONCLUSION: Boys who carry the GG genotype of CRP +2147 A/G and the CC genotype of IL-6R rs2229238 C/T have a greater risk of having abnormal BW, BMI, WC, HC, BF and WHtR and of developing obesity than individuals who do not have these genotypes.

Intramedullary cavity as implantation site for bioartifical pancreas: preliminary in vivo study.

BACKGROUND: The intramedullary cavity is a widely distributed well-vascularized microenvironment capable of sustaining grafts, and is a potential site for islet transplantation. The bone marrow offers sufficient space that may also be suitable for bioartificial pancreas (BAP) implantation. OBJECTIVE: To evaluate the feasibility of bone marrow as an implantation site for BAPs. MATERIALS AND METHODS: A calcium phosphate cement chamber satisfies the criteria for immunoisolation. Mouse insulinoma cells were suspended with agarose gel and enclosed in a calcium phosphate cement chamber to create a BAP, which was implanted in the intramuscular space in diabetic swine or the intramedullary cavity in diabetic dogs. Blood glucose and C-peptide concentrations were determined perioperatively. RESULTS: In the swine, the mean ± SD blood glucose concentration decreased from 413 ± 24 mg/dL to 285 ± 47 mg/dL, and was maintained in the range of 285 to 336 mg/dL for 15 days. It increased to 368 to 450 mg/dL after the BAPs were implanted in the intramuscular space. In the dogs, the blood glucose concentration decreased from 422 ± 32 mg/dL to 247 ± 52 mg/dL, and was maintained in the range of 247 to 347 mg/dL after the BAPs were implanted in the intramedullary cavity. The C-peptide concentration increased from 6.1 ± 2.8 pmol/L to 104.7 ± 16.4 pmol/L when the BAPs were implanted in the intramedullary cavity. CONCLUSION: This study indicates superior effectiveness of BAPs implanted in the intramedullary cavity compared with the intramuscular space. This observation may be attributed to the greater oxygen tension in the bone marrow. The BAPs in direct contact with the circulatory system receive sufficient blood flow for function and survival. This preliminary study demonstrates that the intramedullary cavity may be an implantation site for BAP transplantation.

A novel mesoporous biomaterial for treating dentin hypersensitivity.

An ideal material has yet to be discovered that can completely treat dentin hypersensitivity; however, calcium phosphate precipitation has exhibited potential value for the treatment of dentin hypersensitivity by the occlusion of dentinal tubules. We hypothesized that a novel mesoporous silica biomaterial (nano CaO@mesoporous silica, NCMS) containing nano-sized calcium oxide particles mixed with 30% phosphoric acid can efficiently occlude dentinal tubules and significantly reduce dentin permeability, even with the presence of pulpal pressure. This highly supersaturated Ca(2+)-and HPO(4)(2-)ion-containing NCMS paste was brushed onto dentin surfaces, and the ions diffused deeply into the dentinal tubules and formed a CaHPO(4).2H(2)O precipitation with a depth of 100 microm. The results of the dentin permeability tests showed that the novel mesoporous material exhibited a significant reduction in dentin permeability (p < 0.05), even under simulated pulpal pressure, as compared with our previously developed material, DP-bioglass, and a commercial desensitizing material, Seal & Protect.

Chitosan/gelatin hydrogel prolonged the function of insulinoma/agarose microspheres in vivo during xenogenic transplantation.

PURPOSE: A chitosan/gelatin solution with glycerol 2-phosphate disodium salt hydrate in liquid phase at room temperature becomes a hydrogel at 37 degrees C. The material can be used as an injectable cell carrier into the human body for gelation in situ. We hoped that the chitosan/gelatin hydrogel provided extra protection for insulinoma/agarose microspheres during xenogenic transplantation. MATERIALS AND METHODS: Mouse insulinoma was microencapsulated in agarose as microspheres, which were macroencapsulated in chitosan/gelatin hydrogel. Insulin secreting profiles were first demonstrated in vitro. Diabetic rats were injected subcutaneously with insulinoma/agarose microspheres or insulinoma/agarose microspheres suspended in chitosan/gelatin solution. The nonfasting blood glucose concentrations (NFBG) of diabetic rats were measured perioperatively. Rats were humanely killed 1 month postoperatively and the hydrogel was retrieved for histological examination. RESULTS: The insulinoma/agarose microspheres continually secreted insulin for 1 month when macroencapsulated in chitosan/gelatin hydrogel in vitro. The NFBG of diabetic rats injected with insulinoma/agarose microspheres decreased to euglycemic status albeit hyperglycemia was restored within 10 days. The NFBG of diabetic rats injected with chitosan/gelatin hydrogel, which contained insulinoma/agarose microspheres, was maintained at less than 200 mg/dL for 25 days. The histological section revealed immune cell infiltration and accumulation within the hydrogel and around the iusulinoma/agarose microspheres that may have contributed to the slowly increasing NFBG after day 25. CONCLUSION: This study showed that chitosan/gelatin hydrogel can be used as a cell carrier for an injectable bioartificial pancreas; the hydrogel prolonged the function of cells encapsulated in agarose microspheres during xenogenic transplantation.

Preparation and surface characterization of HMDI-activated 316L stainless steel for coronary artery stents.

Poor compatibility between blood and metallic coronary artery stents is one reason for arterial restenosis. Immobilization of anticoagulant agents on the stent's surface is feasible for improving compatibility. We examined possible surface-coupling agents for anticoagulant agent immobilization. Hexamethylene diisocyanate (HMDI) and 3-aminopropyl-triethoxysilane (APTS) were examined as surface-coupling agents to activate 316L stainless steel (e.g., stent material). The activated surface was characterized using Fourier transformation infrared spectroscopy (FTIR), atomic force microscope (AFM), surface plasmon resonance (SPR), and trinitrobenzene sulfonic acid (TNBS) assay. In FTIR analysis, HMDI and APTS were both covalently linked to 316L stainless steel. In AFM analysis, it was found that the HMDI-activated surface was smoother than the APTS-activated one. In SPR test, the shift of SPR angle for the APTS-activated surface was much higher than that for the HMDI-activated surface after being challenged with acidic solution. TNBS assay was used to determine the amount of immobilized primary amine groups. The HMDI-activated surface was found to consist of about 1.32 micromol/cm(2) amine group, whereas the APTS-activated surface consisted of only 0.89 micromol/cm(2) amine group. We conclude that the HMDI-activated surface has more desirable surface characteristics than the APTS-activated surface has, such as chemical stability and the amount of active amine groups.

Magnetoencephalographic mapping of interictal spike propagation: a technical and clinical report.

Distinguishing propagated epileptic activity from primary epileptic foci is of critical importance in presurgical evaluation of patients with medically intractable focal epilepsy. We studied an 11-year-old patient with complex partial epilepsy by using simultaneous magnetoencephalography (MEG) and electroencephalography (EEG). In EEG, bilateral interictal discharges appeared synchronous, whereas MEG source analysis suggested propagation of spikes from the right to the left frontal lobe.