Endogenous stem cell mobilization and localized immunosuppression synergistically ameliorate DSS-induced Colitis in mice.

BACKGROUND: Stem cell therapy is a promising alternative for inflammatory diseases and tissue injury treatment. Exogenous delivery of mesenchymal stem cells is associated with instant blood-mediated inflammatory reactions, mechanical stress during administration, and replicative senescence or change in phenotype during long-term culture in vitro. In this study, we aimed to mobilize endogenous hematopoietic stem cells (HSCs) using AMD-3100 and provide local immune suppression using FK506, an immunosuppressive drug, for the treatment of inflammatory bowel diseases. METHODS: Reactive oxygen species (ROS)-responsive FK506-loaded thioketal microspheres were prepared by emulsification solvent-evaporation method. Thioketal vehicle based FK506 microspheres and AMD3100 were co-administered into male C57BL6/J mice with dextran sulfate sodium (DSS) induced colitis. The effect of FK506-loaded thioketal microspheres in colitis mice were evaluated using disease severity index, myeloperoxidase activity, histology, flow cytometry, and gene expression by qRT-PCR. RESULTS: The delivery of AMD-3100 enhanced mobilization of HSCs from the bone marrow into the inflamed colon of mice. Furthermore, targeted oral delivery of FK506 in an inflamed colon inhibited the immune activation in the colon. In the DSS-induced colitis mouse model, the combination of AMD-3100 and FK506-loaded thioketal microspheres ameliorated the disease, decreased immune cell infiltration and activation, and improved body weight, colon length, and epithelial healing process. CONCLUSION: This study shows that the significant increase in the percentage of mobilized hematopoietic stem cells in the combination therapy of AMD and oral FK506 microspheres may contribute to a synergistic therapeutic effect. Thus, low-dose local delivery of FK506 combined with AMD3100 could be a promising alternative treatment for inflammatory bowel diseases.

Study on the Synthesis of ZnO Nanoparticles Using Azadirachta indica Extracts for the Fabrication of a Gas Sensor.

This paper compared the effects of A. indica plant proteins over chemical methods in the morphology of zinc oxide nanoparticles (ZnO NPs) prepared by a co-precipitation method, and ethanol sensing performance of prepared thin films deposited over a fluorene-doped tin oxide (FTO) bind glass substrate using spray pyrolysis technique. The average crystallite sizes and diameters of the grain-sized cluster ZnO NPs were 25 and (701.79 ± 176.21) nm for an undoped sample and 20 and (489.99 ± 112.96) nm for A. india dye-doped sample. The fourier transform infrared spectroscopy (FTIR) analysis confirmed the formation of the Zn-O bond at 450 cm-1, and also showed the presence of plant proteins due to A. indica dye extracts. ZnO NPs films exhibited good response (up to 51 and 72% for without and with A. indica dye-doped extracts, respectively) toward ethanol vapors with quick response-recovery characteristics at a temperature of 250 °C for undoped and 225 °C for A. indica dye-doped ZnO thin films. The interaction of A. indica dye extracts helps to decrease the operating temperature and increased the response and recovery rates of the sensor, which may be due to an increase in the specific surface area, resulting in adsorption of more oxygen and hence high response results.

New Inhibitors of Laccase and Tyrosinase by Examination of Cross-Inhibition between Copper-Containing Enzymes.

Coppers play crucial roles in the maintenance homeostasis in living species. Approximately 20 enzyme families of eukaryotes and prokaryotes are known to utilize copper atoms for catalytic activities. However, small-molecule inhibitors directly targeting catalytic centers are rare, except for those that act against tyrosinase and dopamine-ß-hydroxylase (DBH). This study tested whether known tyrosinase inhibitors can inhibit the copper-containing enzymes, ceruloplasmin, DBH, and laccase. While most small molecules minimally reduced the activities of ceruloplasmin and DBH, aside from known inhibitors, 5 of 28 tested molecules significantly inhibited the function of laccase, with the Ki values in the range of 15 to 48 µM. Enzyme inhibitory kinetics classified the molecules as competitive inhibitors, whereas differential scanning fluorimetry and fluorescence quenching supported direct bindings. To the best of our knowledge, this is the first report on organic small-molecule inhibitors for laccase. Comparison of tyrosinase and DBH inhibitors using cheminformatics predicted that the presence of thione moiety would suffice to inhibit tyrosinase. Enzyme assays confirmed this prediction, leading to the discovery of two new dual tyrosinase and DBH inhibitors.

Comparative evaluation of torque prescription of commercially available 018Roth and 022MBT PEA brands in maxillary anterior teeth.

BACKGROUND: Torque is an important component of preadjusted edgewise prescriptions to achieve ideal/optimum tooth position and more so in aesthetics sensitive maxillary anterior teeth. Thus, the need to audit available commercial brands of 018Roth and 022MBT was felt and in vitro analysis of eight brands namely 3M Unitek, Dentaurum, d-tech, IMD Medical, Libral Leone, Modern Orthodontics, Ormco and Ortho Organizer, was carried out. METHODS: The method involved perfect superimposition of two standardized images: one delineating facial axis of the tooth with stainless steel straight wire and other with full dimension arch wire engagement in bracket. The two images were superimposed and opacity of one of the images altered using Adobe Photoshop software to reveal the position of two wires. The angle obtained between two wires gave a direct read-out of torque expression. The comparison was statistically done with one-way ANOVA and Tukey's HSD test. RESULTS: In 018Roth group, IMD Medical did not show any significant difference from the standard while comparison independent of standard showed that IMD, Modern Orthodontics and Ormco were not significantly different from each other. In 022MBT group, IMD Medical, d-tech, 3M Unitek and Modern Orthodontics did not have statistically significant difference from and independent of standard. CONCLUSION: Significant variations from the standard values of both 018 Roth and 022 MBT exist in the market products and thus selection of product must be based on proper guidance in addition to clinical acumen/experience. Also the methodology provides easy to use, inexpensive set-up in the clinical settings.

Comparison of the newer proposed diagnostic score with the World Heart Federation criteria for echocardiographic detection of rheumatic heart disease.

INTRODUCTION: Echocardiography has been found to be a much better screening tool compared to clinical examination for the detection of rheumatic heart disease (RHD) in asymptomatic school children living in the RHD endemic areas. Recently, World Heart Federation (WHF) published echocardiographic criteria for the diagnosis of RHD. The present study was done to compare the performance of the newer proposed, quantitative diagnostic score against the qualitative WHF criteria in a field survey of asymptomatic school children belonging to the district having high prevalence of RHD. METHODS: 3000 asymptomatic school children studying in rural and urban schools of Bikaner district were screened both by clinical examination and echocardiography performed in parallel. The WHF criteria and the proposed diagnostic score were applied simultaneously for the diagnosis of RHD. RESULTS: A high prevalence of subclinical RHD was found. There was complete agreement between the two sets of criteria for the diagnosis of RHD. However, there was discrepancy in grading the severity of disease. The diagnostic score proved superior to the WHF criteria in grading the disease severity accurately. CONCLUSIONS: Diagnostic score captures the disease spectrum of RHD better than WHF criteria and reduces the subjectivity in the diagnosis of RHD.

Himalayan honey loaded iron oxide nanoparticles: synthesis, characterization and study of antioxidant and antimicrobial activities.

Background: Himalayan honey, a natural product of wild honey bees found in the Himalayan mountains of Nepal, has been used in medicine for many years. The successful development of nanotechnology and beneficial effects of honey would bring a new opportunity to synthesize hybrid nanomaterials for biomedical applications. Thus, the purpose of this study was to load Himalayan honey onto iron oxide nanoparticles (IO-NPs) and study their antioxidant and antimicrobial activities. Methods: Himalayan honey loaded iron oxide nanoparticles (HHLIO-NPs) were synthesized and X-ray diffraction (XRD) and scanning electron microscope (SEM) analyses were performed for characterization. UV-VIS spectra confirmed the loading of honey onto nanoparticles. The antioxidant activity of these nanoparticles was studied against 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical system. We also tested antimicrobial activity of HHLIO-NPs using well diffusion method towards both Gram-positive and Gram-negative bacterial strains of Staphylococus aureus & Escherichia coli. Results: From XRD analysis, the average particle size was found to be 33-40 nm. The SEM images show needle shape porous structures of HHLIO-NPs compared to free IO-NPs indicating the surfactant-like behaviour of honey. In DPPH radical system, the scavenging activities of Himalayan honey (HH), free IO-NPs and HHLIO-NPs ranged 7.93-35.99%, 11.02-52.02% and 16.10-80.52% respectively, with corresponding IC50 values of 1.36 mg/mL, 1.09 mg/mL and 0.52 mg/mL. The antimicrobial property of all test samples showed a noteworthy inhibition on both bacterial strains. However, the HH and HHLIO-NPs exhibited strong antibacterial activity against E. coli. Conclusion: This work reveals that the biological activity of HH is enhanced significantly after loading into IO-NPs. Thus, the HHLIO-NPs would be a promising alternative for antioxidant and antimicrobial agents.

Neonatal sepsis due to glycopeptide resistant Enterococcus faecium from colonized maternal gut- rare case evidence.

Background: Vancomycin-resistant enterococcal infections in the neonatal ICU are growing global problems. We report a case of neonatal septicemia by multidrug-resistant vancomycin-resistant Enterococcus faecium (VRE), the source of infection being the mother's gut. Case presentation: A newborn male child admitted to the neonatal intensive care unit (NICU) was diagnosed to have mild meconium aspiration syndrome, early onset neonatal septicemia, and bacteremia by multidrug and vancomycin-resistant Enterococcus faecium. Screening of gut flora of the baby and the mother were carried out to trace the source of infection. Stool cultures of the mother and the baby yielded Vancomycin-Resistant Enterococcus faecium. All three isolates of Enterococcus faecium had similar antibiogram, harbored the vanA gene and similar pulsed-field gel electrophoresis pattern. Baby responded to the 1 week therapy with oral linezolid suspension 20 mg/kg/day, 1 ml/t.d.s. No VRE was isolated from baby on a repeat stool culture 1 week after the linezolid therapy. He was discharged with the advice for the continuance of linezolid for seven more days. Conclusion: Isolation of MDR-VRE from the blood culture of the baby and stool specimens of the mother and the baby with the same antibiogram profile and clonal similarities reveals that maternal gut colonization was responsible for neonatal sepsis. Optimal infection control measures and the development of guidelines for monitoring VRE colonization in pregnant women might be useful in reducing the occurrence of neonatal sepsis.

Comparative evaluation of soft tissue changes one year post-treatment in Twin Block and FORSUS FRD treated patients.

BACKGROUND: The objective of this study was to compare and evaluate the effects of two functional treatment modalities, namely, Twin Block (TB) and FORSUS fatigue resistant device (FORSUS FRD) on facial soft tissues before and at one-year post-treatment. METHODS: This was a retrospective cephalometric study involving 10 patients with skeletal class II abnormalities in each group. The mean age of patients was 12.5 ± 1.5 and 13.5 ± 1 years and treatment duration 20 ± 2 and 18 ± 2 months, respectively for TB and FORSUS FRD groups, respectively. The pre-treatment (T0) and one-year post-treatment cephalograms (T1) were compared for evaluation. Data were analysed using a paired t-test and independent sample t-test for within-group and between-group comparisons, respectively. RESULTS: The groups were compared at T0 and T1, and treatment/observation differences (T1 - T0) were evaluated with paired samples t-test at P < 0.05 level and unpaired sample t-test for group comparison. Statistically significant treatment changes were found for soft tissue changes in both TB and FORSUS FRD groups. Between the two groups, TB showed significant increase in the LAFH compared to the FORSUS FRD group. CONCLUSION: Statistically significant soft tissue changes were observed after TB and FORSUS FRD appliance therapy, resulting in improvement of facial balance and aesthetics. Both, TB and FORSUS FRD, have similar effects on soft tissues, but the effect of TB on LAFH and that of FORSUS on mentolabial sulcus was more profound.

Prevalence of non-alcoholic fatty liver disease: population based study.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease and liver transplantation in western countries. Increasing incidence of NAFLD has been well documented from Asian countries like Japan and China. Diabetes mellitus (DM), obesity, hyperinsulinemia are predisposing factors for NAFLD. There is increase in incidence of DM, obesity and insulin resistance in India in last two decades. Hence it is logical to expect increase in incidence of NAFLD in India. There is limited data on the prevalence of NAFLD from India. Majority of data comes from hospital based studies including small number of patients. Therefore this study was planned to estimate the prevalence of NAFLD in general population. MATERIAL AND METHODS: Residents of two Railway colonies were evaluated on history, clinical examination, anthropometric measurements, biochemical tests and abdominal ultrasound. RESULTS: 1,168 participants were evaluated. Persons with any amount of alcohol consumption, HBs Ag positive, Anti HCV positive, persons with other known liver diseases and taking medications causing liver disease were excluded. Prevalence of NAFLD on ultrasound was 16.6%. Out of 730 subjects above the age of 20 years (341 male 384 female 389) mean age 39.08 +/- 12.3 years, 4% had diabetes, 57% had central obesity. Prevalence of NAFLD based on the ultrasound above 20 years of age was 18.9%. NAFLD was more prevalent in male than female (24.6% vs 13.6%, p < 0.001). Risk factors associated with NAFLD were age more than 40 years, male gender, central obesity, high BMR > 25, elevated fasting blood sugar, raised AST and ALT. CONCLUSION: Prevalence of NAFLD in Indian population is comparable to the west.

Overview of cases and prevalence of jaundice in neonatal intensive care unit.

This study was undertaken to know the pattern of jaundice prevalent among the babies admitted at the Neonatal Intensive Care Unit (NICU) of the B. P. Koirala Institute of Health Sciences (BPKIHS). A total of 293 neonates including 201 (68.6%) males and 92 (31.4%) females were admitted over a period of one year (15th June 2001 to 14th June 2002). Prematurity (30.0%), birth asphyxia (29.0%), neonatal septicemia (25.9%) and respiratory distress (23.9%) were the most common reasons for admission to the NICU. There were 42 cases of neonatal jaundice, among which babies born to primigravidae (59.5%), exceeded those born to multigravidae (40.5%). Pathological jaundice was found in 64.3% of the admitted cases of neonatal jaundice. Prematurity (33.3%) and neonatal septicemia (25.9%) were the most common causes of pathological jaundice, while prematurity with neonatal septicemia (14.8%), ABO incompatibility (11.1%), Rh incompatibility (7.4%) and prematurity, neonatal septicemia and ABO incompatibility combined (7.4%) accounted for the remaining cases of jaundice. A more detailed study related to the pathogenesis of jaundice among neonates is needed for the prevention of this disease in them.