Cyclodextrin Complexes of Reduced Bromonoscapine in Guar Gum Microspheres Enhance Colonic Drug Delivery

Here, we report improved solubility and enhanced colonic delivery of reduced bromonoscapine (Red-Br-Nos), a cyclic ether brominated analogue of noscapine, upon encapsulation of its cyclodextrin (CD) complexes in bioresponsive guar gum microspheres (GGM). Phase−solubility analysis suggested that Red-Br-Nos complexed with β-CD and methyl-β-CD in a 1:1 stoichiometry, with a stability constant (Kc) of 2.29 × 103 M−1 and 4.27 × 103 M−1. Fourier transforms infrared spectroscopy indicated entrance of an O−CH2 or OCH3−C6H4−OCH3 moiety of Red-Br-Nos in the β-CD or methyl-β- CD cavity. Furthermore, the cage complex of Red-Br-Nos with β-CD and methyl-β-CD was validated by several spectral techniques. Rotating frame Overhauser enhancement spectroscopy revealed that the Ha proton of the OCH3−C6H4−OCH3 moiety was closer to the H5 proton of β-CD and the H3 proton of the methyl-β-CD cavity. The solubility of Red-Br-Nos in phosphate buffer saline (PBS, pH ∼ 7.4) was improved by ∼10.7-fold and ∼21.2-fold when mixed with β-CD and methyl-β-CD, respectively. This increase in solubility led to a favorable decline in the IC50 by ∼2-fold and ∼3-fold for Red-Br-Nos−β-CD-GGM and Red-Br-Nos−methyl-β-CD-GGM formulations respectively, compared to free Red-Br-Nos−β-CD and Red-Br-Nos−methyl-β-CD in human colon HT-29 cells. GGM-bearing drug complex formulations were found to be highly cytotoxic to the HT-29 cell line and further effective with simultaneous continuous release of Red-Br-Nos from microspheres. This is the first study to showing the preparation of drug-complex loaded GGMS for colon delivery of Red-Br-Nos that warrants preclinical assessment for the effective management of colon cancer

Collaborating to Compete: Blood Profiling Atlas in Cancer (BloodPAC) Consortium

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136731/1/cpt666.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136731/2/cpt666_am.pd

Fe and Cr doping of liquid‐phase epitaxial In0.53Ga0.47As/InP

Fe and Cr doping of liquid‐phase epitaxial In0.53Ga0.47As grown at 650 °C on InP substrates have been investigated. Varying amounts of high‐purity Fe and Cr have been added to the growth melt. The resistivity of Fe‐doped layers increases with increase of Fe added to the melt, and layers with ND−NA as low as 2.0×1012 cm−3 can be grown consistently. From analysis of temperature‐dependent Hall data on conducting Fe‐doped samples, the Fe acceptor ionization energy is found to be 0.46 eV. No additional feature is seen in the 4 K band‐edge photoluminescence spectra of Fe‐doped layers. Cr doping seems to produce donorlike behavior and the electron concentration increases monotonically with increased addition of Cr to the melt. An additional peak, separated from the band‐gap energy by 24 meV is seen in the photoluminescence spectra of Cr‐doped samples. It is believed that Cr itself, or a complex defect involving Cr is responsible for the formation of a donorlike center.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71081/2/JAPIAU-57-2-333-1.pd

Methods in Molecular Biology

Not AvailableParticle bombardment/biolistic delivery is a very popular method of genetic transformation of diverse targets including cells and intact tissues. Delivery of DNA through particle bombardment is genotype and species independent, nevertheless, an ef fi cient protocol for large-scale generation of transgenic plants through embryogenic tissues with a high ( ³ 80%) shoot regeneration ef fi ciency is a prerequisite. Young embryogenic tissues or multiple shoot buds in early stages of induction are the most suited target tissues for recovery of transgenic plants. We describe the protocol for delivery of foreign genes using particle delivery system (Biorad gene gun, PDS-1000/He) in to the meristematic tissues of embryonic axes derived from mature seeds of castor. With the optimized physical and biological parameters, putative transformants were obtained at a frequency of 1.4% through particle gun bombardment of castor embryo axes. Also, transformation of embryogenic calli of sorghum using particle in fl ow gun (PIG) is described.Not Availabl

Differences in risk factors between early and late diagnosed developmental dysplasia of the hip

Copyright © 2006 by the BMJ Publishing Group Ltd.Background: Developmental dysplasia of the hip (DDH) is common, affecting 7.3 per 1000 births in South Australia. Clinical screening programmes exist to identify the condition early to gain the maximum benefit from early treatment. Although these screening programmes are effective, there are still cases that are missed. Previous research has highlighted key risk factors in the development of DDH. Objective: To compare the risk factors of cases of DDH identified late with those that were diagnosed early. Methods: A total of 1281 children with DDH born in 1988–1996 were identified from the South Australian Birth Defects Register. Hospital records of those who had surgery for DDH within 5 years of life were examined for diagnosis details. Twenty seven (2.1%) had been diagnosed at or after 3 months of age and were considered the late DDH cases (a prevalence of 0.15 per 1000 live births). Various factors were compared with early diagnosed DDH cases. Results: Female sex, vertex presentation, normal delivery, rural birth, and discharge from hospital less than 4 days after birth all significantly increased the risk of late diagnosis of DDH. Conclusions: The results show differences in the risk factors for early and late diagnosed DDH. Some known risk factors for DDH are in fact protective for late diagnosis. These results highlight the need for broad newborn population screening and continued vigilance and training in screening programmes.P Sharpe, K Mulpuri, A Chan, P J Cund

Annealing of Ion-implanted SiC by Laser-pulse-exposure-generated Shock-waves

Athermal annealing in phosphorus, boron, and aluminum/boron implanted 4H-SiC is explored by launching mechanical shock waves, induced by exposure to a laser pulse. Annealing is observed in a 3.2 mm outer diameter donut-shaped area surrounding the laser exposed spot. The minimum sheet-resistance within this area in phosphorus-implanted sample is close to the thermally annealed value of 400 Ω/□. Unlike thermal annealing, shock annealing did not cause any redistribution of the implant, including boron, a known transient enhanced diffuser in SiC. Optimization of parameters like laser power and/or pulse duration or investigation of an alternate mechanical shockwave launching method is required to achieve athermal annealing far away from the center of the exposed region and similar to that of the thermal annealed material. Results of this study might help in the manufacturing of silicon carbide high-power, high-temperature, and radiation hardened devices in the future

Management of long bone fractures and traumatic hip dislocations in paediatric patients: study protocol for a prospective global multicentre observational cohort registry

ABSTRACT Introduction Management controversy and clinical equipoise exist in treatments of long bone fractures and traumatic hip dislocation in paediatric patients due to the lack of high-quality clinical evidence. This protocol describes the effort of a large prospective global multicentre cohort study (registry) aiming at providing quality data to assist evidence-based treatment decisionmaking. Methods and analysis Eligible paediatric patients (N=750–1000) with open physes suffering from proximal humerus fractures, distal humerus fractures, proximal radius fractures, forearm shaft fractures, traumatic hip dislocations, femoral neck fractures or tibial shaft fractures will be recruited over a period of 24–36 months. Hospitalisation and treatment details (including materials and implants) will be captured in a cloudbased, searchable database. Outcome measures include radiographic assessments, clinical outcomes (such as range of motion, limb length discrepancies and implant removal), patient-reported outcomes (Patient Reported Outcomes Of Fracture, Patient-Reported Outcomes Measurement Information System (PROMIS) and EuroQol5D (EQ-5D-Y)) and adverse events. Aside from descriptive statistics on patient demographics, baseline characteristics, types of fractures and adverse event rates, research questions will be formulated based on data availability and quality. A statistical analysis plan will be prepared before the statistical analysis. Ethics and dissemination Ethics approval will be obtained before patients are enrolled at each participating site. Patient enrolment will follow an informed consent process approved by the responsible ethics committee. Peer-reviewed publication is planned to disseminate the study results. Trial registration number NCT04207892