Preparation and characterization of novel derivatives of chitosan and trimethyl chitosan conjugated with dipeptides and vitamin B12 as candidates for oral delivery of insulin

Chitosan and its derivatives are widely used in drug delivery systems due to their bio-degradebility, bio-compatibility and absorption enhancing properties. Many peptide and protein derived therapeutics cannot be administered through oral rout because of the proteolytic condition of gastro-intestinal tract and their low bio-availability. Insulin is a peptide drug which is widely used in diabetics as repeated daily injection. Due to the fact that there are receptors for didpeptides and vitamine B12 in small intestine, in this research work novel derivatives of chitosan and trimethyl chitosan conjugated with glycyl-glycine, alanyl-alaninie and vitamine B12 were synthesized and characterized. The structure of conjugates as well as substitution of different functional groups was confirmed by different instrumental analytical methods such as Fourier transform infrared, magnetic resonance, and X-ray diffraction spectroscopy. Nano-particles of aforementioned loaded with insulin were prepared and their size, surface electrical charge and morphology characterized and their release profile were studied. The results are promising and reveal that these new chitosan and trimethyl chitosan derivatives are potential vehicles for protein and peptide drug molecules.     

Optimal control of steel structures by improved particle swarm

Active control is one of the modern approaches in seismic design of steel structures. Recently, induced by economic considerations, especially high expenses of control systems, optimality has become an important issue. In this paper an active system is used to control a steel structure’s displacements by a simplified pole assignment method. To optimize the number, the locations, and the total driving force of the required actuators, an improved particle swarm algorithm is presented focusing on the parameters of the velocity equation. A Geographical neighborhood topology and an adaptive inertia weight are used to improve the standard PSO algorithm. In addition to the local and global best solutions, the positions of the best particles in the geographical neighborhood are mathematically represented in an additional term. The performance of the proposed algorithm is compared with the traditional Genetic Algorithm (GA) and the standard particle swarm considering the optimal control of a 12-story steel structure as a numerical example. High capabilities of the proposed method in terms of the control target, convergence rate, and accuracy are simultaneously clarified by the results.     

A simulation study of some tooling problems in automated manufacturing

A simulation model has been developed to analyze the effects of tool configuration, tool replenishing, and tool sharing. A feature of the model is its ability to keep track of tool usage (age). The application of the model is demonstrated using an example problem. Some findings are discussed.     

A SAS macro for stepwise correlated binary regression

Changes in complete blood count (CBC), bone marrow, reticulocyte count, coagulation profile, biochemical analysis, and serum iron, transferrin, and immunoglobulin M (IgM) concentrations were measured three and 10 days after splenectomy in 12 dogs. Spleens were cultured aerobically for bacteria and submitted for histopathological evaluation in 23 dogs undergoing splenectomy. There were no consistent changes in red blood cell (RBC), white blood cell (WBC), or platelet counts; bone-marrow samples; or biochemical profiles. Serum iron, transferrin, and IgM concentrations remained normal. Eight (35%) bacterial cultures yielded growth. Five of the 23 dogs had pyrexic episodes two-to-five days after surgery. In contrast to previous reports done on healthy dogs, this study shows that dogs with splenic disease have no characteristic changes in hematological or biochemical parameters after splenectomy. Rather, the changes tended to reflect the primary disease process. Splenic vascular compromise or a decrease in processing of bacteria may have resulted in the bacterial growth. There was no direct correlation to pyrexic postoperative episodes.     

Immunochemical properties of a 60 kDa cell surface-associated heat shock-protein (Hsp60) from Helicobacter pylori

Western blot analysis (immunoblotting) of cell surface-associated proteins from Helicobacter pylori confirmed our previous findings that binding of human IgG is a common property (among H. pylori strains). Purification of the IgG-binding proteins (IGBP) was achieved by two purification steps, affinity chromatography on IgG-Sepharose and nickel chelate affinity chromatography. SDS-PAGE and immunoblotting analysis revealed a 60 kDa protein with affinity for peroxidase labeled human IgG. Solid phase binding assays showed that IgG binds to an immobilized protein (IGBP). The 60 kDa IGBP binds human IgG1, IgG3 and IgM. Binding could be inhibited by the kappa chain of the human IgG, but not with its Fc fragment, nor with IgA or IgM. In addition, rabbit polyclonal antibodies raised against the 60 kDa IGBP blocked IgG binding. Monoclonal antibodies, specific to the Hsp60 heat shock protein of H. pylori recognized the 60 kDa IGBP as revealed by immunoblotting analysis, both in crude preparations and in the purified fractions.     

Coupled B-snake grids and constrained thin-plate splines foranalysis of 2-D tissue deformations from tagged MRI

Magnetic resonance imaging (MRI) is unique in its ability to noninvasively and selectively alter tissue magnetization and create tagged patterns within a deforming body such as the heart muscle. The resulting patterns define a time-varying curvilinear coordinate system on the tissue, which the authors track with coupled B-snake grids. B-spline bases provide local control of shape, compact representation, and parametric continuity. Efficient spline warps are proposed which warp an area in the plane such that two embedded snake grids obtained from two tagged frames are brought into registration, interpolating a dense displacement vector field. The reconstructed vector field adheres to the known displacement information at the intersections, forces corresponding snakes to be warped into one another, and for all other points in the plane, where no information is available, a C¹ continuous vector field is interpolated. The implementation proposed in this paper improves on the authors' previous variational-based implementation and generalizes warp methods to include biologically relevant contiguous open curves, in addition to standard landmark points. The methods are validated with a cardiac motion simulator, in addition to in-vivo tagging data sets     

Twenty-month outcome in ventilator-dependent, very low birth weight infants born during the early years of dexamethasone therapy

We sought to examine the effect of the introduction of dexamethasone therapy on health, growth, and neurodevelopmental outcome in very low birth weight (VLBW) infants at 20 months of age. We compared outcomes in all 86 VLBW infants (mean birth weight 871 gm, mean gestational age 26.4 weeks) who were ventilator dependent on day 21 of life during the 2 years preceding October 1988 (period 1), when dexamethasone therapy became accepted clinical practice in our unit, with outcomes in all 124 infants (mean birth weight 891 gm, mean gestational age 26.9 weeks) with similar ventilator status during the subsequent 2 years (period 2). In addition, we compared outcomes in infants who received dexamethasone during period 2 with those in a concurrent cohort of less ill infants who were not given dexamethasone. There were no significant differences between periods 1 and 2 in mortality rates after 21 days (17% vs 21%), need for home oxygen (23% vs 25%), oxygen dependence at 20 months of corrected age (11% vs 10%), rate of neurosensory impairment (24% vs 25%), and mean Bayley Mental scores (81.5 vs 77.2) or Psychomotor Development Index (81.6 vs 71.1). Infants who received dexamethasone during period 2 had significantly more severe lung disease and poorer respiratory, growth, and developmental outcomes. We conclude that VLBW infants with ventilator-dependent chronic lung disease have very poor outcomes, even when treated with dexamethasone. More information is needed from prospective, randomized trials before dexamethasone can be accepted as routine therapy for chronic lung disease.     

Enantioseparation of anaesthetic drugs by capillary zone electrophoresis using cyclodextrin-containing background electrolytes

The enantiomers of five racemic anaesthetic drugs were resolved with cyclodextrins using capillary zone electrophoresis. Parameters which affected the chiral resolution, such as type and concentration of cyclodextrin, temperature, and addition of organic modifier were investigated. The results show that the enantiomeric discrimination of the solutes is influenced by the structural shape of the solute molecules, separation temperature, and type of cyclodextrin. It was found that alpha-cyclodextrin was the best enantioselector for resolution of prilocaine and ketamine, while the enantiomers of mepivacaine, ropivacaine, and bupivacaine were resolved with beta-cyclodextrin and/or modified beta-cyclodextrins, i.e., methyl- and 2-hydroxypropyl-beta-cyclodextrin, as chiral selectors. The length of the alkyl chain on the amino group of the drug molecule had a strong effect on the enantioresolution of mepivacaine, ropivacaine, and bupivacaine. Baseline separation of racemic ketamine was achieved with alpha- and methyl-beta-cyclodextrin at 15 degrees C. Addition of 5 M urea to the running buffer containing beta-cyclodextrin at high concentrations resulted in the enantioseparation of prilocaine, mepivacaine, and ketamine. Enantioresolution was improved upon the addition of 10% methanol to the buffer containing urea and beta-cyclodextrin. Generally, the complex formed between the S-enantiomers and modified beta-cyclodextrins was stronger than the corresponding R-forms. An exception was prilocaine where the R-form gave a more stable complex both with alpha- and beta-cyclodextrin.     

Vibration control of tall buildings

Objectionable vibrations have been experienced in modern tall buildings. To alleviate the vibrations one may increase the structural stiffness and damping or use a passive control device such as a ‘tuned mass damper’. The drawback of the above mentioned methods is the greatly increased cost. An alternative approach is to use active control devices providing control forces based on the feed back control theory. This paper presents a systematic approach of first reducing a multistorey structure to a simpler equivalent system. Then a pole placement method is developed to obtain the conrol forces. A successive approximation method is used to reduce the responses to permissible magnitudes. An example is presented to demonstrate the feasibility of the method.