EFFECT OF ETHANOLIC EXTRACT OF TERMINALIA ARJUNA ON LIVER FUNCTIONS AND HISTOPATHOLOGY OF LIVER IN ALBINO RATS FED WITH HYPERLIPIDEMIC DIET

Objective: The aim of the present study was to assess the effect of Ethanolic extract of Terminalia Arjuna on Liver functions, Lipid profile and histopathology of liver of albino rats fed with Hyperlipidemic diet.Methods: Extraction of Terminalia arjuna bark by Soxhlet apparatus using 99% ethanol at 60 ° temp for 22 h and Phytochemical analysis was done. Group 1 served as normal control. Group 2 Fed with Isocaloric diet. Group 3 Fed with Hyperlipidimic diet. Group 4 Hyperlipidemic diet 21 d+Terminalia arjuna 21 d.Dose of Ethonolic extract of Terminalia arjuna: (500 mg/kg Body weight daily).Results: %body weight gain and hepatosomatic index were significantly improved in hyper lipidemic rats treated with Terminalia arjuna. There was significant improvement in markers of liver functions. Liver shown microvescicular and macrovesicular fatty changes in hyper lipidemic rats and normal Hepatocytes in Hyperlipidimic rats treated with Terminalia arjuna. Conclusion: It can be summarized that Terminalia arjuna is good, natural therapeutics in hyperlipidemia and liver disorders.Â

No ordinary proteins: Adsorption and molecular orientation of monoclonal antibodies

The interaction of monoclonal antibodies (mAbs) with air/water interfaces plays a crucial role in their overall stability in solution. We aim to understand this behavior using pendant bubble measurements to track the dynamic tension reduction and x-ray reflectivity to obtain the electron density profiles (EDPs) at the surface. Native immunoglobulin G mAb is a rigid molecule with a flat, “Y” shape, and simulated EDPs are obtained by rotating a homology construct at the surface. Comparing simulations with experimental EDPs, we obtain surface orientation probability maps showing mAbs transition from flat-on Y-shape configurations to side-on or end-on configurations with increasing concentration. The modeling also shows the presence of β sheets at the surface. Overall, the experiments and the homology modeling elucidate the orientational phase space during different stages of adsorption of mAbs at the air/water interface. These finding will help define new strategies for the manufacture and storage of antibody-based therapeutics

Early feeding practices in infants with phenylketonuria across Europe

Background: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. Methods: We sent a cross sectional, survey monkey (R) questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. Results: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months. 53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, >= 26 weeks in 12% and <17 weeks in 3%. Discussion: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development.Peer reviewe

Weaning practices in phenylketonuria vary between health professionals in Europe

Background: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. Methods: A cross sectional questionnaire (survey monkey (R)) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. Results: Weaning started at 17-26 weeks in 85% (n=81/95) of centres, > 26 weeks in 12% (n=11/95) and 26 weeks. First solids were mainly low Phe vegetables (59%, n=56/95) and fruit (34%, n=32/95). A Phe exchange system to allocate dietary Phe was used by 52% (n=49/95) of centres predominantly from Northern and Southern Europe and 48% (n=46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods. A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n=39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n=35/95) at infant age > 1y mainly from Southern Europe. 53% (n=50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. Conclusions: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.Peer reviewe

Phase and frequency modulation : computer simulations, reconstruction methods and bessel functions

In this thesis, phase and frequency modulation, used mainly in communication theory, is being the major issue. In particular, the thesis emphases phase modulation. Phase and frequency modulation are two different ways to transform signals, so they can more easily be transmitted and received. The equations for these transformations are being considered. Some methods for reconstruction of the signals are implemented and tested. Also, the problem with noisy signals is being dealt with. Further on, an extensive analysis of the Fourier coefficients of such transformed signals and their connection to Bessel functions is performed. Finally the connection between Bessel functions an the energies of these modulated signals is studied using analytic methods and computer experiments.Validerat; 20101217 (root

Dynamics and Phase Behavior of Mixed Antibody-Excipient Adsorption at an Air/Water Interface

Monoclonal antibodies (mAbs) have become a leading candidate for oncological therapeutics due to their unparalleled selectivity. Monoclonal antibodies are amphiphilic, containing polar and nonpolar amino acid residues on their biomolecular surfaces. Their amphiphilic nature drives mAbs to strongly adsorb to air/water interfaces. Interfacial adsorption presents a central problem to the production and use of antibody-based pharmaceuticals. Air/water interfaces are frequently generated during the manufacture (filtration and chromatography) and production (freezing, thawing, filtration and filling) of the drug product. Moreover, air/water interfaces are present during the storage, transportation and administration of the therapeutics. When an air/water interface is created, the antibodies adsorb and expose their hydrophobic residues to the gas phase leading to irreversible adsorption, partial unfolding, interfacial aggregation, and recruitment of additional proteins from the solution phase. Depletion from solution of the therapeutically effective, native form of the mAb biologic leads inaccurate dosage and shortened shelf life. The pharmaceutical industry uses multicomponent formulations to circumvent adsorption issues, adding ‘inert’ FDA approved surfactants to the mAb solutions to populate the interface and thereby prevent the adsorption of the antibody (Fig. 1). However, the mechanism of the adsorption behavior of mAbs in the presence of surfactant is still an open scientific question and understanding the mechanism of adsorption is critical to the production and administration of the next generation mAb-based pharmaceuticals. This work elucidates the interfacial behavior of the multicomponent system at the molecular level. This dissertation will focus on the three key aspects of mAb-surfactant adsorption. The first part is based on the transport controlled competitive dynamics between surfactant (Polysorbate 80) and two different mAbs. Pendant bubble tensiometry and X-ray reflectivity (XR) are used to quantify the rate at which the molecules “race” to the interface. The experiments show a phase space in mAb/surfactant concentration where co-adsorption of both the mAbs and surfactants occur at the air/water interface (Fig. 1a) and a phase space where surfactant dominates. A key finding is that the competitive behavior of the mAbs and the surfactants for the interface correlates with surface activity of the mAb. Additionally, this work presents a clear elucidation of the transport mechanisms underlying the armoring of the interface with the surfactants to inhibit mAb adsorption to the surface and sub-surface domain. The second aspect of this work is to understand the dynamic orientational change in the adsorbed mAb as a function of concentration at the air/water interface using XR coupled with homology modeling (Fig. 1b,c). The confined “Y” shaped structure of mAbs, provides a contrast in the adsorption behavior of mAbs to globular proteins. The effect of the surface packing and unfolding of the mAbs at the interface will be addressed with the emphasis on how this affects the formulation of the drug product. Overall, the experiments and the homology modeling provide a complex landscape of orientational phase space during different stages of adsorption of mAbs at the air/water interface. This information about the complex phase space can be of value in designing methodologies for transferring and administrating the antibodies with maximal dosage. Lastly, a theoretical model is developed to identify the “critical” surfactant concentration that needs to be present in therapeutic formulations to protect the air/water interface from mAb adsorption (Fig. 1d). This is based on the theoretical modeling of the kinetic adsorption mechanism for different surface-active mAbs and a diffusion-controlled adsorption for surfactants guided by our findings described above. A phase diagram that defines the surfactant dominant regime for four different hydrophobic mAbs will be presented. In summary, this thesis develops experimental tools and a transport analysis to quantify critical parameters important to the competitive adsorption of mAbs and surfactants to the air/water interface. The work presented here constructs a general model to predict concentration regimes in which surfactant protects the interface from adsorption. Taken together, this study is intended to help the pharmaceutical industry to accelerate the stability of the therapeutics during the manufacturing, storage and delivery via intravenous injection of the drugs