Preparation and Characterization of Benzathine Penicillin G Solid Dispersions Using Different Hydrophilic Carriers

Several technical factors related to penicillin G intramuscular injection can affect its bioavailability and hence reduce the efficacy of rheumatic fever prevention program. When small amount of diluent is used, the powder is not completely dissolved and the thick suspension frequently causes obstruction of injection needle. The study aimed to characterize the solid-state properties of solid dispersion systems of benzathine penicillin G (BPG) prepared with hydrophilic carriers by applying solvent evaporation method. The results of spectroscopic studies; Fourier transform-infra red (FTIR), Nuclear Magnetic Spectroscopy (1HNMR) and Differential Scanning Calorimetry (DSC) revealed no chemical interaction between the drug and carriers. No significant changes in drug crystalline state were observed by X-ray diffraction and Scanning Electron Microscope (SEM) studies, even with using amorphous carriers; polyvinyl pyrrolidone (PVP-K30) and hydroxypropyl methylcellulose (HPMC). All the prepared solid dispersions demonstrated 76-93% yield and % drug content dependent on the polymer type and concentration. The hydrophilic polymers demonstrated potential effect on improving the flowability, wettability and dissolution characters of the drug. The results revealed that it is possible to enhance the dissolution rate of BPG (hydrophobic drug) by increasing the surface area of the drug adsorbed on the surface of hydrophilic polymer by solid dispersion method. Finally, solid dispersion BPG: PEG 4000 at ratio 50:50 gave uniform flowability of the powder (around 30), wettability (12 min) and faster dissolution rates among all the formulations. Thus, it was selected as the best formulation in this study

Preparation and Characterization of Benzathine Penicillin G Solid Dispersions Using Different Hydrophilic Carriers

Several technical factors related to penicillin G intramuscular injection can affect its bioavailability and hence reduce the efficacy of rheumatic fever prevention program. When small amount of diluent is used, the powder is not completely dissolved and the thick suspension frequently causes obstruction of injection needle. The study aimed to characterize the solid-state properties of solid dispersion systems of benzathine penicillin G (BPG) prepared with hydrophilic carriers by applying solvent evaporation method. The results of spectroscopic studies; Fourier transform-infra red (FTIR), Nuclear Magnetic Spectroscopy (1HNMR) and Differential Scanning Calorimetry (DSC) revealed no chemical interaction between the drug and carriers. No significant changes in drug crystalline state were observed by X-ray diffraction and Scanning Electron Microscope (SEM) studies, even with using amorphous carriers; polyvinyl pyrrolidone (PVP-K30) and hydroxypropyl methylcellulose (HPMC). All the prepared solid dispersions demonstrated 76-93% yield and % drug content dependent on the polymer type and concentration. The hydrophilic polymers demonstrated potential effect on improving the flowability, wettability and dissolution characters of the drug. The results revealed that it is possible to enhance the dissolution rate of BPG (hydrophobic drug) by increasing the surface area of the drug adsorbed on the surface of hydrophilic polymer by solid dispersion method. Finally, solid dispersion BPG: PEG 4000 at ratio 50:50 gave uniform flowability of the powder (around 30), wettability (12 min) and faster dissolution rates among all the formulations. Thus, it was selected as the best formulation in this study

The Concept of Text from the Perspective of Heritage and Modernity: Its Impact on Formulating the Theory of a Literary Text

This research aims to discuss the problem of the textual concept in the Arab critical heritage and the Western critical thought and to show its impact on formulating the contemporary literary textual theory. It is the problem that stems from the assumption that Arab critical thought has originated in the components of this theory, which we find have roots and references in our critical, literary, rhetorical and philosophical heritage. Hence, the textual theory in the contemporary critical thought is an extension of this legacy, benefiting from the achievements of philosophers, linguists and critics, and the achievements of contemporary critical approaches. The research attempts answer some important questions such as: was the critical study concerned with theorizing the text? Does the critical heritage have the mechanisms for dealing with the text? What is the role of this critical heritage in the formulation of contemporary literary textual theory? To answer these questions, we follow a procedural plan that falls into three axes. The first one is dedicated to the analysis of the components of textual theory and its references in our critical and rhetorical heritage. The second one is devoted to the components of the textual theory in the Western critical thought. The last one is dedicated to the effect of the concept of the text in formulating the features and dimensions of the literary textual theory

UTeM`s Amphibious Hybrid Vehicle: Ride and Handling Analysis

The vehicle ride and handling analysis is one of the important aspects in vehicle dynamics. This paper takes a model of amphibious vehicle to establish the exact virtual behavior of vehicle’s riding and handling base on the virtual design parameter. This vehicle can operate both on ground and water, therefore the analysis model is developed using seven degree of freedom model for ground operation and one degree of freedom model for water operation. The seven DOF are moment of roll, pitch, yaw and all four tires motion while the rest is buoyancy. Therefore, the ability and limitation of the vehicle demonstrate the behavior of unexpected case happened. These facts in turn to be used to improve the ride and handling level during acceleration, deceleration, cornering and step steer. The model also capable to function on the water where as the design of the body work considers the buoyancy concept for stability on every condition of wave surface. The analysis of buoyancy and stability for this model shows the vehicle ability to perform in the state of equilibrium condition under heeling and capsizing on water surface

Low HDL cholesterol is associated with increased atherogenic lipoproteins and insulin resistance in women classified with metabolic syndrome

Both metabolic syndrome (MetS) and elevated LDL cholesterol (LDL-C) increase the risk for cardiovascular disease (CVD). We hypothesized that low HDL cholesterol (HDL-C) would further increase CVD risk in women having both conditions. To assess this, we recruited 89 women with MetS (25-72 y) and LDL-C ≥ 2.6 mmol/L. To determine whether plasma HDL-C concentrations were associated with dietary components, circulating atherogenic particles, and other risk factors for CVD, we divided the subjects into two groups: high HDL-C (H-HDL) (≥ 1.3 mmol/L, n = 32) and low HDL-C (L-HDL) (< 1.3 mmol/L, n = 57). Plasma lipids, insulin, adiponectin, apolipoproteins, oxidized LDL, Lipoprotein(a), and lipoprotein size and subfractions were measured, and 3-d dietary records were used to assess macronutrient intake. Women with L-HDL had higher sugar intake and glycemic load (P < 0.05), higher plasma insulin (P < 0.01), lower adiponectin (P < 0.05), and higher numbers of atherogenic lipoproteins such as large VLDL (P < 0.01) and small LDL (P < 0.001) than the H-HDL group. Women with L-HDL also had larger VLDL and both smaller LDL and HDL particle diameters (P < 0.001). HDL-C was positively correlated with LDL size (r = 0.691, P < 0.0001) and HDL size (r = 0.606, P < 0.001), and inversely correlated with VLDL size (r = -0.327, P < 0.01). We concluded that L-HDL could be used as a marker for increased numbers of circulating atherogenic lipoproteins as well as increased insulin resistance in women who are already at risk for CVD

Challenges in Using Cultured Primary Rodent Hepatocytes or Cell Lines to Study Hepatic HDL Receptor SR-BI Regulation by Its Cytoplasmic Adaptor PDZK1

Background: PDZK1 is a four PDZ-domain containing cytoplasmic protein that binds to a variety of membrane proteins via their C-termini and can influence the abundance, localization and/or function of its target proteins. One of these targets in hepatocytes in vivo is the HDL receptor SR-BI. Normal hepatic expression of SR-BI protein requires PDZK1 - <5% of normal hepatic SR-BI is seen in the livers of PDZK1 knockout mice. Progress has been made in identifying features of PDZK1 required to control hepatic SR-BI in vivo using hepatic expression of wild-type and mutant forms of PDZK1 in wild-type and PDZK1 KO transgenic mice. Such in vivo studies are time consuming and expensive, and cannot readily be used to explore many features of the underlying molecular and cellular mechanisms. Methodology/Principal Findings: Here we have explored the potential to use either primary rodent hepatocytes in culture using 2D collagen gels with newly developed optimized conditions or PDZK1/SR-BI co-transfected cultured cell lines (COS, HEK293) for such studies. SR-BI and PDZK1 protein and mRNA expression levels fell rapidly in primary hepatocyte cultures, indicating this system does not adequately mimic hepatocytes in vivo for analysis of the PDZK1 dependence of SR-BI. Although PDZK1 did alter SR-BI protein expression in the cell lines, its influence was independent of SR-BI’s C-terminus, and thus is not likely to occur via the same mechanism as that which occurs in hepatocytes in vivo. Conclusions/Significance: Caution must be exercised in using primary hepatocytes or cultured cell lines when studying the mechanism underlying the regulation of hepatic SR-BI by PDZK1. It may be possible to use SR-BI and PDZK1 expression as sensitive markers for the in vivo-like state of hepatocytes to further improve primary hepatocyte cell culture conditions.National Institutes of Health (U.S.) (Grant HL052212)National Institutes of Health (U.S.) (Grant HL066105)National Institutes of Health (U.S.) (Grant ES015241)National Institutes of Health (U.S.) (Grant GM068762

An Integrated Transcriptomic and Meta-Analysis of Hepatoma Cells Reveals Factors That Influence Susceptibility to HCV Infection

Hepatitis C virus (HCV) is a global problem. To better understand HCV infection researchers employ in vitro HCV cell-culture (HCVcc) systems that use Huh-7 derived hepatoma cells that are particularly permissive to HCV infection. A variety of hyper-permissive cells have been subcloned for this purpose. In addition, subclones of Huh-7 which have evolved resistance to HCV are available. However, the mechanisms of susceptibility or resistance to infection among these cells have not been fully determined. In order to elucidate mechanisms by which hepatoma cells are susceptible or resistant to HCV infection we performed genome-wide expression analyses of six Huh-7 derived cell cultures that have different levels of permissiveness to infection. A great number of genes, representing a wide spectrum of functions are differentially expressed between cells. To focus our investigation, we identify host proteins from HCV replicase complexes, perform gene expression analysis of three HCV infected cells and conduct a detailed analysis of differentially expressed host factors by integrating a variety of data sources. Our results demonstrate that changes relating to susceptibility to HCV infection in hepatoma cells are linked to the innate immune response, secreted signal peptides and host factors that have a role in virus entry and replication. This work identifies both known and novel host factors that may influence HCV infection. Our findings build upon current knowledge of the complex interplay between HCV and the host cell, which could aid development of new antiviral strategies

ATP synthase: evolution, energetics, and membrane interactions

The synthesis of ATP, life's 'universal energy currency', is the most prevalent chemical reaction in biological systems, and is responsible for fueling nearly all cellular processes, from nerve impulse propagation to DNA synthesis. ATP synthases, the family of enzymes that carry out this endless task, are nearly as ubiquitous as the energy-laden molecule they are responsible for making. The F-type ATP synthase (F-ATPase) is found in every domain of life, and is believed to predate the divergence of these lineages over 1.5 billion years ago. These enzymes have therefore facilitated the survival of organisms in a wide range of habitats, ranging from the deep-sea thermal vents to the human intestine. In this review, we present an overview of the current knowledge of the structure and function of F-type ATPases, highlighting several adaptations that have been characterized across taxa. We emphasize the importance of studying these features within the context of the enzyme's particular lipid environment: Just as the interactions between an organism and its physical environment shape its evolutionary trajectory, ATPases are impacted by the membranes within which they reside. We argue that a comprehensive understanding of the structure, function, and evolution of membrane proteins -- including ATP synthase -- requires such an integrative approach.Comment: Review article; 29 pages, 6 figures/1 tabl

Role of Yeast F₁F₀-ATP Synthase Subunit g in the Formation of Supercomplexes in the Mitochondrial Inner Membrane

Mitochondria are essential organelles, which are not only responsible of the synthesis of energy in the cells in form of ATP hut are also required for other cellular functions like lipid metabolism, calcium signaling, FeS cluster biogenesis and apoptosis. Mitochondria produces ATP by a process termed as oxidative phosphorylation (OXPHOS), where the electrons from NADH are passed along the respiratory chain complexes to molecular oxygen. This process of electron transport is coupled to the translocation of protons from the matrix to the intermembrane space and creates an electrochemical gradient which is utilized by the F1F0-ATP synthase to generate ATP in the matrix. The electrochemical gradient and ATP also support other essential mitochondrial functions like mitochondrial fusion, fission, segregation, protein insertion and assembly of protein complexes. These OX-PHOS complexes are embedded within the mitochondrial inner membrane, where together they form higher-ordered assembly states called \u27supercomplexes\u27. Although the organization of these complexes into supercomplexes is accepted in literature and the formation is evolutionary conserved, the precise function(s) of these supercomplexes is currently unknown. This dissertation study centres on the molecular characterization of one of these supercomplexes, the dimeric ATP synthase complex. Throughout the course of this work a relationship between this supercomplex and another OX-PHOS complex, the cytochrome bc1-cytochrome oxidase supercomplex, was also established. The dimeric ATP synthase complex contains three dimer-specific subunits, subunit g (Sug), subunit e (Su e) and subunit k (Su k), which play an essential role in the physical association of the two neighboring ATP synthase complexes. Although both Su g and Sue are non-essential subunits of the ATP synthase complex, their presence is required to develop normal mitochondrial morphology, in particular the development of cristae structures of the inner membrane. Another interesting phenotype associated with the null mutants of Su g (also Sue) is that they display reduced levels of cytochrome oxidase (COX) enzymatic activity. Prior to this dissertation, these phenotypes of Su g and Su e were known; however, the role of Su g in these processes remained to be elucidated. Thus, to gain insight into the functions of these proteins, the S. cerevisiae Su g protein was further characterized in this dissertation. The molecular environment of Su g within the ATP synthase was determined. Using a chemical cross-linking approach, interacting patner protein(s) of Su g was identified. Alignment of subunit g amino acid sequences indicates a highly conserved GXXXG motif (G is Gly, and X represents any amino acid) located in its transmembrane segment, and a partially conserved carboxy-terminal domain present in the intermembrane space region. The GXXXG motif may function as a dimerization motif and supports helix-helix interaction between two neighboring transmembrane helices. These conserved regions of Su g were also analyzed to determine their importance for the function(s) of Su g. Lastly, the relationship between dimeric-ATP synthase subunit g and cytochrome oxidase (COX) complex was also explored to understand how a dimer-specific Su g affects the enzymatic activity and the assembly of the COX complex. In conclusion, the data obtained indicate that both Su g and Su e are important for the assembly of dimeric ATP synthase complex and the cytochrome bc,-COX supercomplex, and together these supercomplexes may form an organized platfonn of OX-PH OS complexes to ensure the maintenance of highly efficient OX-PHOS activity. The majority of ATP within a cell is produced in the mitochondria through the process of OX-PHOS and dysfunctions in this process are often associated with metabolic disorders, which affect variety of organs like heart, liver, skeletal muscles and brain. At present, the molecular nature of many of the mitochondrial disorders is unknown. Therefore, to cure these disorders, it is important to first fully understand these disorders, which can be achieved by studying the OXPHOS complexes at the molecular level of their subunit composition, organization and the assembly within the inner membrane. Thus, deciphering the function(s) of Su g protein could lead to better understanding of the respiratory chain complexes and may provide insight into the mitochondrial function(s) and disorders