Botanical candidates from Saudi Arabian flora as potential therapeutics for Plasmodium infection

Malaria is a lethal parasitic disease affecting over two hundred million people worldwide and kills almost half a million people per year. Until now, there is no curative treatment for this disease that has a substantial morbidity. The available chemotherapeutic agents are unable to completely control the infection with the continuous appearance of drug resistance. Consequently, the search for new therapeutic agents with high safety profiles and low side effects is of paramount importance. Several natural products have been investigated and proven to have antimalarial effects either in vivo or in vitro. A large number of plants have been studied globally for their antimalarial activities. However, studies that have been conducted in this field in Saudi Arabia are not enough. This article presents global and local research on the need for novel natural antimalarial agents with a particular emphasis on studies involving plants from Saudi Arabian flora.     

On the macro-micro-morphology of organs of host invasion in hemiparasite Helicanthes elasticus (Desv.) Danser

Loranthaceae family includes hemiparasitic members which are seen invading a wide range of commercial crops. Helicanthes elasticus (Desv.) Danser is very common on mango trees. Though parasitic in nature, this mistletoe is also medicinally important as fetoprotective, against vesicular calculi and kidney infections. This study is an attempt to document macro-microscopical features of parasitic root, fruit and host-mistletoe tissue interaction in the haustorium of H. elasticus growing on mango stems. Collection, preservation, sectioning, staining and photomicrography of the root, fruit and host-mistletoe union were done as per standard methodologies of anatomical studies. Though there is resemblance to the normal roots in morphology as well as anatomy, the microscopic finding of large number of branched stone cells in the roots is interesting. The morpho-anatomical features recorded would help in understanding the infection biology of this mistletoe. The eradication during the earlier stages of its establishment from seed or from the root creeping over the surface of the host can help in controlling this parasite infection on commercially important host plants.     

Studies on the Performance of Ethylamine-Modified Chitosan Carbonized Rice Husk Composite Beads for Adsorption of Metal Ion

Heavy metals in the soil and ground water have endangered our environment and human bodies by direct or indirect pathways. Currently, bioremediation is a developing process that offers the possibility to destroy various contaminants using natural biological activity. Biopolymers are industrially attractive because of their capability of lowering transition metal ion concentrations to parts per billion, they are widely available, and they are environmentally safe. This paper deals with the preparation of an ethylamine-modified biopolymer (chitosan) and carbon from biowaste (rice husk) composite beads (EAM-CCRCB) for metal ion removal. The prepared adsorbent was used for the adsorption of hexavalent chromium ions from aqueous solutions. The activation and surface properties of the adsorbent were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and Brunauer-Emmett-Teller (BET) analyses. The effect of process variables such as initial metal ion concentration, adsorbent dosage, and pH of the solution on the performance of percentage removal and adsorption capacity were studied. Various isotherm and kinetic models were fitted with experimental data to describe the solute interaction and nature of adsorption with the adsorbent through batch studies. Mass thermodynamic parameters were determined. Regeneration studies were attempted to check the stability and activity of the adsorbent.     

Spectrofluorimetric determination of certain biologically active phenothiazines in commercial dosage forms and human plasma

A validated simple and sensitive spectrofluorimetric method was developed for the determination of chlorpromazine hydrochloride, promethazine hydrochloride, trifluperazine hydrochloride, thioridazine hydrochloride, perazine maleate and oxomemazine. The method was based on condensation of malonic acid/acetic anhydride (MAA) under the catalytic effect of the tertiary amine moiety of the studied phenothiazines to provide a deep yellow to brown colour with green florescence. Relative fluorescence intensity of the products was measured at λ_exc 398 nm and λ_em 432 nm. Different variables affecting the reaction were studied and optimized. The method was successfully applied for the determination of the studied drugs in commercial dosage forms. The lower detection limits allowed the application of this method for the determination of the compounds in plasma as an example of a biological fluid. In addition, the method was considered specific for the determination of tertiary amines in the presence of primary and secondary amines; as a result, it was deemed suitable for the determination of the cited drugs in the presence of their degradation products resulting from N‐dealkylation or oxidation of the corresponding sulphoxides or sulphones. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis,Conformational and Configurational Studies of Some New Acetylated Glycosides of 2-Thio-3-aryl-4(3H)-quinazolinones,Their Thiono and 3,1-Benzothiazin-2,4-dithione

Abstract

A series of some new acetylated S-glycosides of 2-thioxoquinazolin-4-ones, their thiono analogues and 3,1-benzothazin-2,4-dithione derivatives, including a D-glucose and a D-galactose derivatives and a D-xylose, and an L-arabinose derivatives have been synthesized. The conformation and configuration of these carbohydrate derivatives were determined by analysing their ¹H and ¹³C NMR chemical shifts and coupling constants. The biological activity of these compounds has been studied.     

Good Manufacturing Practices (GMP) manufacturing of advanced therapy medicinal products: a novel tailored model for optimizing performance and estimating costs

Background aimsAdvanced therapy medicinal products (ATMP) have gained considerable attention in academia due to their therapeutic potential. Good Manufacturing Practice (GMP) principles ensure the quality and sterility of manufacturing these products. We developed a model for estimating the manufacturing costs of cell therapy products and optimizing the performance of academic GMP-facilities.MethodsThe “Clean-Room Technology Assessment Technique” (CTAT) was tested prospectively in the GMP facility of BCRT, Berlin, Germany, then retrospectively in the GMP facility of the University of California-Davis, California, USA. CTAT is a two-level model: level one identifies operational (core) processes and measures their fixed costs; level two identifies production (supporting) processes and measures their variable costs. The model comprises several tools to measure and optimize performance of these processes. Manufacturing costs were itemized using adjusted micro-costing system.ResultsCTAT identified GMP activities with strong correlation to the manufacturing process of cell-based products. Building best practice standards allowed for performance improvement and elimination of human errors. The model also demonstrated the unidirectional dependencies that may exist among the core GMP activities. When compared to traditional business models, the CTAT assessment resulted in a more accurate allocation of annual expenses. The estimated expenses were used to set a fee structure for both GMP facilities. A mathematical equation was also developed to provide the final product cost.ConclusionsCTAT can be a useful tool in estimating accurate costs for the ATMPs manufactured in an optimized GMP process. These estimates are useful when analyzing the cost-effectiveness of these novel interventions.     

Serotonin Receptor B May Lock the Gate of PTTH Release/Synthesis in the Chinese Silk Moth,Antheraea pernyi; A Diapause Initiation/Maintenance Mechanism?

The release of prothoracicotropic hormone, PTTH, or its blockade is the major endocrine switch regulating the developmental channel either to metamorphosis or to pupal diapause in the Chinese silk moth, Antheraea pernyi. We have cloned cDNAs encoding two types of serotonin receptors (5HTR_{A and B}). 5HTR_A-, and 5HTR_B-like immunohistochemical reactivities (-ir) were colocalized with PTTH-ir in two pairs of neurosecretory cells at the dorsolateral region of the protocerebrum (DL). Therefore, the causal involvement of these receptors was suspected in PTTH release/synthesis. The level of mRNA^5HTRB responded to 10 cycles of long-day activation, falling to 40% of the original level before activation, while that of 5HTR_A was not affected by long-day activation. Under LD 16:8 and 12:12, the injection of dsRNA^5HTRB resulted in early diapause termination, whereas that of dsRNA^5HTRA did not affect the rate of diapause termination. The injection of dsRNA^5HTRB induced PTTH accumulation, indicating that 5HTR_B binding suppresses PTTH synthesis also. This conclusion was supported pharmacologically; the injection of luzindole, a melatonin receptor antagonist, plus 5th inhibited photoperiodic activation under LD 16:8, while that of 5,7-DHT, induced emergence in a dose dependent fashion under LD 12:12. The results suggest that 5HTR_B may lock the PTTH release/synthesis, maintaining diapause. This could also work as diapause induction mechanism.     

Genetic Structure and Evolution of the Leishmania Genus in Africa and Eurasia: What Does MLSA Tell Us

Leishmaniasis is a complex parasitic disease from a taxonomic, clinical and epidemiological point of view. The role of genetic exchanges has been questioned for over twenty years and their recent experimental demonstration along with the identification of interspecific hybrids in natura has revived this debate. After arguing that genetic exchanges were exceptional and did not contribute to Leishmania evolution, it is currently proposed that interspecific exchanges could be a major driving force for rapid adaptation to new reservoirs and vectors, expansion into new parasitic cycles and adaptation to new life conditions.To assess the existence of gene flows between species during evolution we used MLSA-based (MultiLocus Sequence Analysis) approach to analyze 222 Leishmania strains from Africa and Eurasia to accurately represent the genetic diversity of this genus. We observed a remarkable congruence of the phylogenetic signal and identified seven genetic clusters that include mainly independent lineages which are accumulating divergences without any sign of recent interspecific recombination. From a taxonomic point of view, the strong genetic structuration of the different species does not question the current classification, except for species that cause visceral forms of leishmaniasis (L. donovani, L. infantum and L. archibaldi). Although these taxa cause specific clinical forms of the disease and are maintained through different parasitic cycles, they are not clearly distinct and form a continuum, in line with the concept of species complex already suggested for this group thirty years ago. These results should have practical consequences concerning the molecular identification of parasites and the subsequent therapeutic management of the disease.