Vaccine developments to ricin toxin

Ricin is a potent lethal cytotoxin derived from castor seeds and combatting its toxicity is a tedious task.Currently no effective antidote has ever been formulated so far and makes therapy difficult.It also places the victims survival purely as a matter of chance.As chemotherapy andd other mehods fail to produce productive results,scientists have started to employ vaccines as a possible tool to tackle the toxin.

US researchers from Army Laboratory in Frederick have found a vaccine containing an inactivated toxin that selectively retains an activity to boost the immune system without inducing lethal toxicity to mount systemic defence response in the body by protein engineering princples and found to be effective on animal models.The US Army has reported that currently trials are underway in 30 human volunteers and plans to conduct clinical trials as well at Fort Detrick.

Vaccines are powerful tools to produce solutions in a timely consistent and biologically safe way.Historical credits to vaccines in global health are something extraordinary  with reference to pathogenic diseases and attempts such as this to focus on vaccine vehicles and expanding their horizon to toxins neutralization would most probably yield a fruitful result in future to address the problems of global threat from castor toxin.

For reference: http://www.biosciencetechnology.com/News/FeedsAP/2011/04/army-starts-clinical-trials-on-ricin-vaccine/

Secondary metabolite profile in castor seed

Plant systems are rich in secondary metabolites as they play vital roles in plant development, interactions, resistance to abiotic and biotic stress etc as regulatory activators and suppressors of signal transduction physiology to mount the preprogrammed response. Virtually any evolved plant is packed with a vast array of metabolites and is well studied in medicinal herbs and shrubs, agricultural crops etc. However analysis of such functionally potent molecules in castor seed debris is rudimentary.

Secondary metabolites are  broad category compounds and scientists of this study have chosen to characterize one of the principal categories, phenolics from castor deoiled cake.The phenolics being non polar in nature differential extraction of molecules in cake was made with methanol-ether bisolvent system and they ended up with a biochemical mixture. Spetroscopic analysis showed a strong absorbance corresponding to phenolics and further chemical disintegration revealed five principal compounds namely p-coumaric acid, ferulic acid, o-coumaric acids, syringic, and cinnamic acids .

This is a remarkable metabolite profile for the presence of secondary metabolites. Eventhough the authors did not disclose the functional significance of them in seeds, it  could most probably be associated with herbivore feeding deterrent activity.

For reference: http://www.informaworld.com/smpp/content~db=all~content=a781971780

Microsatellite profiling in castor accessions

Markers are tags applied to detect polymorphism and are of different categories as phenotypic, protein, metabolite and DNA markers. Every marker tag has its unique advantage and DNA based markers are the most recently developed, routinely exploited to detect close polymorphic differences among subjects where the other classes do not reveal. Among multitude of DNA markers, micro satellite markers are notables as they seem to be single locus, co-dominant and multiallelic in nature. So it is employed to analyze polymorphism across the individuals in  bio-population since the principle claims that repetitive sequences for a locus in genome are highly variable and found to be unique for each individual.

Plant molecular biologists of Brazil chose PCR based microsatellite to identify polymorphism present in the accessions of castor germplasm. The application of genetic markers exposed eleven loci in typing but revealed only a diversity of two to five alleles in study loci on 76 accessions.

Marker assisted detection is important for polymorphism, hybridization, seed testing and germplasm management etc. It is a novel work followed in castor in spite of restricted degree in polymorphism in experimentation. The study can most probably be extended by increasing the number of markers of distinct classes to undertstand polymorphism in a deep way for intense crop improvement programmes.

For reference: http://www.amjbot.org/content/98/4/e87.abstract

Catalytic transformation of castor cake by Penicillium fungus

Castor cake is a by product from castor seed but remains as a substance with restricted application potential due to its allergenic and toxic properties.People traditionally have treated the castor cake by wild fermentation for the catalytic transformation of anti-metabolites into their corresponding non-toxic forms for improving its utility.

This age-old practice was scientifically approached by the Brazilian researchers where they subjected castor cake to solid state fermentation.Penicillium simplicissimum fungus was chosen as the catalytic factor because of its potency to manipulate in castor cake substrate and generate lipid metabolizing lipase enzymes.Solid state fermentation(dessicated fermentation) was performed for the cultivation of fungus and the products, enzyme and fermented castor cake were partitioned by solid-liquid phase differential extraction.Enzyme lipase magnitude in crude isolated fraction was determined from its activity against synthetic substrate while the debris cake fermented was evaluated for its toxic protein contents and functional activities by immunoassays and immuno sensitive cell culture assays respectively.The results proved to be promising as the toxin titre and allergens induced cell degranulation were seen to be minimum and the microbial enzyme production was noticed to a significant extent as well from specific activity studies.

Results turn out to be promising but the experiment would have been better if an utility for the fermented castor cake in biology was defined.The solid state technology by fungus seems to be a viable one on commodities like castor cake to generate high value products when time factor is not signified to a greater extent.

For referencehttp://www.scribd.com/doc/14281716/Use-of-a-Lowcost-Methodology-for-Bio-Detoxification-of-Castor-Bean-Waste

Medium formulation in ricin vaccine

Ricin is a noxious cytotoxin present in castor bean.People have long been pursuing research to understand its functional activities,physical structure and quantitative magnitude in beans etc.In spite of such extensive studies, no effective solution has been formulated to ricin intoxication. However researchers have found vaccine therapy as a promising route to combat the toxin.In ricin vaccinology, the wild toxin has been modified in such a way so that it tends to retain its antigenicity to boost the host defence system but not the toxic activity, called it as “ricin toxoid”.Genetic engineering  is a standardized technique to precisely produce variants in ricin and the candidate with expected property are subsequently chosen.

US scientists have identified an elite ricin toxoid from earlier studies and made an evaluation on vaccine formulation to achieve enhanced antigenicity and stability.Initially they treated the protein in phosphate buffer solution and found structural and functional tolerance in protein after cyclic exposures to extreme temperature ranges.To further improve its adjuvant adherence and related antigenicity, toxoid was treated with aluminium hydroxide adjuvant in succinate buffer and evaluated by differential centrifugation and immuno assays.The results indicated that aluminium hydroxide showed a good compatibility with toxoid by co-sedimentation of protein with gel matrix and also elicited a strong immune response, confirmed by antibody titre studies.Functional confirmation did not seem to be significantly affected by conjugation with adjuvant and Fourier transform infrared spectroscopy was applied to understand it.

Scientists in this study have made a complete profile in ricin vaccine formulation and its influence in conferring active immunity to primitive model systems but the confirmation is to be arrived from human clinical trials as extrapolation of data from mice to humans is difficult .

For reference: http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1006&context=usarmyresearch&sei-redir=1#search=”ricin+breakth

Crystallographic resolution of castor enzyme.

Functional property of a material is determined by the spacial configuration of its constituents and their physical interactions in accordance with laws of exact sciences.Hence an understanding  by a clear resolution is vital for any physical particulate matter to functional association.Several different techniques have been developed so far to accomplish it and crystallography is one among powerful tools to determine the geometry of biomolecules in particular, the proteins which have been characterized by it since the middle of twentieth century.

Swedish researchers have chosen to characterize an enzyme catalyst of castor delta 9 stearoyl acyl carrier protein desaturase by crystallography which is accelerating the synthesis of ricinoleic acid from stearic acid by unsaturation.Enzyme crystal generated was targeted by high energy radiations to produce a fingerprint for analysis of constituents and their orientation.They identified multiple alpha helical folding pattern with two iron atoms in a co-ordinate covalent bonding with charged amino acids of the protein moiety.An holistic structural analysis of the enzyme revealed it as a hollow cylinder to accommodate the substrate fatty acid with its 9th carbon atom exactly interacts with iron atoms for electron transfers to make the unsaturated carbon-carbon bonding by metal ion catalysis.

Scientists have prepared an elegant picture for the key regulatory desaturase enzyme in castor.Protein purification and crystallization are painstaking processes to resolve it from solution as the influence of temperature,pressure,concentration of solute protein etc are significant.However the quality of information by crystallography is definitely superior to other in silico structural studies.

For reference: http://www.ncbi.nlm.nih.gov/pubmed/8861937

Castor oil based matrix for drug delievery

Drug delievery is an exciting branch of pharmaceutical chemistry where scientists tend to apply importance for carrier matrices to precisely release the drug at the specific targets for its mechanism of action. Medium formulation is a classical process where pharmaceutical minds have exploited a diversified range of solvents varying in their electrostatic behavior with the drug for delievery at defined dosages but frequently encountered limitations in toxicity and biodegradation properties in spite of their potential activities which led to bio-based medium with self-destructive nature.

Researchers from India have utilized castor oil as a key source for the synthesis of bio-polymer based medium in drug delivery process as it well noted earlier that castor oil is an excellent substrate for the production of polyamides and polyesters etc. Experimenters have synthesized a co-polyester with castor oil and citric acid in a catalytic reaction and paracetamol drug of standard concentration was immobilized on to the matrix polymer.They made their initial evaluation under bio simulated,  in vitro conditions for the drug delievery into the surrounding solution and found that the drug was released at elevated levels initially but gradually fell down and it was confirmed through their spectroscopic analysis.They also reported that the matrix  exhibited hydrolytic degradation after a complete release of drug.

The results of the experiment seem to be promising for an alternate carrier medium but it would be convincing to display it under in vivo conditions as the parameters affecting the ligand-receptor dissociation are in multiples under the real gastro-intestinal physiology.It is also worthwhile to note the mechanism of detoxification that the castor oil based co-polyester follows in the body for its wide spectrum of drug delievery applications in a systemic run.

For reference:Iranian Polymer Journal, Volume 5-Number 1 (1996).

Mapping of ricin by tools of molecular biology

Ricin toxin from castor seeds has been well established as a cytotoxin interferring with ribosomal functions.The activity of any protein generally is conferred by the domains present in it. This made scientists to probe the domains and  critical amino acids for the cytotoxic activity of ricin. Researchers in USA have made molecular analysis of castor bean toxin at the genetic level where tools of genetic engineering are exploited to address their domain mapping studies.The experimentation involved synthetic mutation process in genetic determinants of ricin protein for hypothetical amino acid, glutamate to alanine which basically is distant to the former constituent in terms of its physio-chemical properties and makes it an ideal substituent to understand the magnitude of glutamate in the ricin function.Their data in the end from mutant protein’s activity indicated that the target glutamate is not of primary significance in ricin’ toxicological function.

Domain mapping by mutations is an iterative process but an intense technique to make a complete scrutiny of the sub components in a complex molecule and their implications to the ultimate emergence of functions from bulk.

For reading:http://mcb.asm.org/cgi/reprint/9/11/5012.pdf

Castor biodiesel run in Ethiopia

The concept of renewable energy has really taken momentum all around the world as the African nation Ethiopia has made moves to initiate ventures on bio-diesel production from castor oil.The prime objective is to reduce the energy burden of the nation since experts  claim that Ethiopia allocates 90% of its foreign revenue to fossil fuel import and hence focus has been applied to exploit the renewable resources for ensuring the sustainability in nation’s economy.

Among the leading Ethiopian energy investors,Global Energy Ethiopia(GEE) has started its operation on renewable energy  since 2007 by pumping US$ 20 million into castor and jatropha seed farming and processing business.According to sources,GEE firm has an opportunity to process 40,000 tonnes of vegetable oil in its investment on concerned bioenergy crops from 30,000 hectares of leased land.Besides GEE, other firms namely Eco Energy has also entered into  bio-energy sector with collaborations from abroad.

According to Ethiopian Investment Agency(EIA),the potential of 25 million hectares of land suited for bio-diesel farming when tapped completely,Ethiopia becomes one of the highest producers of bio-diesel with an estimated capacity of 20 million liters of crude vegetable oil.

Reports such as this are motivating because the nations that have been torn by the economic crisis,civil wars and political instabilities, would have a tremendous scope to lift their socio-economic and environmental consciousness at the competitive International stage.

For reference: http://energybusinessdaily.com/renewables/ethiopia-sets-its-sights-on-biodiesel/

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Castor oil for nanoparticle fabrication

Nanotechnology is a emerging field of applied sciences where the functional units are in the magnitude of one part of a billion volume and appear to be elite operating than conventional micro units. In-organics and organic materials have been exploited to act as nanomaterials so far and silver nanoparticles(Ag-NPs) are one of the most potent materials among them for nano-composite fabrications.However scientists are hindered to generate Ag-NP units with expected level of functionality because they frequently suffer from limitations of aggregation of Ag-NPs with conventional  solvent medium that interferes with activities of final product and it made them to search for better performing medium. Finally a breakthrough solution to the problem came out from the Malaysian researchers when they revealed the fabrication of Ag-NPs by laser ablation of silver plate in the presence of castor oil.

Researchers claimed that the amphiphilic nature of the castor oil makes it to interact with silver element in an electrostatically regulated way which ultimately generates nanoparticles with expected characteristics.A quantitative analysis by normal distribution showed castor oil based nanoparticles are uniform in their size to a maximum extent and prove to be stable.Final material assessment was studied by advanced spectroscopic and electron microscopic techniques with definite controls.

Castor oil is an affordable material economically on a global scale and exploiting it for such type of advanced studies would shatter the barriers of expensiveness normally witnessed in technological development but it would have been better to realize when experimental confirmation had been made on activities of castor oil based Ag-NPs.

For reference: Zamiri et al, International Journal of Nanomedicine 2011:6 565–568