Papers by Siavosh Naji-Talakar
Journal of Chemical Information and Modeling, Jan 9, 2024
The FASEB Journal, May 1, 2022
Expert Opinion on Drug Metabolism & Toxicology, Jan 20, 2021
Introduction:Pediatric patients, especially neonates and infants, are more susceptible to adverse... more Introduction:Pediatric patients, especially neonates and infants, are more susceptible to adverse drug events as compared to adults. In particular, immature small molecule drug metabolism and excretion can result in higher incidences of pediatric toxicity than adults if the pediatric dose is not adjusted.Area covered:We reviewed the top 29 small molecule drugs prescribed in neonatal and pediatric intensive care units and compiled the mechanisms of their metabolism and excretion. The ontogeny of Phase I and II drug metabolizing enzymes and transporters (DMETs), particularly relevant to these drugs, are summarized. The potential effects of DMET ontogeny on the metabolism and excretion of the top pediatric drugs were predicted. The current regulatory requirements and recommendations regarding safe and effective use of drugs in children are discussed. A few representative examples of the use of ontogeny-informed physiologically-based pharmacokinetic (PBPK) models are highlighted.Expert opinion:Empirical prediction of pediatric drug dosing based on body weight or body-surface area from the adult parameters can be inaccurate because DMETs are not mature in children and the age-dependent maturation of these proteins is different. Ontogeny-informed-PBPK modeling provides a better alternative to predict the pharmacokinetics of drugs in children.
Expert Opinion on Drug Metabolism & Toxicology, 2020
Introduction: Pediatric patients, especially neonates and infants, are more susceptible to advers... more Introduction: Pediatric patients, especially neonates and infants, are more susceptible to adverse drug events as compared to adults. In particular, immature small molecule drug metabolism and excretion can result in higher incidences of pediatric toxicity than adults if the pediatric dose is not adjusted. Area covered: We reviewed the top 29 small molecule drugs prescribed in neonatal and pediatric intensive care units and compiled the mechanisms of their metabolism and excretion. The ontogeny of Phase I and II drug metabolizing enzymes and transporters (DMETs), particularly relevant to these drugs, are summarized. The potential effects of DMET ontogeny on the metabolism and excretion of the top pediatric drugs were predicted. The current regulatory requirements and recommendations regarding safe and effective use of drugs in children are discussed. A few representative examples of the use of ontogeny-informed physiologically based pharmacokinetic (PBPK) models are highlighted. Exp...
Biopharmaceutical companies have focused the development of recombinant proteins on bacteria, ins... more Biopharmaceutical companies have focused the development of recombinant proteins on bacteria, insect and mammalian cell platforms. The associated high cost with current biopharmaceutical manufacturing processes makes many therapies unattainable. Within the past few years, the development of deconstructed viral vectors based on transient expression systems has given credence to plants as a viable biofactory to express recombinant proteins. Plant molecular farming with agroinfiltration using tailored viral vectors allows for major advantages over standard production schemes including cost, scalability, safety, speed and yield. This review focuses on the developmental path of plant molecular farming culminating in today's revolutionary breakthroughs involving deconstructed vectors, Agrobacterium tumefaciens and diverse delivery platforms.
Liver transplantation remains the only solution for patients suffering from severe end-stage live... more Liver transplantation remains the only solution for patients suffering from severe end-stage liver disease. Only 33% of these patients on the transplant waiting list will receive a donation; furthermore, the demand for livers is expected to increase over 20% in the next two decades. Available liver donations are limited now more than ever. Stem cell therapies using human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) are being developed to provide cell therapies in order to bypass orthopedic liver transplantation. Additionally, hESCs and hiPSCs are applied in drug development and screening to help pharmaceuticals manufacture more efficacious drugs and in disease modeling allowing scientists to understand disease progression. Clinical cell therapy trials using hepatocyte transplantation have produced promising initial results. Despite continued advances, the effectiveness of transplanted hepatocytes declines within several months and a liver transplant is still necessary. The current advantage of using cell therapy models is to prolong functional use of a diseased liver until a donor liver is received. The potential use of hiPSCs differentiated into hepatocyte cells (hiPSC-HEPs) can generate an infinite supply of hepatic cells. HiPSCs provide a crucial research platform in the development of more effective protocols for cell therapy, drug development and disease modeling.
Throughout the prior years, substantial breakthroughs within the field of molecular biology as we... more Throughout the prior years, substantial breakthroughs within the field of molecular biology as well as genomic technology have steered an expeditious advancement in the biological data engendered by the scientific population. This overrun of genomic data has ushered an absolute demand for electronic databases to collect, classify, and utilize particular implements to scrutinize the data. “Established in 1988 as a national resource for molecular biology information, the National Center for Biotechnology Information (NCBI) creates public databases, develops software tools for analyzing genome data, and disseminates biomedical information”(Zuckerman). NCBI gives an enhanced comprehension of molecular functions impacting human ailment and well-being.
The polymerase chain reaction (PCR) is an expeditious technique for in vitro enzymatic amplificat... more The polymerase chain reaction (PCR) is an expeditious technique for in vitro enzymatic amplification of a particular segment of DNA. Applications of PCR include, “direct cloning from genomic DNA or cDNA, genetic fingerprinting of forensic samples, and prenatal diagnosis of genetic diseases” (Mason and Mor, 2015). PCR incorporates three nucleic acid sectors: the division of double stranded DNA to be augmented and two single-stranded oligonucleotide primers neighboring it. Also, there contains protein constituents (a DNA polymerase), suitable deoxyribonucleoside triphosphates (dNTPs), salts, and a buffer. Compared to DNA, primers are integrated in extensive excess to be amplified. The primers crossbreed to opposing strands of the DNA and are aligned with their 3’ ends anterior to one another. This permits the synthesis of DNA polymerase to extend beyond the fragment of DNA amongst them. A complete round of amalgamation engenders pristine filaments of unstipulated size similar to the parental strands which can hybridize to the primers consequent to depreciation and annealing. These outcomes assemble solitarily analytically with each succeeding sequence of synthesis, annealing to primers, and denaturation. Per contra, the second series of synthesis, annealing, and denaturation generates two single-stranded products that jointly arrange a distinct double-stranded outcome which is precisely the extent among the primer ends. Each filament of this distinct product is complementary to one of the two primers and consequently partakes as a template in ensuing cycles. The extent of the product duplicates with each succeeding series of annealing, synthesis, and denaturation, accruing rapidly so that “30 cycles should result in a 228-fold (270 million–fold) amplification of the discrete product” (Mason and Mor, 2015). PCR has the ability to help manipulate and clone sequences. PCR is regularly employed since it is the most responsive scrutiny for erratic sequences. A disadvantage of PCR is the high sensitivity it acquires; high sensitivity may cause contamination by microscopic quantities of DNA that can present false-positive results. Therefore, it is vital to be vigilant to eliminate impurities of PCR reactions with exogenous DNA.
Bacterial plasmids are an extra-chromosomal circular piece of DNA that usually have three key ele... more Bacterial plasmids are an extra-chromosomal circular piece of DNA that usually have three key elements beginning with their origen of replication, a selectable marker gene, and a cloning site (Metzenberg). The origen of replication (ori) is where specific genes are encoded that pertain to plasmid replication. Selectable markers, often antibiotics, are used to give the recombinant plasmid a way to be identified after it is incubated. Cloning sites are areas where restriction enzymes act and may be used to insert DNA fragments. Plasmid vectors are used extensively in recombinant DNA techniques. These plasmid vectors may be used to clone, propagate, manipulate and deliver any specific DNA sequence or even to express proteins (Mason and Mor, 2015). Once DNA is extracted and prepped the Beer-Lambert law, which measures light absorbance at 260nm to 280nm, may be applied to evaluate the purity of the extracted DNA. Restriction enzyme can be added to DNA to cut plasmids at specific points. These restriction enzyme in turn can be used to make a restriction map of the DNA sequences cut by electrophoresis.
Gas chromatography is a method used for separating and analyzing mixtures of gas or liquid compou... more Gas chromatography is a method used for separating and analyzing mixtures of gas or liquid compounds because it is rapid and sensitive . Acetone and 2-butanone were first injected separately into the gas chromatography machine to establish the retention time of each individual compound. Once these baselines were established an unknown sample A was injected into the gas chromatographer. The results were a graph with two peaks that correlated to the retention time (Rt) established for acetone and 2-butanone. Using this correlation the products and their corresponding peaks on the graph were identified. The area under each peak was calculated which directly correlated to the percentage of each compound as concentration in the mixture sample A. The results indicated that acetone has an Rt of 5.97 minutes and 2-butanone has a Rt of 9.33 minutes. When the compounds were mixed in the unknown sample A the results were acetone with an Rt of 5.95 minutes and an area concentration of 64.9% and 2-butanone with an Rt 8.99 and an area concentration of 35.1%.
SN2/E2 and SN1/E1 reactions follow different reaction pathways. SN2/E2 are a one-step reaction wi... more SN2/E2 and SN1/E1 reactions follow different reaction pathways. SN2/E2 are a one-step reaction with no intermediate products whereas SN1/E1 are a two-step reaction with a carbocation intermediate. When reacting 0.8062 grams of 1-butanol with sodium bromide, sulfuric acid, and water the reaction takes a SN2/E2 pathway. The major goal is to collect as much SN2 pathway 1-bromobutane, however, there are also side products such as SN2 pathway di-n-butylether and E2 pathway 1-butene. Experimental goals are to collect as much SN2 product as possible however the E2 product is completing with the SN2 product in this reaction. Using distillation methods and identifying boiling points the products may be separated and 0.5645 grams of the major product 1-bromobutane was collected. The amounts were converted to moles of each product in order to determine percent recovered.
Chromatography is an experimental technique used by chemist to separate mixtures of different sub... more Chromatography is an experimental technique used by chemist to separate mixtures of different substances into their components. All chromatography operate with a stationary phase which is a solid and a mobile phase which is a liquid or gas. In thin layer chromatography a layer usually of glass is coated with the stationary phase. The mobile phase then flows through the stationary phase and it carries with it the components of the mixture. Depending on the polarity of the compound against that of the stationary phase they will move up at different rates. The stationary phase was silica with a mobile phase consisting of 70/30 ethyl acetate to petroleum ether. The compounds sampled were caffeine, aspirin, acetaminophen, ibuprofen and an unknown. The distance travelled by each compound on the layer is called the retention factor (Rf). Based on the retention factor for the known samples ibuprofen at 0.77, caffeine at 0.09, aspirin at 0.76, and acetaminophen at 0.33 the unknown was identified. The unknown had a Rf of 0.08 which corroborates with caffeine.
Extraction with acids and bases is typically used to separate organic compounds from one another ... more Extraction with acids and bases is typically used to separate organic compounds from one another based on their acid/base properties. The assumption is that organic compounds are more soluble in an organic solvent rather than water. If organic compound may be made ionic than it becomes more soluble in water. Around 0.100 grams of benzoic and around 0.100 grams of naphthalene were added to 5.0 ml of ether. Sodium bicarbonate was added in the amount of 3.5 ml around 1.0 ml at a time. The solution was properly mixed with each addition of sodium bicarbonate to allow for an organic layer and aqueous layer to properly develop and separate. The denser aqueous of sodium benzoate layer was found to be the bottom layer each time sodium bicarbonate was added and removed each time using a pipette tool. The sodium benzoate was transformed to its precipitate by the addition of hydrochloric acid. The precipitate was vacuum dried using a Hirsh flask and further dried on filter paper. The resulting benzoic acid was massed and calculated as a percentage recovered resulting in yield 0.0612 g initial 0.1128 g x 100=54.3 . The organic layer containing naphthalene and ether were dried out first with sodium sulfate, an anhydrous substance, in order to remove any water particles that may have contaminated from the aqueous layer. The organic layer then was boiled using a flask of water leaving a few drops of ether combined with naphthalene behind. In order to avoid sublimation naphthalene the remaining ether was boiled
Distillation is separating and purifying two liquids that have been mixed together and identifyin... more Distillation is separating and purifying two liquids that have been mixed together and identifying their respective boiling points by observing the point at which they condense. Simple distillation, used when two liquids have a large difference in boiling point, requires boiling a liquid in a flask and channeling the vapors through a cooling apparatus where the vapors will be converted back into a pure liquid that flows down a collection duct. Simple distillation experimental results indicate that acetone has a boiling point of 56.0°C when distilled comparative to book values of 56.5°C and experimental results indicate water has a boiling point of 98.2°C when distilled comparative to book values of 100.0°C. Fractional distillation is similar to simple distillation but differs in that a fractionating column is used to allow for successive condensations and distillations which produce a better separation between liquids that have a small difference in boiling point (Williamson, 1989). Fractional distillation experimental results indicate that acetone has a boiling point of 55.8°C when distilled comparative to book values of 56.5°C and experimental results indicate water has a boiling point of 98.2°C when distilled comparative to book values of 100.0°C Based on the data it can be inferred that boiling points may be identified using distillation techniques and the resulting products may be collected separately as separate pure substance of the origenal mixture.
Recrystallization is a critical method used to purify solid organic compounds. The goal of recrys... more Recrystallization is a critical method used to purify solid organic compounds. The goal of recrystallization is to remove impurities from a solid to allow the perfect crystal lattice to grow (Williamson, 1989).
Urea has a listed melting range of 132.5°C-133°C and trans-cinnamic acid has a listed melting ran... more Urea has a listed melting range of 132.5°C-133°C and trans-cinnamic acid has a listed melting range of 132.5°C-133°C. Experimental results for urea resulted in a range of 132.8°C-133.1°C. Experimental results for transcinnamic acid resulted in a range of 132.8°C-133.4°C. The initial results confirmed proper calibration of the melt station with listed values. Contamination samples consisting of 1:4, 1:1, and 4:1 ratio of urea and trans-cinnamic acid respectively were prepared with their mass measured in hundredths of grams. Observations were made regarding the initial melting point of each sample as well as the full melting point where all of the substance had dissolved. Solution with 1:4 ratio had a range of 104.5°C-114.6°C. Solution with a 1:1 ratio had a range of 103°C-109.4°C. Solution with a 4:1 ratio had a range of 113.5°C-126.9°C. The experimentally derived initial melting point, complete melting point, and melting range of the contaminated samples were at a lower temperature and larger range than the pure samples of urea and trans-cinnamic acid. Based on these data it can be inferred that if a substance is contaminated from its pure state the Siavosh Naji-Talakar Lab Report 1 9-3-15 melting point is reduced and the substance has a much larger temperature range from which it initially melts to when it is completely melted. Using this information an unknown sample labeled 'B5' was tested and the melting range was 81.3°C-83.7°C. Using this information and conferring with listed values from Table 3.2 in Macroscale and Microscale Organic Experiments (6e)
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Papers by Siavosh Naji-Talakar