The antisens strategy is based on specific inhibition of the mutant gene expression by oligodeoxy... more The antisens strategy is based on specific inhibition of the mutant gene expression by oligodeoxynucleotides (OGN), capable of selectively hybridizing with target DNA or RNA. Molecular mechanisms of the antisense oligonucleotide comprise: inhibition of splicing, inhibition of 5'-capping and 3'-polyadenylation, activation of RN-ase H, small interfering RNA, ribozymes. The antisense strategy is applied to: rational design of potent, selective therapeutic agents, target validation and detection of pathologic gene expression in vivo. The main aim of the antisense oligonucleotide design is to improve the affinity for target RNA and the resistance to nucleolytic degradation.
Antimicrobial resistance constitutes a topical subject and it is one of the major threats to publ... more Antimicrobial resistance constitutes a topical subject and it is one of the major threats to public health. According to statistics, the incidence of multidrug-resistant microorganisms, such as bacteria, fungi and protozoa has increased in the last decades and it continues to spread. Therefore, the development of novel antimicrobial agents to combat drug-resistant infections is very important, among other research directions in this field. Quinoline ring is a very interesting structure for researchers because of its diverse biological properties (antimicrobial, anticancer, anticonvulsant, antiinflamatory and cardiovascular). On the other hand several studies showed good antibacterial activity (including anti-Pseudomonas effects) and antifungal properties of rutin or vegetal species with a high flavonoids (especially rutin) concentration. Based on the above considerations, eight novel rutin derivatives carrying 4-and 8-aminoquinoline moiety were designed, synthesized and characterized by FTIR, 1H NMR and elemental analysis. All compounds were evaluated for their in vitro antimicrobial activities against representative Gram-positive, Gram-negative and fungal pathogens. The results indicated that all rutin derivatives exhibited good antibacterial activities, similar to ciprofloxacin.
Background Aryl-propionic acid derivatives with ibuprofen as representative drug are very importa... more Background Aryl-propionic acid derivatives with ibuprofen as representative drug are very important for therapy, being recommended especially for anti-inflammatory and analgesic effects. On other hand 1,3-thiazolidine-4-one scaffold is an important heterocycle, which is associated with different biological effects such as anti-inflammatory and analgesic, antioxidant, antiviral, antiproliferative, antimicrobial etc. The present study aimed to evaluated the toxicity degree and the anti-inflammatory and analgesic effects of new 1,3-thiazolidine-4-one derivatives of ibuprofen. Methods For evaluation the toxicity degree, cell viability assay using MTT method and acute toxicity assay on rats were applied. The carrageenan-induced paw-edema in rat was used for evaluation of the anti-inflammatory effect while for analgesic effect the tail-flick test, as thermal nociception in rats and the writhing assay, as visceral pain in mice, were used. Results The toxicological screening, in terms of cy...
... Informational risk in pharmacogenetic research If the ethical, social and legal challenges of... more ... Informational risk in pharmacogenetic research If the ethical, social and legal challenges ofpharmacogenetics are regarded as less prevalent ... This informational risk derives from personal, familial and social nature of genetic information, as well as its potential to discriminate ...
Revista medico-chirurgicală̆ a Societă̆ţ̜ii de Medici ş̧i Naturaliş̧ti din Iaş̧i
The antisens strategy is based on specific inhibition of the mutant gene expression by oligodeoxy... more The antisens strategy is based on specific inhibition of the mutant gene expression by oligodeoxynucleotides (OGN), capable of selectively hybridizing with target DNA or RNA. Molecular mechanisms of the antisense oligonucleotide comprise: inhibition of splicing, inhibition of 5'-capping and 3'-polyadenylation, activation of RN-ase H, small interfering RNA, ribozymes. The antisense strategy is applied to: rational design of potent, selective therapeutic agents, target validation and detection of pathologic gene expression in vivo. The main aim of the antisense oligonucleotide design is to improve the affinity for target RNA and the resistance to nucleolytic degradation.
There are more things in heaven and in earth, Horatio, Than are dreamt of in your philosophy... W... more There are more things in heaven and in earth, Horatio, Than are dreamt of in your philosophy... W. Shakespeare, Hamlet act I scene 5 2. Pharmacogenetics: Conceptual evolution to pharmacogenomics 2.1 Pharmacogenetics: Brief history and definition The first clinical observations of interpatient variability in clinical response to standard therapeutic doses and the pioneering contributions of Sir Archibald Garrod, Arno Motulsky,
BRAIN. BROAD RESEARCH IN ARTIFICIAL INTELLIGENCE AND NEUROSCIENCE, 2020
The broad arsenal of psychotropic medications is characterised by significant interindividual var... more The broad arsenal of psychotropic medications is characterised by significant interindividual variability in clinical response and adverse effects, stringent monitoring requirements, potential drug-drug interactions, difficult long-term adherence and high costs. Pharmacogenomics investigates the correlation between genetic polymorphisms and responsiveness to drugs and could provide a valuable guide to fulfill the promise of personalized therapy in the context of the genomic medicine era, by tailoring treatment based on the patient's specific genetic markers. The present paper overviews the current advances in the clinical applications of pharmacogenomics to individualized psychotropic therapy. Material and methods. The relevant recent pharmacogenomics literature is selected and analysed in order to illustrate the impact on the clinical outcomes and quality of life in psychiatric patients of the genetic variants in the neurotransmitter receptors (dopamine and serotonin), metabolic pathways of drugs (cytochrome CYP450 2D6 and 2C19) and the human leukocyte antigen system. The paper focuses on some of the major psychotropic drug classes, such as: antipsychotics, antidepressants and mood stabilizers. Validation of statistically significant pharmacogenomics relationships has enabled the development and market approval of some predictive tests which are already integrated into some psychotropic drugs label. Results and discussions. Predictive pharmacogenomics tests have changed the classical approach of prescription "trial-and error" and "one dose fits all patients" towards personalized therapy. In addition, in new therapeutic candidates' clinical development, pharmacogenomics practically guides the clinical studies design, by substantially reducing the failure rates, costs and exposure risks of non-responders patients to new drugs. Current translation barriers of predictive pharmacogenomic tests from bench to clinical practice are also discussed. Conclusion. The paper emphasizes the current progress and future prospects in the field of pharmacogenomics as a guide to personalized therapy of psychiatric disorders, by: a) pretreatment selection of the right drug, prescribed in its optimized dose, to the right patient, according to one's specific genetic biomarkers; b) by improved clinical trials design based on genetic stratification of patients' population into responders versus nonresponders, especially in the costly phases III and IV.
In recent decades, drug delivery systems (DDSs) based on nanotechnology have been attracting subs... more In recent decades, drug delivery systems (DDSs) based on nanotechnology have been attracting substantial interest in the pharmaceutical field, especially those developed based on natural polymers such as chitosan, cellulose, starch, collagen, gelatin, alginate and elastin. Nanomaterials based on chitosan (CS) or chitosan derivatives are broadly investigated as promising nanocarriers due to their biodegradability, good biocompatibility, non-toxicity, low immunogenicity, great versatility and beneficial biological effects. CS, either alone or as composites, are suitable substrates in the fabrication of different types of products like hydrogels, membranes, beads, porous foams, nanoparticles, in-situ gel, microparticles, sponges and nanofibers/scaffolds. Currently, the CS based nanocarriers are intensely studied as controlled and targeted drug release systems for different drugs (anti-inflammatory, antibiotic, anticancer etc.) as well as for proteins/peptides, growth factors, vaccines,...
The understanding of neuroscientific substrates of suicidal behavior is essential for enhancing p... more The understanding of neuroscientific substrates of suicidal behavior is essential for enhancing predictability and development of adequate therapeutical strategies. The goal of brain exploring by means of morphometrics, neurochemistry and recent methods of molecular biology and genetics is to create a map of cerebral neurochemical circuits correlated with self-aggression behavior. From the neurobiological viewpoint amygdala with its connections to the orbitoprefrontal and anterior cingulate cortices is the keystone of behavior. Serotonin is the most intensively studied neurotransmitter because it plays a key role in aggression and impulsivity and serotonergic functions have been demonstrated to bear similar relationships to aggression in animal models and clinical studies on suicide. Antagonists of 5-HT 2A receptors and selective serotonin reuptake inhibitors have antiaggressive efficacy on both animal models and clinical trials. Lithium has antisuicidal effects acting directly on orbitoprefrontal and cingulate cortices. Advances in the understanding of the neurobiology of violence will contribute to a rational assessment and treatment of patients with suicidal behavior.
The antisens strategy is based on specific inhibition of the mutant gene expression by oligodeoxy... more The antisens strategy is based on specific inhibition of the mutant gene expression by oligodeoxynucleotides (OGN), capable of selectively hybridizing with target DNA or RNA. Molecular mechanisms of the antisense oligonucleotide comprise: inhibition of splicing, inhibition of 5'-capping and 3'-polyadenylation, activation of RN-ase H, small interfering RNA, ribozymes. The antisense strategy is applied to: rational design of potent, selective therapeutic agents, target validation and detection of pathologic gene expression in vivo. The main aim of the antisense oligonucleotide design is to improve the affinity for target RNA and the resistance to nucleolytic degradation.
Antimicrobial resistance constitutes a topical subject and it is one of the major threats to publ... more Antimicrobial resistance constitutes a topical subject and it is one of the major threats to public health. According to statistics, the incidence of multidrug-resistant microorganisms, such as bacteria, fungi and protozoa has increased in the last decades and it continues to spread. Therefore, the development of novel antimicrobial agents to combat drug-resistant infections is very important, among other research directions in this field. Quinoline ring is a very interesting structure for researchers because of its diverse biological properties (antimicrobial, anticancer, anticonvulsant, antiinflamatory and cardiovascular). On the other hand several studies showed good antibacterial activity (including anti-Pseudomonas effects) and antifungal properties of rutin or vegetal species with a high flavonoids (especially rutin) concentration. Based on the above considerations, eight novel rutin derivatives carrying 4-and 8-aminoquinoline moiety were designed, synthesized and characterized by FTIR, 1H NMR and elemental analysis. All compounds were evaluated for their in vitro antimicrobial activities against representative Gram-positive, Gram-negative and fungal pathogens. The results indicated that all rutin derivatives exhibited good antibacterial activities, similar to ciprofloxacin.
Background Aryl-propionic acid derivatives with ibuprofen as representative drug are very importa... more Background Aryl-propionic acid derivatives with ibuprofen as representative drug are very important for therapy, being recommended especially for anti-inflammatory and analgesic effects. On other hand 1,3-thiazolidine-4-one scaffold is an important heterocycle, which is associated with different biological effects such as anti-inflammatory and analgesic, antioxidant, antiviral, antiproliferative, antimicrobial etc. The present study aimed to evaluated the toxicity degree and the anti-inflammatory and analgesic effects of new 1,3-thiazolidine-4-one derivatives of ibuprofen. Methods For evaluation the toxicity degree, cell viability assay using MTT method and acute toxicity assay on rats were applied. The carrageenan-induced paw-edema in rat was used for evaluation of the anti-inflammatory effect while for analgesic effect the tail-flick test, as thermal nociception in rats and the writhing assay, as visceral pain in mice, were used. Results The toxicological screening, in terms of cy...
... Informational risk in pharmacogenetic research If the ethical, social and legal challenges of... more ... Informational risk in pharmacogenetic research If the ethical, social and legal challenges ofpharmacogenetics are regarded as less prevalent ... This informational risk derives from personal, familial and social nature of genetic information, as well as its potential to discriminate ...
Revista medico-chirurgicală̆ a Societă̆ţ̜ii de Medici ş̧i Naturaliş̧ti din Iaş̧i
The antisens strategy is based on specific inhibition of the mutant gene expression by oligodeoxy... more The antisens strategy is based on specific inhibition of the mutant gene expression by oligodeoxynucleotides (OGN), capable of selectively hybridizing with target DNA or RNA. Molecular mechanisms of the antisense oligonucleotide comprise: inhibition of splicing, inhibition of 5'-capping and 3'-polyadenylation, activation of RN-ase H, small interfering RNA, ribozymes. The antisense strategy is applied to: rational design of potent, selective therapeutic agents, target validation and detection of pathologic gene expression in vivo. The main aim of the antisense oligonucleotide design is to improve the affinity for target RNA and the resistance to nucleolytic degradation.
There are more things in heaven and in earth, Horatio, Than are dreamt of in your philosophy... W... more There are more things in heaven and in earth, Horatio, Than are dreamt of in your philosophy... W. Shakespeare, Hamlet act I scene 5 2. Pharmacogenetics: Conceptual evolution to pharmacogenomics 2.1 Pharmacogenetics: Brief history and definition The first clinical observations of interpatient variability in clinical response to standard therapeutic doses and the pioneering contributions of Sir Archibald Garrod, Arno Motulsky,
BRAIN. BROAD RESEARCH IN ARTIFICIAL INTELLIGENCE AND NEUROSCIENCE, 2020
The broad arsenal of psychotropic medications is characterised by significant interindividual var... more The broad arsenal of psychotropic medications is characterised by significant interindividual variability in clinical response and adverse effects, stringent monitoring requirements, potential drug-drug interactions, difficult long-term adherence and high costs. Pharmacogenomics investigates the correlation between genetic polymorphisms and responsiveness to drugs and could provide a valuable guide to fulfill the promise of personalized therapy in the context of the genomic medicine era, by tailoring treatment based on the patient's specific genetic markers. The present paper overviews the current advances in the clinical applications of pharmacogenomics to individualized psychotropic therapy. Material and methods. The relevant recent pharmacogenomics literature is selected and analysed in order to illustrate the impact on the clinical outcomes and quality of life in psychiatric patients of the genetic variants in the neurotransmitter receptors (dopamine and serotonin), metabolic pathways of drugs (cytochrome CYP450 2D6 and 2C19) and the human leukocyte antigen system. The paper focuses on some of the major psychotropic drug classes, such as: antipsychotics, antidepressants and mood stabilizers. Validation of statistically significant pharmacogenomics relationships has enabled the development and market approval of some predictive tests which are already integrated into some psychotropic drugs label. Results and discussions. Predictive pharmacogenomics tests have changed the classical approach of prescription "trial-and error" and "one dose fits all patients" towards personalized therapy. In addition, in new therapeutic candidates' clinical development, pharmacogenomics practically guides the clinical studies design, by substantially reducing the failure rates, costs and exposure risks of non-responders patients to new drugs. Current translation barriers of predictive pharmacogenomic tests from bench to clinical practice are also discussed. Conclusion. The paper emphasizes the current progress and future prospects in the field of pharmacogenomics as a guide to personalized therapy of psychiatric disorders, by: a) pretreatment selection of the right drug, prescribed in its optimized dose, to the right patient, according to one's specific genetic biomarkers; b) by improved clinical trials design based on genetic stratification of patients' population into responders versus nonresponders, especially in the costly phases III and IV.
In recent decades, drug delivery systems (DDSs) based on nanotechnology have been attracting subs... more In recent decades, drug delivery systems (DDSs) based on nanotechnology have been attracting substantial interest in the pharmaceutical field, especially those developed based on natural polymers such as chitosan, cellulose, starch, collagen, gelatin, alginate and elastin. Nanomaterials based on chitosan (CS) or chitosan derivatives are broadly investigated as promising nanocarriers due to their biodegradability, good biocompatibility, non-toxicity, low immunogenicity, great versatility and beneficial biological effects. CS, either alone or as composites, are suitable substrates in the fabrication of different types of products like hydrogels, membranes, beads, porous foams, nanoparticles, in-situ gel, microparticles, sponges and nanofibers/scaffolds. Currently, the CS based nanocarriers are intensely studied as controlled and targeted drug release systems for different drugs (anti-inflammatory, antibiotic, anticancer etc.) as well as for proteins/peptides, growth factors, vaccines,...
The understanding of neuroscientific substrates of suicidal behavior is essential for enhancing p... more The understanding of neuroscientific substrates of suicidal behavior is essential for enhancing predictability and development of adequate therapeutical strategies. The goal of brain exploring by means of morphometrics, neurochemistry and recent methods of molecular biology and genetics is to create a map of cerebral neurochemical circuits correlated with self-aggression behavior. From the neurobiological viewpoint amygdala with its connections to the orbitoprefrontal and anterior cingulate cortices is the keystone of behavior. Serotonin is the most intensively studied neurotransmitter because it plays a key role in aggression and impulsivity and serotonergic functions have been demonstrated to bear similar relationships to aggression in animal models and clinical studies on suicide. Antagonists of 5-HT 2A receptors and selective serotonin reuptake inhibitors have antiaggressive efficacy on both animal models and clinical trials. Lithium has antisuicidal effects acting directly on orbitoprefrontal and cingulate cortices. Advances in the understanding of the neurobiology of violence will contribute to a rational assessment and treatment of patients with suicidal behavior.
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