The switch from patented medicine to the generic one: an option or a necessity?

This paper assesses the influence of a number of factors taken into account when a brand name drug is replaced by a generic one. It also evaluates responses of health professionals – physicians and pharmacist—and patients regarding the issue of switching. We compared and contrasted their responses in order to identify new points of cooperation for the intended benefit of the patient. Thus, the sample drew from all three groups, consisting of 50 doctors, 50 pharmacists, and 50 patients. We collected information regarding the age, residence, income level, and education level for the patients, and age and experience for the specialists. Based on responses to the survey, replacing the original medication with a generic one raises many issues, such as lack of information for the patient and specialist, lack of collaboration between physician and pharmacist, ineffective communication between specialist and patient, and the influence of the overall profit motive

White matter abnormalities in the Hdc knockout mouse, a model of tic and OCD pathophysiology

INTRODUCTION: An inactivating mutation in the MATERIALS AND METHODS: We performed exploratory RNA-seq to identify pathological alterations in several brain regions in RESULTS: Exploratory RNA-Seq analysis revealed, unexpectedly, that genes associated with oligodendrocytes and with myelin production are upregulated in the dorsal striatum of these mice. This was confirmed by qPCR, immunostaining, and immunoblotting. These results suggest an abnormality in myelination in the striatum. To test this in an intact mouse brain, we performed whole-brain DISCUSSION: While the DTI literature in individuals with TS is sparse, these results are consistent with findings of disrupted descending cortical projections in patients with tics. Th

Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2.

Failed or altered gliogenesis is a major characteristic of diffuse white matter injury in survivors of premature birth. The developmentally regulated long noncoding RNA (lncRNA) H19 inhibits S-adenosylhomocysteine hydrolase (SAHH) and contributes to methylation of diverse cellular components, such as DNA, RNA, proteins, lipids, and neurotransmitters. We showed that the pregnancy-derived synthetic PreImplantation Factor (sPIF) induces expression of the nuclear receptor corepressor 2 (NCOR2) via H19/SAHH-mediated DNA demethylation. In turn, NCOR2 affects oligodendrocyte differentiation markers. Accordingly, after hypoxic-ischemic brain injury in rodents, myelin protection and oligodendrocytes' fate are in part modulated by sPIF and H19. Our results revealed an unexpected mechanism of the H19/SAHH axis underlying myelin preservation during brain recovery and its use in treating neurodegenerative diseases can be envisioned

The switch from patented medicine to the generic one: an option or a necessity?

This paper assesses the influence of a number of factors taken into account when a brand name drug is replaced by a generic one. It also evaluates responses of health professionals – physicians and pharmacist—and patients regarding the issue of switching. We compared and contrasted their responses in order to identify new points of cooperation for the intended benefit of the patient. Thus, the sample drew from all three groups, consisting of 50 doctors, 50 pharmacists, and 50 patients. We collected information regarding the age, residence, income level, and education level for the patients, and age and experience for the specialists. Based on responses to the survey, replacing the original medication with a generic one raises many issues, such as lack of information for the patient and specialist, lack of collaboration between physician and pharmacist, ineffective communication between specialist and patient, and the influence of the overall profit motive

Long-term treatment with chloroquine increases lifespan in middle-aged male mice possibly via autophagy modulation, proteasome inhibition and glycogen metabolism

Previous studies have shown that the polyamine spermidine increased the maximum life span in C. elegans and the median life span in mice. Since spermidine increases autophagy, we asked if treatment with chloroquine, an inhibitor of autophagy, would shorten the lifespan of mice. Recently, chloroquine has intensively been discussed as a treatment option for COVID-19 patients. To rule out unfavorable long-term effects on longevity, we examined the effect of chronic treatment with chloroquine given in the drinking water on the lifespan and organ pathology of male middle-aged NMRI mice. We report that, surprisingly, daily treatment with chloroquine extended the median life span by 11.4% and the maximum life span of the middle-aged male NMRI mice by 11.8%. Subsequent experiments show that the chloroquine-induced lifespan elevation is associated with dose-dependent increase in LC3B-II, a marker of autophagosomes, in the liver and heart that was confirmed by transmission electron microscopy. Quite intriguingly, chloroquine treatment was also associated with a decrease in glycogenolysis in the liver suggesting a compensatory mechanism to provide energy to the cell. Accumulation of autophagosomes was paralleled by an inhibition of proteasome-dependent proteolysis in the liver and the heart as well as with decreased serum levels of insulin growth factor binding protein-3 (IGFBP3), a protein associated with longevity. We propose that inhibition of proteasome activity in conjunction with an increased number of autophagosomes and decreased levels of IGFBP3 might play a central role in lifespan extension by chloroquine in male NMRI mice.UEFISCDI (EU Horizon 2020 Research and Innovation Programme), Consiliul National al Cercetarii Stiintifice (CNCS), Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (UEFISCDI

Implementation of a CRISPR-Based System for Gene Regulation in Candida albicans.

Clustered regularly interspaced short palindromic repeat (CRISPR) methodology is not only an efficient tool in gene editing but also an attractive platform to facilitate DNA, RNA, and protein interactions. We describe here the implementation of a CRISPR-based system to regulate expression in the clinically important yeast By fusing an allele of Cas9 devoid of nuclease activity to a transcriptional repressor (Nrg1) or activator (Gal4), we were able to show specific repression or activation of the tester gene , encoding the cytosolic catalase. We generated strains where a 1.6-kbp upstream regulatory region of controls the expression of the green fluorescent protein (GFP) and demonstrated the functionality of the constructs by quantitative PCR (qPCR), flow cytometry, and analysis of sensitivity/resistance to hydrogen peroxide. Activation and repression were strongly dependent on the position of the complex in this regulatory region. We also improved transcriptional activation using an RNA scaffolding strategy to allow interaction of inactive variants of Cas9 (dCas9) with the RNA binding protein MCP (monocyte chemoattractant protein) fused to the VP64 activator. The strategy shown here may facilitate the analysis of complex regulatory traits in this fungal pathogen. CRISPR technology is a new and efficient way to edit genomes, but it is also an appealing way to regulate gene expression. We have implemented CRISPR as a gene expression platform in using fusions between a Cas9 inactive enzyme and specific repressors or activators and demonstrated its functionality. This will allow future manipulation of complex virulence pathways in this important fungal pathogen

Mapping Extracellular pH of Gliomas in Presence of Superparamagnetic Nanoparticles: Towards Imaging the Distribution of Drug-Containing Nanoparticles and Their Curative Effect on the Tumor Microenvironment

Since brain’s microvasculature is compromised in gliomas, intravenous injection of tumor-targeting nanoparticles containing drugs (D-NPs) and superparamagnetic iron oxide (SPIO-NPs) can deliver high payloads of drugs while allowing MRI to track drug distribution. However, therapeutic effect of D-NPs remains poorly investigated because superparamagnetic fields generated by SPIO-NPs perturb conventional MRI readouts. Because extracellular pH (pHe) is a tumor hallmark, mapping pHe is critical. Brain pHe is measured by biosensor imaging of redundant deviation in shifts (BIRDS) with lanthanide agents, by detecting paramagnetically shifted resonances of nonexchangeable protons on the agent. To test the hypothesis that BIRDS-based pHe readout remains uncompromised by presence of SPIO-NPs, we mapped pHe in glioma-bearing rats before and after SPIO-NPs infusion. While SPIO-NPs accumulation in the tumor enhanced MRI contrast, the pHe inside and outside the MRI-defined tumor boundary remained unchanged after SPIO-NPs infusion, regardless of the tumor type (9L versus RG2) or agent injection method (renal ligation versus coinfusion with probenecid). These results demonstrate that we can simultaneously and noninvasively image the specific location and the healing efficacy of D-NPs, where MRI contrast from SPIO-NPs can track their distribution and BIRDS-based pHe can map their therapeutic impact

The switch from patented medicine to the generic one: an option or a necessity?

This paper assesses the influence of a number of factors taken into account when a brand name drug is replaced by a generic one. It also evaluates responses of health professionals – physicians and pharmacist—and patients regarding the issue of switching. We compared and contrasted their responses in order to identify new points of cooperation for the intended benefit of the patient. Thus, the sample drew from all three groups, consisting of 50 doctors, 50 pharmacists, and 50 patients. We collected information regarding the age, residence, income level, and education level for the patients, and age and experience for the specialists. Based on responses to the survey, replacing the original medication with a generic one raises many issues, such as lack of information for the patient and specialist, lack of collaboration between physician and pharmacist, ineffective communication between specialist and patient, and the influence of the overall profit motive