Perception and attitude of physicians toward local generic medicines in Saudi Arabia: A questionnaire-based study

AbstractObjectives: The current study aimed to explore the knowledge, perception, and attitude of physicians toward generic medicines in Saudi Arabia.Background: The local market of generic medicine share in Saudi Arabia is low compared to global and regional statistics. The reason for this low market share and the role of physicians has not previously been investigated. The purpose of this study was to assess health practitioner level of perceived knowledge, opinions and attitudes about local generic medication, and identify factors that influence infrequency of generic prescriptions.Methods: A random sample of 231 physicians was recruited from two hospitals in Riyadh (one government one private) and 178 (77%) responded. Information on the physicians’ perceived knowledge, opinions and attitude toward local generic medication was extracted, analyzed and interpreted. Factors that influence infrequent prescription of local generic drugs were identified.Results: Among the 178 participants in the physicians’ survey, 76% and 47% reported that they are knowledgeable about the terms “generic” and “bioequivalence” respectively, while 44% reported that they are able to explain bioequivalence to their patients. Approximately 52% of physicians reported that local generics should be substituted for brands if suitable for the case, and 21.9% reported that they believe SFDA approved local generics are therapeutically equivalent to their brands. Clinical effectiveness was reported by 71.9% of physicians as the most influential factor effecting prescription of brand over local generic medication. The three independent significant predictors for infrequent prescription of local generics among physicians: Government sector employment (OR=3.74, [95%CI 1.50–9.43]), consultant level (OR=3.94, [95%CI 1.50–10.31]) and low level of knowledge about local generics (OR=4.11, [95%CI 1.56–10.84]).Conclusion: The low market share of local generics medicines attributed to low prescription rates is significantly more among senior-level physicians working in governmental hospitals. Low level of knowledge about generic drugs among physicians was the strongest predictive factor for low prescription. Future bigger studies are needed to confirm these results

The chemopreventive effect of Ginkgo biloba and Silybum marianum extracts on hepatocarcinogenesis in rats

<p>Abstract</p> <p>Background/objective</p> <p>This study was designed to evaluate the potential chemopreventive activities of <it>Ginkgo biloba </it>extract (EGb) and <it>Silybum marianum </it>extract (silymarin) against hepatocarcinogenesis induced by N-nitrosodiethylamine (NDEA) in rats.</p> <p>Methods</p> <p>Rats were divided into 6 groups. Group 1 served as normal control rats. Group 2 animals were intragastrically administrated NDEA at a dose of 10 mg/kg five times a week for 12 weeks to induce hepatocellular carcinoma (HCC). Groups 3 and 4 animals were pretreated with silymarin and EGb respectively. Groups 5 and 6 animals were posttreated with silymarin and EGb respectively. The investigated parameters in serum are alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) and vascular endothelial growth factor (VEGF). The investigated parameters in liver tissue are malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and comet assay parameters.</p> <p>Results</p> <p>In NDEA group, MDA level was elevated with subsequent decrease in GSH level and SOD, GPx and GR activities. In addition, NDEA group revealed a significant increase in serum ALT, AST and GGT activities and VEGF level. Furthermore, NDEA administrated animals showed a marked increase in comet assay parameters. These biochemical alterations induced by NDEA were confirmed by the histopathological examination of rat livers intoxicated with NDEA that showed an obvious cellular damage and well differentiated HCC.</p> <p>In contrast, silymarin+NDEA treated groups (3&5) and EGb+NDEA treated groups (4&6) showed a significant decrease in MDA level and a significant increase in GSH content and SOD, GPx and GR activities compared to NDEA group. Silymarin and EGb also beneficially down-regulated the increase in serum ALT, AST, GGT activities and VEGF level induced by NDEA. In addition, silymarin and EGb significantly decreased comet assay parameters. Histopathological examination of rat livers treated with either silymarin or EGb exhibited an improvement in the liver architecture compared to NDEA group.</p> <p>Conclusions</p> <p>The obtained findings suggested that silymarin and EGb may have beneficial chemopreventive roles against hepatocarcinogenesis through their antioxidant, antiangiogenic and antigenotoxic activities.</p

Some entanglement features of three-atoms Tavis-Cummings model: Cooperative case

In this paper we consider a system of identical three two-level atoms interacting at resonance with a single-mode of the quantized field in a lossless cavity. The initial cavity field is prepared in the coherent state while the atoms are taken initially to be either in the uppermost excited state "$|eee>$" or The $\textmd{GHZ}$-state or the $\textmd{W}$-state. For this system we investigate different kinds of atomic inversion and entanglement, which arise between the different parts of the system due to the interaction. Also the relationship, between entanglement and some other nonclassical effects in the statistical properties, such as collapses and revivals in the atomic inversion where superharmonic effects appear, is discussed. The $Q$-functions for different cases are discussed. Most remarkably it is found that the $\textmd{GHZ}$-state is more robust against energy losses, showing almost coherent trapping and Schr\"odinger-cat states can not be produced from such state. Also the entanglement of $\textmd{GHZ}$-state is more robust than the $\textmd{W}$-state. Another interesting feature found is that the state which has no pairwise entanglement initially will have a much improvement of such pairwise entanglement through the evolution. Sudden death and sudden revival of atoms-pairwise entanglement are produced with the $\textmd{W}$-state.Comment: 14 pages, 7 figure

Development of Interspecific Hybrids between a Cultivated Eggplant Resistant to Bacterial Wilt (Ralstonia solanacearum) and Eggplant Wild Relatives for the Development of Rootstocks

[EN] Bacterial wilt caused by Ralstonia solanacerum is one of the most economically and destructive eggplant diseases in many tropical and subtropical areas of the world. The objectives of this study were to develop interspecific hybrids, as potential rootstocks, between the eggplant (Solanum melongena) bacterial wilt resistant line EG203 and four wild accessions (S. incanum UPV1, S. insanum UPV2, S. anguivi UPV3, and S. sisymbriifolium UPV4), and to evaluate interspecific hybrids along with parents for resistance to bacterial wilt strains Pss97 and Pss2016. EG203 was crossed successfully with wild accessions UPV2 and UPV3 and produced viable seeds that germinated when wild accessions were used as a maternal parent in the crosses. In addition, viable interspecific hybrids between EG203 and UPV1 were obtained in both directions of the hybridization, although embryo rescue had to be used. Hybridity was confirmed in the four developed interspecific hybrid combinations with three SSR markers. EG203 was resistant to both strains Pss97 and Pss2016, while UPV1 and UPV3 were, respectively, resistant and moderately resistant to Pss2016. The four interspecific hybrids with UPV2, UPV3, and UPV1 were susceptible to both bacterial wilt strains, indicating that the resistance of EG203, UPV1, and UPV3 behaves as recessive in interspecific crosses. However, given the vigor of interspecific hybrids between eggplant and the three cultivated wild species, these hybrids may be of interest as rootstocks. However, the development of interspecific hybrid rootstocks resistant to bacterial wilt will probably require the identification of new sources of dominant resistance to this pathogen in the eggplant wild relatives.This research and the APC were funded by Global Crop Diversity Trust [GS20001]. This work was undertaken as part of the initiative "Adapting Agriculture to Climate Change: Collecting, Protecting and Preparing CropWild Relatives" which is supported by the Government of Norway. The project is managed by the Global Crop Diversity Trust with the Millennium Seed Bank of the Royal Botanic Gardens, Kew UK and implemented in partnership with national and international genebanks and plant breeding institutes around the world. For further information, go to the project website: http://www.cwrdiversity.org/.This work has also been funded in part byWorldVeg Innovation Fund project through core funds from China (Taiwan), UK aid, United States Agency for International Development (USAID), Australian Centre for International Agricultural Research (ACIAR), Germany, Thailand, Philippines, Korea, and Japan.Rakha, M.; Namisy, A.; Chen, J.; El-Mahrouk, ME.; Metwally, E.; Taha, N.; Prohens Tomás, J.... (2020). Development of Interspecific Hybrids between a Cultivated Eggplant Resistant to Bacterial Wilt (Ralstonia solanacearum) and Eggplant Wild Relatives for the Development of Rootstocks. Plants. 9(10):1-13. https://doi.org/10.3390/plants9101405S11391

Copy number variation and expression of exportin-4 associates with severity of fibrosis in metabolic associated fatty liver disease

Background: Liver fibrosis risk is a heritable trait, the outcome of which is the net deposition of extracellular matrix by hepatic stellate cell-derived myofibroblasts. Whereas nucleotide sequence variations have been extensively studied in liver fibrosis, the role of copy number variations (CNV) in which genes exist in abnormal numbers of copies (mostly due to duplication or deletion) has had limited exploration. Methods: The impact of the XPO4 CNV on histological liver damage was examined in a cohort comprised 646 Caucasian patients with biopsy-proven MAFLD and 170 healthy controls. XPO4 expression was modulated and function was examined in human and animal models. Findings: Here we demonstrate in a cohort of 816 subjects, 646 with biopsy-proven metabolic associated liver disease (MAFLD) and 170 controls, that duplication in the exportin 4 (XPO4) CNV is associated with the severity of liver fibrosis. Functionally, this occurs via reduced expression of hepatic XPO4 that maintains sustained activation of SMAD3/SMAD4 and promotes TGF-β1-mediated HSC activation and fibrosis. This effect was mediated through termination of nuclear SMAD3 signalling. XPO4 demonstrated preferential binding to SMAD3 compared to other SMADs and led to reduced SMAD3-mediated responses as shown by attenuation of TGFβ1 induced SMAD transcriptional activity, reductions in the recruitment of SMAD3 to target gene promoters following TGF-β1, as well as attenuation of SMAD3 phosphorylation and disturbed SMAD3/SMAD4 complex formation. Interpretation: We conclude that a CNV in XPO4 is a critical mediator of fibrosis severity and can be exploited as a therapeutic target for liver fibrosis. Funding: ME and JG are supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney; a National Health and Medical Research Council of Australia (NHMRC) Program Grant (APP1053206) and Project and ideas grants (APP2001692, APP1107178 and APP1108422). AB is supported by an Australian Government Research Training Program (RTP) scholarship. EB is supported by Horizon 2020 under grant 634413 for the project EPoS

Targeting methionyl tRNA synthetase: design, synthesis and antibacterial activity against Clostridium difficileof novel 3-biaryl-N-benzylpropan-1-amine derivatives

The synthesis of a series of benzimidazole-N-benzylpropan-1-amines and adenine-N-benzylpropan-1-amines is described. Subsequent evaluation against two strains of the anaerobic bacterium Clostridium difficile was performed with three amine derivatives displaying MIC values of 16 μg/mL. Molecular docking studies of the described amines determined that the amines interact within two active site pockets of C. difficile methionyl tRNA synthetase with methoxy substituents in the benzyl ring and an adenine biaryl moiety resulting in optimal binding interaction

Mistranslation Drives Alterations in Protein Levels and the Effects of a Synonymous Variant at the Fibroblast Growth Factor 21 Locus

Fibroblast growth factor 21 (FGF21) is a liver-derived hormone with pleiotropic beneficial effects on metabolism. Paradoxically, FGF21 levels are elevated in metabolic diseases. Interventions that restore metabolic homeostasis reduce FGF21. Whether abnormalities in FGF21 secretion or resistance in peripheral tissues is the initiating factor in altering FGF21 levels and function in humans is unknown. A genetic approach is used to help resolve this paradox. The authors demonstrate that the primary event in dysmetabolic phenotypes is the elevation of FGF21 secretion. The latter is regulated by translational reprogramming in a genotype- and context-dependent manner. To relate the findings to tissues outcomes, the minor (A) allele of rs838133 is shown to be associated with increased hepatic inflammation in patients with metabolic associated fatty liver disease. The results here highlight a dominant role for translation of the FGF21 protein to explain variations in blood levels that is at least partially inherited. These results provide a framework for translational reprogramming of FGF21 to treat metabolic diseases

Expression of hepcidin mRNA is uniformly suppressed in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>The present study evaluated the expression of hepcidin mRNA in hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>Samples of cancerous and non-cancerous liver tissue were taken from 40 patients with HCC who underwent hepatectomy. Expression of hepcidin mRNA was evaluated by real-time PCR, and compared in tumors differing in their degree of differentiation, number of tumors, and vessel invasion. Correlations between hepcidin expression and the interval until HCC recurrence, and the serum concentration of hepcidin were evaluated, together with the expression of mRNAs for other iron metabolism molecules, ferroportin and transferrin receptor 2 (Trf2).</p> <p>Results</p> <p>Hepcidin mRNA expression in non-cancerous and cancerous tissues was 1891.8 (32.3–23187.4) and 53.4 (1.9–3185.8), respectively (<it>P </it>< 0.0001). There were no significant differences in hepcidin expression among tumors differing in their degree of differentiation, number of tumors, or vessel invasion. There was no significant correlation between hepcidin expression and the interval until HCC recurrence. The serum concentration of hepcidin-25 was not correlated with hepcidin-mRNA expression. Finally, there were no significant differences in the expression of mRNA for ferroportin and Trf2 between cancerous and non-cancerous tissues.</p> <p>Conclusion</p> <p>Expression of hepcidin mRNA is strikingly suppressed in cancerous, but not in non-cancerous tissues, in patients with HCC, irrespective of ferroportin or Trf2 expression. Uniform suppression of hepcidin may be linked to the development of HCC.</p