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Fulltext Does sildenafil citrate affect the pharmacokinetics of metformin in rats? Screening of mechanism through analytical and molecular docking approach

Dewani AP, Rab SO, Tripathi P, Shrivastava S, Tripathi R, Tripathi AS, et al.

Indian J Pharmacol, 2024 May 01;56(3):178-185.
PMID: 39078181 DOI: 10.4103/ijp.ijp_562_23

OBJECTIVE: In the present study, the effect of sildenafil on the pharmacokinetics of metformin was studied in experimental rats, and we also postulated the molecular mechanism by performing molecular docking studies.
MATERIALS AND METHODS: Analysis of metformin and sildenafil (SIL) from rat plasma was done by high performance liquid chromatography. Optimum chromatographic separation and quantification of MET, SIL and Cetirizine was achieved on Phenomenex EVO C18 column with triethyl amine (0.3%): Methanol: Acetonitrile (70:05:25 v/v) as mobile phase maintaining flow rate of 1 ml/min, the detector was tuned at 224 nm. The extraction of MET and sildenafil from rat plasma was achieved by solid-phase extraction using Strata-X cartridges. The method was validated as per the ICH guidelines. For docking studies, the crystal structure of organic cation transporter 1 (OCT1) protein and multidrug and toxin extrusion (MATE) protein (5XJJ) were downloaded from the PubChem database. The docking study was performed by PyRx virtual screening software, and the results were analyzed by BIOVIA Discovery Studio.
RESULTS: The validation of HPLC method was done, intraday and interday precision study of HPLC method demonstrated %RSD values less than 5%, the extraction recovery for MET and SIL were near to 80 % for low, medium and high QC samples. The plasma stability of MET and SIL showed % RSD values <10% for low, medium, and high QC samples. A sensitivity study for MET and SIL in rat plasma suggested a lower limit of quantification values of 8 and 10 ng/mL, respectively. The pharmacokinetic parameters were recorded, Cmax of experimental and control rats was 611.2 and 913.2 ng/mL; t1/2 1.66 and 1.98, AUC (0-t) 1637.5 and 2727.24, AUC (0-∞) 1832.38 and 2995.24 for MET. The results suggested that the Cmax of MET in experimental rats (MET + SIL) was 33.07% lower than the control (MET only) and also the t1/2 was 0.32 h shorter. Docking analysis suggested a higher binding affinity of sildenafil with MATE protein (5XJJ) compared to OCT1, suggesting possible involvement of MATE family proteins for pharmacokinetic alterations of MET.
CONCLUSIONS: The HPLC and solid-phase extraction method were developed and applied successfully for the pharmacokinetics of MET and SIL. Intake of SIL altered the pharmacokinetics of MET in rats. Molecular docking studies suggested the involvement of MATE family proteins for alterations of MET pharmacokinetics.
Framework for Adoption of Next-Generation Sequencing (NGS) Globally in the Oncology Area

Horgan D, Hamdi Y, Lal JA, Nyawira T, Meyer S, Kondji D, et al.

Healthcare (Basel), 2023 Feb 02;11(3).
PMID: 36767006 DOI: 10.3390/healthcare11030431

Radical new possibilities of improved treatment of cancer are on offer from an advanced medical technology already demonstrating its significance: next-generation sequencing (NGS). This refined testing provides unprecedentedly precise diagnoses and permits the use of focused and highly personalized treatments. However, across regions globally, many cancer patients will continue to be denied the benefits of NGS as long as some of the yawning gaps in its implementation remain unattended. The challenges at the regional and national levels are linked because putting the solutions into effect is highly dependent on cooperation between regional- and national-level cooperation, which could be hindered by shortfalls in interpretation or understanding. The aim of the paper was to define and explore the necessary conditions for NGS and make recommendations for effective implementation based on extensive exchanges with policy makers and stakeholders. As a result, the European Alliance for Personalised Medicine (EAPM) developed a maturity framework structured around demand-side and supply-side issues to enable interested stakeholders in different countries to self-evaluate according to a common matrix. A questionnaire was designed to identify the current status of NGS implementation, and it was submitted to different experts in different institutions globally. This revealed significant variability in the different aspects of NGS uptake. Within different regions globally, to ensure those conditions are right, this can be improved by linking efforts made at the national level, where patients have needs and where care is delivered, and at the global level, where major policy initiatives in the health field are underway or in preparation, many of which offer direct or indirect pathways for building those conditions. In addition, in a period when consensus is still incomplete and catching up is needed at a political level to ensure rational allocation of resources-even within individual countries-to enable the best ways to make the necessary provisions for NGS, a key recommendation is to examine where closer links between national and regional actions could complement, support, and mutually reinforce efforts to improve the situation for patients.
Empowering quality data - the Gordian knot of bringing real innovation into healthcare system

Horgan D, Hamdi Y, Lal JA, Nyawira T, Meyer S, Kondji D, et al.

Diagnosis (Berl), 2023 May 01;10(2):140-157.
PMID: 36548810 DOI: 10.1515/dx-2022-0115

OBJECTIVES: The introduction of Personalised Medicine (PM) into healthcare systems could benefit from a clearer understanding of the distinct national and regional frameworks around the world. Recent engagement by international regulators on maximising the use of real-world evidence (RWE) has highlighted the scope for improving the exploitation of the treasure-trove of health data that is currently largely neglected in many countries. The European Alliance for Personalised Medicine (EAPM) led an international study aimed at identifying the current status of conditions.
METHODS: A literature review examined how far such frameworks exist, with a view to identifying conducive factors - and crucial gaps. This extensive review of key factors across 22 countries and 5 regions revealed a wide variety of attitudes, approaches, provisions and conditions, and permitted the construction of a comprehensive overview of the current status of PM. Based on seven key pillars identified from the literature review and expert panels, the data was quantified, and on the basis of further analysis, an index was developed to allow comparison country by country and region by region.
RESULTS: The results show that United States of America is leading according to overall outcome whereas Kenya scored the least in the overall outcome.
CONCLUSIONS: Still, common approaches exist that could help accelerate take-up of opportunities even in the less prosperous parts of the world.
Fulltext Fighting Cancer around the World: A Framework for Action

Horgan D, Mia R, Erhabor T, Hamdi Y, Dandara C, Lal JA, et al.

Healthcare (Basel), 2022 Oct 25;10(11).
PMID: 36360466 DOI: 10.3390/healthcare10112125

Tackling cancer is a major challenge right on the global level. Europe is only the tip of an iceberg of cancer around the world. Prosperous developed countries share the same problems besetting Europe-and the countries and regions with fewer resources and less propitious conditions are in many cases struggling often heroically against a growing tide of disease. This paper offers a view on these geographically wider, but essentially similar, challenges, and on the prospects for and barriers to better results in this ceaseless battle. A series of panels have been organized by the European Alliance for Personalised Medicine (EAPM) to identify different aspects of cancer care around the globe. There is significant diversity in key issues such as NGS, RWE, molecular diagnostics, and reimbursement in different regions. In all, it leads to disparities in access and diagnostics, patients' engagement, and efforts for a better understanding of cancer.
Global Study of Social Odor Awareness

Sorokowska A, Groyecka A, Karwowski M, Frackowiak T, Lansford JE, Ahmadi K, et al.

Chem. Senses, 2018 08 24;43(7):503-513.
PMID: 29955865 DOI: 10.1093/chemse/bjy038

Olfaction plays an important role in human social communication, including multiple domains in which people often rely on their sense of smell in the social context. The importance of the sense of smell and its role can however vary inter-individually and culturally. Despite the growing body of literature on differences in olfactory performance or hedonic preferences across the globe, the aspects of a given culture as well as culturally universal individual differences affecting odor awareness in human social life remain unknown. Here, we conducted a large-scale analysis of data collected from 10 794 participants from 52 study sites from 44 countries all over the world. The aim of our research was to explore the potential individual and country-level correlates of odor awareness in the social context. The results show that the individual characteristics were more strongly related than country-level factors to self-reported odor awareness in different social contexts. A model including individual-level predictors (gender, age, material situation, education, and preferred social distance) provided a relatively good fit to the data, but adding country-level predictors (Human Development Index, population density, and average temperature) did not improve model parameters. Although there were some cross-cultural differences in social odor awareness, the main differentiating role was played by the individual differences. This suggests that people living in different cultures and different climate conditions may still share some similar patterns of odor awareness if they share other individual-level characteristics.
Corrigendum: The Associations of Dyadic Coping and Relationship Satisfaction Vary between and within Nations: A 35-Nation Study

Hilpert P, Randall AK, Sorokowski P, Atkins DC, Sorokowska A, Ahmadi K, et al.

Front Psychol, 2016;7:1404.
PMID: 27698648

[This corrects the article on p. 1106 in vol. 7, PMID: 27551269.].
Fulltext Corrigendum: Marital Satisfaction, Sex, Age, Marriage Duration, Religion, Number of Children, Economic Status, Education, and Collectivistic Values: Data from 33 Countries

Sorokowski P, Randall AK, Groyecka A, Frackowiak T, Cantarero K, Hilpert P, et al.

Front Psychol, 2017;8:1728.
PMID: 29021774 DOI: 10.3389/fpsyg.2017.01728

[This corrects the article on p. 1199 in vol. 8, PMID: 28785230.].
Fulltext Marital Satisfaction, Sex, Age, Marriage Duration, Religion, Number of Children, Economic Status, Education, and Collectivistic Values: Data from 33 Countries

Sorokowski P, Randall AK, Groyecka A, Frackowiak T, Cantarero K, Hilpert P, et al.

Front Psychol, 2017;8:1199.
PMID: 28785230 DOI: 10.3389/fpsyg.2017.01199
Fulltext The Associations of Dyadic Coping and Relationship Satisfaction Vary between and within Nations: A 35-Nation Study

Hilpert P, Randall AK, Sorokowski P, Atkins DC, Sorokowska A, Ahmadi K, et al.

Front Psychol, 2016;7:1106.
PMID: 27551269 DOI: 10.3389/fpsyg.2016.01106

OBJECTIVE: Theories about how couples help each other to cope with stress, such as the systemic transactional model of dyadic coping, suggest that the cultural context in which couples live influences how their coping behavior affects their relationship satisfaction. In contrast to the theoretical assumptions, a recent meta-analysis provides evidence that neither culture, nor gender, influences the association between dyadic coping and relationship satisfaction, at least based on their samples of couples living in North America and West Europe. Thus, it is an open questions whether the theoretical assumptions of cultural influences are false or whether cultural influences on couple behavior just occur in cultures outside of the Western world.
METHOD: In order to examine the cultural influence, using a sample of married individuals (N = 7973) from 35 nations, we used multilevel modeling to test whether the positive association between dyadic coping and relationship satisfaction varies across nations and whether gender might moderate the association.
RESULTS: RESULTS reveal that the association between dyadic coping and relationship satisfaction varies between nations. In addition, results show that in some nations the association is higher for men and in other nations it is higher for women.
CONCLUSIONS: Cultural and gender differences across the globe influence how couples' coping behavior affects relationship outcomes. This crucial finding indicates that couple relationship education programs and interventions need to be culturally adapted, as skill trainings such as dyadic coping lead to differential effects on relationship satisfaction based on the culture in which couples live.