Drug Metabolism in Human Brain: High Levels of Cytochrome P4503A43 in Brain and Metabolism of Anti-Anxiety Drug Alprazolam to Its Active Metabolite

Cytochrome P450 (P450) is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP) in brain and liver, relatively more α-hydroxy alprazolam (α-OHALP) is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both α-OHALP and 4-hydroxy alprazolam (4-OHALP) while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of α-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of α-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action

A qualitative study of culturally embedded factors in complementary and alternative medicine use

Abstract Background Within the intercultural milieu of medical pluralism, a nexus of worldviews espousing distinct explanatory models of illness, our research aims at exploring factors leading to complementary and alternative medicine (CAM) use with special attention to their cultural context. Methods The results are based on medical anthropological fieldwork (participant observation and in-depth interviews) spanning a period from January 2015 to May 2017 at four clinics of Traditional Chinese Medicine in Budapest, Hungary. Participant observation involved 105 patients (males N = 42); in-depth interviews were conducted with patients (N = 9) and practitioners (N = 9). The interviews were coded with Interpretative Phenomenological Analysis; all information was aggregated employing Atlas.ti software. Results In order to avoid the dichotomization of “push and pull factors,” results obtained from the fieldwork and interviews were structured along milestones of the patient journey. These points of reference include orientation among sources of information, biomedical diagnosis, patient expectations and the physician-patient relationship, the biomedical treatment trajectory and reasons for non-adherence, philosophical congruence, and alternate routes of entry into the world of CAM. All discussed points which are a departure from the strictly western therapy, entail an underlying socio-cultural disposition and must be scrutinized in this context. Conclusions The influence of one’s culturally determined explanatory model is ubiquitous from the onset of the patient journey and exhibits a reciprocal relationship with subjective experience. Firsthand experience (or that of the Other) signifies the most reliable source of information in matters of illness and choice of therapy. Furthermore, the theme of (building and losing) trust is present throughout the patient journey, a determining factor in patient decision-making and dispositions toward both CAM and biomedicine

Patient Complexity: More Than Comorbidity. The Vector Model of Complexity

BACKGROUND: The conceptualization of patient complexity is just beginning in clinical medicine. OBJECTIVES: This study aims (1) to propose a conceptual approach to complex patients; (2) to demonstrate how this approach promotes achieving congruence between patient and provider, a critical step in the development of maximally effective treatment plans; and (3) to examine availability of evidence to guide trade-off decisions and assess healthcare quality for complex patients. METHODS/RESULTS: The Vector Model of Complexity portrays interactions between biological, socioeconomic, cultural, environmental and behavioral forces as health determinants. These forces are not easily discerned but exert profound influences on processes and outcomes of care for chronic medical conditions. Achieving congruence between patient, physician, and healthcare system is essential for effective, patient-centered care; requires assessment of all axes of the Vector Model; and, frequently, requires trade-off decisions to develop a tailored treatment plan. Most evidence-based guidelines rarely provide guidance for trade-off decisions. Quality measures often exclude complex patients and are not designed explicitly to assess their overall healthcare. CONCLUSIONS/RECOMMENDATIONS: We urgently need to expand the evidence base to inform the care of complex patients of all kinds, especially for the clinical trade-off decisions that are central to tailoring care. We offer long- and short-term strategies to begin to incorporate complexity into quality measurement and performance profiling, guided by the Vector Model. Interdisciplinary research should lay the foundation for a deeper understanding of the multiple sources of patient complexity and their interactions, and how provision of healthcare should be harmonized with complexity to optimize health

Clinical and Non-Clinical Aspects of Distal Radioulnar Joint Instability

Untreated distal radioulnar joint (DRUJ) injuries can give rise to long lasting complaints. Although common, diagnosis and treatment of DRUJ injuries remains a challenge. The articulating anatomy of the distal radius and ulna, among others, enables an extensive range of forearm pronosupination movements. Stabilization of this joint is provided by both intrinsic and extrinsic stabilizers and the joint capsule. These structures transmit the load and prevent the DRUJ from luxation during movement. Several clinical tests have been suggested to determine static or dynamic DRUJ stability, but their predictive value is unclear. Radiologic evaluation of DRUJ instability begins with conventional radiographs in anterioposterior and true lateral view. If not conclusive, CT-scan seems to be the best additional modality to evaluate the osseous structures. MRI has proven to be more sensitive and specific for TFCC tears, potentially causing DRUJ instability. DRUJ instability may remain asymptomatic. Symptomatic DRUJ injuries treatment can be conservative or operative. Operative treatment should consist of restoration of osseous and ligamenteous anatomy. If not successful, salvage procedures can be performed to regain stability

A life-course and time perspective on the construct validity of psychological distress in women and men. Measurement invariance of the K6 across gender

<p>Abstract</p> <p>Background</p> <p>Psychological distress is a widespread indicator of mental health and mental illness in research and clinical settings. A recurrent finding from epidemiological studies and population surveys is that women report a higher mean level and a higher prevalence of psychological distress than men. These differences may reflect, to some extent, cultural norms associated with the expression of distress in women and men. Assuming that these norms differ across age groups and that they evolve over time, one would expect gender differences in psychological distress to vary over the life-course and over time. The objective of this study was to investigate the construct validity of a psychological distress scale, the K6, across gender in different age groups and over a twelve-year period.</p> <p>Methods</p> <p>This study is based on data from the Canadian National Population Health Survey (C-NPHS). Psychological distress was assessed with the K6, a scale developed by Kessler and his colleagues. Data were examined through multi-group confirmatory factor analyses. Increasing levels of measurement and structural invariance across gender were assessed cross-sectionally with data from cycle 1 (n = 13019) of the C-NPHS and longitudinally with cycles 1 (1994-1995), 4 (2000-2001) and 7 (2006-2007).</p> <p>Results</p> <p>Higher levels of measurement and structural invariance across gender were reached only after the constraint of equivalence was relaxed for various parameters of a few items of the K6. Some items had a different pattern of gender non invariance across age groups and over the course of the study. Gender differences in the expression of psychological distress may vary over the lifespan and over a 12-year period without markedly affecting the construct validity of the K6.</p> <p>Conclusions</p> <p>This study confirms the cross-gender construct validity of psychological distress as assessed with the K6 despite differences in the expression of some symptoms in women and in men over the life-course and over time. Findings suggest that the higher mean level of psychological distress observed in women reflects a true difference in distress and is unlikely to be gender-biased. Gender differences in psychological distress are an important public health and clinical issue and further researches are needed to decipher the factors underlying these differences.</p