ABSTRACT
Background The calcineurin inhibitor, Tacrolimus (Tac), exhibits variable absorption and undergoes first-pass metabolism when administered orally. The narrow therapeutic window and individual variability of this immunosuppressive agent make therapeutic drug monitoring essential. We hypothesized that the Tac metabolism rate - defined as the blood concentration normalized by its daily dose (the C/D ratio) - is associated with post-renal transplant (RTx) function. Methodology A retrospective observational study was conducted including 40 RTx patients. Clinical reports from four follow-up ambulatory appointments at one, three, six, and 12 months were analyzed. Tac dose and its blood levels were used to calculate the Tac concentration/dose (C/D) ratio. Patients with a Tac C/D ratio <1.05 ng/mL x 1/mg and a C/D ratio >1.05 ng/mL x 1/mg were categorized as fast and slow metabolizers. Serum creatinine levels were compared between the two groups, and their association with the Tac C/D ratio was analyzed. Student's unpaired t-test and the Mann-Whitney U test were used to analyze the difference in the C/D ratio between the groups. Spearman correlation analysis was conducted to analyze the association of the C/D ratio with serum creatinine in both groups. A P-value of <0.05 was considered statistically significant. Results Fast metabolizers showed increased serum creatinine (P < 0.05), and the C/D ratio correlated with creatinine levels. ROC analysis used to identify fast metabolizers for the C/D ratio at three months had an area of 0.925 (P < 0.01). Conclusions The Tac C/D ratio can be used as an earlier diagnostic tool to predict the development of nephrotoxicity in RTx patients.
ABSTRACT
For a long time, neurons held the position of central players in the nervous system. Since there are far more astrocytes than neurons in the brain, it makes us wonder if these cells just take up space and support the neurons or if they are actively participating in central nervous system (CNS) homeostasis. Now, astrocytes' contribution to CNS physiology is appreciated as they are known to regulate ion and neurotransmitter levels, synapse formation and elimination, blood-brain barrier integrity, immune function, cerebral blood flow, and many more. In many neurological and psychiatric disorders, astrocyte functions are altered. Advancements in microscopic and transcriptomic tools revealed populations of astrocytes with varied morphology, electrophysiological properties, and transcriptomic profiles. Neuron-circuit-specific functions and neuron-specific interactions of astroglial subpopulations are found, which suggests that diversity is essential in carrying out diverse region-specific CNS functions. Investigations on heterogeneous astrocyte populations are revealing new astrocyte functions and their role in pathological conditions, opening a new therapeutic avenue for targeting neurological conditions. The true extent of astrocytic heterogeneity and its functional implications are yet to be fully explored. This review summarizes essential astrocytic functions and their relevance in pathological conditions and discusses astrocytic diversity in relation to morphology, function, and gene expression throughout the CNS.
Subject(s)
Military Personnel , Nervous System Diseases , Humans , Astrocytes/metabolism , Central Nervous System , Brain , Nervous System Diseases/metabolismABSTRACT
Background and objective Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly contagious infectious disease that has affected many countries globally. Attangaogam, known in Sanskrit as "Ashtanga yoga", is a practice associated with the spiritual and cultural heritage of India whose origins can be traced back to the very dawn of civilization; the practice of yoga promotes health, healing, and longevity. This study aimed to analyze the effects of Attangaogam (Athanam) yoga asana-Pranayamam practice on biochemical, inflammatory, and hematological markers in the management of COVID-19. Materials and methods A prospective observational study was conducted from August 2021 to February 2022 among hospitalized adult patients of both sexes who consented to participate and tested positive for COVID-19 reverse transcription-polymerase chain reaction (RT-PCR). Convenience sampling was employed and the study was approved by Institutional Ethics Committee (VMCIEC/74/2021). Clinical details, inflammatory markers, D-dimer, lactate dehydrogenase (LDH), ferritin, procalcitonin (PCT), interleukin 6 (IL-6), and complete blood count (CBC) were analyzed for all the volunteering patients on admission and before commencing yoga-pranayamam practices. Also, the parameters were recorded after practicing the scheduled protocol: on the day of discharge, and after the first and third months of discharge. Microsoft Excel 2013 was used for statistical analysis. Results Of the 76 patients, 32 were followed up regularly; the mean age of the cohort was 50.6 ± 4.95 years, and 62% were males. All the patients attained normal oxygen saturation and got discharged in 7-14 days. The comparison of clinical, hematological, inflammatory, and biochemical investigations between pre- and post-Attangaogam yoga-Pranayamam practice sessions showed statistically significant differences and the patients attained normal levels for all variables within three months except for serum albumin. Conclusion Based on our findings, the practice of Attangaogam yoga-Pranayamam contributed to the successful treatment of COVID-19 with the early restoration of protracted hypermetabolic and hyperinflammatory markers to normal status. The evidence related to biomarkers revealed that the patients attained metabolic normalcy of cell health with the aid of personalized physical rehabilitation counteracting inï¬ammation and promoting tissue repair thanks to holistic natural and innate immunity provided by Attangaogam yoga-pranayamam practices.
