Micronutrient Deficiency in Pulmonary Tuberculosis – Perspective on hepatic drug metabolism and pharmacokinetic variability of first-line anti-tuberculosis drugs: Special reference to fat-soluble vitamins A, D, & E and nutri-epigenetics

2021 ◽  
Vol 14 ◽  
Author(s):  
Jeyakumar Shanmugam Murugaiha
Keyword(s):  
Pulmonary Tuberculosis ◽  
Nutritional Status ◽  
Special Reference ◽  
Therapeutic Drug ◽  
Epigenetic Changes ◽  
Pharmacokinetic Variability ◽  
First Line ◽  
Hepatic Drug ◽  
Fat Soluble Vitamins

: The liver plays a crucial role in endogenous metabolic activity and homeostasis of macro and micronutrients. Further, it acts as a metabolic hub in mammals, where the ingested food-derived nutrients and xenobiotics or drugs are metabolized for utilization and/or excretion through its enzymatic and non-enzymatic machinery. Nutritional deficiency, one of the major public health problems, is associated with global disease burden, including pulmonary tuberculosis (PTB) caused by Mycobacterium tuberculosis (Mtb) infection. Though it is a curable and preventable infectious disease, millions of people succumb to death, and people in numbers larger than this are still suffering. This scenario is further complicated by the addition of new cases, disease recurrence, and the emergence of drug-resistant, all of which contribute to the spread of this epidemic. Though the manifestation of TB disease has multiple aetiologies, poor nutritional status and sub-optimal therapeutic concentrations of first-line anti-TB drugs are considered as potential contributors to its widespread prevalence. Among various factors, the pharmacokinetic variability of anti-TB drugs is one of the main causes for sub-optimal therapeutic drug concentration in TB patients, which is influenced by the host’s genetic make-up and nutritional status, besides several others. However, the role of epigenetic changes in hepatic drug metabolic pathways and their transcript levels is largely unexplored. Therefore, in this review, an attempt has been made to understand the role of micronutrient deficiencies with special reference to fat-soluble vitamins, namely vitamin A, D, & E in pulmonary TB, their possible impact on epigenetic changes on the drug-metabolizing pathway genes, thus their expression levels and plausible influence on pharmacokinetic variability of anti-TB drugs, besides discussing the limitations and emerging potential opportunities. Eventually, this would help in developing the host-directed/personalized therapeutic strategies for the elimination of pulmonary tuberculosis (PTB).

Optimizing treatment outcome of first-line anti-tuberculosis drugs: the role of therapeutic drug monitoring

2016 ◽  
Vol 72 (8) ◽  
pp. 905-916 ◽  
Author(s):  
Roger K. Verbeeck ◽  
Gunar Günther ◽  
Dan Kibuule ◽  
Christian Hunter ◽  
Tim W. Rennie
Keyword(s):  
Treatment Outcome ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
First Line

scholarly journals Intrapulmonary Pharmacokinetics of First-line Anti-tuberculosis Drugs in Malawian Patients With Tuberculosis

2020 ◽  
Author(s):  
Andrew D McCallum ◽  
Henry E Pertinez ◽  
Laura J Else ◽  
Sujan Dilly-Penchala ◽  
Aaron P Chirambo ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Drug Exposure ◽  
Plasma Concentrations ◽  
Clinical Treatment ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
High Dose ◽  
Alveolar Cells ◽  
First Line ◽  
Drug Concentrations

Abstract Background Further work is required to understand the intrapulmonary pharmacokinetics of first-line anti-tuberculosis drugs. This study aimed to describe the plasma and intrapulmonary pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol, and explore relationships with clinical treatment outcomes in patients with pulmonary tuberculosis. Methods Malawian adults with a first presentation of microbiologically confirmed pulmonary tuberculosis received standard 6-month first-line therapy. Plasma and intrapulmonary samples were collected 8 and 16 weeks into treatment and drug concentrations measured in plasma, lung/airway epithelial lining fluid (ELF), and alveolar cells. Population pharmacokinetic modeling generated estimates of drug exposure (Cmax and AUC) from individual-level post hoc Bayesian estimates of plasma and intrapulmonary pharmacokinetics. Results One-hundred fifty-seven patients (58% HIV coinfected) participated. Despite standard weight-based dosing, peak plasma concentrations of first-line drugs were below therapeutic drug-monitoring targets. Rifampicin concentrations were low in all 3 compartments. Isoniazid, pyrazinamide, and ethambutol achieved higher concentrations in ELF and alveolar cells than plasma. Isoniazid and pyrazinamide concentrations were 14.6-fold (95% CI, 11.2–18.0-fold) and 49.8-fold (95% CI, 34.2–65.3-fold) higher in ELF than plasma, respectively. Ethambutol concentrations were highest in alveolar cells (alveolar cell–plasma ratio, 15.0; 95% CI, 11.4–18.6). Plasma or intrapulmonary pharmacokinetics did not predict clinical treatment response. Conclusions We report differential drug concentrations between plasma and the lung. While plasma concentrations were below therapeutic monitoring targets, accumulation of drugs at the site of disease may explain the success of the first-line regimen. The low rifampicin concentrations observed in all compartments lend strong support for ongoing clinical trials of high-dose rifampicin regimens.

scholarly journals Validasi Metode Bioanalisis Vankomisin HCl dalam Spiked-plasma Manusia Menggunakan KCKT-UV untuk Aplikasi PKOD

2019 ◽  
Vol 19 (1) ◽  
pp. 57-70
Author(s):  
Ari Wibowo ◽  
Damas Inggil Maulidina ◽  
Wahyuni Shalatan Fitri ◽  
Vitarani Ningrum
Keyword(s):  
Staphylococcus Aureus ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Therapeutic Index ◽  
Therapeutic Drug ◽  
Pharmacokinetic Variability ◽  
First Line ◽  
Narrow Therapeutic Index ◽  
Spiked Plasma

As the first-line antibiotic for the treatment of infections caused by methicillin-resistant Staphylococcus aureus  (MRSA), vancomycin has  a narrow therapeutic index with high pharmacokinetic   variability. Therefore, it is deemed necessary to examine its concentration in the blood as a strategy to monitor the fulfillment of therapeutic levels  in patients receiving vancomycin. This study aimed to validate vancomycin bioanalysis  in  spiked-human  plasma  for  the  applications  of  therapeutic  drug  monitoring  (TDM).

Social Representations and Commitment

2018 ◽  
Vol 23 (3) ◽  
pp. 233-249 ◽  
Author(s):  
Eric Bonetto ◽  
Fabien Girandola ◽  
Grégory Lo Monaco
Keyword(s):  
Social Representations ◽  
Social Representation ◽  
Second Line ◽  
Review Of The Literature ◽  
First Line ◽  
Research Perspectives ◽  
The Social ◽  
Bibliographic Search ◽  
English Articles

Abstract. This contribution consists of a critical review of the literature about the articulation of two traditionally separated theoretical fields: social representations and commitment. Besides consulting various works and communications, a bibliographic search was carried out (between February and December, 2016) on various databases using the keywords “commitment” and “social representation,” in the singular and in the plural, in French and in English. Articles published in English or in French, that explicitly made reference to both terms, were included. The relations between commitment and social representations are approached according to two approaches or complementary lines. The first line follows the role of commitment in the representational dynamics: how can commitment transform the representations? This articulation gathers most of the work on the topic. The second line envisages the social representations as determinants of commitment procedures: how can these representations influence the effects of commitment procedures? This literature review will identify unexploited tracks, as well as research perspectives for both areas of research.

A REVIEW ON THE ROLE OF TYROSINE KINASE INHIBITORS AVAILABLE FOR THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA

2020 ◽  
Vol 7 (2) ◽  
pp. 205-211
Author(s):  
Kaynat Fatima ◽  
Syed Tasleem Raza ◽  
Ale Eba ◽  
Sanchita Srivastava ◽  
Farzana Mahdi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Protein Kinases ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

The function of protein kinases is to transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are linked to the initiation and development of human cancer. The recent development of small molecule kinase inhibitors for the treatment of different types of cancer in clinical therapy has proven successful. Significantly, after the G-protein-coupled receptors, protein kinases are the second most active category of drug targets. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI), approved for chronic myeloid leukemia (CML) treatment. Imatinib induces appropriate responses in ~60% of patients; with ~20% discontinuing therapy due to sensitivity, and ~20% developing drug resistance. The introduction of newer TKIs such as, nilotinib, dasatinib, bosutinib, and ponatinib has provided patients with multiple options. Such agents are more active, have specific profiles of side effects and are more likely to reach the necessary milestones. First-line treatment decisions must be focused on CML risk, patient preferences and comorbidities. Given the excellent result, half of the patients eventually fail to seek first-line treatment (due to discomfort or resistance), with many of them needing a third or even further therapy lines. In the present review, we will address the role of tyrosine kinase inhibitors in therapy for chronic myeloid leukemia.

HUBUNGAN PERAN KADER POSYANDU DENGAN STATUS GIZI BALITA

2018 ◽  
Vol 9 (02) ◽  
pp. 192
Author(s):  
Wiwid Wahyuningsih ◽  
Atik Setiyaningsih
Keyword(s):  
Nutritional Status ◽  
Total Sample ◽  
Nutrition Status ◽  
P Value ◽  
Chi Square ◽  
Cross Sectional ◽  
Central Java ◽  
Good Nutrition ◽  
Nutritional Status Of Children

ABSTRAKLatar Belakang : Keberadaan kader di posyandu sebagai salah satu sistem penyelenggarakan pelayanan sangat dibutuhkan. Mereka adalah ujung tombak  pelayanan kesehatan yang merupakan kepanjangtanganan puskesmas Jawa Tengah tahun 2011 jumlah gizi kurang 5,35% dan gizi buruk 0,10%. Untuk Kabupaten Semarang dari 23.562 balita yang ditimbang pada tahun 2011 gizi lebih 1,13%, gizi baik 93,51%, gizi kurang 4,86% dan gizi buruk 0,49% (DepKes Prov Jateng, 2011). Tujuan Penelitian : Penelitian ini bertujuan untuk mengetahui hubungan peran kader posyandu dengan status gizi balita. Metode Penelitian : Desain penelitian ini adalah survey analitik dengan menggunakan pendekatan cross sectional. Populasi dalam penelitian ini adalah seluruh balita di Posyandu Mawar di Desa Gedangan sejumlah 40 responden, dengan teknik total sampling dan analisa data chi square. Hasil Penelitian : Hasil perhitungan chi square di peroleh X² hitung 10.644 pada df=4, P.value 0.031 dimana probabilitas lebih kecil dari level of significant 5 % (0,001 < 0,05) berarti Ha diterima dan Ho ditolak. Kesimpulan : ada hubungan antara peran kader posyandu dengan status gizi pada balita.Kata Kunci : peran kader , status gizi balitaCADERE ROLE RELATIONSHIP WITH NUTRITIONAL STATUS OF CHILDREN POSYANDUABSTRACTBackground : posyandu cadre in Existence as one of the 56th's service system is urgently needed. They are the tip of the Spear is a kepanjangtanganan health services clinics in Central Java in 2011 the amount of nutrition less 5.35% 0.10% and malnutrition. To Semarang from 23.562 toddler who weighed in 2011 more nutritional 1.13%, 93,51%, good nutrition nutrition less 4.86% and 0.49% poor nutrition (Department of Health Central Java Prov., 2011). Objective : the research aims to find out the relationship role of posyandu cadre with the nutritional status of children. Methods : the design of this research is a survey using the analytic approach of cross sectional. The population in this study are all the toddlers at the Rose in the village of Posyandu Gedangan some 38 respondents, with total sample techniques and data analysis a chi square. The results :. The chi square calculation results in getting X ² count 10.644 on df = 4, P. value 0.031 where probability is smaller than the level of significant 5% (0.001 < 0.05) mean Ha Ho accepted and rejected. Conclusion : there is a connection between the role of cadres of posyandu with nutritional status on toddlers.Keywords : the role of cadres, toddler nutrition status

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