This commentary critically examines the modern paradigm of natural volatiles in 'medical aromatherapy', first by explaining the semantics of natural volatiles in health, then by addressing chemophenetic challenges to authenticity or reproducibility, and finally by elaborating on pharmacokinetic and pharmacodynamic processes in food, therapy, and disease prophylaxis. Research over the last 50 years has generated substantial knowledge of the chemical diversity of volatiles, and their strengths and weaknesses as antimicrobial agents. However, due to modest in vitro outcomes, the emphasis has shifted toward the ability to synergise or potentiate non-volatile natural or pharmaceutical drugs, and to modulate gene expression by binding to the lipophilic domain of mammalian cell receptors. Because essential oils and natural volatiles are small and lipophilic, they demonstrate high skin penetrating abilities when suitably encapsulated, or if derived from a dietary item they bioaccumulate in fatty tissues in the body. In the skin or body, they may synergise or drive de novo therapeutic outcomes that range from anti-inflammatory effects through to insulin sensitisation, dermal rejuvenation, keratinocyte migration, upregulation of hair follicle bulb stem cells or complementation of anti-cancer therapies. Taking all this into consideration, volatile organic compounds should be examined as candidates for prophylaxis of cardiovascular disease. Considering the modern understanding of biology, the science of natural volatiles may need to be revisited in the context of health and nutrition.

• Klíčová slova
• anti-inflammatory, antimicrobial, aromatherapy, gas chromatography, headspace, pathogen, pharmacodynamics, pharmacokinetics,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Busulfan (BU) dose adjustment following therapeutic drug monitoring contributes to better outcome of hematopoietic stem cell transplantation (HSCT). Further improvement could be achieved through genotype-guided BU dose adjustments. To investigate this aspect, polymorphism within glutathione S transferase genes were assessed. Particularly, promoter haplotypes of the glutathione S transferase A1 (GSTA1) were evaluated in vitro, with reporter gene assays and clinically, in a pediatric multi-center study (N =138) through association with BU pharmacokinetics (PK) and clinical outcomes. Promoter activity significantly differed between the GSTA1 haplotypes (p<0.001) supporting their importance in capturing PK variability. Four GSTA1 diplotype groups that significantly correlated with clearance (p=0.009) were distinguished. Diplotypes underlying fast and slow metabolizing capacity showed higher and lower BU clearance (ml/min/kg), respectively. GSTA1 diplotypes with slow metabolizing capacity were associated with higher incidence of sinusoidal obstruction syndrome, acute graft versus host disease and combined treatment-related toxicity (p<0.0005). Among other GST genes investigated, GSTP1 313GG correlated with acute graft versus host disease grade 1-4 (p=0.01) and GSTM1 non-null genotype was associated with hemorrhagic cystitis (p=0.003). This study further strengthens the hypothesis that GST diplotypes/genotypes could be incorporated into already existing population pharmacokinetic models for improving first BU dose prediction and HSCT outcomes. (No Clinicaltrials.gov identifier: NCT01257854. Registered 8 December 2010, retrospectively registered).

• Klíčová slova
• busulfan, hematopoietic stem cell transplantion, pharmacogenetics, pharmacokinetics, toxicity,
• Publikační typ
• časopisecké články MeSH

While 5-fluorouracil used as single agent in patients with metastatic colorectal cancer has an objective response rate around 20%, the administration of combinations of irinotecan with 5-fluorouracil/folinic acid or oxaliplatin with 5-fluorouracil/folinic acid results in significantly increased response rates and improved survival. However, the side effects of systemic therapy such as myelotoxicity, neurotoxicity or gastrointestinal toxicity may lead to life-threatening complications and have a major impact on the quality of life of the patients. Therefore, biomarkers that would be instrumental in the choice of optimal type, combination and dose of drugs for an individual patient are urgently needed. The efficacy and toxicity of anticancer drugs in tumor cells is determined by the effective concentration in tumor cells, healthy tissues and by the presence and quantity of the drug targets. Enzymes active in drug metabolism and transport represent important determinants of the therapeutic outcome. The aim of this review was to summarize published data on associations of gene and protein expression, and genetic variability of putative biomarkers with response to therapy of colorectal cancer to 5-fluorouracil/leucovorin/oxaliplatin and 5-fluorouracil/leukovorin/irinotecan regimens. Gaps in the knowledge identified by this review may aid the design of future research and clinical trials.

• Klíčová slova
• 5-Fluorouracil, Chemotherapy, Colorectal cancer, Irinotecan, Oxaliplatin,
• MeSH
• biotransformace genetika   MeSH
• chemorezistence genetika   MeSH
• farmakogenetika * MeSH
• fenotyp MeSH
• fluoruracil aplikace a dávkování   MeSH
• individualizovaná medicína * MeSH
• irinotekan MeSH
• kamptothecin aplikace a dávkování   analogy a deriváty   MeSH
• kolorektální nádory farmakoterapie   genetika   MeSH
• leukovorin aplikace a dávkování   MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• organoplatinové sloučeniny aplikace a dávkování   MeSH
• oxaliplatin MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• fluoruracil MeSH
• irinotekan MeSH
• kamptothecin MeSH
• leukovorin MeSH
• nádorové biomarkery MeSH
• organoplatinové sloučeniny MeSH
• oxaliplatin MeSH