Leptospira
Dongyou Liu in Handbook of Foodborne Diseases, 2018
Cultures: Isolation and identification of leptospires are the gold standard method for diagnosis of leptospirosis. Leptospiremia starts before the onset of symptoms and dips by the end of the first week of acute illness. But for Leptospira spp., being fastidious and slow organisms, this technique has poor sensitivity [41]. Blood cultures should be collected and sent as soon as possible and preferably inoculated at the bedside [42]. The bottles should be inoculated at 28°C–30°C and examined weekly by dark-field microscopy, for at least up to 14 weeks. Isolation of leptospires from blood is only successful in 5%–50% of cases [40]. CSF should also be inoculated at the first week. Urine should be inoculated at the beginning of the second week as the leptospires are excreted in urine during the second week [43]. Fatty acid–based commercial medium should be used for isolation, as carbohydrate-based mediums are not suitable. Leptospires utilize fatty acids as they cannot synthesize fatty acids de novo. The pyrimidine analogue, 5-fluorouracil is used in the medium to inhibit other organisms. Leptospires incorporate purine bases into their nucleic acid but not pyrimidine, and therefore, they are resistant to pyrimidine analogue. The colonies are subsurface and become visible in 7–14 days [41].
Understanding Pharmacokinetics and Pharmacodynamics: Application to the Antimicrobial Formulary Decision Process
Robert C. Owens, Paul G. Ambrose, Charles H. Nightingale in Antibiotic Optimization, 2004
Similar pharmacodynamic analyses have been undertaken with drugs from several antifungal drug classes. The concepts developed with antibacterials appear to also be important for these compounds. Each of the three pharmacodynamic measures (peak/MIC ratio, AUC/MIC ratio, and T>MIC) are represented. Drugs from the polyene class, such as amphotericin B, and from the new echinocandin class demonstrate concentration-dependent killing and prolonged persistent effects (8). The peak/MIC ratio is the critical PK-PD determinant of activity. However, for the pyrimidine analogue flucytosine, high drug concentrations do not induce extensive killing and only minimal post-antifungal effects are observed. T>MIC is the important PK-PD measure. For the many drugs from the triazole class, there is a lack of concentration-dependent antifungal activity; however, prolonged post-antifungal effects have been described in animal models. The 24 h AUC/MIC ratio has been found important in predicting efficacy in a variety of animal models. The target AUC/MIC value in treatment of Candida infections in animals and in clinical trials is near 25 (8,50). In the largest analysis of the relationship between Candida spp MIC and efficacy, the fluconazole dosing regimen producing efficacy against organisms labeled susceptible supports the AUC/MIC target of 25. In studies of several drugs from the triazole antifungal class, free drug levels were demonstrated to be important.
Chemotherapy in pregnancy
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
Much like methotrexate, 5-FU, a pyrimidine analog, has been associated with multiple congenital abnormalities when it has been used during the first trimester, including radial dysplasia, absent digits, and hypoplasias of the lungs, aorta, esophagus, duodenum, and ureters (61). However, Berry et al. reported on 24 patients treated for breast cancer in pregnancy. They noted no fetal abnormalities or neonatal complications with the use of a combination of fluorouracil, doxorubicin, and cyclofosfamide (12). Fluorouracil is also used in topical form to treat conditions of the vulva and vagina. Several patients have been inadvertently treated with this preparation in the first trimester, without any report of deformities (62).
Surface modified nanoliposome formulations provide sustained release for 5-FU and increase cytotoxicity on A431 cell line
Published in Pharmaceutical Development and Technology, 2020
Ümran Yaman, Minela Aslan, Sukru Ozturk, Kezban Ulubayram, İpek Eroğlu
5-FU (5-Fluoro-2,4-dihydroxy pyridine) is a cytotoxic drug commonly used in the treatment of many types of cancer (Miura et al. 2010). It is an antimetabolite of fluoropyrimidine and is used in the treatment protocols of many types of cancer including skin cancer. It is classified as a pyrimidine analog because it interferes with DNA and RNA synthesis by mimicking the building blocks necessary for synthesis (Kim et al. 2018). 5-FU is generally administered to patients every day as i.v. bolus for 5 consecutive days followed by re-administration after 28days in 3 cycles. In case surgery is not convenient, 5-FU can be applied as intravenous injection or topical form for skin cancer treatment (Thomas et al. 2011). Therefore, the aim of this study was to prepare 5-FU loaded nanoliposomes and polymer coated 5-FU loaded nanoliposomes for intra-tumoral injection. Poly-L-lysine (PLL) and Polyethyleneimine (PEI) at different polymer:liposome concentrations were used for the coating of the nanoliposomes. Nanoliposome formulations were fully characterized and cytotoxicity studies on the A431 epidermoid carcinoma cell line were carried out. Results from this study suggests that, this novel approach could provide an effective and reliable treatment option for skin cancer as compared to currently existing treatment strategies.
Colon targeted dosage form of Capecitabine using folic acid anchored modified carbon nanotube: in vitro cytotoxicity, apoptosis and in vivo roentgenographic study
Published in Drug Development and Industrial Pharmacy, 2021
Dheeraj S. Randive, Akshata S. Gavade, Kiran P. Shejawal, Mangesh A. Bhutkar, Somnath D. Bhinge, Namdeo R. Jadhav
Capecitabine entrapments were observed to be 94.63 ± 1.07%. Being an aromatic heterocyclic compound, it exhibits unique property of π–π staging and therefore hydrophobic interactions are possible in side wall of CNTs and the chances of increasing its entrapment in CNTs. It is a pyrimidine analogue containing C = O and N–H group. Thus, the present COOH and OH group in the f-SWCNTs form strong hydrogen bond with C = O and NH group.
A novel anticancer chromeno-pyrimidine analogue inhibits epithelial-mesenchymal transition in lung adenocarcinoma cells
Published in Toxicology Mechanisms and Methods, 2021
Venkateswarareddy Nallajennugari, Sankar Pajaniradje, Srividya Subramanian, Suhail Ahmad Bhat, Parthasarathi D, Savitha Bhaskaran, Syed Ali Padusha M, Rukkumani Rajagopalan
The complicated side effects of existing chemotherapeutic agents underscore the current cancer field to develop more efficient agents. With the evolving knowledge in chemistry, a variety of chemical compounds are being screened to find new potential drugs, including pyrimidine analogues. Novel modifications resulting in new pyrimidine analogue structures may offer hope for simpler chemotherapeutic agents.
Related Knowledge Centers
- Antimetabolite
- Cytarabine
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- Pyrimidine
- Thymidylate Synthase
- Nucleic Acid Analogue
- Floxuridine
- Nucleoside Analogue
- Gemcitabine