Metabolic profiling, comparative

The microsomes from the CMO-fed rats produced the most striking differences in metabolic profile compared to the control microsomes. The data shown in Table III and Fig 3 (for clarity) demonstrate that microsomes from animals fed the cysteine monoxide diet (AIN/CMO) are far more efficient at metabolizing BaP (more BaP oxidized per mole cytochrome P-450/unit time) than are microsomes from rats fed the control diet (AIN/MET). Lower recovery of BaP and metabolites was obtained from the microsomes of the AIN/CMO-fed rats compared to the AIN/M-fed rats (87 to 91%) and a control run containing no NADPH (94% recovery). This result is probably due to the fact that the tetrols and the unknown metabolite, both present in much greater amounts in the CMO case than in the MET (control) case, are not quantifiable, and thus have not been considered in the calculations. Microsomes from the chow-fed rats behaved similarly to the microsomes from AIN/CMO-fed rats, while the other cases showed intermediate values of recovery (data not shown). In every case,... 

Tlie analysis of the intracellular metabolites, the metabolome, by means of comparison of mutants metabolic profiles (comparative metabolomics) aids in understanding the networks of proteins and the presence of silent genes. 

Pillai BVS, Swamp (2002) Elucidation of the flavonoid catabolism pathway in Pseudomonas putida PML2 by comparative metabolic profiling. Appl Environ Microbiol 68 143-151. 

Aripiprazole shares a similar metabolic profile to risperidone, being metabolized by CYP2D6 and 3A4 (Kubo etal, 2005). Few studies exist to compare and contrast aripiprazole effects in different ethnic groups. A recent study indicated that Chinese... 

Figure 3.12 Metabolic profiling by capillary electrophoresis, (a) Comparative carbohydrate profiles of M. truncatula tissue obtained using 4-aminobenzonitrile derivatization, capillary electrophoresis with a 150 mM borate buffer, pH = 9, and on-column UV detection at 214 nm. (b) Anion profile from M. truncatula using capillary electrophoresis and indirect UV detection. The separation buffer was 5 mM K2C1O4, 1% Waters OFM-Anion BT, pH 8.0.

In this report we compare several properties of hepatic microsomal AHH activity in control and DBA-treated little skates (including metabolic profiles obtained from c-benzo(a)pyrene as elucidated by high pressure liquid chromatography [HPLC]), we describe the partial purification of two different forms of cytochrome P-450 (cytochrome P-448 and cytochrome P-451) from hepatic microsomes of DBA-pretreated little skates and we report polycyclic hydrocarbon-like induction in large numbers of winter flounder assayed in Maine during June, July, and August, which was quite different than data obtained with sheepshead examined in Florida during the same period. 

Among the various antidepressants, TCAs appear to have a different metabolic profile in women compared with that in men. This is potentially clinically important because TCA levels are linked with response and toxicity. OCs have been shown to inhibit selected P450 isoenzymes and may further increase TCA levels. This is more meaningful for the older, higher-dose OCs rather than the newer agents. 

VPA may also benefit the maintenance and the prophylactic phases as well, but there are only limited data in this regard, in contrast to lithium, which remains the best-studied maintenance therapy. VPA has a favorable and relatively safe side effect profile compared with other agents and can be combined with other commonly used psychotropics without significantly altering their metabolism or compromising adequacy of blood levels ( 155). There are also limited anecdotal data that this agent can be safe and effective in the elderly patient (156, 157). 

Interpretation of complex metabolic profiles and communication of lab results to clinicians has been one of the greatest challenges in dried blood spot analysis by MS/MS for acylcamitines and amino acids. Following its introduction, MS/MS defined numerous diseases of fatty acid and organic acid metabolism that were uncommonly encountered in a typical practice and not well understood by most pediatricians. Furthermore, even in disorders such as PKU that were well known, the improvements made by MS/MS screening for PKU compared with older technology such as BIA or fluorometry were not well... 

VRLB is a semisynthetic derivative ofVLB (5 -noranhydrovinblastine), structurally distinguished from other members of its class by the modification of the cathar-anthine nucleus rather than the vindoline ring. This alteration is probably responsible for differences in its antitumor activity and tolerability profile compared with other vinca alkaloids [68]. VRLB is effective as monotherapy or in combination with a platinum derivative in patients with advanced NSCLC and advanced breast cancer [69,70]. Myelosuppression is the major dose-limiting toxicity. VRLB is administered weekly nadirs are usually reached within 14 days and patients recover within the next two weeks [71]. VRLB is also well absorbed orally. Oral and i.v. forms show similar interindividual variability, the same metabolism pattern, reproducible intrapatient blood exposure, and the same pharmacokinetic-pharmacodynamic relationship. Given at 60 mg/m /week for the first three administrations and then increased to 80 mg/m /week it achieved the same efficacy as i.v. VRLB (30 mg/m ) in terms of progression-free survival, overall survival, and objective response [70]. 

Principal component analysis enables reduction of a large data matrix into two or three main components that include orthogonally relevant information. In such a way, changes in metabolic profiles, described by many variables, can be measurably determined and compared. Subsequently, using other calculation procedures for the reduced data matrix, the importance of variables (metabolites) can be determined and assessed. Discrimination or regression calculation methods are of great importance in this step of the analysis. 

The study was performed employing GC-MS, using bis-trimethylsilyl-trifluor-oacetamide (BSTFA) as derivatization agent during sample preparation. The aim of the study was to compare the metabolic profiles of urine samples from patients with liver cancer (n = 20) and healthy volunteers (n = 20) and, subsequently, to develop a diagnostic model that would include selected metabolites of potential diagnostic significance in HCC [21]. 

Hydroxybenzodiazepines represent active metabolites of many clinically useful benzodiazepines (e.g., diazepam), and consequently a large number of 3-substituted derivatives have been prepared and evaluated as anxiolytics in their own right. These compounds often show comparable potency to that of the parent benzodiazepines, but have a dramatically different metabolic profile. In hu-... 

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