Biochemistry

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Patrick Chene - One of the best experts on this subject based on the ideXlab platform.

  • can Biochemistry drive drug discovery beyond simple potency measurements
    Drug Discovery Today, 2012
    Co-Authors: Patrick Chene
    Abstract:

    Among the fields of expertise required to develop drugs successfully, Biochemistry holds a key position in drug discovery at the interface between chemistry, structural biology and cell biology. However, taking the example of protein kinases, it appears that biochemical assays are mostly used in the pharmaceutical industry to measure compound potency and/or selectivity. This limited use of Biochemistry is surprising, given that detailed biochemical analyses are commonly used in academia to unravel molecular recognition processes. In this article, I show that Biochemistry can provide invaluable information on the dynamics and energetics of compound-target interactions that cannot be obtained on the basis of potency measurements and structural data. Therefore, an extensive use of Biochemistry in drug discovery could facilitate the identification and/or development of new drugs.

Sean M. Bagshaw - One of the best experts on this subject based on the ideXlab platform.

  • Assessment of Urine Biochemistry
    Critical Care Nephrology, 2019
    Co-Authors: Pierre-marc Villeneuve, Sean M. Bagshaw
    Abstract:

    Abstract To regulate the body's electrolytes and acid-base and volume status the kidneys adjust urinary excretion. Urine Biochemistry can provide important ancillary diagnostic information. This chapter summarizes the common uses of urine Biochemistry in the intensive care unit (ICU) and how they may aid in the diagnosis, investigation, and monitoring in a variety of conditions. It also presents some available literature on the topic. Urine sodium, fractional excretion of sodium, urine osmolality, and fractional excretion of urea have been used as surrogates of kidney perfusion and for discriminating transient (prerenal) and established AKI (acute tubular necrosis). However, their value in ICU settings may be questionable. Urine osmolality and urine sodium are important measures in the evaluation of sodium and water imbalance. Urine chloride can aid in discriminating the cause of metabolic alkalosis. Urine potassium, urine magnesium, and urine calcium can be important tools for investigating the cause of disorders of serum potassium, magnesium, and calcium, respectively. Urine anion gap and urine osmolality can assist in the evaluation of nonanion gap metabolic acidosis. Urine Biochemistry can have an important adjuvant role in the diagnosis and evaluation of a number of clinical problems; however, it may be confounded in ICU settings and ideally should be integrated into the broader clinical context to inform about optimal management.

  • urine Biochemistry in septic and non septic acute kidney injury a prospective observational study
    Journal of Critical Care, 2013
    Co-Authors: Sean M. Bagshaw, Michael J Bennett, Prasad Devarajan, Rinaldo Bellomo
    Abstract:

    Purpose Determine whether there are unique patterns to the urine Biochemistry profile in septic compared with non-septic acute kidney injury (AKI) and whether urinary Biochemistry predicts worsening AKI, need for renal replacement therapy and mortality.

Heiner-fokkema M. Rebecca - One of the best experts on this subject based on the ideXlab platform.

  • Correlations of blood and brain Biochemistry in phenylketonuria: Results from the Pah-enu2 PKU mouse
    'Elsevier BV', 2021
    Co-Authors: Dijkstra, Allysa M., Van Vliet Ninke, Van Vliet Danique, Romani Cristina, Huijbregts, Stephan C.j., Van Der Goot Els, Hovens, Iris B., Van Der Zee, Eddy A., Kema, Ido P., Heiner-fokkema M. Rebecca
    Abstract:

    Background: In phenylketonuria (PKU), treatment monitoring is based on frequent blood phenylalanine (Phe) measurements, as this is the predictor of neurocognitive and behavioural outcome by reflecting brain Phe concentrations and brain biochemical changes. Despite clinical studies describing the relevance of blood Phe to outcome in PKU patients, blood Phe does not explain the variance in neurocognitive and behavioural outcome completely. Methods: In a PKU mouse model we investigated 1) the relationship between plasma Phe and brain Biochemistry (Brain Phe and monoaminergic neurotransmitter concentrations), and 2) whether blood non-Phe Large Neutral Amino Acids (LNAA) would be of additional value to blood Phe concentrations to explain brain Biochemistry. To this purpose, we assessed blood amino acid concentrations and brain Phe as well as monoaminergic neurotransmitter levels in in 114 Pah-Enu2 mice on both B6 and BTBR backgrounds using (multiple) linear regression analyses. Results: Plasma Phe concentrations were strongly correlated to brain Phe concentrations, significantly negatively correlated to brain serotonin and norepinephrine concentrations and only weakly correlated to brain dopamine concentrations. From all blood markers, Phe showed the strongest correlation to brain Biochemistry in PKU mice. Including non-Phe LNAA concentrations to the multiple regression model, in addition to plasma Phe, did not help explain brain Biochemistry. Conclusion: This study showed that blood Phe is still the best amino acid predictor of brain Biochemistry in PKU. Nevertheless, neurocognitive and behavioural outcome cannot fully be explained by blood or brain Phe concentrations, necessitating a search for other additional parameters. Take-home message: Brain Biochemistry in PKU is still best explained by blood phenylalanine. Nevertheless, neurocognitive and behavioural outcome cannot fully be explained by blood or brain phenylalanine concentrations, necessitating a search for other additional parameters

Rinaldo Bellomo - One of the best experts on this subject based on the ideXlab platform.

U. Roelcke - One of the best experts on this subject based on the ideXlab platform.

  • PET: Brain tumor Biochemistry
    Journal of Neuro-Oncology, 1994
    Co-Authors: U. Roelcke
    Abstract:

    Most mechanisms of drugs which are used in brain tumor chemotherapy are well characterized: alkylation of DNA components (nitrosoureas), binding with tubulin protein resulting in metaphase arrest (vincristine), chromatid breaks and chromosome translocations (procarbazine), or inhibition of ribonucleotide reductase (hydroxyurea) [1]. These drugs exert their effects mainly during certain cell cycle phases of proliferating cells, particularly when DNA is synthesized. From this it can be assumed that the efficacy of these drugs depends on the fraction of proliferating cells. Thus it would be of great importance to estimate the proliferation rate of brain tumors which could guide chemotherapy in individual patients. Positron emission tomography (PET) measures quantitatively the in vivo tissue uptake of tracer substances. In tumors, the uptake appears to be altered in a characteristic way determined by biochemical properties of tumor tissue. Some aspects of brain tumor metabolism which are theoretically related to proliferation have been investigated with PET. In the following, the literature is reviewed with regard to: 1) tracer substances whose uptake has been thought to reflect tumor malignancy (11C-methionine, 18F-fluoro-deoxyglucose), and 2) tracers which theoretically could reflect mechanisms specifically related to DNA synthesis (11C-putrescine, ligands for peripheral benzodiazepine receptors).