Half-Life

ETHNOPHARMACOLOGICAL RELEVANCE: The dried fruit of Terminalia chebula (fructus chebulae) is an important Traditional Medicine used for intestinal and hepatic detoxification. Gurigumu-7 which is made of fructus chebulae and 6 other traditional medicines is one of the most frequently used compound Mongolian and Tibet medicines for liver diseases. Terminalia phenolics are considered as the bioactive constituents of fructus chebulae and consequently of Gurigumu-7.

Coordinated expression of mitochondrial and nuclear genes is required to maintain proper mitochondrial function. However, the precise mechanisms that ensure this coordination are not well defined. We find that signaling from mitochondria to the nucleus is influenced by mammalian target of rapamycin (mTOR) activity via changes in autophagy and p62/SQSTM1 turnover. Reducing mTOR activity increases autophagic flux, enhances mitochondrial membrane potential, reduces reactive oxygen species within the cell, and increases replicative life span.

In polyglutamine (polyQ) diseases, only certain neurons die, despite widespread expression of the offending protein. PolyQ expansion may induce neurodegeneration by impairing proteostasis, but protein aggregation and toxicity tend to confound conventional measurements of protein stability. Here, we used optical pulse labeling to measure effects of polyQ expansions on the mean lifetime of a fragment of huntingtin, the protein that causes Huntington's disease, in living neurons.

Aging is characterized by accumulation of potentially harmful altered proteins that could lead to gradual deterioration of cellular functions and eventually result in increased probability of death. Metabolic turnover of proteins thus plays an essential role in maintaining the life of an organism. In this article we summarize our current knowledge on age-related changes in protein turnover with special reference to degradation. Increase in half-life of proteins with advancing age is well documented.

A sensitive and specific high-performance liquid chromatographic assay was developed for the measurement of etomidate in human plasma following extraction of the drug and the internal standard. Using 0.5-ml aliquots of plasma, the assay was linear in the concentration range of 20-2000 ng of etomidate/ml of plasma. This method was used to evaluate a preliminary clinical study of an etomidate infusion regimen for hypnosis in a total intravenous anesthesia protocol in 23 patients.

Over the last 20 years standardized techniques have been employed for the investigation of intravenous hypnotics, psychotropic and neuroleptic drugs. Sleep has been studied with the help of EEG measures and side-effects have been evaluated by psychometric tests. The EEG is a proven parameter with regard to dosage determination and as objective means to find sleep-inducing quantities of drugs. By means of vigilosomnograms we have established dose-effect curves and have made comparisons between related drugs in the form of equivalence studies.

STUDY OBJECTIVES: To investigate the pharmacokinetics of propofol in combination with epidural anesthesia or with intravenous (i.v.) alfentanil infusion, and to investigate the clinical feasibility of this anesthetic technique in lower abdominal surgery. DESIGN: Randomized, open clinical study. SETTING: Operating theaters and postanesthesia recovery unit at the department of gynecology of a university medical center. PATIENTS: 20 healthy, consenting ASA physical status I and II adult female patients undergoing lower abdominal surgery. INTERVENTIONS: A total i.v.

The effects of BZ drugs result from interaction at the GABAA receptor within the CNS, producing anxiolysis, hypnosis, and amnesia in a dose-dependent fashion. These sedative effects are best titrated to reproducible clinical endpoints, using scoring systems such as the Ramsay scale. All BZs exhibit similar pharmacologic effects, but the important differences in pharmacokinetics and pharmacodynamics should be recognized to use these drugs safely and effectively within the ICU.

BACKGROUND: The relationship between measures of drug effect such as bispectral index (BIS) and end-tidal (ET) levels of anaesthetic agents is described by the 'effect site equilibrium half-time', t(1/2)(ke0). There are limited data available on sevoflurane t(1/2)(ke0) during routine anaesthesia and surgery. Preliminary observations suggested t(1/2)(ke0) for the degree of hypnosis as estimated by BIS is different from that for burst suppression of the electroencephalograph, occurring at 'deep' levels of anaesthesia.

This study investigated the effect of Danshen on the pharmacodynamic-pharmacokinetic (PD-PK) effects of midazolam, a model CYP3A probe substrate. The effects of acute and 3-day Danshen treatment on the pharmacokinetics of a low dose midazolam (10 mg/kg, i.p.) were determined in vivo in the rat. Danshen (200 mg/kg, i.p.) treatment decreased midazolam clearance by 16%, with increases in the AUC by 22% and the half-life by 14%. 3-Day Danshen treatment (200 mg/kg/day, i.p.) for 3 days decreased the clearance, with increases in the T(1/2) and AUC.