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Essential and nonessential heavy metals like iron (Fe), nickel (Ni), manganese (Mn), zinc (Zn), copper (Cu), cadmium (Cd), chromium (Cr), and lead (Pb) were analyzed in four selected medicinal plants such as Capparis spinosa, Peganum harmala, Rhazya stricta, and Tamarix articulata by flame atomic absorption spectrophotometer (FAAS). These medicinal plants are extensively used as traditional medicine for treatment of various ailments by local physicians in the area from where these plants were collected. The concentration level of heavy metals in the selected plants was found in the decreasing order as Fe > Zn > Mn > Cu > Ni > Cr > Cd > Pb. The results revealed that the selected medicinal plants accumulate these elements at different concentrations. Monitoring such medicinal plants for heavy metals concentration is of great importance for physicians, health planners, health care professionals, and policymakers in protecting the public from the adverse effects of these heavy metals.

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A variety of techniques have been developed to monitor the depth of anaesthesia. Propofol's pharmacokinetics and response vary greatly, which might be explained by genetic polymorphisms. We investigated the impact of genetic variations on dosage, anaesthetic depth and recovery after total intravenous anaesthesia with propofol. A total of 101 patients were enrolled in the study. The plasma concentration of propofol during anaesthesia was measured using high-performance liquid chromatography. EEG was monitored during the surgical procedure as a measure of anaesthetic depth. Pyrosequencing was used to determine genetic polymorphisms in CYP2B6, CYP2C9, the UGTIA9-promotor and the GABRE gene. The correlation between genotype and to plasma concentration at the time of loss of consciousness (LOC), the total induction dose, the time to anaesthesia, eye opening and clearance were investigated. EEG monitoring showed that the majority of the patients had not reached a sufficient level of anaesthetic depth (subdelta) at the time of loss of consciousness despite a high induction dose of propofol. Patients with UGT1A9-331C/T had a higher propofol clearance than those without (p = 0.03) and required a higher induction dose (p = 0.03). The patients with UGT1A9-1818T/C required a longer time to LOC (p = 0.03). The patients with CYP2C9*2 had a higher concentration of propofol at the time of LOC (p = 0.02). The polymorphisms in the metabolizing enzymes and the receptor could not explain the large variation seen in the pharmacokinetics of propofol and the clinical response seen. At LOC, the patients showed a large difference in EEG pattern.The clinical signs of loss of consciousness (LOC) during induction of anaesthesia include hypoventilation and the loss of verbal response and eyelash reflex [1]. The transition from consciousness to unconsciousness is a complex phenomenon involving working memory, motor control, respiration and cardio-vascular performance. It is well known that the time as well as the anaesthetic dose needed for LOC (measured as loss of eyelash reflex) varies widely between patients. Additionally, anaesthesia-induced LOC can be detected by typical electroencephalogram (EEG) patterns consisting of low-frequency and high-amplitude activity [2]. In the last 10-15 years, a variety of EEG-based techniques have been developed for monitoring the depth of anaesthesia. None of these techniques have been proven to distinguish between consciousness and unconsciousness in individual patients in a validated and reliable way [3]. The gold standard to assess cerebral activity and anaesthetic depth therefore remains the traditional EEG.Propofol (2,6-diisopropylphenol) exerts its pharmacological action through the activation of the GABAA receptor [4] by inhibiting the nerve impulse in the neural network in the brain. Although the major molecular target for propofol effect in the brain, like the GABA A -R is known, we still lack the knowledge as to how propofol disrupts neural transmission and stops the nerve impulse fro...

Abstract:The influence of genetic variants on paclitaxel-induced toxicity is of considerable interest for reducing adverse drug reactions. Recently the genetic variants CYP2C8*3, CYP2C8-HapC, and CYP3A5*3 were associated with paclitaxel-induced neurotoxicity. We therefore investigated the impact of CYP2C8-HapC and CYP3A5*3 on paclitaxel/carboplatin-induced myelosuppression and neurotoxicity. Thirty-three patients from a prospective pharmacokinetics study were genotyped using pyrosequencing. Patients with variant alleles of CYP2C8-HapC were found to have significantly lower nadir values of both leukocytes and neutrophils (p < 0.05) than wild type patients. CYP3A5*3/*1 patients were shown to have borderline significantly lower nadir values of leukocytes (p = 0.07) than *3/*3 patients. Combining the two genotypes resulted in a significant correlation with both leukopenia and neutropenia (p = 0.01). No effect of these genetic variants on the neurotoxicity could be shown in this rather small study, but their importance for paclitaxel-induced toxicity could be confirmed.