Electrochemical biosensors: Towards point-of-care cancer diagnostics

ContextWidespread use of herbal medications among the presurgical population
may have a negative impact on perioperative patient care.ObjectivesTo review the literature on commonly used herbal medications in the
context of the perioperative period and provide rational strategies for managing
their preoperative use.Data SourcesThe MEDLINE and Cochrane Collaboration databases were searched for articles
published between January 1966 and December 2000 using the search terms herbal medicine, phytotherapy,
and alternative medicine and the names of the 16
most commonly used herbal medications. Additional data sources were obtained
from manual searches of recent journal articles and textbooks.Study SelectionWe selected studies, case reports, and reviews addressing the safety
and pharmacology of 8 commonly used herbal medications for which safety information
pertinent to the perioperative period was available.Data ExtractionWe extracted safety, pharmacodynamic, and pharmacokinetic information
from the selected literature and reached consensus about any discrepancies.Data SynthesisEchinacea, ephedra, garlic, ginkgo, ginseng, kava, St John's wort, and
valerian are commonly used herbal medications that may pose a concern during
the perioperative period. Complications can arise from these herbs' direct
and pharmacodynamic or pharmacokinetic effects. Direct effects include bleeding
from garlic, ginkgo, and ginseng; cardiovascular instability from ephedra;
and hypoglycemia from ginseng. Pharmacodynamic herb-drug interactions include
potentiation of the sedative effect of anesthetics by kava and valerian. Pharmacokinetic
herb-drug interactions include increased metabolism of many drugs used in
the perioperative period by St John's wort.ConclusionsDuring the preoperative evaluation, physicians should explicitly elicit
and document a history of herbal medication use. Physicians should be familiar
with the potential perioperative effects of the commonly used herbal medications
to prevent, recognize, and treat potentially serious problems associated with
their use and discontinuation.

https://jamanetwork.com/journals/jama/articlepdf/194003/JRV10013.pdf

Herbal Medicines and Perioperative Care

GABA(B) receptors are broadly expressed in the nervous system and have been implicated in a wide variety of neurological and psychiatric disorders. The cloning of the first GABA(B) receptor cDNAs in 1997 revived interest in these receptors and their potential as therapeutic targets. With the availability of molecular tools, rapid progress was made in our understanding of the GABA(B) system. This led to the surprising discovery that GABA(B) receptors need to assemble from distinct subunits to function and provided exciting new insights into the structure of G protein-coupled receptors (GPCRs) in general. As a consequence of this discovery, it is now widely accepted that GPCRs can exist as heterodimers. The cloning of GABA(B) receptors allowed some important questions in the field to be answered. It is now clear that molecular studies do not support the existence of pharmacologically distinct GABA(B) receptors, as predicted by work on native receptors. Advances were also made in clarifying the relationship between GABA(B) receptors and the receptors for gamma-hydroxybutyrate, an emerging drug of abuse. There are now the first indications linking GABA(B) receptor polymorphisms to epilepsy. Significantly, the cloning of GABA(B) receptors enabled identification of the first allosteric GABA(B) receptor compounds, which is expected to broaden the spectrum of therapeutic applications. Here we review current concepts on the molecular composition and function of GABA(B) receptors and discuss ongoing drug-discovery efforts.

Molecular Structure and Physiological Functions of GABAB Receptors

The gamma-aminobutyric acid(B) (GABA(B)) receptor was first demonstrated on presynaptic terminals where it serves as an autoreceptor and also as a heteroreceptor to influence transmitter release by suppressing neuronal Ca(2+) conductance. Subsequent studies showed the presence of the receptor on postsynaptic neurones where activation produces an increase in membrane K(+) conductance and associated neuronal hyperpolarization. (-)-Baclofen is a highly selective agonist for GABA(B) receptors, whereas the established GABA(A) receptor antagonists, bicuculline and picrotoxin, do not block GABA(B) receptors. The receptor is G(i)/G(o) protein-coupled with mixed effects on adenylate cyclase activity. The receptor comprises a heterodimer with similar subunits currently designated 1 and 2. These subunits are coupled via coiled-coil domains at their C termini. The evidence for splice variants is critically reviewed. Thus far, no unique pharmacological or functional properties have been assigned to either subunit or the variants. The emergence of high-affinity antagonists for GABA(B) receptors has enabled a synaptic role to be established. However, the antagonists have generally failed to establish the existence of pharmacologically distinct receptor types within the GABA(B) receptor class. The advent of GABA(B1) knockout mice has also failed to provide support for multiple receptor types.

https://pharmrev.aspetjournals.org/content/pharmrev/54/2/247.full.pdf

International Union of Pharmacology. XXXIII. Mammalian γ-Aminobutyric AcidB Receptors: Structure and Function

The underground organs of members of the genus Valeriana (Valerianaceae), as well as related genera such as Nardostachys, are used in the traditional medicine of many cultures as mild sedatives and tranquillizers and to aid the induction of sleep. V. officinalis is the species most commonly used in northern Europe and still retains its official pharmacopoeial status although it is most commonly encountered as an ingredient of herbal medicines. This plant is still the subject of considerable research aimed at establishing the chemical and pharmacological basis of the activity which has been clearly shown in a number of animal and clinical studies. The constituents of the volatile oil are very variable due to population differences in genetics and to environmental factors. The major constituents include the monoterpene bornyl acetate and the sesquiterpene valerenic acid, which is characteristic of the species, in addition to other types of sesquiterpene. Some of these have been shown to have a direct action on the amygdaloid body of the brain and valerenic acid has been shown to inhibit enzyme-induced breakdown of GABA in the brain resulting in sedation. The non-volatile monoterpenes known as valepotriates were first isolated in 1966 and contribute to the overall activity by possessing sedative activity based on the CNS although the mode of action is not clearly known. The valepotriates themselves act as prodrugs which are transformed into homobaldrinal which has been shown to reduce the spontaneous motility of mice. More recent studies have shown that aqueous extracts of the roots contain appreciable amounts of GABA which could directly cause sedation but there is some controversy surrounding the bioavailability of this compound. Another recent finding is the presence of a lignan, hydroxypinoresinol, and its ability to bind to benzodiazepine receptors. Valerian is a good example of both the negative and positive aspects of herbal drugs. The considerable variation in its composition and content as well as the instability of some of its constituents pose serious problems for standardization but the range of components which contribute to its overall activity suggest that it may correct a variety of underlying causes of conditions which necessitate a general sedative or tranquilizing effect.

The scientific basis for the reputed activity of Valerian.

http://www1.ci.uc.pt/pessoal/anabrett/pdfs/PDF-1996-1999/43-DNA-Mitoxantrone-B+B.pdf

Voltammetric behaviour of mitoxantrone at a DNA-biosensor.

Cell death and reactive oxygen species production have been suggested to be involved in neurodegeneration induced by the drugs of abuse. In this study we analyze the toxicity of the following drugs of abuse: heroin, morphine, d-amphetamine, and cocaine in undifferentiated PC12 cells, used as dopaminergic neuronal models. Our data show that opioid drugs (heroin and morphine) are more toxic than stimulant drugs (d-amphetamine and cocaine). Toxic effects induced by heroin are associated with a decrease in intracellular dopamine, an increase in DOPAC levels, and the formation of ROS, whereas toxic effects induced by amphetamine are associated with a decrease in intracellular dopamine and in ATP/ADP levels. In contrast with cocaine, both amphetamine and heroin induced features of apoptosis. The data suggest that the death of cultured PC12 cells induced by the drugs of abuse is correlated with a decrease in intracellular dopamine levels, which can be associated with an increased dopamine turnover and oxidative cell injury.

/pdf/toxic-effects-of-opioid-and-stimulant-drugs-on-593njb6a5t.pdf

Toxic Effects of Opioid and Stimulant Drugs on Undifferentiated PC12 Cells

An electrochemical method for the determination of the anticancer platinum drug carboplatin using a DNA-modified electrode was developed. This electrode was successfully used for the electrochemical determination of carboplatin in serum samples of patients with ovarian cancer undergoing treatment. The electrochemical results clearly demonstrated that, for low concentrations, carboplatin interacts preferentially with adenine rather than guanine groups in the DNA and they can contribute to clarifying the mechanisms of interaction of platinum anticancer drugs with DNA. The pharmacokinetics corm ondIng to the administration of the drug was followed electrochemically and the detection limit in serum samples was 5.7 x 10 M. Due to a similar mechanism of reaction with DNA other platinum anticancer drugs can be determined by this method.

/pdf/electrochemical-determination-of-carboplatin-in-serum-using-2h4jj65t2a.pdf

Electrochemical determination of carboplatin in serum using a DNA‐modified glassy carbon electrode

The effect of an aqueous extract obtained from the roots of Valeriana officinalis was investigated on the uptake and release of GABA in synaptosomes isolated from rat brain cortex. Aqueous extract of valerian inhibited the uptake and stimulated the release of [3H]GABA, either in the absence or in the presence of K+ depolarization. The release was Na(+)-dependent and independent of the presence of Ca2+ in the external medium. It is concluded that valerian extract releases [3H]GABA by reversal of the GABA carrier, which is Na(+)-dependent and Ca(2+)-independent. This increase in [3H]GABA release appears to be independent from Na(+)-K(+)-ATPase activity and the membrane potential.

T.R.A. Macedo

Papers

Voltammetric behaviour of mitoxantrone at a DNA-biosensor.

Toxic Effects of Opioid and Stimulant Drugs on Undifferentiated PC12 Cells

Electrochemical determination of carboplatin in serum using a DNA‐modified glassy carbon electrode

Synaptosomal GABA release as influenced by valerian root extract--involvement of the GABA carrier.

An aqueous extract of valerian influences the transport of GABA in synaptosomes