Key Factors in Effective Patient-Tailored Dosing of Fluoroquinolones in Urological Infections: Interindividual Pharmacokinetic and Pharmacodynamic Variability.

Fluoroquinolones (FQs) are a critical group of antimicrobials prescribed in urological infections as they have a broad antimicrobial spectrum of activity and a favorable tissue penetration at the site of infection. However, their clinical practice is not problem-free of treatment failure, risk of emergence of resistance, and rare but important adverse effects. Due to their critical role in clinical improvement, understanding the dose-response relation is necessary to optimize the effectiveness of FQs therapy, as it is essential to select the right antibiotic at the right dose for the right duration in urological infections.

The Taste of Caffeine.

Many people avidly consume foods and drinks containing caffeine, despite its bitter taste. Here, we review what is known about caffeine as a bitter taste stimulus. Topics include caffeine's action on the canonical bitter taste receptor pathway and caffeine's action on noncanonical receptor-dependent and -independent pathways in taste cells.

Does eating good-tasting food influence body weight?

Does eating good-tasting food influence body weight? To investigate, we first established some concentrations of sucralose and mineral oil in chow that mice strongly preferred. Then, in Experiment 1, we compared groups of 16 mice fed plain chow (i.e.

Cognitive control deficits during mecamylamine-precipitated withdrawal in mice: Possible links to frontostriatal BDNF imbalance.

Nicotine is a major psychoactive and addictive component of tobacco. Although cessation of tobacco use produces various somatic and affective symptoms, withdrawal-related cognitive deficits are considered to be a critical symptom that predict relapse. Therefore, delineating the cognitive mechanisms of nicotine withdrawal may likely provide gainful insights into the neurobiology of nicotine addiction.

Maltodextrin Acceptance and Preference in Eight Mouse Strains.

Rodents are strongly attracted to the taste(s) of maltodextrins. A first step toward discovery of the underlying genes involves identifying phenotypic differences among inbred strains of mice. To do this, we used 5-s brief-access tests and 48-h 2-bottle choice tests to survey the avidity for the maltodextrin, Maltrin M040, of mice from 8 inbred strains (129S1/SvImJ, A/J, CAST/EiJ, C57BL/6J, NOD/ShiLTJ, NZO/HlLtJ, PWK/PhJ, and WSB/EiJ).

Normal Taste Acceptance and Preference of PANX1 Knockout Mice.

Taste compounds detected by G protein-coupled receptors on the apical surface of Type 2 taste cells initiate an intracellular molecular cascade culminating in the release of ATP. It has been suggested that this ATP release is accomplished by pannexin 1 (PANX1). However, we report here that PANX1 knockout mice do not differ from wild-type controls in response to representative taste solutions, measured using 5-s brief-access tests or 48-h two-bottle choice tests.

Concentration- and age-dependent effects of chronic caffeine on contextual fear conditioning in C57BL/6J mice.

Chronic caffeine exerts negligible effects on learning and memory in normal adults, but it is unknown whether this is also true for children and adolescents. The hippocampus, a brain region important for learning and memory, undergoes extensive structural and functional modifications during pre-adolescence and adolescence. As a result, chronic caffeine may have differential effects on hippocampus-dependent learning in pre-adolescents and adolescents compared with adults.

Contributions of β2 subunit-containing nAChRs to chronic nicotine-induced alterations in cognitive flexibility in mice.

Rationale: Deficits in executive functions underlie compulsive drug use, and understanding how nicotine influences these cognitive processes may provide important information on neurobiological substrates of nicotine addiction. Accumulating evidence suggests that β2 subunit-containing nicotinic receptors (nAChRs) are involved in the reinforcing process of nicotine addiction. Whether these nAChRs also contributes to the detrimental effects of chronic nicotine on flexible decision-making is not known.

17β-Estradiol regulates histone alterations associated with memory consolidation and increases Bdnf promoter acetylation in middle-aged female mice.

Histone acetylation is essential for hippocampal memory formation in young adult rodents. Although dysfunctional histone acetylation has been associated with age-related memory decline in male rodents, little is known about whether histone acetylation is altered by aging in female rodents. In young female mice, the ability of 17β-estradiol (E2) to enhance object recognition memory consolidation requires histone H3 acetylation in the dorsal hippocampus.

Donepezil reverses nicotine withdrawal-induced deficits in contextual fear conditioning in C57BL/6J mice.

Withdrawal from chronic nicotine is associated with cognitive deficits. Therapies that ameliorate cognitive deficits during withdrawal aid in preventing relapse during quit attempts. Withdrawal-induced deficits in contextual learning are associated with nicotinic acetylcholine receptor upregulation.

Reactivation of cocaine reward memory engages the Akt/GSK3/mTOR signaling pathway and can be disrupted by GSK3 inhibition.

Rational: Memories return to a labile state following their retrieval and must undergo a process of reconsolidation to be maintained. Thus, disruption of cocaine reward memories by interference with reconsolidation may be therapeutically beneficial in the treatment of cocaine addiction.

Objective: The objectives were to elucidate the signaling pathway involved in reconsolidation of cocaine reward memory and to test whether targeting this pathway could disrupt cocaine-associated contextual memory.

The GSK3 signaling pathway is activated by cocaine and is critical for cocaine conditioned reward in mice.

The Akt - GSK3 signaling pathway has been recently implicated in psychostimulant-induced behavioral and cellular effects. Here, the ability of cocaine to regulate the activity of Akt and GSK3 was investigated by measuring the phosphorylation states of the two kinases. The anatomical specificity of the response was determined, as was the contributions of dopamine and NMDA receptors to the actions of cocaine.

Nicotine shifts the temporal activation of hippocampal protein kinase A and extracellular signal-regulated kinase 1/2 to enhance long-term, but not short-term, hippocampus-dependent memory.

Acute nicotine enhances hippocampus-dependent learning through nicotine binding to β2-containing nicotinic acetylcholine receptors (nAChRs), but it is unclear if nicotine is targeting processes involved in short-term memory (STM) leading to a strong long-term memory (LTM) or directly targeting LTM. In addition, the molecular mechanisms involved in the effects of nicotine on learning are unknown. Previous research indicates that protein kinase A (PKA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein synthesis are crucial for LTM.

Divergent functional effects of sazetidine-a and varenicline during nicotine withdrawal.

Smoking is the largest preventable cause of death in the United States. Furthermore, a recent study found that <10% of quit attempts resulted in continuous abstinence for 1 year. With the introduction of pharmacotherapies like Chantix (varenicline), a selective α4β2 nicotinic partial agonist, successful quit attempts have significantly increased.

Learning and nicotine interact to increase CREB phosphorylation at the jnk1 promoter in the hippocampus.

Nicotine is known to enhance long-term hippocampus dependent learning and memory in both rodents and humans via its activity at nicotinic acetylcholinergic receptors (nAChRs). However, the molecular basis for the nicotinic modulation of learning is incompletely understood. Both the mitogen activated protein kinases (MAPKs) and cAMP response element binding protein (CREB) are known to be integral to the consolidation of long-term memory and the disruption of MAPKs and CREB are known to abrogate some of the cognitive effects of nicotine.

Human AlkB homologue 5 is a nuclear 2-oxoglutarate dependent oxygenase and a direct target of hypoxia-inducible factor 1α (HIF-1α).

Human 2-oxoglutarate oxygenases catalyse a range of biological oxidations including the demethylation of histone and nucleic acid substrates and the hydroxylation of proteins and small molecules. Some of these processes are centrally involved in regulation of cellular responses to hypoxia. The ALKBH proteins are a sub-family of 2OG oxygenases that are defined by homology to the Escherichia coli DNA-methylation repair enzyme AlkB.

Cleaning up sterile services.

STAFF IN sterile service units (SSUs) decontaminate reusable surgical equipment and deliver it, as required, to operating theatres.