Live Imaging of Kv7.2/7.3 Cell Surface Dynamics at the Axon Initial Segment: High Steady-State Stability and Calpain-Dependent Excitotoxic Downregulation Revealed.

Unlabelled: The voltage-gated K(+) channels Kv7.2 and Kv7.3 are located at the axon initial segment (AIS) and exert strong control over action potential generation.

Molecular and functional characterization of Kv 7 channels in penile arteries and corpus cavernosum of healthy and metabolic syndrome rats.

Background And Purpose: KCNQ-encoded voltage-dependent potassium channels (Kv 7) are involved in the regulation of vascular tone. In this study we evaluated the influence of Kv 7 channel activation on smooth muscle relaxation in rat penile arteries and corpus cavernosum from normal and spontaneously hypertensive, heart failure-prone (SHHF) rats - a rat model of human metabolic syndrome.

Experimental Approach: Quantitative PCR and immunohistochemistry were used to determine the expression of KCNQ isoforms in penile tissue.

pH-dependent inhibition of K₂P3.1 prolongs atrial refractoriness in whole hearts.

In isolated human atrial cardiomyocytes, inhibition of K2P3.1 K(+) channels results in action potential (action potential duration (APD)) prolongation. It has therefore been postulated that K2P3.

Fundamental role for the KCNE4 ancillary subunit in Kv7.4 regulation of arterial tone.

Key Points: KCNE4 alters the biophysical properties and cellular localization of voltage-gated potassium channel Kv7.4. KCNE4 is expressed in a variety of arteries and, in mesenteric arteries, co-localizes with Kv7.

Is Timing of Medical Therapy Related to Outcome in Painful Chronic Pancreatitis?

Objectives: The authors investigated if timing of medical treatment is associated with the analgesic effect of pregabalin or placebo in patients with chronic pancreatitis (CP).

Methods: Sixty-four patients received pregabalin (150-300 mg twice a day) or matching placebo for 3 consecutive weeks. Responders to treatment were defined as patients with a reduction in clinical pain scores of 30% or greater.

Protein kinase A stimulates Kv7.1 surface expression by regulating Nedd4-2-dependent endocytic trafficking.

The potassium channel Kv7.1 plays critical physiological roles in both heart and epithelial tissues. In heart, Kv7.

Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients.

Background: Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs nonresponders) to placebo or pregabalin treatment.

Methods: This study was part of a randomized, double-blind, placebo-controlled trial evaluating the analgesic effects of pregabalin and placebo in chronic pancreatitis.

Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval.

Aims: We studied whether variants previously associated with congenital long QT syndrome (cLQTS) have an effect on the QTc interval in a Danish population sample. Furthermore, we assessed whether carriers of variants in cLQTS-associated genes are more prone to experience syncope compared with non-carriers and whether carriers have an increased mortality compared with non-carriers.

Methods And Results: All genetic variants previously associated with cLQTS were surveyed using the Human Gene Mutation Database.

Analysis of the Antitumor Activity of Clotrimazole on A375 Human Melanoma Cells.

Aim: The current study was designed to characterize the anticancer effects of clotrimazole on human cutaneous melanoma cells.

Materials And Methods: The v-raf murine sarcoma viral oncogene homolog B1 V600E mutant melanoma cell line A375 was used as an in vitro model. Characterization tools included analyses of cell viability, gene expression, cell-cycle progression, annexin V reactivity and internucleosomal DNA fragmentation.

Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2.

Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with both Kv4 to conduct the fast-recovering transient outward K(+) current (Ito,f) and with CaV1.2 to mediate the inward L-type Ca(2+) current (ICa,L).

A New Method for Sham-Controlled Acupuncture in Experimental Visceral Pain - a Randomized, Single-Blinded Study.

Objective: Acupuncture is increasingly used as an alternative to medical therapy for various pain conditions. To study the effect of acupuncture in experimental and clinical studies, a control condition with sham acupuncture is needed. However, as such models have not been established in assessment of acupunctures effect against visceral pain, this study aimed to validate a new method for blinded sham acupuncture in experimental rectal pain.

Natural bacterial communities serve as quantitative geochemical biosensors.

Unlabelled: Biological sensors can be engineered to measure a wide range of environmental conditions. Here we show that statistical analysis of DNA from natural microbial communities can be used to accurately identify environmental contaminants, including uranium and nitrate at a nuclear waste site. In addition to contamination, sequence data from the 16S rRNA gene alone can quantitatively predict a rich catalogue of 26 geochemical features collected from 93 wells with highly differing geochemistry characteristics.

Can we rely on predicted basal metabolic rate in chronic pancreatitis outpatients?

Background/objectives: Malnutrition is a common complication to chronic pancreatitis (CP) and many patients need nutritional support. An accurate estimation of the basal metabolic rate (BMR) is essential when appropriate nutritional support is to be initiated, but in the clinical settings BMR is cumbersome to measure. We therefore investigated whether BMR can be reliable predicted from a standard formula (the Harris-Benedict equation) in CP outpatients.

[Autoimmune hepatitis preceded by hepatitis A].

Autoimmune hepatitis is characterized by unresolving inflammation and fibrosis of the liver, which untreated may lead to cirrhosis. The pathogenesis remains unclear and reflects a complex interaction between autoantigens, genetic predisposition, triggering factors and immune regulation. In rare cases, acute hepatitis A has been suspected as a triggering factor.

IKs Gain- and Loss-of-Function in Early-Onset Lone Atrial Fibrillation.

Introduction: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. The potassium current IKs is essential for cardiac repolarization. Gain-of-function mutation in KCNQ1, the gene encoding the pore-forming α-subunit of the IKs channel (KV 7.

Study protocol for a randomised, double-blinded, placebo-controlled, clinical trial of S-ketamine for pain treatment in patients with chronic pancreatitis (RESET trial).

Introduction: Chronic pancreatitis (CP) is an inflammatory disease that causes irreversible damage to pancreatic tissue. Pain is its most prominent symptom. In the absence of pathology suitable for endoscopic or surgical interventions, pain treatment usually includes opioids.

How financial hardship is associated with the onset of mental health problems over time.

Purpose: Poor mental health has been consistently linked with the experience of financial hardship and poverty. However, the temporal association between these factors must be clarified before hardship alleviation can be considered as an effective mental health promotion and prevention strategy. We examined whether the longitudinal associations between financial hardship and mental health problems are best explained by an individual's current or prior experience of hardship, or their underlying vulnerability.

Stability of the human Hsp90-p50Cdc37 chaperone complex against nucleotides and Hsp90 inhibitors, and the influence of phosphorylation by casein kinase 2.

The molecular chaperone Hsp90 is regulated by co-chaperones such as p50Cdc37, which recruits a wide selection of client protein kinases. Targeted disruption of the Hsp90-p50Cdc37 complex by protein-protein interaction (PPI) inhibitors has emerged as an alternative strategy to treat diseases characterized by aberrant Hsp90 activity. Using isothermal microcalorimetry, ELISA and GST-pull down assays we evaluated reported Hsp90 inhibitors and nucleotides for their ability to inhibit formation of the human Hsp90β-p50Cdc37 complex, reconstituted in vitro from full-length proteins.

Systematic mechanism-orientated approach to chronic pancreatitis pain.

Pain in chronic pancreatitis (CP) shows similarities with other visceral pain syndromes (i.e., inflammatory bowel disease and esophagitis), which should thus be managed in a similar fashion.

Altered cortical causality after remifentanil administration in healthy volunteers: a novel approach for pharmaco-EEG.

Alterations in cortical causality information flow induced by remifentanil infusion in healthy volunteers was investigated in a placebo-controlled double-blind cross-over study. For each of the 21 enrolled male subjects, 2.5 minutes of resting electroencephalography (EEG) data were collected before and after infusion of remifentanil and placebo.

Pain severity reduces life quality in chronic pancreatitis: Implications for design of future outcome trials.

Background/objectives: Chronic pancreatitis (CP) is a disabling disease characterised by abdominal pain, and various pancreatic and extra-pancreatic complications. We investigated the interactions between pain characteristics (i.e.

Disruption of cortical connectivity during remifentanil administration is associated with cognitive impairment but not with analgesia.

Background: The authors investigated the effect of remifentanil administration on resting electroencephalography functional connectivity and its relationship to cognitive function and analgesia in healthy volunteers.

Methods: Twenty-one healthy male adult subjects were enrolled in this placebo-controlled double-blind cross-over study. For each subject, 2.

BK channel activators and their therapeutic perspectives.

The large conductance calcium- and voltage-activated K(+) channel (KCa1.1, BK, MaxiK) is ubiquitously expressed in the body, and holds the ability to integrate changes in intracellular calcium and membrane potential. This makes the BK channel an important negative feedback system linking increases in intracellular calcium to outward hyperpolarizing potassium currents.

Dynamic spectral indices of the electroencephalogram provide new insights into tonic pain.

Objective: This study aimed to investigate reliability of electroencephalography (EEG) during rest and tonic pain. Furthermore, changes in EEG between the two states as well as dynamics and relation to pain ratings were investigated.

Methods: On two separate days EEG was recorded in 39 subjects during rest and tonic pain (cold pressor test: left hand held in 2°C water for 2 min.