Topically applied novel TRPV1 receptor antagonist, ACD440 Gel, reduces evoked pain in healthy volunteers, a randomized, double-blind, placebo-controlled, crossover study.

Background: The TRPV1 receptor is a key molecule in pain generation. Previous development of oral TRPV1-antagonists was halted due to systemic heat insensitivity and body temperature alterations. The present Phase 1b study investigated the efficacy, safety and plasma exposure of a topically administered TRPV1-antagonist (ACD440 Gel) in healthy subjects.

Characterization and ex vivo expansion of rare in situ cytokine secreting T cell populations from tumor tissue and blood of oral squamous cell carcinoma patients.

Rare subpopulations of tumor antigen-reactive memory T cells, which actively secrete type-1 effector cytokines, particularly TNF-α in situ, possess anti-tumor activity and prognostic relevance. These cells are relevant for cancer immunotherapy; however, their low frequencies make them difficult to study and novel protocols for their culture and expansion ex vivo are needed. Here, we studied the presence of T cells secreting type-1 cytokines (CyT cells) in the blood and tumors of 24 patients with oral squamous cell carcinomas (OSCC) and explored possibilities for their isolation and expansion.

Crystal Structure of a Variant PAM2 Motif of LARP4B Bound to the MLLE Domain of PABPC1.

Eukaryotic cells determine the protein output of their genetic program by regulating mRNA transcription, localization, translation and turnover rates. This regulation is accomplished by an ensemble of RNA-binding proteins (RBPs) that bind to any given mRNA, thus forming mRNPs. Poly(A) binding proteins (PABPs) are prominent members of virtually all mRNPs that possess poly(A) tails.

Response patterns of routinely measured inflammatory and coagulatory parameters in sepsis.

Background: Sepsis is characterized by a pro-inflammatory and pro-coagulatory shift which can induce life-threatening complications. Close monitoring and risk stratification of sepsis patients is crucial for proper treatment and consequently patient outcome. Therefore, this study focuses on the response patterns of inflammatory and coagulatory parameters used in clinical routines to estimate the course of sepsis.

A Phase I, Randomized, Double-Blind, Laser-Evoked Potential Study to Evaluate the Analgesic/Antihyperalgesic Effect of ASP9226, a State-Dependent N-Type Voltage-Gated Calcium Channel Inhibitor, in Healthy Male Subjects.

Objective: Evaluate the analgesic/antihyperalgesic effects of ASP9226, a state-dependent N-type voltage-gated calcium channel inhibitor, in healthy male subjects.

Design: Randomized, double-blind, double-dummy, placebo- and active comparator-controlled crossover study.

Setting: HPR Dr.

A Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Phase I Study of Analgesic/Antihyperalgesic Properties of ASP8477, a Fatty Acid Amide Hydrolase Inhibitor, in Healthy Female Subjects.

Objectives: To evaluate the analgesic/antihyperalgesic effect of ASP8477.

Design: Randomized, double-blind, double-dummy, cross-over, placebo- and active comparator-controlled study.

Setting: HPR Dr.

Investigation of the predictive validity of laser-EPs in normal, UVB-inflamed and capsaicin-irritated skin with four analgesic compounds in healthy volunteers.

Aims: The aim of the present study was to assess the predictivity of laser-(radiant-heat)-evoked potentials (LEPs) from the vertex electroencephalogram, using an algesimetric procedure, testing the anti-nociceptive/anti-hyperalgesic effects of single oral doses of four marketed analgesics (of different compound classes) vs. placebo, in healthy volunteers with three skin types.

Methods: This was a randomized, placebo-controlled, single-blind, five-way-crossover trial.

LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation.

mRNAs are key molecules in gene expression and subject to diverse regulatory events. Regulation is accomplished by distinct sets of trans-acting factors that interact with mRNAs and form defined mRNA-protein complexes (mRNPs). The resulting "mRNP code" determines the fate of any given mRNA and thus controlling gene expression at the post-transcriptional level.

No benefit adding eleutherococcus senticosus to stress management training in stress-related fatigue/weakness, impaired work or concentration, a randomized controlled study.

Introduction: Plant adaptogens are traditionally used for stress-related symptoms, but clinical evidence is inconsistent. This trial explored the effects of 120 mg/day Eleutherococcus senticosus root extract (ES), 2-day professional stress management training (SMT) and a combination of both (COM).

Methods: 144 participants suffering from asthenia and reduced working capacity related to chronic stress were randomized to the treatments.

An oral TRPV1 antagonist attenuates laser radiant-heat-evoked potentials and pain ratings from UV(B)-inflamed and normal skin.

Aims: Laser (radiant-heat) evoked potentials (LEPs) from vertex-EEG peak-to-peak (PtP) amplitude were used to determine acute antinociceptive/antihyperalgesic efficacy of ABT-102, a novel TRPV1 antagonist efficacious in preclinical pain models, compared with active controls and placebo in normal and UV(B)-inflamed skin.

Methods: This was a randomized, placebo- and active-controlled, double-blind, intra-individual, crossover trial. Twenty-four healthy subjects received six sequences of single doses of ABT-102 (0.

Dose-response relationship after single oral dose administrations of morphine and oxycodone using laser-evoked potentials on UVB- and capsaicin-irritated skin in healthy male subjects.

The aim of the study was to evaluate the analgesic/antihyperalgesic efficacy and to establish the dose-response relationship of morphine immediate release (IR) and oxycodone IR in a human experimental algesimetric model. Calculated effect ratios for peak-to-peak (PtP) amplitudes of laser-evoked potentials (LEPs) and visual analog scales (VAS) postlaser pain on UVB-irradiated skin (main target variables) were 1.68 and 1.

Effects of multiple-dose esomeprazole and pantoprazole on diazepam pharmacokinetic profile and pharmacodynamic effects on cognitive and psychomotor function in healthy volunteers.

A randomized, double-blind, 2-way crossover trial of 24 healthy volunteers investigated the influence of esomeprazole (CAS 119141-88-7) and pantoprazole (CAS 102625-70-7), both 1 x 40 mg orally for 11 days, on the pharmacokinetics and pharmacodynamics of diazepam (CAS 439-14-5). Single-dose intravenous diazepam 0.1 mg/kg was administered on day 6.

A stimulatory role for the La-related protein 4B in translation.

La-related proteins (LARPs) belong to an evolutionarily conserved family of factors with predicted roles in RNA metabolism. Here, we have analyzed the cellular interactions and function of LARP4B, a thus far uncharacterized member of the LARP family. We show that LARP4B is a cytosolic protein that accumulates upon arsenite treatment in cellular stress granules.

Predicting therapeutic efficacy - experimental pain in human subjects.

The pharmaceutical industry faces tough times. Despite tremendous advances in the science and technology of new lead identification and optimization, attrition rates for novel drug candidates making it into the clinic remain unacceptably high. A seamless boundary between basic preclinical and clinical arms of the discovery process, embodying the concept of 'translational research' is viewed by many as the way forward.

Hypericum extract reverses S-ketamine-induced changes in auditory evoked potentials in humans - possible implications for the treatment of schizophrenia.

Background: Auditory evoked potentials (AEP) provide a correlate of cognitive dysfunction in schizophrenia. Both cognitive dysfunction and AEP-characteristics might be related to reduced glutamatergic neurotransmission as induced by glutamate-antagonist like ketamine. Hypericum extract LI160 has demonstrated a ketamine-antagonising effect.

Comparison of the analgesic effects of a fixed-dose combination of orphenadrine and diclofenac (Neodolpasse) with its single active ingredients diclofenac and orphenadrine: a placebo-controlled study using laser-induced somatosensory-evoked potentials from capsaicin-induced hyperalgesic human skin.

Objective: The aim of this study was to investigate the analgesic efficacy of Neodolpasse, a fixed-dose combination of orphenadrine and diclofenac, compared with those of its single active ingredients in a human pain model.

Methods: The study was designed as a randomised, double-blind, placebo-controlled, four-period crossover study. Twenty-four healthy female and male subjects received single infusions of Neodolpasse, orphenadrine, diclofenac or saline solution over 60 minutes.

Analgesic effects of low-dose intravenous orphenadrine in the state of capsaicin hyperalgesia. A randomised, placebo-controlled, double-blind cross-over study using laser somatosensory evoked potentials obtained from capsaicin-irritated skin in healthy volunteers.

The present investigation aimed to elucidate the analgesic efficacy of 30 mg of intravenous orphenadrine citrate (CAS 4682-36-4) in a human pain model. Eighteen healthy female and male subjects were enrolled and received single infusions of 30 mg orphenadrine citrate and matching placebo in two periods which were separated by a 1 week washout period. The study was designed as a randomised, double-blind, placebo-controlled, two-period, cross-over trial.

Comparison of two different preparations of ibuprofen with regard to the time course of their analgesic effect. A randomised, placebo-controlled, double-blind cross-over study using laser somatosensory evoked potentials obtained from UW-irritated skin in healthy volunteers.

In the treatment of painful conditions the time to onset of a drug's analgesic effect is of great relevance. Plain ibuprofen acid (Ibu, CAS 15687-27-1) is relatively slowly absorbed after oral administration (t(max) is about 90-120 min). If, however, ibuprofen is given in form of a lysine salt, absorption is much quicker.

Effects of Hypericum extract (LI160) on the change of auditory evoked potentials by cortisol administration.

Target symptoms treated with Hypericum extract, i.e. somatisation, fatigue and depression could be related to an increased activity of glucocorticoids in the brain.

Effect of the new H1-antagonist ReN1869 on capsaicin-induced hyperalgesia in human skin/Human phase-I trial using somatosensory evoked potentials induced by a CO2 laser.

Extensive pre-clinical investigations have shown that the tricyclic compound ReN1869 ((R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3-piperidine carboxylic acid, CAS 170149-99-2) is a potent H1-antagonist with pronounced antinociceptive properties. In this human phase-I trial the effect of different acute and multiple doses of ReN1869 on capsaicin induced neurogenic inflammation and hyperalgesia was investigated. Twenty-one healthy male subjects were enrolled in this randomised, double-blind, three-period, crossover trial design--consisting of acute and one week b.

A randomised, placebo-controlled study comparing two formulations of dimenhydrinate with respect to efficacy in motion sickness and sedation.

It is known that sedation by H1 antihistaminic drugs can be reduced or avoided if slow release formulations are used for their administration, probably because of a slower increase of the drug concentration in plasma and brain. The aim of this study was to compare two different formulations of dimenhydrinate (CAS 523-87-5), a single fast release tablet with three chewing gums (divided dose principle), with regard to their efficacy in a motion sickness model and their detrimental effect on vigilance and central nervous system (CNS) performance. Caloric stimulation of the eardrum (air at 44 degrees C) was used to induce the symptoms of motion sickness in 24 symptomatic volunteers in a three-way cross-over design comparing three chewing gums (Superpep forte, chewed for 30 min each) containing 20 mg dimenthydrinate each with a 50 mg dimenhydrinate tablet and placebo.

[Analgesic effect of the selective noradrenaline reuptake inhibitor reboxetine].

Background: Reboxetine is a selective noradrenaline reuptake inhibitor (NARI). As noradrenaline plays a relevant role in antinociceptive mechanisms, the hypothesis was investigated in this study whether reboxetine has analgetic efficacy.

Methods: Twenty-four healthy volunteers were investigated in a crossover design.

Determination of low-level glucose and fructose in raw and refined crystalline sugar by high-performance anion-exchange chromatography: collaborative study.

A method was developed and a collaborative study was performed under the auspices of the International Commission of Uniform Methods for Sugar Analysis. The collaborators used high-performance anion-exchange chromatography (HPAEC) to determine trace amounts of glucose and fructose in 3 raw and 3 refined sugar samples provided as blind duplicates. Fourteen laboratories participated in the study.

Dimethindene maleate in the treatment of sunburn. A double-blind, placebo-controlled pilot study.

The efficacy of topical dimethindene maleate (DMM, CAS 31614-69-5, Fenistil Gel) in the treatment of sunburn was evaluated in a placebo-controlled, 1-period crossover trial in 24 healthy volunteers. An UV-erythema (sunburn) of a well-defined intensity and extent was experimentally induced on three different skin test-areas by means of UV-A/B irradiation with three times the minimal erythema dose (MED). About 24 h after irradiation, one skin test-area was subjected to a 1-h occlusive treatment with DMM gel, the second test area was subjected to treatment with a placebo gel and the third one remained untreated.

Bioavailability of escin after administration of two oral formulations containing aesculus extract.

In a steady-state cross-over study in 18 healthy volunteers, the relative bioavailability of beta-escin (CAS 11072-93-8) after oral administration of a new immediate release enteric-coated test formulation containing aesculus extract was evaluated in comparison with a prolonged-release reference preparation. The subject received the test and the reference preparation in randomised sequence for 7 days each with no washout period in between. The daily dose was 50 mg escin b.