Acute Caffeine Supplementation in Regular Caffeine Consumers Minimally Affects Strength in Knee Flexors

Please refer to the pdf version of the abstract located adjacent to the title

Four Days of Caffeine Withdrawal in Caffeine Consumers Lowers Strength in Knee Flexors and Extensors

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Quality and clinical supply considerations of Paediatric Investigation Plans for IV preparations-A case study with the FP7 CloSed project

A Paediatric Investigation Plan (PIP) is a development plan that aims to ensure that sufficient data are obtained through studies in paediatrics to support the generation of marketing authorisation of medicines for children. This paper highlights some practical considerations and challenges with respect to PIP submissions and paediatric clinical trials during the pharmaceutical development phase, using the FP7-funded Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit (CloSed) project as a case study. Examples discussed include challenges and considerations regarding formulation development, blinding and randomisation, product labelling and shipment and clinical trial requirements versus requirements for marketing authorisation. A significant quantity of information is required for PIP submissions and it is hoped that future applicants may benefit from an insight into some critical considerations and challenges faced in the CloSed project

Investigation of photoplethysmographic signals and blood oxygen saturation values on healthy volunteers during cuff-induced hypoperfusion using a multimode PPG/SpO2 sensor

Photoplethysmography (PPG) is a technique widely used to monitor volumetric blood changes induced by cardiac pulsations. Pulse oximetry uses the technique of PPG to estimate arterial oxygen saturation values (SpO2). In poorly perfused tissues, SpO2 readings may be compromised due to the poor quality of the PPG signals. A multimode finger PPG probe that operates simultaneously in reflectance, transmittance and a combined mode called “transreflectance”’ was developed, in an effort to improve the quality of the PPG signals in states of hypoperfusion. Experiments on 20 volunteers were conducted to evaluate the performance of the multimode PPG sensor and compare the results with a commercial transmittance pulse oximeter. A brachial blood pressure cuff was used to induce artificial hypoperfusion. Results showed that the amplitude of the transreflectance AC PPG signals were significantly different (p\0.05) than the AC PPG signals obtained from the other two conventional PPG sensors (reflectance and transmittance). At induced brachial pressures between 90 and 135 mmHg, the reflectance finger pulse oximeter failed 25 times (failure rate 42.2 %) to estimate SpO2 values, whereas the transmittance pulse oximeter failed 8 times (failure rate 15.5 %). The transreflectance pulse oximeter failed only 3 times (failure rate 6.8 %) and the commercial pulse oximeter failed 17 times (failure rate 29.4 %)

A mini-review of non-parenteral clonidine preparations for paediatric sedation

OBJECTIVE: To provide an overview of non-parenteral clonidine formulations and assess the feasibility of their use for paediatric sedation. / METHODS: A literature search was conducted using electronic databases and a combination of search terms. Forty articles met the inclusion criteria. Publications were grouped into different dosage forms and assessed for their potential application for sedation of children in intensive care. / KEY FINDINGS: Several routes of clonidine administration have been investigated for numerous indications in children, including perioperative sedation and analgesia. These include oral liquids, tablets, oral transmucosal systems, nasal sprays and rectal suspensions. Conflicting studies on oral transmucosal clonidine formulations suggest that further research is required to fully establish efficacy. Nasal sprays and rectal suspensions have the advantages of rapid onset of action and potential for dose flexibility, but predictable absorption is difficult to obtain. CONCLUSIONS: Provided age-appropriate strengths are available, IV formulations remain the most predictable in terms of bioavailability and flexible in terms of dose adjustment. However, as with all routes, down-titration is difficult given the long half-life of clonidine. Oral transmucosal systems, nasal sprays and rectal suspensions have potential in a less acute setting, but significant clinical work is required to elucidate a full pharmacokinetic and pharmacodynamic profile

Research for recovery: a review of the drugs evidence base.

A review of international evidence to support Scotland's National Drugs Strategy, The Road to Recovery. This report presents evidence on effective treatment and recovery from substance misuse

The role of the RACK1 ortholog Cpc2p in modulating pheromone-induced cell cycle arrest in fission yeast

The detection and amplification of extracellular signals requires the involvement of multiple protein components. In mammalian cells the receptor of activated C kinase (RACK1) is an important scaffolding protein for signal transduction networks. Further, it also performs a critical function in regulating the cell cycle by modulating the G1/S transition. Many eukaryotic cells express RACK1 orthologs, with one example being Cpc2p in the fission yeast Schizosaccharomyces pombe. In contrast to RACK1, Cpc2p has been described to positively regulate, at the ribosomal level, cells entry into M phase. In addition, Cpc2p controls the stress response pathways through an interaction with Msa2p, and sexual development by modulating Ran1p/Pat1p. Here we describe investigations into the role, which Cpc2p performs in controlling the G protein-mediated mating response pathway. Despite structural similarity to Gβ-like subunits, Cpc2p appears not to function at the G protein level. However, upon pheromone stimulation, cells overexpressing Cpc2p display substantial cell morphology defects, disorientation of septum formation and a significantly protracted G1 arrest. Cpc2p has the potential to function at multiple positions within the pheromone response pathway. We provide a mechanistic interpretation of this novel data by linking Cpc2p function, during the mating response, with its previous described interactions with Ran1p/Pat1p. We suggest that overexpressing Cpc2p prolongs the stimulated state of pheromone-induced cells by increasing ste11 gene expression. These data indicate that Cpc2p regulates the pheromone-induced cell cycle arrest in fission yeast by delaying cells entry into S phase